NSB Exam 1

Tissues with CT

"Hyperdense" tissues appear white -Bone -Calcifications -Clotted blood (due to fibrin protein) "Hypodense" tissues appear black -Air -Fat -Cerebral spinal fluid (dark gray) -Acute infarct "Isodense" tissues appear gray -Gray matter -White matter, contains myelin which has a high lipid content and appears slightly darker than gray matter -Flowing blood

Meningitis

"Lepto"meningitis is an inflammation of the soft meninges, the pia mater and arachnoid -Aseptic (viral) meningitis -Chronic (viral) meningitis -Acute (Pyogenic or bacterial) meningitis -Mycobacteria and fungi - subacute (course) meningitis Symptoms -Fever -Headache and stiff neck -Sensitivity to light -Confusion -Nausea/vomiting -Cold hands and feet -rash

Communicating hydrocephalus

"non-obstructive", CSF flow is blocked outside of the ventricular system

Non-communicating hydrocephalus

"obstructive", impairment of CSF flow within the ventricular system

Neonatal Acute (bacterial) meningitis

(maternal genital flora)- community acquired Most common microbe, Group B Strep. (agalactiae) E.coli - hemorrhage, necrotizing arteritis, necrosis, roughly same incidence in this age group as Strep.Agalactiae Listeria - microabscesses

Macroglia

(oligodendrocytes, OL; astrocytes, AS) are so termed because their cell bodies are larger (8-10 µm) than those of microglia (4-5 µm) and their branching is more expansive. Together the three cell types outnumber neurons in the CNS. The OLs drawn here lack their enormous myelin sheaths and represent a reserve population poised to make myelin and remyelinate axons if needed. They have been termed satellite OL, and reside both in gray and white matter.

BBB transport of essential amino acid

(phenylalanine, leucine, tyrosine, isoleucine, valine, tryptophan) are not synthesized in brain and must be supplied by dietary intake, protein breakdown and transport across BBB. All compete for L-type transport proteins to gain entry. Elevated plasma levels of one amino acid, e.g. phenylalanine in phenylketonuria (PKU), will inhibit the intake of others due to competition for L-type transport proteins. Note: important one is tyrosine which are needed for the synthesis of catecholamine neurotransmitters

What is the normal ICP of a supine adult

10-15 torr

No neuron is farther than _____ from a capillary

100 µm

What is the peak time to detect maternal circulation of alpha fetoprotein?

13 to 16 weeks

Hemorrhagic stroke

15% of strokes Results form an arterial tear or rupture (aneurysm) Causes #1 trauma (sheared vessels in the SAS) #2 ruptured aneurysm - large vessel aneurysm - small vessel pathology such as in lacunar infarcts * caused by HTN, diabetes, sickle disease, stimulant drugs * ruptured Charcot-Bouchard aneurysms at termini of deep penetrators

Only about ____ of the CSF is formed by choroid plexuses

2/3 The other 1/3 derives from fluid that traverses the capillary and venule walls of dense microvessel beds within CNS parenchyma. In addition to contributing to brain ECF, this fluid diffuses from within brain tissue across the pial surface into the SAS, and also across the ependymal lining into the ventricles (arrow) to add to the volume of CSF.

At any time, how much of the CSF is within the subarachnoid space?

2/3, the rest is in the ventricles

Gyri normally from in the _____ trimester

2nd They form consequent to migration and proliferation that inverses the brain surface area Note: the gyration of the cerebral cortex should be compete by birth

The spinal cord derives from ______

3 germinal origins Alar plate -> dorsal horn (2°sensory neurons) Basal plate -> ventral horn (somatic/autonomic motor neurons) Neural crest -> sensory ganglia -> 1°sensory neurons The plates and undifferentiated neural crest disappear by birth - no more germinal centers; central canal closed at birth

Neuronal migration defects leads to a _________ instead of a six layer cortex

4 layer cortex

Within the cerebral hemispheres there are 4 distinct lobes with each histologically organized with:

4 lobes: frontal, parietal, temporal, occipital Each lobe is histologically organized with an outer cortex and subcortical white matter. The frontal lobe also contains deep gray matter, syn. deep nuclei.

The neural tube closes during week ___

4, it concludes with closure of anterior and posterior neuropores

Foramen of Magendie

4th ventricle to subarachnoid space.

The estimated luminal surface area of CNS capillaries/venules with a BBB, compared to those without a BBB, is ______

5000:1. Therefore, a small physiologic leak here and there does not matter significantly in determining a drug's overall volume of distribution in the CNS.

Goal is to maintain a cerebral perfusion pressure about ______

70 mmHg Note: CPP = MAP -ICP

In order to illustrate the features of a meta-analysis, let's look at how the decision to treat within the 3-4.5 hr. window came to be:

821 patients were randomized to receive Alteplase in a dose of 0.9 mg./kg. or placebo The primary end point was little or no disability at three months, that is, a score of 0 to 1 in the Modified Rankin Scale (mRS). The mRS is a simplified overall assessment of function: a score of 0 indicates the absence of symptoms and a score of 6 indicates death. In the trial, the median time for administration of Alteplase was 3 hrs. 59 minutes

Varicella zoster virus (chicken pox) teratogen effect

85-95% women are immune 1-7 out of 10,000 develop chicken pox during pregnancy Infection in first 20 wks: 2% chance of congenital varicella infection Child can develop: - Microcephaly/microencephaly/cortical atrophy - Congenital encephalomyelitis - Ventriculomegaly - Blindness -cataracts/chorioretinitis - Mental retardation - Seizures - Intrauterine growth retardation - Limb hypoplasia - Scarring

Intraparietal sulcus

90 degrees from the postcentral gyrus and separates the superior parietal lobule from the inferior parietal lobule

Germinal matrix bleeds

< 34 weeks, premature Immature vessels w/o stroma Hypoxic stress Ischemic endothelial cells

Stroke

= neurologic deficit resulting from an abrupt incident of vascular insufficiency to the brain. The incident does not have to stop blood flow. Merely reducing the flow rate from a normal 55 ml/100g of CNS/min to about 20 ml/100 g/min causes cessation of neuronal signaling and eventual cell death if flow is not restored. Necrotic brain tissue resulting from stroke is called an infarct. Ischemic strokes (85% of all strokes) are commonly caused by a thrombus (clot formed within vessel wall) or an embolus (mobilized piece of foreign matter, e.g. atherosclerotic plaque). Hemorrhagic strokes (15% incidence) occur from tears in the vessel wall, e.g a ruptured brain aneurysm.

ICP treatment should be initiated for an ICP _______

> 20 mmHg

Occlusive stroke

A "plug" in the piping 85% of cases Can be cortical, lacunar, and stem infarcts

Glial fibrillary acidic protein (GFAP)

A 50kDa, cell type-specific intermediate filament subunit protein expressed within the CNS only in the cytoskeleton of astrocytes. Therefore, antibodies to GFAP can be used for immunocytochemistry

Blood CSF barrier

A CSF compartment, the inner boundary of which is the apical surface of CPs and the outer boundary being the arachnoid membrane. Brain tissue and CSF reside in between the two boundaries.

Concussion

A blow to the head that results in temporary loss of normal function 12% of all ED visits Often no external signs of head trauma Don't have to lose consciousness - symptoms can include headaches, irritability, vomiting, loss of memory, seizure, and confusion Days to weeks to fully recover

Enhanced CT

A computed tomogram taken after introduction of an intravenous contrast agent. Facilitates visualization of suspected neoplasms or brain abscess Contrast material containing hyperdense material such as iodine highlights areas of increased vascularity and areas of blood-brain barrier breakdown Must be done within 48 hrs BUN test and 72 Hrs within a creatine test. This is because the contrast is often nephrotoxic

aphasia

A cortical inability to produce language resulting from a cortical lesion

Fornix gross

A fiber bundle that projects from the paired hippocampi toward the midline to fuse as the roof of the third ventricle, where it's termed body of the fornix, before separating and projecting inferiorly toward the mammillary bodies of hypothalamus as the columns of the fornix. The columns form part of the lateral walls of the interventricular formamina. The fornix is a major projection pathway of the limbic system involved in short term memory processing.

Systemic review

A form of research that provides a summary of medical reports on a specific clinical question A systematic review utilizes established methods to: -Search the literature to find all relevant articles, both published and unpublished -Critically appraise the quality of the studies gathered -Synthesize the findings systematically A systematic review is particularly useful in bringing together a number of separately conducted studies, sometimes with conflicting findings, and synthesizing their results

Disorders which damage (open) the BBB: High altitude cerebral edema (HACE)

A generalized opening of the BBB throughout the brain may be due to hypoxia-induced vasodilation and an uncompensated increase in the intravascular pressure that overwhelms tight junctions. Potentially fatal vasogenic edema results unless the patient is rushed to lower altitude.

Funnel plot

A graphical display used in meta-analysis to look for publication bias.

What is the key difference between systematic review and meta analysis?

A meta-analysis will usually start with a systematic review but it ends with the pooling of data from individual studies using established statistical methods, to provide a pooled estimate of the "effect size". The process of statistical synthesis of the data differentiates the meta-analysis

holoprosencephaly

A midline patterning defect Usually sporadic but also has been demonstrated to have an autosomal dominant pattern A single telencephalic ventricle with continuity of the cerebral hemisphere across the midline Associated with craniofacial abnormalities, most severe being cyclopia

Tuberous Sclerosis (Complex) Syndrome

A multisystem disorder Autosomal dominant, causing infantile spasms, autism, and mental delays Due to disrupted neuronal migration along with an abnormal neuronoglial differentiation

interpenduncular fossa gross

A pit walled laterally by the two cerebral peduncles

Spina bifida cystica (myelomeningocele)

A posterior neuropore closure failure Alpha fetoprotein is elevated only if the cyst breaks This is the most common open form and 90% co-present with Chiari 2 malformation, communicating hydrocephalus (can't go down into the spine) Cyst contains CSF, meninges, and the spinal cord (in particular the conus medullaris and maybe L5) Due to a vertebral arch split/ missing central canal

Spina bifida cystica (meningocele)

A posterior neuropore closure failure Neurologic effects are minimal and alpha fetoprotein only increases if the cyst breaks Cyst contains CSF and meninges only and is covered by thin skin

Spina bifida: occulta

A posterior neuropore closure filature Presents with no elevated alpha fetoprotein and no neurological effects The vertebral arches do not completely fuse and present with a hairline fissure; however the cord is contained and functional (the skin is closed and the meninges are contained) May present with hair patch or mole over it

Subdural space

A potential space between the dura and arachnoid

Epidural space

A potential space between the dura and cavaria

Choroid plexus papilloma

A rare benign choroid plexus tumor histologically appears like choroid plexus

Golgi stain

A silver method for staining the complete neuron. For unclear reasons, Golgi staining labels neurons sporadically

Cavernous sinus

A sinus containing venous blood located on each side of the body of the sphenoid bone, near the base of the brain, behind the bridge of the nose

Occlusive "dry" infarct signs (cortical branches)

ACA - limited to contralateral lower extremity - paresis/paraylsis and/or sensory deficits MCA - contralateral face, upper extremity and torso potential affected - Paresis/paralysis and/or sensory defects - Possible aphasia PCA - Visual sensory deficits (bilateral) - Potential short-term memory deficits

Perfusion of the corona radiata and internal capsule

ACA supplies the most anterior portion MCA supplies the slightly anterior portion PCA supplies the posterior portion

Vessels of anterior circulation of the brain

AComm ACA ICA MCA

syphilitic meningitis

AKA - Meningovascular Syphilis. An inflammation of the meninges of the brain. The bacteria likes to live within small blood vessels causing obliterative endarteritis

Aggressive attempts to maintain CPP >70 should be avoided because risk of ______

ARDS

Five suddens of stroke

Actue onset of: -weakness on one side of the face/body -trouble speaking -change or loss of vision -severe dizziness or imbalance -severe headache

60-year-old man presents to the ED unable to move his arm or leg

Acute infarct with midline shift and cingulate/subfalcine herniation

Fat/Air emboli in brain

All the little hemorrhages indicates something obstructing all those little blood vessels Fat emboli can enter the blood via multiple long bone fractures Air can enter the blood most often mechanically

Reverse "sink effect" of CSF

Allows for removal of waste products that accumulate in brain tissue The concentration of most molecules in brain tissue is greater than in CSF, creating a physiologic gradient between the two entities. The constant flow of CSF through the ventricles and throughout the SAS provides a "sink" that reduces steady state concentrations of molecules that otherwise build up in the brain and CSF. Waste products include neurotransmitter metabolites, homovanillic acid (HVA) and 5-hydroxy-indoleacetic acid (5-HIAA). These compounds diffuse down their concentration gradients and across the ependymal or pial linings into CSF. They are in turn cleared by CPs using active transporters working in a reverse, apical-to-basolateral, brain-to-blood direction across the CEC into CP capillaries. Solutes diffusing into SAS can also leave the brain passively in CSF as it flows through arachnoid villi into the superior sagittal sinus and the venous return from the head.

CN VI: Abducens Nerve root gross

Along the caudal junction of the pons, which is easily distinguished from the more caudal medulla o blongata, emerge the paired abducens nerves (CN6) on either side of the basilar sulcus at the pontomedullary junction. The abducens motor nuclei are located in the caudal pons.

Paramedian pontine branches gross

Along the length of the basilar artery which pass directly into the pons,

What is the predominant protein in the fetal circulation during the 1st trimester

Alpha-fetoprotein (AFP) Note: Fetal NTDs that open body wall allow AFP made in the fetal liver to "leak" into the amniotic fluid and eventually enter the maternal blood stream.

Normal pressure hydrocephalus

Also called intracranial HTN Increase in CSF production or a decrease in absorption

Lateral apertures gross

Also found within the CPA is a wisp of choroid plexus, which protrudes from the lateral apertures of the 4thventricle, through which cerebrospinal fluid enter the subarachnoid space.

Interhemispheric (median longitudinal)

Also known as the median longitudinal (sagittal) fissure, separates the cerebral hemispheres in the mid-sagittal plane

Guideline for early management of acute ischemic stroke

Alteplase, a tissue plasminogen activator manufactured by recombinant DNA technology, that acts as a fibrinolytic agent Recommendation: -IV alteplase (0.9 mg/kg, maximum dose 90 mg over 60 minutes with initial 10% of dose given as bolus over 1 minute) is recommended for selected patients who can be treated within 3 hours of ischemic stroke symptom onset or patient last known well or at baseline state. -IV alteplase (0.9 mg/kg, maximum dose 90 mg over 60 minutes with initial 10% of dose given as bolus over 1 minute) is also recommended for selected patients who can be treated within 3 and 4.5 hours of ischemic stroke symptom onset or patient last known well or at baseline state. Note: wisdom of treating with Aletplase was accrued via several trials and meta-analyses thereof

Circle of Willis

Anastomosis of anterior and posterior circulation Collateralizing but normally little flow around the circle Designed for anastomotic flow in a pinch High incidence of imperfection/asymmery

What is the most common site of vascular pathology in the brain?

Anterior circulation (left Middle cerebral artery)

Biggest to smallest neurons with cell bodies residing in the CNS

Anterior horn cells (lower motor neurons, alpha motor neurons) Neocrotical pyramidal neurons Purkinje cells Primary sensory afferent neurons Granule neurons Note: the first 3 are projection neurons!

Vermis gross

Any parasagittal part of the cerebellum within one centimeter of the midline

Cerebellum hemispheres gross

Anything lateral to the vermis

Infarct

Area of dead/dying tissue due to local loss of oxygen core - anoxia - necrotic cell death-infarction - loss of function penumbra - hypoxia -dysfunctional neurons (apoptosis) -subject to rescue

Thalamoperforating arteries gross

Arise from PCA-P1 to enter the interpeduncular fossa and penetrate the brain through the posterior perforated substance. They supply more posteriorly situated deep telencephalic structures, e.g. especially thalamic nuclei

Paired labyrinthine arteries gross

Arise from the basilar artery These arteries do not provide blood to the CNS, but course directly to structures in the inner ear (they might arise from AICA).

Cerebellum development

Arises from the alar plate of the metencephalon Located posterior to the 4th ventricle, pons, and medulla. Inferior to the occipital lobe This is the last region to generate neurons (3rd trimester -2yr) (but hippocampus doesn't stop) Note: when mature, it contains 50% of the brain neurons within its cortex (most are very small)

Epidural hematoma

Arterial bleed due to a tear in the middle meningeal artery Blood collects in the epidural potential space Forming a biconvex hematoma -Restricted by sutures Fracture of the pterion union of the temporal, frontal, parietal and zygomatic bones

Virchow-Robin space

As blood vessels penetrate the brain from the subarachnoid space, which exists between the innermost two layers of meninges, some of this space also dips into CNS tissue, creating a peri-vascular (Virchow-Robin) space It is important in the nightly increase in the volume of CSF that flushes out your brain and allows concentration of potentially toxic metabolites such as amyolid to be cleared

Anterior spinal artery gross

As the vertebral a. fuse to form the basilar a. they each give rise to a tiny medial branch that merges in the midline to produce the single anterior spinal artery It descends caudally along the anterior median fissure of the spinal cord and perfuses the anterior portion of the spinal cord Infarction of this tiny artery where it forms at the branchpoint with vertebral a. gives rise to a protoypical stroke lesion, the medial medullary syndrome

Cryptococcal Meningitis

Associated with AIDS Encapsulated yeasts, narrow neck buds found in the subarachnoid space into the Virchow-Robin spaces Visualized with India ink preps, PAS, silver stains, and mucicarmine Note: a form of chronic meningitis

Brain ATP consumption

At 2% of body wt (3 lbs), it uses ~20% of body's consumed O2 for ATP production The most ATP-dependent cellular processes -Maintenance of resting membrane potential -Axon transport The most ATP-dependent function -Cognition

Disorders which damage (open) the BBB: Multiple sclerosis

At the outset of the formation of the glial plaque, i.e., the random, focal MS lesion, the BBB therein becomes leaky and then subsequently reforms. Although MS is an autoimmune disease, opening of the BBB may be a causal to the disease, which allows immune cells to access the otherwise immunologically privileged CNS. Astrocytes within the plaque undergo hypertrophy (reactive gliosis). This and other cellular changes of astrocytes contribute to BBB breakdown, which appears to recover in older lesions for unclear reasons.

Axoplasm, axolemma, microtube, and neurofilament

Axolemma= axon plasma membrane Axoplasm= cytoplasm of the axon Microtubules and neurofilaments are found within the axon

Axoaxonic synapse

Axon to axon synapse

Axosomatic synapse

Axon to soma synapse Often inhibitory

Axodendritic synapse

Axon-to-dendrite synapses. (e.g. dendritic spines) Often excitatory

Characteristics of axons

Axons are much longer than dendrites, up to 1.5 m in length They branch distally into collaterals ending as presynaptic terminals Average diameter is about 1 µm

Setup for supratentorial herniations

Basically a portion of the temporal lobe herniates under the tentorium cerebelli into the tentorial notch This is lead to tract of CN III and eyes will not dilate on the side of the herniation, compression of the reticular formation causing altered mental status, and ipsilateral motor problem

40-year-old woman is hit in the face with a baseball bat Bruising around the eyes, bruising behind the ear (mastoid process), blood coming from the ears

Basilar skull fracture Base of the skull is at about 45 degrees to the ground so impact to the face can damage the base of the skull; especially since this area has many holes for cranial nerves to leave Note: the internal carotid goes through the carotid canal and then coming up through the foramen lacerum. Fracture to this area can lacerate this artery leading to bleeding around the brain, eyes, ears, etc) Note: may be referred to as a hinge fracture

Normal elongation of the spine and cord

Beginning at the end embryonic development within the first 8 weeks, they are the same length. You begin to have nerve roots as well Around g24 weeks (end of 2nd trimester) there is a noticeable elongation of the vertebral column relative to the spinal cord. Conus tip around S1-S2 In the newborn, there is considerable elongation of the vertebral column that continues into adulthood. Conus tip around L3-L4 in newborn and L1-L2 in adults Note: as the vertebral column elongates, the conus tip tends to go higher up

Meningioma

Benign tumor of the meninges 80% low grade and doesn't metastasize, Arises from meningothelial cells Well-circumscribed enhancing lesions Most common in the 3rd decade of life

subarachnoid space

Between the Pia and arachnoid Within it are the brain blood vessels

Olfactory sulcus gross

Between the straight gyri and the orbital gyri and is the location of the olfactory tract and bulb (related to CN I) sit

61 yo awake and talking but with saw blade in head that cut through his anterior 1/3 of his SSS What should be done

Bi-coronal craniotomy and post-op antibiotics

Thalamus gross

Bi-lobed inferior to the body of the fornix Separated by the third ventricle

Types of neuronal projections

Bilateral Ipsilateral Contralateral Commissural Decussation

3 y o male GCS 3 ICP>40 There is no shift but there is no cisterns around the brainstem What can be done?

Bilateral decompressive craniectomy Then do a craniplasty 2 months post-op

Medical management of Brain trauma

Blood pressure and oxygenation: Maintain SBP>90, PaO2<60 or O2 sat. <90% avoided. Hyperosmolar therapy: Mannitol is effective for control of increased ICP at doses of .25 to 1 gm/kg body wt. Avoid hypotension(SBP<90). Prophylactic hypothermia: Not associated with decreased mortality. Deep vein thombosis prophylaxis: Recommend intermittent pneumatic compression stockings. Pharmacologic DVT prophylaxis in pts with severe TBI reduces risk of DVT, but data shows a trend to increased risk of intracranial bleeding. Indications for ICP monitoring: GCS</= 8. ICP thresholds: Treatment should be initiated for ICP > 20. Cerebral perfusion thresholds: Maintain CPP within range 50-70 mm Hg. Aggressive attempts to maintain CPP>70 should be avoided because risk of ARDS. Anesthetics, analgesics, and sedatives: Propofol is recommended to help control increased ICP. Prophylactic barbiturates to induce burst suppression on EEG is not recommended. Nutrition: Pts should be fed full caloric replacement by post-injury day 7. Anti-seizure prophylaxis: Prophylactic use of Dilantin or valproate is not recommended for preventing late post-traumatic SZ(PTS). Anti-convulsants can be used to decrease incidence of early PTS within 7 days of injury. Early PTS is not associated with worse outcomes. Steriods: Use of steriods for reducing ICP not recommended. High dose Methylprednisolone is associated with increased mortality in severe TBI. Hyperventilation: Prophylactic hyperventilation (C02 of 25 or less) is not recommended. However, hyperventilation can be used as a temporizing measure for short term reduction of increased ICP.

Collateral sulcus gross

Borders laterally the parahippocampal gyrus

The CNS has what 3 components?

Brain Spinal cord Cranial nerve 2 (optic nerve-retina)

Organs often involved with Tuberous Sclerosis (Complex) Syndrome

Brain - neocortical tubers (immature neuron/ glia cell that forms a firm mass that is nonfunctional) - subependymal nodules - subependymal giant cells astrocytomas (SEGAs) Heart - Rhabdomyomas (can lead to arrhythmia) Kidneys - Angiomyolipomas (hamartoma) Skin - superficial angiofibromas/ fibromas

Cranial contents

Brain parenchyma (80%) CSF volume (8%) Blood volume (12%)

microglia

Brain resident macrophages We will discuss only microglia (M) here. They are the brain's resident macrophages. Their name derives from a tiny (4-5 µm) cell body Microglia exist in two reversible states: non-activated (syn, ramified, resting) cells have elaborate processes, and are plentiful and evenly dispersed across GM and WM. Their branches promote surveillance capacity due to a high surface area bearing receptors for local signals released by dying cells and immune infiltrates. Activated M retract most of their processes, become amoeboid, and migrate to sites where brain remodeling occurs during development and, alternatively, to sites of injury or automimmune lesions. Activated M phagocytose unused or damaged cells, and can function as antigen-presenting cells capable of producing inflammatory cytokines in autoimmune diseases of the CNS

Diffuse Axonal Injury (DAI)

Brain rotational injury causing axonal and micro vessel damage Note: this is an acceleration/decceleration injury Note: a lot of theses axons are not actually broken, they are just stretched and collapse

Cushing's triad

Brainstem's response to descending pressure cone as ICP exceeds CPP Systolic hypertension + reflex bradycardia + Cheyne-Stokes respiration This indicates central herniation advancement deep into posterior fossa and generally has a poor outcome Note: caused by increased firing of the hypothalamus that ramps up the activity of the preganglionic sympathetics

A2 branch of ACA

Branch of the ACA which circles around the corpus callosum Those arteries branching off of this are the pericallosal artery and callosomarginal artery

Lenticulostriate arteries

Branches of the MCA Most common of the perforators to hemorrhage Perfusion territory is close to region where motor/somatosensory axons for lower extremity + upper extremity converge

Anterior communicating artery gross

Bridges the ACA-A1 segments Small, 2-4 mm Spans the interhemispheric fissure Thi connection may be absent or atypical in about 25% of brains

The pars opercularis and triangularis in the dominant hemisphere (most people will be on the left side) are collectively known as _____

Broca's area This area is where motor programs for language output in all forms (verbal, written, and sign) are stored and utilized. It is frequently damaged by embolic strokes or other cerebral vascular lesion in the cortical territory perfused by the middle cerebral artery and results in severe disability impairing all forms of language output (Broca's aphasia)

Brain contusion

Bruises the occur over the crest of the gyri due to an external force Blood vessels rupture causing hemorrhage, and cellular ischemia and swelling (edema) Can be focal, diffuse, acute, or chronic

Intracranial pressure graph

Buffers for increased volumes include vascular and CSF volumes. A lesion such as a hematoma can be compensated by a displacement of CSF into the spinal thecal sac and decreases in cerebral venous blood. Failure of intracranial compensation occurs when ICP is greater than approximately 25 mm Hg.

Strategies to enhance drug entry into the brain

Bypass the BBB by intrathecal administration - usually by drug infusion into the lumbar cistern Transiently open the BBB or exploit the disease itself which can also open the barrier, if only temporarily, to administer drug. For example, gliomas lacking a barrier are being examined as sites for targeted chemotherapy. Agents co-administered at doses that temporarily open the barrier, e.g. histamine, bradykinins, mannitol, are being used to deliver a bolus of chemotherapeutic drugs selectively to tumors. Synthesize drug derivatives with high BBB permeability and without capacity to bind to transporters that export drug from brain to improve CNS entry and retention - always a major emphasis for designer drugs in the pharmaceutical industry.

C1-C2 subluxation

C1 is typically very close to the foramen magnum A violent force pushes C1 forward causing its dislocation. This can compress the brain stem/ beginning of spinal cord against C2 Can be fatal or repairable if not too bad

CBF is determined chemically by ___, metabolically by _______ and neurochemically by ________

CBF is determined chemically by PaCO2, metabolically by K+o and neurochemically by glutamatergic synaptic activity PaCO2 is a much more potent CNS vasodilator than PaO2 -Hypercapnea leads to vasodilation - Hypocapnea leads to vasoconstriction (this can decrease the ICP to maintain the CPP, but it renders the brain ischemic) Increased synaptic activity occurs in brain regions undergoing tasks. Interstitial fluid [K+] increase due to v-gated K+ channel activity. Elevated [K+]o triggers vasodilation to meet increased metabolic demand

Choroid plexuses location

CP clusters protrude from the inferior surface of the lateral ventricles, extend through the interventricular formina and protrude from the roof of the 3rd ventricle, and from the posterior surface of the 4th ventricle and out the lateral apertures into the subarachnoid space (SAS). The largest clump of CP, the glomus, forms in the atrium (syn, trigone) of the lateral ventricle.

Cerebral perfusion pressure

CPP = MAP - ICP Normally around 70-90 Torr in adults

Interventricular foramen gross

CSF flows from each lateral ventricle through an interventricular foramen into the common midline third ventricle

Cerebral spinal fluid (CSF) flow

CSF, made from the choroid plexus of the lateral ventricles, flow through the interventricular foramens (Monro) and enters the third ventricle CSF, manufactured from the choriod plexus of the lateral ventricles and the third ventricle, flows through the cerebral aqueduct into the fourth ventricle CSF, made from choroid plexus of the lateral, third and fourth ventricles, exits the fourth ventricle through two lateral (Luschka) and one medial (Magendie) foramena CSF surrounds the spinal cord and brain within the subarachnoid space CSF exits the subarachnoid space by flowing through the arachnoid granulations and draining into the superior sagittal sinus

hypoglossal nerve roots

Can be found within the preolivary sulcus

Inferior frontal gyrus gross

Can further be divided into the pars orbitalis, pars triangularis, and the pars opercularis

Arterial, early venous and late venous phases of conventional arteriogram

Can see the dye move from the arterial phase -> capillary phase -> venous phase

Carbon monoxide poisoning brain

Carbon monoxide like to attack the globus pallidus

Dandy-Walker malformation

Caused by genetic defects, infections, toxins and medications Malformations -Enlargement of the posterior fossa -Vermal aplasia -Elevation of the tentorium -Causing hydrocephalus Symptoms include -Developmental delays -Seizures -Vision and hearing impairment -Poor muscle tone, balance and coordination

Waterhouse-Friderichsen syndrome

Caused by meningococcal Meningitis Aderocortical hemorrhage Septicaemia > Endotoxemia > Adrenal hemorrhage (90%) > DIC > Shock

Histologic signatures of damaged during and dead neurons

Central chromatolysis "Red and Dead" hypoxic-ischemic change

What are the 2 bends in the neural tube?

Cephalic flexure which around where the midbrain will be in the adult and this stays Cervical flexure occurs between the medulla and spinal cord, it eventually straightens out and disappears

The brain consists of what 3 main components

Cerebellum Brainstem Cerebrum

Energy demand requires constant, tightly regulated _____

Cerebral blood flow (CBF) Utilizes 18% of cardiac output, or about 750 ml/min

Axes of orientation and synonyms

Cerebrum and diencephalon - rostral = anterior - caudal = posterior - dorsal = superior - ventral = inferior Brainstem and cord - rostral = superior - caudal = inferior - dorsal = posterior - ventral = anterior

Posterior fossa (hindbrain) malformations

Chiari malformations Dandy-Walker malformation

Mom presents to your pediatric clinic with her 5-year-old child and a chief complaint of her child awakes from sleep with a headache that improves during the day

Choroid Plexus papilloma Note: awakes from sleep with a headache that improves during the day tell you that something is obstructing CSF flow

Cerebrospinal Fluid (CSF)

Choroid plexus is the organ that secretes CSF Similarities to the CSF/choroid plexus to the glomerular filtrate/kidney On average, 25 ml fills the ventricles and the choroid plexus makes 600-700 ml /day CSF is absorbed across the arachnoid villi into the venous circulation

______ gives rise to choroid plexuses

Choroidal arteries (anterior and posterior)

______ line the ventricles

Ciliated ependymal cells They transition to microvillous CECs at locations where CPs protrude into ventricles. Remember that CECs have microvilli, not cilia, at their apical surface facing the ventricular lumen. By contrast, ependymal cells have beating cilia facing the ventricular lumen, not microvilli. A single cell layer of CECs completely surrounds the core capillary to complete the CP structure. CECs exist only in CPs.

Connectome

Collective distribution of labeled fibers that are measured by an MRI technique that follows the pathway of water along axon bundles "tractography"

You examine the brain of a 20-year-old man who was in a MVA He has a recent history of fainting with a quick recovery

Colloid cyst

Infancy and childhood acute (bacterial) meningitis

Community acquired Most common microbe, Strep. Pneumonia (pneumococcus) Haemophilus influenza type b (Hib) was the most common microbe until the 1990s and the Hib vaccination Neisseria meningitis (meningococcus), (Waterhouse-Friderichsen syndrome in children) -epidemic outbreaks, associated with young adult army recruits and colleges (day cares and children?) -MPSV4 and MCV4 vaccination for military recruits and now for children -Basal

Imaging modalities

Computerized tomography (CT) Magnetic resonance imaging (MRI) Neuroangiography -Ultrasound -Magnetic resonance angiography (MRA) -CT angiography Functional MRI (fMRI) -Positron emission tomography (PET) -Single photon emission computerized tomography (SPECT) -Perfusion MRI -Diffusion weighted MRI -Blood oxygen level-dependent f MRI (BOLD f MRI)

Arnold-Chiari malformations

Condition in which the brain extends through the foramen magnum Type I, minimal brain tissue extends downward -Symptoms include neck pain, unsteady gait, dizziness, numbness, poor coordination, dysphagia, hoarseness Type II, greater amounts of brain tissue extends downward and a myelomeningocele and hydrocephalus 90% - Small posterior fossa and enlarged foramen magnum - Often identified with ultrasound during pregnancy Type III, most severe and rare, includes cerebellum and brainstem extending downward

Causes of Berry aneurysm

Congenital Genetic HTN Cigarette smoking

Brain arteriovenous malformation (AVM)

Congenital large vessel anastamoses without intervening capillary bed; little or no brain tissue - LOOKS LIKE WORM HOLES Asymptomatic or symptomatic <1% general population: usually discovered in young adults incidentally Can degenerate, rupture and convert to hemorrhagic stroke Found anywhere in brain or cord - rare

Straight sinus gross

Connects inferior sagittal sinus to confluence of sinuses

Inter-ventricular foramen of monro

Connects the lateral ventricle with the 3rd ventricle

Posterior communicating artery gross

Connects the posterior cerebral artery to the internal carotid artery

Middle cerebral artery (M1) gross

Considered to be the direct continuation of the internal carotid artery It courses into the lateral fissure

Insular gyri gross

Consists of the short and long insular gyri These gyri function as visceral sensory cortex, where visceral pain sensation is initially decoded. Those insular gyri directly inferior to the pre- and postcentral gyri and overhang of the parietal operculum function as primary taste cortex

Cerebellar cortex histology

Contains 3 neuronal layers of the cortex (Molecular layer, Purkinje cell layer, and Granular layer) The cerebellar cortex has the same trilaminar construction regardless of location in the tissue section. With three cellular layers, it meets the minimum criterion for being cortex.

Most capillaries outside of the CNS are constructed in what ways?

Continuous capillaries that have leaky junctions Fenestrated capillaries that have large pores These allow for immune cell surveillance, blood-to-tissue movement of water, and tissue distribution of small blood-borne proteins such as growth factors and other paracrine signals, e.g. histamine.

Somatotopic map

Control of motor function and sensation to body parts maps across the postcentral and precentral gyrus Precentral gyrus: primary motor cortex with neurons that direct voluntary movement Postcentral gyrus: primary sensory cortex with neuron that decode tactile/position sensation Homunculus reflects disproportionate bodily representation - face/oral (inf. 1/3) - hand (middle 1/3) - arm/torso (upper 1/3) - leg/foot (maps to medial surface)

Imaging planes

Coronal Horizontal (axial) Sagittal

What 3 commissures connect the two cerebral hemispheres?

Corpus callosum Anterior commissure Posterior commissure

Branches of the MCA, ACA, PCA

Cortical branches - where you most often see cardioembolic strokes occur Deep penetrating branches - where you often see hemorrhagic strokes

______ also lines the insular gyri which are buried deep within the lateral fissure but were once exposed on the surface of the developing cerebrum

Cortical gray matter

________ lines the entire external surface of the cerebrum and cerebellum and follows the ridges and crevasses

Cortical gray matter

CT vs MRI

Cortical of the bone is black (around the bone) MRI. Takes advantage of the spin of protons Cortical of the bone is white (around the bone) CT. Takes multiple X-rays

What drains in the superior sagittal sinus?

Cortical veins exit the subarachnoid space and enter the potential subdural space forming the bridging veins Bridging veins then drain into the superior sagittal sinus

Callosomarginal artery gross

Course in the cingulate sulci Important because it provides blood to the paracentral lobule, the location of leg and foot representation fo primary motor and somatosensory cortices

Pericallosal artery gross

Course in the pericallosal sulci just superior to the corpus callosum

SCALP

Covers the cranium Includes: - Skin - subcutaneous Connective tissue - galea Aponeurotic - Loose areolar connective tissue - Pericranium (periosteum)

Fetal NTDs that may present with varying levels of AFP

Craniorachischisis** Anencephaly** Myeloschisis** Encephalocele* Spina bifidas -occult -cystica* -apertura** Chiari malformation (no elevation) Hydromyelia (no elevation) **Maternal serum testing and amniocentesis detects elevated AFP in "open" NTDs, but can have false positives needing confirmation and other causes. *Broken cyst will elevate AFP

35 y o male, fixed dilated R pupil There is a subdural hematoma with a midline shift (about 15mm) What can be done?

Craniotomy

Consequences of unchecked central herniation

Creates pressure cone distorting brainstem stem downward Midbrain perforators and paramedian branches of the basilar a. subject to tear Dysregulation of cardiac and respiratory centers Lethal Duret hemorrhages infarct midbrain/pons

20-year-old man presents to ED after a fight Smells of alcohol Confused and has clear liquid draining from his nose

Cribriform plate fracture which can cause pneumoencephalitis

Commissural projections

Crosses midline to the same level of the neuraxis ex: corpus callosum, anterior commissure, and posterior commissure

Lead encephalopathy

Decreased attention span Memory loss - evidence of hippocampal Pb accumulation Cognitive impairment, eventually lowered IQ Cerebral edema

What drains in the inferior sagittal sinus?

Deep cortical veins

The cerebrum and cerebellum contain:

Deep nuclei (islands of gray matter) surrounded by subcortical white matter, which in turn underlies cortex (gray matter) The outer bark of these large structures are located just under the meningeal surface

Lacunar (small vessel) infarcts result from tiny ischemic strokes affecting ___

Deep penetrating branches Promoted by chronic hypertension, smoking and diabetes Intraluminal microatheromas cause stenosis and occlusion Liquifaction necrosis of the ischemic territory results in lacunar infarcts of <15 mm3 and effects ranging from occult to lethal Localize to the termini of penetrating vessels within basal ganglia, thalamus, internal capsule, or pons Potential for conversion to hemorhage

3 basic components of a neuron

Dendrite (function as the cell's antenna by receiving the majority of its synaptic inputs) Soma (where most of the cell's synthetic machinery is located and where incoming electrical signals integrate) Axon (the signaling output domain)

Lamina terminalis gross

Developmentally, the lamina terminalis is the site of closure of the anterior neuropore and represents the rostral end of the early neural tube. Functionally the neurons and microvasculature it contains play a critical role in thermoregulation and fever production

Prevention of neural tube defects

Dietary folate supplement. You should begin supplement 30d prior to conception

A 17-year-old man presents to the ED after a MVA with LOC

Diffuse Axonal Injury (DAI) Note: white dots show this in imaging

Contusion types

Direct (coup), occur to gyri beneath the site of impact Indirect (contrecoup), occur to gyri located opposite to a direct contusion -inferior frontal and temporal lobes Herniations occur due to compressed herniated neocortex

Crania bifida

Disorder of anterior neuropore closure failure A cyst protrudes through the skull, 80% occipital type, 20% frontoethmoidal Caused by incomplete closure of fontanelles or defects near the foramen magnum The meninges, CSF ± brain tissue protrudes into the cyst - meningocele involves herniation of the subarachnoid space and doesn't involve brain tissue - meningoencephalocele involves herniation of the brain tissue as well Visible by sonogram, but alpha fetoprotein is not elevated if the cyst remains unbroken

Anencephaly (meroencephaly)

Disorder of anterior neuropore closure failure The cerebrum, overlying meninges and calvarium is absent (acrania) or hypoplastic Present with craniorachischisis (open skull fissure) Craniofacial dysplasia Can be seen on sonogram with diagnosis usually in the 2nd trimester Labs show high alpha fetoprotein This is the most commonly anomaly in stillborn Correlated with polyhydramnios (fetus can't eliminate (swallow) enough amniotic fluid compared to its production)

Alcohol-related neurodevelopmental disorder (ARND)

Disorder of post-migratory neuronal differentiation Due to alcohol intake during the 2nd and 3rd trimesters Has a milder effect than FAS Continuum of cognitive difficulties underscores graded effects Subtle effects on developing cortical circuitry Altered higher-order cognitive skills - forebrain effects - decision-making, judgement, foresight affected Hippocampal changes not significant Facial features and head circumference normal

Tonsillar (coning) herniation

Displacement of the cerebellar tonsils through the foramen magnum

What is the major component of neurofibrillary tangles (the hallmark neuropathological finding in cortex affected by Alzheimer's disease_

Dissociated tau protein that forms paired helical filaments

Most neuroactive drugs are effective because they _______

Dissolve in membrane lipids and diffuse across the walls of brain endothelial cells into brain parenchyma For example, heroin and morphine are structurally similar. Heroin has two acetyl groups, making it more lipid soluble and explaining its more rapid onset of action. Once in the brain, heroin is deacetylated enzymatically into morphine, which partitions in brain and slowly leaves it. The high abuse potential of other potentially neurotoxic drugs also directly relates to their lipophilicity and rapid access to brain, e.g. methamphetamine, cocaine. Other potent neurotoxins, e.g. mercury and lead, organic inhalants, readily partition into brain because of their lipophilic properties. Many drugs of potential therapeutic value, e.g. macrolide antibiotics, do not readily enter the brain due to low lipid solubility, or because they fail to utilize transporters that normally traverse the BBB and/or blood-CSF barrier. At neutral pH, their pKa renders them charged, so they cannot cross the diffusion barriers formed by tight junctions at either barrier. In other cases, lipophilic drugs that otherwise could diffuse across the EC membranes encounter transport proteins expressed in BBB ECs. These ATP-driven pumps can export chemotherapeutic drugs, having diffused across the luminal membrane of parenchymal ECs, right back out again into the vessel lumen.

What is the most common heritable cause of cognitive mental impairment?

Downs syndrome (Trisomy 21) They present with: -intellectual disability - variable - ave. IQ = 50 -delayed speech, gross and fine motor skills -greatly accelerated risk of Alzheimer's disease

Central herniation

Downward shift of the diencephalon through the tentorial notch Due to a more centralized downward pressure vector -coma (GCS≤8) -extensor posturing to pain (bilateral) -pupils fixed and dilated

Internal cerebral veins gross

Drains into great cerebral vein of Galen

Great cerebral vein of Galen

Drains into the straight sinus

The dramatic enlargement of the brain during the 3rd trimesters is due to:

Dramatic enlargement of the brain during the 3rd trimester is due not to addition of more cells but instead to more interconnections made between them. Collectively, these interconnections are termed neuropil and consist of dendrites, non-myelinated axons, and the interconnecting processes of glial cells also found in gray matter.

What separates the parietal lobe from the temporal lobe?

Draw a line that is 90 degrees from the occipital lobe and extends to the end fo the lateral fissure

GCS score

Drowsy/lethargy - ≥13 Obtunded/stupor - 9-12 Coma - 3-8 Note: Break down score in patient note e.g. E3V3M5 = GCS 11 NoteL multiple scores are taken

Antenatal Disruptive Lesions

Due to disruptions of normal development and not malformations Porencephaly, cavitary necrosis of the cerebrum, extending to the surface of the brain usually involving the territory of the middle cerebral artery Schizencephaly, is a cleft of the cerebrum without ventricular communication, leading to disorganized growth of the gray and white matter Germinal matrix bleeds Cerebral palsy

Fetal alcohol syndrome (FAS)

Due to maternal alcohol intake during the 1st trimester Causes decreased neuroblast proliferation and migration and increased apoptosis during cerebral corticogenesis Most common cause of lasting cognitive mental impairment

Falx cerebri

Dura mater infolding that extends into the longitudinal fissure separating the two cerebral hemispheres - contains the superior and inferior sagittal sinuses

Tentorium cerebelli

Dura mater infolding that separates the cerebrum from the cerebellum and allows the midbrain/brainstem to pass through - contains the straight sinus, transverse sinuses, and sigmoid sinuses

Capillary/venule ultrafiltrate that flows into Virchow-Robin spaces is modified by ____

EC transporters to produce fluid of CSF composition. The fluid in turn diffuses across the pial membrane into the subarachnoid space (in the direction of the white arrows).

Acute Epidural hematoma surgical treatment

EDH: surgical evacuation for 5-mm midline shift or > 15mm thickness. EDH with GCS<9 with anisocoria should have surgical evacuation ASAP.

Determinants of focal infarct size

Embolus size (stem vs cortical branch affected) Collateral perfusion (stem or major branch infarct size is smaller than predicted from theoretical perfusion territory due to perfusion overlap at the interface between two major circles fo willis vessel territories) - The MCA-ACA overlap - The MCA-PCA overlap

Occulomotor nerve gross

Emerge between the posterior cerebral artery and the superior cerebellar artery

Disorders which damage (open) the BBB: Alzheimer's disease

Entry and deposition of amyloid beta deposits in the brain may occur as the result of BBB breakdown.

Dural bleeds

Epidural Subdural Subarachnoid

Are granule cells excitatory or inhibitory?

Excitatory They release glutamate as their excitatory neurotransmitter at synapses on Purkinje cell dendrites, which extend into the molecular layer Note: these cells are non-myelinated and are local circuit neurons

_______ can grow the infarct

Excitotoxicity An infarct size can expand in brain due to release of cytotoxic levels of glutamate from dead neurons in the ischemic core If you know how body parts and language facilities map across the brain, you can predict a growing infarct territory from a temporal decline in a patient's functions Note: it expands ischemic penumbra and can evoke seizures Note: the glutamate actives postsynaptic NMDA GLU receptors which lead to further increase in Ca2+ eventually leading to apoptotic cell death

Arachnoid granulations

Extensions of the arachnoid mater that allow excess CSF to be absorbed by the dural sinuses. They can calcify with age Can be become obstructed with free blood in the subarachnoid space

Holoprosencephaly

Failed prosencephalization Most common congenital forebrain malformation - alobar (no separation of the cerebral hemispheres) - semilobar (partial separation) Multifactorial etiology - ~25% have mutations in Shh or its signaling system (Patched1 and Gli2) -Additional genes and maternal EtOH intake 1st trimester implicated Facial malformations occur in 80% of cases - cyclopia - hypotelorism - cleft palate - cleft lip Midline brain malformations -merged or partially merged lateral ventricles -olfactory bulb agenesis/hypoplasia -missing or partial falx cerebri -missing or partial median longitudinal fissure -agenesis of corpus callosum

Causes of neuronal migration defects

Failure of neurons to migrate from the periventricular region (periventricular heterotopia) or half way (subcortical band heterotopia) Scattered neuron arrangement in the cerebral cortex - Lissencephaly - Pachygyria - Cobblestone cortex Late stage neuronal migration with cortical disorganization - polymicrogyria

Types of astrocytes

Fibrous AS are stellate and elongate and adopt this morphology in WM. Protoplasmic AS have a tighter, bushier and more symmetric branching pattern, and localize to GM

External germinal layer neuron migration

Follow an "outside-in" migration which is unique to the cerebellar cortex EGL = proliferative neuroblasts 7-8 cells deep on surface of developing CB; finally cease division at postnatal years 1-2. Post-mitotic EGL neurons migrate inwardly - "outside-in" along radial glia and past the pre-formed Purkinje Layer to form Inner Granule Layer Granule neurons leave behind axons that form the Molecular Layer Purkinje cells form the Purkinje layer by an earlier outward migration from the ventricular germinal zone in 4th ventricle wall

Marginal sulcus gross

Follow the cingulate sulcus caudally as it curves toward the brain vertex to form the marginal sulcus, the caudal border of the paracentral lobule. Note that neurosurgeons accessing the brain through the interhemispheric fissure use the marginal sulcus as a landmark for identifying (and thus avoiding) the paracentral lobule

supramarginal gyrus

Follow the lateral fissure up, where it looks like it ends in a loop. This is the supramarginal gyrus Within the inferior parietal lobule

pars opercularis

Follow the precentral gyrus down and it will loop up within the inferior frontal gyrus. The pars opercularis is the upswing

Pars opercularis gross

Follow the precentral gyrus, and where it loops back up is this structure Typically found in the inferior frontal gyrus

Orbital frontal gyri gross

Fond on the inferior surface of the frontal lobe Lateral to the straight gyri (gyri recti)

What sports are concussions most often reported

Football, hockey, rugby, soccer, basketball and cheerleading Females are 2X more likely to sustain a concussion 40% more concussions in female soccer players compared to men

Superior sagittal sinus

Formed by a split of the periosteal and meningeal layers of dura at the junction with the falx cerebri, the dural reflection which partially divides the cerebral hemispheres.

Neuropil

Formed by the tiny, dense network of interactive cellular extensions (processes) of neurons and glial cells, leaving minimal extracellular space It is traversed by blood vessels providing O2 and glucose

Secondary induction (secondary neurulation)

Forms S3-S5 and coccygeal cord segments during g20-g24 Forms conus medullar is and filum terminale AFP is not elevated Distal neural tube differentiates from multipotent germinal center in the caudal eminence, not the notochord

Straight gyrus (gyrus rectus) gross

Found on the inferior surface of the frontal lobe, just lateral to the interhemispheric fissure

Cortical branches of the Anterior cerebral artery perfusion territory

Frontal lobe -Medial, dorsolateral and ventromedial -Frontal poles -Homunculus: lower extremity -Executive functions Parietal lobe -Rostral half, medial and dorsolateral Note: - Pericallosal artery lies along the corpus callosum. The callosomarginal branch of ACA supplies the paracentral lobule

Cortical branches of the Middle cerebral artery perfusion territory

Frontal, parietal and temporal lobes: -Much of lateral aspect -Homunculus: head and upper extremity - Language (perisylvian) cortex Ventrolateral frontal lobes -Executive functions, mood Temporal poles - Limbic structures (amygdala) Note: -Superior division- homunculus, Broca's area -Inferior division - includes Wernicke's area

Retinoic acid receptor (RAR-ß)

Functions as a transcription factor Expressed in the caudal brainstem and cord

Retinoic acid (RA)

Functions endogenously as inductive signal at fmol levels RA binds intracellular receptor, RAR-ß RA-RAR complex translocates to nucleus and binds promoters turning on HOX gene expression; products activate cascades of other genes while inhibiting others

Immunostain for astrocytomas

GFAP

Contrast enhanced MRI

Gadolinium contrast enhancement produces a bright white enhancement in areas of increased vascularity and brain blood-barrier breakdown

Neuronal pathway terminology

Ganglion (PNS) vs Nucleus (CNS) - exception: basal "ganglia" = deep nuclei of cerebrum Nerve (PNS) vs tract/fasciculus/bundle (CNS)

CT of middle meningeal artery rupture

Generates an epidural hematoma (above the dura)

In addition to oxygen, the brain normally requires ____ as its sole energy substrate

Glucose Uses 60-70% of body's glucose - constant demand No capacity to store glucose; some glycogen stored in astrocytes Fatty acids not useful - don't cross BBB After 3 days on low carb diet, 25% of brain energy derived from ketone bodies Starvation and type 1 diabetes dramatically elevate liver ketogenesis Ketone bodies transported into CNS, converted to AcetylCoA for ATP production via citric acid cycle, and overtake glucose as primary utilized fuel Newer evidence for lactate as energy source in energy-depleted states

BBB transport of glucose

Glucose binds to the GLUT-1 transport protein, which is highly enriched in brain microvessel endothelium. Lumbar puncture can detect genetically low levels of a rare GLUT-1 deficiency linked to severe learning disabilities

CBF is regulated on demand by synaptic release of ____

Glutamate (highly specific to brain circuits utilized by task) Neurons in brain engaged for a specific task show increased demand, for O2 and glucose, which requires locally increased blood flow to that specific brain region Mechanism: 95% of neurons in any cortical region release glutamate (GLU) as a neurotransmitter. Some of this GLU is spilled and diffuses away from synaptic cleft to activate GLU receptors on perisynaptic astrocytes GLU-receptor signaling in astrocytes causes them to release of vasodilatory signals, e.g. eicosanoids, prostaglandins CBF increases blood flow to exact region(s) of activity to meet these neurons' increased metabolic demand

Among the most important anterograde cargo are ____

Golgi vesicles packaged with peptide neurotransmitter molecules and modulators destined for release at the presynaptic terminal, and tubulin monomers used for axon elongation.

Cellular components of gray matter

Gray matter (GM) is made gray by the near absence of myelin. A few myelinated axons course through it but not enough to change the gross appearance. Importantly, GM contains the somata (cell bodies) of Np as well as the smaller, much more numerous, non-myelinated local circuit neurons (syn, interneurons) (Ni) in their entirety, which "stay in gray". Also can find neuropil and consist of dendrites, non-myelinated axons, and the interconnecting processes of glial cells also found in gray matter. Also in GM is a replacement pool of OL, termed satellite OL, a reserve population that stops short of making myelin until presumably recruited to do so. Like WM, the GM is also populated with numerous AS and M.

What drains in the straight sinus?

Great cerebral vein of Galen and the inferior sagittal sinus

it is necessary to consider whether the degree of similarity of studies to be included in the meta-analysis; that is, it is necessary to consider the ______of studies

HETEROGENEITY

Pars triangularis gross

Has a triangular shape to it

Acute Concussion Evaluation (ACE)

Help to determine if the patient is experiencing a concussion and if they should be sent to the ER

Periventricular (subependymal) Heterotopia

Heterotopia- normal neurons/ glia found in the wrong place Collections of neurons found under the ependyma of the lateral ventricles Unilateral variants are silent and incidental findings during imaging studies

Subcortical Neuronal (Band) Heterotopia

Heterotopia- normal neurons/ glia found in the wrong place Collections of neurons in the cerebral white matter diffusely scattered, clustered into nodules, bands or grouped in large masses Can be silent, or may cause seizures just depends on how much interaction they have with the normal neurons

_______ is the exception to early neuron development in the cerebrum

Hippocampus This is found in the inferior, medial temporal lobe It has 3 layers- termed archicortex It is the last cerebral cortical region to population majority of its neurons (during 3rd trimester through birth) Small number turn over daily in adulthood (neuronal regeneration)

Causes of tonsillar herniation

Hydrocephalus, tumors, and bleeds of the posterior fossa These can produce ischemic death of the medullary cardioaccelerator controllers

Dry strokes appear _______ by diffusion-weighted MRI

Hyperintense MRI signal is based on the accumulation of water because edema rapidly follows dry strokes

"Red and Dead" hypoxic-ischemic change

Hypoxia, ischemia, and hypoglycemia cause acute, irreversible neuronal injury and death. Within 12-24 hrs after injury, affected neurons become pyknotic (they shrink), leaving spaces of their former size, and become intensely eosinophilic due to condensation of mitochondria. Their nuclei condense, and the nucleolus and Nissl bodies disappear. Such neurons are dead. They are eventually phagocytosed by activated microglia or invasive monocytes that penetrate a porous blood-brain barrier due to injury. This is the classic sequence of events that typify focal brain damage consequent to ischemic stroke

The 6 layers of the neocortex that makes up the cerebral cortex

I. Outer plexiform (molecular) layer: sparse neurons and glia II. Outer granular layer: small pyramidal and stellate neurons III. Outer pyramidal layer: moderate sized pyramidal neurons IV. Inner granular layer: densely packed stellate neurons; predominates in primary sensory cortex. V. Inner pyramidal layer: large pyramidal neurons; predominates in primary motor cortex VI. Multiform cell layer: mixture of small pyramidal and stellate neurons, forming the deepest layer next to subcortical WM

Indirect contrecoup gross and imagining

If on the inferior temporal lobe and inferior frontal lobe, it will be indirect

Seizure meds teratogen effect Ex: Dilantin (phenytoin) Valproic acid Carbamazepine

If phenytoin taken in first trimester: 10% chance of "fetal hydantoin syndrome" And 33% chance of baby born with the following: -Growth deficiency -Develpmental delay -Cleft palate -Facial characteristics -Heart defects -Genitourinary disorders With maternal use, phenytoin crosses the placenta to give a higher dose to the fetus due to differences in drug metabolism.

2 major statistical methods to combine the effect sizes

If we believe that the differences in the effect estimates are simply due to random variation, then we use the Fixed Effects model If we believe that the differences in the effect estimates are due to random variation PLUS some other factors , then we use the Random Effects Model What are "other factors"? Here a few examples: -Length of follow up can cause studies to be very different: if outcome was assessed at 24 hrs. in some studies but at 30 days in others, then there is a large difference between studies -Severity of stroke could make studies differ considerably: if one study includes minor strokes only, and another includes only severe strokes, then the studies might not be truly similar

Indicators of a uncal/transtentorial herniation

Imaging - midline shift, ventriculomegaly Neurologic Acute -altered mental status -contralateral (75%) or ipsilateral (25%) hemiparesis -sluggish pupillary reaction to light on the side of the herniation -CN3 is most sensitive CN readout for impending herniation due to traction on midbrain -> parasympathetic dysfunction Progressive -posturing, usually decorticate, unilateral to bilateral -GCS score deceases to comatose -fixed and dilated pupil

Precuneus gross

Immediately caudal to the marginal sulcus , part of the parietal lobe, which is bordered caudally by the parieto-occipital sulcus Precuneus functions as visual association cortex

Median eminence

Immediately surrounds the infundibulum

Antibodies to neurofilament

Immunocytochemical marker that labels and identifies neurons in this tissue section of cerebral cortex Note: type of microfilament

A 61-year-old woman was diagnosed with beast cancer had a right-sided invasive ductal carcinoma and left-sided ductal carcinoma 1 year prior to her neurologic evaluation. She underwent right-side modified radical mastectomy and left-side total mastectomy thereafter. The tumor was confirmed to be an adenocarcinoma that was strongly positive for estrogen and progesterone receptors but was negatively stained for human epidermal growth factor receptor-2 (HER2). The patient was further treated with local radiotherapy and chemotherapy with cyclophosphamide, doxorubicin, and paclitaxel, without notable adverse effects. The patient experienced progressive recent and remote memory impairment and cognitive dysfunction 1 year after her diagnosis of breast cancer. She was also found to have mild weakness (4/5) of the right upper and lower limbs. Cranial functions and other neurologic examinations were unremarkable. Further CT and MRI demonstrated that the patient had multiple brain lesions, including a large tumor located at left parieto-occipital subcortical regions extending into the ipsilateral splenium of the corpus callosum, and two other small, but separate lesions in the lateral ventricle wall and the parietal cortex of the ipsilateral brain Adjacent tissue sections of patient's tumor stained with (A) H&E, (B) cytokeratin 7 antibody, (C) GFAP antibody and (D) a nuclear marker for cycling cells.

Immunoperoxidase staining of tumor tissue (A, H&E) was CYK-negative (B) and GFAP-positive (C), revealing the tumor was a primary astrocytoma, not a metastasis of her breast cancer. Immunostaining for various CK's also distinguishes renal, endo- metrial, and lung non-small cell carcinoma met's to the brain from primary brain tumors.

Area postrema gross

In the anterior wall of the 4th ventricle is the area postrema, which extends from the obex bilaterally for 2-3 mm along the anterior surface of the 4th ventricle, within the caudal medulla. The area postrema lacks a blood brain barrier and contains chemoreceptor neurons that are part of the emetic center and accessible to blood-borne toxins.

Hypothalamus gross

In the mid-sagittal plane the hypothalamus extends rostrally inclusive of the lamina terminalis and caudally to include the mammillary bodies

Risk factors for stroke

Includes lifestyle, genetic, and acquired factors -Obesity -Hypertension -Hypercholesterolemia -Untreated atrial fibrillation -Sickle cell anemia -Family history - e.g. ADPCKD increases chance of brain aneurysm 5-fold -Smoking Higher incidence in medical diseases -Inflammatory -Malignancy -Congenital heart disease -Cancers: the younger the pt. the greater the chance of dying later of stroke

Basal ganglia image

Includes the caudate and lenticular nucleus

Cerebrum gross

Includes the cerebral hemispheres and the diencephalon

Hydrocephalus

Increased accumulation of CSF within the ventricles Due to overproduction of CSF or an imbalance between production and absorption Causes: -Impedance of flow of CSF *Malformations, most common (75%) is aqueductal stenosis *Obstructions (tumors) -CNS infections followed by scarring of the ventricular system -Trauma followed by scarring of the ventricular system

3rd trimester events

Increased cerebral mass & volume due to connections (differentiation), not more neurons Neuronal programmed cell death (apoptosis) and circuit remodeling eliminates unused neurons generated in overabundance as circuits form Hard-wiring of post-migratory neurons begins and will continue Synaptogenesis makes connections functional Onset of active generation of glia and beginning of myelination by the oligodendrocytes

Are Purkinje cells excitatory or inhibitory?

Inhibitory Purkinje neurons are the only projection neurons of the cerebellar cortex, sending their axons through subcortical white matter to deep cerebellar nuclei. They are inhibitory in their stimulus of other neurons, releasing gamma-butyric acid (GABA) as their inhibitory neurotransmitter

Induction (neurulation)

Initiated at the gastrula stage (week 3) Triggered by diffusible notochord- derived signal Dorsal ectoderm differentiates into neuroectoderm, forming a neural plate > neural folds

_______ are buried within the lateral fissure

Insular gyri and primary auditory cortex Note: these are exposed on the surface of the fetal brain, but it is then overgrown

anterior choroidal artery is a branch of ___

Internal carotid artery

What two arterial sources perfuse the brain?

Internal carotid artery which supplies the anterior circulation Vertebral artery which supplies posterior circulation (vertebrobasilar system)

The subarachnoid space widens into cisterns:

Interpeduncular Quadrigeminal Pontine Magna Lumbar

Strategies to reduce ICP

Interventional - Craniotomy> Extraventricular drain (EVD) and ICP monitoring - Optional decompressive craniectomy Ventilation - To normocapnia, >90% SpO2 - Hyperventilation...risky (can lead to vasoconstriction and ischemia) - Systolic pressure >90mmHg Osmotic diuretics - Draw interstitial water into capillaries - I.v. mannitol -bolus takes 20-30 min to act - I.v. hypertonic saline bolus (3%-7.5%) - Contraindications? Medical-induced coma - propopfol - CNS depressants reduce metabolic rate and thus energy demand - Neurons less vulnerable to ischemic cell death - Reversible

When to use CT related to the brain

Intracranial Hemorrhage (no contrast!) - < 1 week old appear hyperdense - 1 to 2 weeks old appear isodense - > 2 weeks old appear hypodense (getting reabsorbed at this point) Skull fractures - Detected with bone windows Cerebral infarcts - > 12 hours appears hypodense along the tissue distribution of the involved artery due to increased edema - Weeks to months appear hyperdense due to gliosis along with parenchymal loss Neoplasms -Appear hyperdense, isodense or hypodense depending on the type of neoplasm Mass effect -Any of the above that causes distortion of the normal brain anatomy

Cellular components of white matter

It contains densely packed bundles of myelinated axons. At normal body temperature the lipid-rich myelin membrane surrounding axons is relatively non-fluid and whitened, like gravy stored in the refridgerator. It also contains oligodendrocytes (OL), which make and remain connected to myelin membrane, and also astrocytes (AS), and microglia (M).

A late 1st trimester embryo before peak corticogenesis vs the adult brain

It has a smooth surface which reflect few neurons in the cortex Post-mitotic neurons migrate radially from the ventricular wall to stratify and thicken the cortex during the 2nd trimester. Massive # of neurons requires infolding to fit the brain within the confines of the calvarium (giving its the classic infolding shape)

Where is white matter and gray matter in the spinal cord?

It is reversed from the brain! White matter is positioned exterior to the "central gray"

What causes speckling of the ventral horn when using basophilic stain?

It represents large, individual anterior horn cells consisting of alpha and gamma motor neurons. These neurons use ACh as their neurotransmitter at the neuromuscular junction and muscle spindle respectively

Precentral sulcus gross

Just anterior to the precentral gyrus

CN IV: Trochlear Nerve gross

Just caudal to the inferior colliculi

Angular gyrus gross

Just caudal to the supramarginal gyrus

Postolivary sulcus

Just lateral to each olive, and this is where Place were the fine rootlets of the glossopharyngeal nerve (CN9) and vagus nerve (CN10) appear in rostal-to-caudal sequence

Postcentral sulcus gross

Just posterior to post-central gyrus

pars triangularis

Just rostral to the pars opercularis within the inferior frontal gyrus

Composition of normal CSF and in disease

Know the Acute meningitis vs Chronic meningitis

9yo GCS 13 Imaging show temporal hematoma from gunshot wound, midline shift, and uncal herniation What should be done

L Decompressive Craniectomy, Removal Temporal Lobe Hematoma

16 yo jumped out of car Next day, ICP >25 and imaging showed growing hematoma What should be done

L frontal craniotomy to remove the hematoma

_____ vertebral arches most often affected in spina bifida; can be higher level

L5-S1 Note: detectable on sonogram

Wernicke's area

Language comprehension Involves the supramarginal gyrus, angular gyrus, and the posterior 1/3 of the superior temporal gyrus Stroke here creates "word salad" they are able to form speech but it is nonsense and they also can't understand what someone is saying to them

Gyri (gyrus)

Large folds of tissue covering the surface of the cerebrum

The longer the axon of a neuron, the _____ is its soma

Larger The large cell body is needed to house most of the organelles required for continuous turnover of macromolecules at distant synaptic terminals

The presentation of Downs syndrome is attributed to:

Late problem with post-migratory neuronal differentiation (3rd trimester) -simpler neuronal morphology of cerebral cortical neurons underlies cognitive limitations -fewer synaptic contacts (reduced dendritic spines) Recent evidence of a much earlier problem -reduced neural stem cell number and neuronal production

CN VIII: Vestibulocochlear Nerve roots gross

Lateral to abducens nerves emanate the paired facial nerves (CN7), whose nuclei are also located within the caudal pons, and just lateral to them are the vestibulocochlear nerves (CN8). The nuclei associated with CN8 bridge the pons and medulla.

48 yo GCS 15 Imaging shows bullet lodged in the brain What should be done?

Leave the bullet in, only operate if there is a hematoma or midline shift!

Superior temporal gyrus

Lies between the lateral fissure and the superior temporal sulcus

Quadrigeminal cistern

Lies dorsal to midbrain Contains great vein of Galen Posterior to the tectum of the midbrai

Hypothalamic sulcus

Lies inferior to the mass intermediate and delimited the dorsal thalamus (superiorly) and the hypothalamus (inferiorly)

Middle temporal gyrus

Lies ventral to the superior temporal gyrus and is separated via the superior temporal sulcus

Ependymal cells

Line the ventricles of the brain and the conduits between them. They are typically cuboidal, a single layer in thickness, and often have beating cilia used to propel CSF though the ventricular system There is no diffusional batter to CSF and its solutes, e.g. electrolytes, drugs, and macromolecules, across the ependymal lining. These are not secretory!

Luxol fast blue stain

Lipid stain for white matter Note: subcortical white matter normally exhibits a bilateral symmetric staining pattern across the midline interhemispheric fissure

Cobblestone cortex

Lissencephaly type II The cortex has irregular grooves forming a cobblestone pattern No cortical layers form, instead there is a total disarray of the cortex Neurons migrate past the cortex and terminate in the subarachnoid space

Mutations in genes that can lead to neuron migration failure

Lissencephaly1 (LIS1): affects excitatory neurons Doublecortin (DCX): affects excitatory neurons Reelin: affects excitatory neurons ARX: affects GABA neurons

_______ enables functional (real-time) neuroimaging while a task is undertaken

Locally elevated blood flow Blood oxygen level-dependent functional MRI (BOLD-fMRI) measures brain activity indirectly as a function of blood flow - permits functional brain mapping - neurosurgical planning

Posterior commissure gross

Located near the base of the pineal gland (see below). This commissure is essential for the bilateral response of the pupillary light reflex.

Preolivary sulcus gross

Location where fine rootlets of the hypoglossal nerve (CN XII) emerge

Axial plane through lenticular nucleus, limbs of the internal capsule

Look for septum pellucidum (separates the lateral ventricles) corpus callosum, genu (portion of the corpus callosum nearest the frontal lobe) optic radiations (white matter band around the lateral margin of the occipital horn of the lateral ventricle. This carries visual information to the primary visual cortex) corpus callosum, splenium (portion of the corpus callosum nearest the occipital lobe) fornix (columns) (C-shaped bundle of nerve fibers in the brain that acts as the major output tract of the hippocampus, will see bordering the anterior commissure) lenticular nucleus = [putamen + globus pallidus] (seen bordering the posterior limb of the internal capsule) caudate nucleus, head (seen protruding in the lateral wall of the anterior horn of the lateral ventricle) thalamus (borders the 3rd ventricle) 3rd ventricle (located between the thalamus) internal capsule (anterior, genu, posterior limbs) BEST lateral ventricle (ant. & post. horns, atrium = trigone) (anterior horns nearest the frontal lobe more superior; posterior horns nearest the occipital lobe; atrium =trigone the region of the lateral horn where the temporal and occipital horns are confluent with the body of the lateral ventricle; glomus (found within the trigone, is the heaviest concentration of the choroid plexus) Median longitudinal (interhemispheric) fissure (the large fissure that separates the cerebral hemispheres) lateral fissure (fissure that separates the temporal lobe from the frontal and parietal lobe) insula (will see within the lateral sulcus, looks like gyri under the outer cortex) cingulate gyrus (follows the corpus callosum, will see at both ends just proximal/distal to the corpus) cingulum

Axial plane superior to the body of the corpus callosum

Look for: Corpus callosum (body) (will see two sides to it, the one towards the genu (near frontal) and the splenium (near occipital) median longitudinal fissure (the main huge fissure separating the cerebral hemispheres) frontal lobe lateral ventricle, body corona radiata (white matter sheet that continues ventrally as the internal capsule)

Coronal plane level of the anterior commissure

Look for: Extreme capsule (series of nerve tracts between the claustrum and the insular cortex) lateral ventricle (anterior horn) lateral fissure (separates the temporal lobe from the parietal and frontal lobes) insula (gyri within the lateral fissure) temporal lobe corpus callosum (body) internal capsule (anterior limb) (will be seen separating the caudate nucleus and the lenticulate nucleus) caudate nucleus, head (seen protruding into the anterior horn of the lateral ventricle) lenticular nucleus (globus pallidus and putamen) cingulate gyrus (the first gyrus that is just superior to the corpus callosum cingulum (portion of white matter that protrudes into the cingulate gyrus) callosomarginal a. (branch of the ACA which is superior to the perimarginal artery and its supplies the paracentral lobule) septum pellucidum (separates the lateral ventricles) frontal lobe

Axial plane through the anterior commissure

Look for: anterior commissure (band of fibers that run along the rostral end of the 3rd ventricle) thalamus (borders the 3rd ventricle) massa intermedia (apparently functionless mass of gray matter in the midline of the third ventricle that is found in many but not all human brains and is formed when the surfaces of the thalami protruding inward from opposite sides of the third ventricle make contact and fuse) third ventricle (located between the thalamus) frontal cortex occipital cortex temporal cortex median longitudinal (interhemispheric) fissure (main fissure that separates the cerebral hemispheres) insula (will see within the lateral sulcus, looks like gyri under the outer cortex) caudate nucleus (head) optic radiations (white matter band around the lateral margin of the occipital horn of the lateral ventricle. carries visual info to the primary visual cortex) lateral ventricles (anterior, posterior, inferior horns, atrium glomus (found within the trigone, is the heaviest concentration of the choroid plexus)

Coronal plane through body of fornix

Look for: caudate nucleus (body) (doesn't protrude into the lateral ventricle as much!) internal capsule (posterior limb) (separates the thalamus which borders the 3rd ventricle from the lenticular nucleus) amygdaloid nuclear complex (located in the temporal lobe, will be seen inferior to the thalamus and lenticular nucleus. At the level of the uncus) lateral fissure (separates the temporal lobe from the frontal and parietal lobes) lentiform nucleus: globus pallidus, putamen corpus callosum (body) uncus (anterior extremity of the parahippocampal gyrus) lateral ventricle, body third ventricle (inferior to the fornix, and bordered by the thalamus) insula interpeduncular fossa (rhomboid-shaped area of the base of the brain, inferior to the 3rd ventricle and mammillary body) crus cerebri (cerebral peduncles) (continuation of the internal capsule)

Coronal plane through posterior thalamus and midbrain

Look for: cingulate gyrus (the first gyrus that is just superior to the corpus callosum cingulum (portion of white matter that protrudes into the cingulate gyrus) caudate nucleus (tail - be aware of its presence, located just superior to the hippocampal formation) septum pellucidum (separates the lateral ventricles) fornix (body) (serves as the roof of the 3rd ventricle) hippocampal formation (located in the temporal lobe of each cerebral cortex, medial to the inferior horn of the lateral ventricle) parahippocampal gyrus (gyrus surrounding the hippocampus) internal capsule (posterior limb) (separates the thalamus from the lenticular nucleus) thalamus (various nuclei) (borders the wall of the 3rd ventricle) lateral ventricle (body, inferior horn) interpeduncular fossa (rhomboid-shaped area of the base of the brain, inferior to the 3rd ventricle and mammillary body) crus cerebri (cerebral peduncles) (continuation of the corona radialis) pons (portion of the brain stem that bulges out) medullary pyramids (paired white matter structures of the brainstem's oblongata that contain motor fibers of the corticospinal and corticobulbar tracts)

Axial plane just inferior to the body of the corpus callosum

Look for: corpus callosum, splenium, genu ACA (can identify the A3 segments within the cingulate gyrus, cingulate sulcus, and callosal sulcus. Note that the pericallosal artery will be closest to the corpus) septum pellucidum (separates the lateral ventricles) lateral ventricle, anterior horns (portion that is nearest to the frontal lobe) caudate nucleus (head) (should see protruding in the wall of the anterior horn of the lateral ventricle) thalamus (bilaterally borders the 3rd ventricle) insula (will see within the lateral sulcus, looks like gyri under the outer cortex) internal capsule (anterior, posterior limbs, genu) (posterior limb projects back toward the occipital lobe, kinda between the thalamus and the Linticular nucleus. The genu is the area where the internal capsule appears to begin to bend and it marks the transition between the anterior and posterior. Anterior projects back toward the frontal lobe) lenticular nucleus (putamen + globus pallidus borders the posterior limb of the internal capsule) pineal gland

Coronal plane at level of uncus, anterior thalamus and hypothalamus

Look for: lateral fissure (separates the temporal lobe from the frontal and parietal lobe cingulate gyrus (the first gyrus that is just superior to the corpus callosum cingulum (portion of white matter that protrudes into the cingulate gyrus) temporal lobe sup. temporal gyrus (portion of the temporal lobe which lies in the inferior floor of the lateral fissure) amygdaloid nuclear complex (located in the temporal lobe, will be seen inferior to the thalamus and lenticular nucleus. At the level of the uncus) lateral ventricle (body) caudate nucleus (head-to-body transition) (will see less of a protrusion into the lateral ventricle!) corpus callosum (body) lenticular nucleus (globus pallidus and putamen) insular cortex

Coronal plane level of anterior horn of lateral ventricle

Look for: lateral ventricle (anterior horn) lateral fissure (separates the temporal lobe from the parietal and frontal lobe) insula (within the lateral fissure) temporal lobe corpus callosum (rostrum, genu) caudate nucleus, head (protrude out of the anterior horn of the lateral ventricle) lentiform (lenticular) nucleus (globus pallidus and putamen) cingulate gyrus (the first gyrus that is just superior to the corpus callosum cingulum (portion of white matter that protrudes into the cingulate gyrus) nucleus accumbens (area of continuity between the head of the caudate and the putamen) anterior cerebral arteries (can be seen in the area of the anterior portion of the median longitudinal fissure, closest to the corpus callosum would be the pericallosal artery of the ACA and the callosal marginal would be above that) gyrus rectus (straight gyrus) (will be found most inferior and medial in the area of the frontal lobe) olfactory tracts (run along the gyrus rectus) orbital gyri (those gyri just superior to the orbit) septum pellucidum (separates the lateral ventricles) globus pallidus (part of the lenticular nucleus, made up of a medial and lateral portion Frontal lobe

Coronal plane at level of splenium, lateral ventricle - posterior horn

Look for: lateral ventricle (rigone-to-posterior horn) internal cerebral veins, great vein of Galen (if present) (lies in the quadrigeminal cistern and curves backward and upward around the posterior border of the splenium of the corpus callosum to drain into the confluence of the inferior sagittal sinusand the straight sinus.) choroid plexus including glomus (produce CSF with the largest conglomerate being the glomus superior (quadrigeminal) cistern (It is located between the colliculi, the splenium of the corpus callosum and the superior surface of the cerebellum and extends from the third ventricle to the great cerebral vein.) cingulate gyrus (the first gyrus that is just superior to the corpus callosum cingulum (portion of white matter that protrudes into the cingulate gyrus) hippocampal formation (best here) fornix (body) (the roof of the 3rd ventricle) caudate nucleus (body) middle cerebellar peduncle (paired structures (left and right) that connect the cerebellum to the pons and are composed entirely of centripetal fibers, i.e. incoming fibers) pyramid third ventricle thalamus (borders the 3rd ventricle) third ventricle lateral ventricle, body and inferior horn cerebellum

Coronal plane at level of the splenium of the corpus callosum

Look for: middle cerebellar peduncle (paired structures (left and right) that connect the cerebellum to the pons and are composed entirely of centripetal fibers, i.e. incoming fibers) corpus callosum (splenium) lateral ventricle, atrium cerebellum

Axial plane through the level of amygaloid nucleus, uncus, hippocampal formation

Look for: temporal lobe lateral ventricle (inferior horn) unus (best on cornal section) (anterior extremity of the parahippocampal gyrus) amygdaloid nuclear complex (best on cornal section) (amygdala, lies in the temporal lobe close to the temporal lobes) hippocampal formation (best on cornal section) (lies just posterior to the amygdala) gyrus rectus (straight gyri that the adjacent to the median longitudinal fissure) frontal, temporal and occipital cortices

Axial plane through the temporal lobes, dorsal hypothalamus, midbrain

Look for: temporal lobe lateral fissure choroid plexus = glomus, largest aggregate found in the atrium of the lateral ventricles lateral ventricle (atrium, occipital horn)

The _____ is the most common site of infarction due to embolism

MCA

Meninges and superficial cerebral veins

Mainly includes: Superficial bridging veins (susceptible to tearing with age due to cortical loss) Superior anastomotic vein (of Trolard) Inferior anastomotic vein (of Labbe) Superficial middle cerebral vein

Osmotic therapy to reduce ICP

Mannitol: 0.25-1 gm/kg bolus iv over 20 minutes. Followed by 0.25 gm/kg q 6 hours for ICP>20. Hypertonic saline: multiple options such as continuous 3% infusion or 10-20 ml of 23% saline. Hold osmotic therapy for serum osmolarity >320 mOsm/L.

Post traumatic brain events

Mass lesions such as hematomas whose volume increases ICP. Brain volume may increase because of cytotoxic edema. CSF volume may increase because of a blockade of the outflow tract(cerebral aqueduct) or restriction of CSF re-absorption. Vascular volume can increase if venous outflow is blocked (superior sagittal sinus thrombosis). Increase in cerebral blood flow because of loss of autoregulation(seizure).

Increased ICP is caused by _____

Mass occupying lesion - cerebral edema (brain tissue) - cerebral hemorrhage - engorged vessels - hydrocephalus - tumor

_______ control the anatomical plan of the brain and spinal cord

Master genes distracted across neuromeres (segments of the neural tube that sculpt the embryonic brain during development) Different neuromeres express different and unique genetic traits regulated by transcription factors, growth factors, and cell adhesion molecules that coordinately dictate the organization of the brain and its circuitry Neuromeres forming the rhombencephalon are called rhombomeres Prosomeres are their counter parts in the prosencephalon

Blood vessels supplying the basal ganglia, caudate nucleus, reticulate nucleus, and thalamus

Medial striates branching off ACA supply the most rostral part Lenticulostriate arteries branching off the MCA supply the middle area Thalamoperforator arteries branching off the PCA supply primarily the thalamus

The brainstem derives from what 3 secondary vesicles

Mesencephalon (midbrain) Mesencephalon (pons) Myelencephalon (medulla)

_______ studies provide the highest level of evidence among all possible sources of medical knowledge.

Meta-analysis

55-year-old chronic alcoholic presents to your ED and dies soon after

Methanol toxicity Methanol tends to attack the putamen and lead to hemorrhage of the putamen

What is the only CNS cell type to be derived from embryonic mesoderm?

Microglia Note: the others derive from ectoderm

Activated microglia

Microglia express cytokines in the activated state and act as antigen-presenting cells that contribute to the pathophysiology of autoimmune and other disease responses of the CNS.

Pachygyria

Midler variant of lissencephaly Broad gyri and a thick correct with few layers Often seen with metabolic disorders of the CNS

What are the 3 planes of neruoimaging used?

Midsagittal Coronal Horizontal (axial = transverse)

CN V Trigeminal nerve root gross

Midway between the rostal and caudal ends of the pons, find the large trigeminal nerve (CN5) stumps

Causes of cerebral edema

Most causes begin focally and can take up to 72 hrs to spread Traumatic brain injury -Closed injury, e.g. coup-contrecoupe, diffuse axonal injury, hematoma -Open injury, e.g. projectile Ischemic strokes Intracerebral hemorrhages and strokes Infections -Meningitis (exudate and neutrophils in the subarachnoid space can actually impede CSF removal), toxoplasmosis, encephalitis Tumors High altitude cerebral edema (HACE)

Subarachnoid hemorrhage

Most common cause is trauma Second most common cause is rupture of an arterial berry aneurysm causing blood to collect in the subarachnoid space -Forms a "5-pointed star" -Overall mortality is 50%

Tethered cord syndrome

Most common disorder of secondary induction Conus tip is pulled as low as L5 and can be due to a thickened filum terminale or adhesive lipoma distorts lumbosacral cord gray matter -> incontinence, saddle anesthesia, possible lower extremity weakness Reason to work up a small child having difficulty with bladder control Up to 25% of repaired myelomeningocele patients later present with tethering due to scar tissue

Aseptic (viral) meningitis

Most common meningitis overall, a benign inflammatory meningeal illness -Most common cause, non-polio enteroviruses (children) late summer and early fall -Mumps -HSV-2 -HIV -West Nile virus

Ependymoma

Most common spinal cord tumor Common in the posterior fossa of children Cell of origin is the radial glial cell On average, 5 yr survival is 80%

Charcot-Bouchard hemorrhages

Most often caused by chronic uncontrolled hypertension or amyloid angiopathy Causes inoperable microaneurysms off termini of penetrating arteries Can account for intracerebral hemorrhages causing stroke Note: example of intra-axial hemorrhage

BBB transport of neurotransmitters

Most presented in blood can work peripherally (e.g. dopamine, norepinephrine) but do not enter the CNS because their weakly acidic or basic PKa renders them charged at neutral pH, and thus hydrophilic and incapable of crossing the BBB, or else luminal transporters for them are not expressed in brain ECs.

Other microtubule associated proteins: Dyneins

Motor protein which has one docking site for transported cargo and another one for tubulin These are minus-end directed motor proteins that work only in the retrograde direction, moving various goodies toward the cell body by hydrolyzing ATP.

Other microtubule associated proteins: Kinesins

Motor protein which has one docking site for transported cargo and another one for tubulin These are plus-end-directed motor proteins and hydrolyze ATP to provide the mechanical energy for shuttling bound vesicles anterogradely, i.e. toward the plus-end of the microtubules.

Outcome of neuronal migration defects

Multiple NMDs are possible at the same time Abnormal migration causes an abnormal gyro pattern NMDs are named by observations of gross malformations Many gene mutations cause NMDs, a well studied gene RELN/Lis, a protein important in guidance and signals for migrating neurons

Living human neurons fall into what 3 general categories distinguished by their branching patterns?

Multipolar neuron (most common, named for the multiple dendritic trunks that emanate from the soma) Bipolar neuron (rare and restricted to special sensory structures such as the retina and inner ear) Pseudounipolar neuron (first order and general sensory in function, project information in the CNS and have their soma located aside from the axon in dorsal root or cranial nerve ganglia. Their entire length behaves electrically as a long axon transmitting information toward the CNS, and is thus myelinated to meet the high conduction velocity demand.)

Lissencephaly

Mutation in Lis1 Presents with a smooth cortex without gyri and a thick cortex with 4 cell layers Microcephaly (small head/ skull) Severe mental delays and intractable seizures

Can you achieve complete hemiparesis or hemisensory loss by infarcting cortical branches of either MCA or ACA?

NO! The ACA supplies mainly the lower extremity coverage The MCA supplies mainly the face, upper extremity, and torso coverage

Are choroid epithelial cells (CECs) ependymal cells?

NO! Their apical membranes face the ventricular lumen and are coated with microvilli forming a "brush border" that is specialized fro high volume secretion and absorption due to its high surface area

Are CSF a protein free ultrafiltrate?

NO, Exchanger proteins in CEC membranes alter formative CSF to match the solute requirement of CNS interstitial (extracellular) fluid

Can deep nuclei be called cortex?

NO, they lack the histological requires of ≥3 neuronal layers

Within the CNS, it resembles mesenchymal tissues in which cells appear set in an extracellular matrix. Is this correct?

NO, this is not extracellular matrix but instead the neuropil of the cerebral gray matter

Cortical dysplasia

NOT a pre-cancer Refers to the cerebral cortical ribbon (gray matter) improperly forming - most common form is focal cortical dysplasia A generic term including heterotopias and polymicrogyria Cortical dysplasia is the most common cause of epilepsy! (the tissue fires more than the surrounding neurons)

What is located on the brush border of the CECs that is required for CSF secretion?

Na/K ATPase

Immunostain for neurobalstomas or metastatic tumor in brain

Neuroblastoma - NSE Metastatic tumor in brain- Cytokeratins

Gestational development of the cerebellum

Neuroblasts migrate out of 4th ventricle mouth through rhombic lips (->) onto exterior cerebellar surface to form an external germinal layer (EGL) As EGL expands, the growing cerebellar surface area requires invagination = foliation Cerebellar cortex continues to develop out to 2 yrs. Last region of brain to generate adult contingent of neurons.

Cerebral palsy

Neurological disorders that appear in infancy or early childhood and permanently affect body movement and muscle coordination but don't worsen over time Caused by abnormalities in parts of the brain that control muscle movements Signs of cerebral palsy usually appear before a child reaches 3 years of age - lack of muscle coordination when performing voluntary movements (ataxia) - stiff or tight muscles and exaggerated reflexes (spasticity) - walking with one foot or leg dragging; walking on the toes, a crouched gait, or a "scissored" gait - muscle tone that is either too stiff or too floppy

Cell type specific markers for neurons

Neuron-specific enolase (NSE) Neurofilament (NF)

Forebrain anomalies

Neuronal migration defects (NMD) Agenesis of the corpus callosum/ Holoprosencephaly

Axonal transport

Neuronal somata retain most of the synthetic machinery that constantly replaces macromolecules and organelles required to meet the metabolic demand of the distal ends of the neuron. Because of the axon's length, a bidirectional transport system, axonal transport, is utilized to shuttle axonal cargo. Includes anterograde and retrograde transport Different microtubule-based mechanisms operate in each direction.

_____ and _____ comprise the parenchymal cells of the CNS

Neurons and glia

Interneurons (local circuit neurons)

Neurons that only send short-range efferents to their local neighbors. These are the vast majority of neurons in the brain that are tiny and never leave the gray matter

When do meds such as anti-epileptogenic have their peak teratogen effects

Neurulation (g18-28)

Cerebral development peak time

Neurulation, g18-28 Prosencephalization, gwk 5-6 Neuronal proliferation, gmo 2-4 Migration, gmo 3 to 5 Gyri, gmo 5-9 Neuronal organization, synaptogenesis, glial cell proliferation and myelination, 3rd trimester - 2nd decade

Large neurons stain for ____

Nissl bodies and a prominent nucleolus

Immunostain for oligodendrogliomas

None reliable Due to 1p/19q co-deletion

Anterior horn cell histology

Note their very large cell bodies High mag would show Nissl bodies within the motor neuron somata

Gun shot wound gross and imaging

Note: doesn't always result in an immediate quick death Note: often times the blast wave around the bullet causes the most damage

Neurulation summary

Note: notochord is driving dorsal ventral patterning and primary induction!

What are some causes of neural tube defects?

Nutritional deficiencies - maternal folates - maternal B12 Drugs - folate antimetabolites (e.g. methotrexate) - valproic acid (fore seizures) - colchicine (for gout) can lead to no induction at all These can leads to 1 carbon transfer reactions (methylations) impairment which is needed for the production of methionine synthesis -> thymidine synthesis -> DNA/RNA synthesis

BBB transport of gases

O2, CO2, CO, and volatile anesthetics rapidly diffuse across ECs into the brain. Again the BBB is not at play here.

Cortical branches of the Posterior cerebral artery perfusion territory

Occipital lobe: -entire sensory vision Parietal lobe -caudal half, medial and dorsolateral Temporal lobe: -most of ventral aspect -visual recognition -hippocampus: learning and memory

Retrograde transport

Occurs from axon terminals towards the soma Half the speed of fast anterograde transport, 100-200 mm/day. endocytotic vesicles formed at the presynaptic terminals, and worn-out organelles destined for lysosomal degradation in the soma. vesicles formed by signaling endosomes containing trophic factor-receptor complexes sampled at the axon terminal, that stimulate growth and survival of neurons once transported to the nucleus where their signaling exerts genomic effects. Neurotropic viruses and microbial toxins, e.g. tetanospasmin, access CNS neurons by retrograde transport along axons of peripheral neurons.

Anterograde transport

Occurs from the soma towards the axon terminal Fast and slow components: - Fast transport, up to 400 mm/day, vesicle-bound cargo, including synaptic vesicles, other vesicles, and mitochondria, Virions, e.g. herpes viruses, harbored in the cell body, travel anterogradely in an outbreak. - Slow transport, at 0.1-1.0 mm/day, moves cytoskeletal proteins, e.g. tubulin monomers, neurofilament segments toward the growing end of the axon - limits rate of axon regeneration

Central chromatolysis

Occurs when there is injury to the axon This causes cell body disaggregation of its rER (Nissl bodies have disappeared) causing the cytoplasm to become euchromatic and smooth in appearance and ballooning of the soma The nucleus is displaced towards the periphery This reaction to injury typifies central chromatolysis, a reversible change that develops during repair of a neuron, typically a lower motor neuron (syn. anterior horn cell), that has been disconnected from its target, and recovers to some extent. Many kinds of CNS neurons, however, do not survive axon transection

Parietal operculum

Overhang of the postcentral gyrus abutting against the lateral fissure

Infundibular recess

Overlies the infundibulum

Supraoptic recess

Overlies the optic chiasm

Vessels of posterior circulation of the brain

PCA SCA BA AICA PICA VA ASA These Perfuses structures within the posterior fossa (cerebellum, medulla and pons); also midbrain, occipital & inferior temporal lobes

Measures to lower ICP

Patient should be intubated. pCO2 about 35mm Hg. Avoid aggressive hyperventilaion to pC02 <28 at all times to prevent vasoconstriction. Elevate Head of bed 30-45. Keep head midline to prevent obstruction of jugular veins. Sedation-> propofol drip. CSF drainage via EVD. Osmotic therapy.

Depressed cranial fractures surgical treatment

Patients with open skull fractures depressed greater than the thickness of the cranium should undergo surgery to prevent infection (usually depression >1cm.

________ determines microtubule stability

Phoshorylation of microtububule-associated protein, tau

3 layers of meninges

Pia mater (adherent to the brain and follows the gyri and sulci) Arachnoid mater (weblike and bridges over the sulci) Dura mater (the outermost layer, it is an inelastic opaque fibrous layer consisting of the outer endosteal and inner meningeal layers)

How the choroid plexus makes CSF

Plasma flowing through CP capillaries at high velocity diffuses through fenestrations in the EC wall. These capillaries derive from the anterior and posterior choroidal arteries. The plasma exudate (interstitial fluid, ISF) produced in this way encounters the adjacent basolateral surface of CECs. RBCs and WBCs are too large to pass through fenestrations and remain in the capillaries. Tight junctions (zona occludens) located between adjacent CECs (purple arrowheads and previous slide) form a diffusion barrier to plasma proteins, growth factors, charged drugs and other macromolecules - these solutes cannot enter CSF. The water of plasma, however, diffuses through water channels made by aquaporins in the basolateral CEC membrane and, in turn, moves across the apical surface into the ventricular lumen due to the osmotic gradient formed by Na+ and Cl- efflux. Specific transporters found in the basolateral or apical surface membranes of CECs are responsible for modifying the distinct concentrations of solutes that match secreted CSF to brain interstitial (extracellular) fluid. The microvillous apical surface membrane imparts a high surface area, which promotes CSF secretion in at a high rate, as well as efficient absorption (clearance) of solutes exported from brain via CSF.

Tegmentum of midbrain gross

Portion of the midbrain anterior to the aqueduct

Tectum of midbrain gross

Portion of the midbrain posterior to the aqueduct

Central neurocytoma histology

Positive for synaptophysin, chromogranin and NSE Cells have a "fried egg" appearance

Wernicke's Area

Posterior 1/3 of the superior temporal gyrus, supramarginal gyrus and angular gyrus on both sides of the brainform the auditory association cortex. On the dominant side, these structures are utilized for language comprehension. On the non-dominant side they are used for interpreting or expressing non-language sounds. On the dominant side this region for language comprehension Damage to Wernicke's area, like Broca's area, also occurs commonly in cortical strokes, but the outcome is different. A stroke to Wernicke's area is much more likely to result in a severe and lasting speech/language defect, known as Wernicke's (or receptive) aphasia, that responds poorly, if at all, to speech therapy. In the Wernicke's aphasic, the fluency of speech output is relatively normal because the cortical motor speech center (Broca's area) is unaffected. However, what the patient typically produces is nonsensensical because the auditory association (sensory) cortex for language, functioning as a storage area for our lexicon and the correct wording and syntax, is lesioned, so the patient does not understand language in any form and therefore does not have the means to produce it meaningfully

Which commissure is responsible for the pupillary light reflex?

Posterior commissure

Cisterna ambiens

Postlateral to the tectum of the midbrain

Insular gyri

Primary visceral sensory cortex decoded here Also functions as part of the limbic system concerned with emotion Can be seen when prying apart the lateral fissure

Endovascular stroke treatment

Process of clot retrieval for occlusive stroke

Deep penetrating branches (perforating or ganglionic branches) of MCA, ACA, PCA

Properties -threadlike caliber -terminal endings -branch 90° to initial segments MCA: lateral lenticulostriates ACA: medial striates, including Recurrent a. of Hübner PCA/PComm: thalamoperforators

The 3 primary vesicles becomes what 5 secondary vesicles?

Prosencephalon - Telencephalon - Diencephalon - becomes the cerebral hemispheres, thalamus, hypothalamus, retina, and other structures Mesencephalon - Mesencephalon - becomes the midbrain Rhombencephalon - Metencephalon - Myelencephalon - becomes the pons, cerebellum, and medulla

What 3 primary brain vesicles initially derive from the cranial region of the neural tube

Prosencephalon= forebrain Mesencephalon Rhombencephalon= hindbrain

Types of MRI images

Proton relaxation times - T1-weighted (z-axis parallel) - T2-weighted (x-y plane parallel) Proton density-weighted images - Contrast between gray and white matter is generally reduced allowing for highlighting subtle abnormalities in the parenchyma

Meningioma gross and histology

Psammoma bodies Epithelial derived, so can be stained with epithelial membrane antigen (EMA +)

Glasgow Coma Scale

Published in 1974 by neurosurgeons Graham Teasdale and Bryan Jennett of the University of Glascow. Minor GCS 13-15 Moderate GCS 9-12 Severe GCS 8-3

Purkinje cell histology

Purkinje neurons (50-70 µm diameter) compared to the tiny dark granule neurons (4-6µm diameter) of the granular layer. Note: they occupy a single layer at the interface of the molecular layer (mostly acellular) and the granular layer (has the smallest neurons in the CNS)

______ laminates the cerebral cortex

Radial "inside-out" neuronal migration The neocortex is formed by 6 neuronal layers (I-VI) arising from ventricular zone (VZ), which are pluripotent, lining the lateral walls of the lateral ventricles Neuroblast (proliferate in the subventricular zone) will stop dividing going into the G0 phase. These post-mitotic neurons then migrate along radial glia cell scaffolding to their final position in cortex Processes is completed by early 3rd trimester VZ then generates glioblasts -> post mitotic, migrate and populate gray and white matter (WM) with macroglia. This continues up until around the 2nd decade of life

Neural tube defects

Range from minor lesions to fatal Prevalence of 1 per 10000 Increased AFP in amniotic fluid Risk factors include - Poorly controlled maternal diabetes mellitus - Anticonvalsants such as valproic acid (VPA) - Deficient in folic acid and vitamin B12

Colloid cyst

Rare benign epidermal cyst arising from the third ventricle near the interventricular foramen Can cause acute obstruction of CSF flow "drop attacks' can be fatal

Venous lesions (thromboses of central veins and dural venous sinuses)

Rare compared to arterial strokes Associated with pregnancy and early postpartum; hypercoagulation disorders Dural venous sinus thrombosis (DVT) -> backpressure on bridging veins -> parasagittal hemorrhages -> lethally elevated ICP -> decreased CPP and herniation

Hydranencephaly

Rare condition, mostly occurring after the 12th week of pregnancy Most likely due to decreased or lack of blood flow Result, almost complete loss of cortical tissue

Central neurocytoma

Rare neuroepithelial intraventricular (foramen of Monro, fornix) tumor Children and young adults 5-year survival 80% Positive for synaptophysin, chromogranin and NSE

Transverse sinus gross

Receives blood from the confluent and will then empty into the sigmoid sinuses

RELN/Lis pathways for neuronal migration

Reelin binds to one of 3 cell membrane receptors A cascade of activated proteins leads to phosphorylation and activation of actin and microtubule synthesis Loss of Lis1 gene causes a decrease in numbers of dividing neurons

Glutamate excitotoxicity: Cellular mechanism

Remember that 95% of the CNS neurons are glutamatergic Necrotic neuron is releasing glutamate, glutaminase, and glutamine GLU then binds to bystander neuron's NMDA Glu receptor which leads to increased intracellular Ca2+ This leads to free radical formation and Ca2+ dependent proteases activated. All leading to apoptotic cell death Some of the oxyradical can bind to EEAC Glu Transporter on astrocytes inhibiting Glu uptake and further increases in glutamate in the extracellular space

Choroid plexuses histology

Resembles a jumbled coil and revealed the histologic arrangement of the core capillary endothelial cells surrounded by a wall of the CECs

Pyramidal neuron

Reside within the cerebral cortex Named for the shape of its soma They can project their axons up to a distance of about 1 m to synapse on other target neurons These are excitatory in their stimulus of other neurons They use glutamate as their neurotransmitter and are thus termed glutamatergic

What drives hindbrain segmentation?

Rhombomere-specific expression patterns of HOX (homeobox) and related segmentation genes, e.g. retinoic acid receptor (RAR),

Folium

Ridges that are kind of like microgyri Note: foliation occurs as the result of the cellular migration and proliferation of granule neurons to form a greatly expanded cerebellar cortex, all contained within the confines of the posterior fossa.

The cerebrum consists of what 3 components

Right cerebral hemisphere Left cerebral hemisphere Diencephalon Note: The cerebrum consists of a right and left cerebral hemisphere partially separated in the midsagittal plane. The hemispheres overly a single midline diencephalon

Preoccipital notch

Right in front of the occipital lobe

Components of the corpus callosum

Rostrum Genu Body Splenium Note: this structures is how the two cerebral hemispheres talk to each other

Subdural hematoma

Rupture of the bridging veins leads to a venous subdural bleed over the cerebral convexities, blood collecting in the subdural potential space Present with midline shift Note: these are fragile and often will "re-bleed"

What 3 major vessels each perfuse parts of the cerebellum and brainstem

SCA (structures over the superior surface of the cerebellum) AICA (anterior inferior surface of the cerebellum) PICA (posterior inferior surface of the cerebellum)

Types of aneurysms

Saccular and Fusiform Saccular common to Circle' junctions & MCA bifurcation (e.g. PKD) Note: their size matters!

duret hemorrhage

Secondary bleed due to increased brain pressure and torsion Hypertensive bleed -cocaine

cingulate sulcus

Separates frontal and parietal lobes from cingulate gyrus

Lateral (Sylvian) fissure

Separates frontal and temporal lobes Runs roughly 90 degrees to the central sulcus

Central sulcus

Separates frontal lobe from parietal lobe Look for 2 gyri that zag together kind of like they are partners It demarcates the caudal limit from the frontal lobe from the rostral limit of the parietal lobe

Inferior frontal sulcus gross

Separates the inferior frontal gyrus from the middle frontal gyrus

Superior frontal sulcus gross

Separates the middle frontal gyrus from the superior frontal gyrus

marginal sulcus

Separates the paracentral gyri from the precuneus

Intraparietal sulcus gross

Separates the superior and inferior parietal lobules Note It is typically incomplete

Lateral (Sylvia) fissure gross

Separates the temporal lobe from the frontal lobe

Brain ventricles

Series of cavities in the CNS that contain cerebrospinal fluid Includes: Lateral ventricle 3rd ventricle 4th ventricle

Neuroblast division in the EGL is signaled by _____

Shh secreted by Purkinje neurons Failure of EGL to cease proliferating is attributed to mutations in Shh signaling pathway in EGL neuroblasts Causal to medulloblastoma (usually in the location of the vermis), a pediatric cerebellar tumor derived from EGL neuroblasts

Gross image of acute meningitis

Shows purulent exudate on brain surface or at the brain base

______ are used to detect cytoskeletal abnormalities in Alzheimer's brain and allow better visualization of cellular connections.

Silver stains

Axons, dendrites, and glial processes that comprise the gray matter neuropil are best demonstrated with _______

Silver stains that deposit ammoniacal silver on cytoskeletal components Some of these structures are darkened with black metallic silver after chemical reduction. Silver staining shows a meshwork of axons and dendrites in the adjacent image. Considering the high density of processes, it is not surprising that the vast majority of the cytoplasm of neurons and glia is actually invested in their processes, not their cell bodies.

pars orbitalis

Sits right over the eye within the inferior frontal gyrus

Monro-Kellie Doctrine

Skull volume is constant. ICP is dependent on the volume of the cranial contents. These include brain, CSF and blood volume. Small increases in cranial content volume can lead to larger increases in ICP because of the rigidity of the skull.

Chronic meningitis

Slow-growing organisms such as fungi and Mycobacterium tuberculosis (will see caseating granulomas) Weeks to months for symptoms to appear

Facial features of fetal alcohol syndrome

Smooth philthrum Thin upper lip Micrognathia Prominent epicanthal folds Short palpebral fissures

_____ cannot enter the brain and spinal cord efficiently by oral or parenteral routes of administration because of two barriers, the blood-CSF barrier detailed in this ILA, and blood-brain barrier.

Solutes >1500 Daltons and charged drugs at pH 7.4 (most drugs) Enormous drug doses by these routes would be required to achieve therapeutic CNS concentrations and cause unwanted side effects in other organ systems. To gain access to the CNS, intrathecal injection (directly into the CSF) is an option. For example, narcotic is usually infused into the subarachnoid space of the lumbar cistern to achieve "spinal" anesthesia because although narcotics are lipophilic and can readily access CNS by parenteral administration, intrathecal administration, i.e. directly into CSF, requires a much smaller dose than other routes to effect. In another example, continuous intrathecal infusion of the muscle relaxant baclofen (GABAB receptor agonist) is used to treat spastic cerebral palsy at 1000-fold smaller dose than would be necessary by other routes, and unwanted side effects on other GABAergic neurons are thus avoided. Balcofen works in the cord to reduce activity of hyperactive lower motor neurons.

Detection methods for neural tube defects

Sonagram and elevated AFP in maternal serum or amniotic fluid - best measured at g16-18 wks Elevated AFP expressed in multiples of normal maternal levels (MoM) at this time; abnormal is >2.5 MoM

What opposing signal gradients drive dorsal-ventral polarization of the spinal cord

Sonic hedgehog (Shh) -induces ventral "floor plate" in formative neural tube -floorplate becomes 2° Shh source -Shh gradient signals motor neuron development in ventral neural tube - "ventralizing signal" BMPs -Secreted by dorsal neuroectoderm -induce neural crest and roof plate -roofplate becomes 2° BMP source -BMP gradient signals sensory neuron development in dorsal neural tube -"dorsalizing signal"

Broca's area

Speech production Involves the pars triangularis and the pars opercularis Stroke here causes people to be unable to say what they are thinking, they can think the words but can't coordinate the production of those words

Weigert method

Stains for lipid. The high lipid content of white matter causes it to preferentially stain dark, unlike the cortical ribbon of gray matter and deep nuclei which appear light Note: it can be used also on the cerebellum and reveals tiny gray matter ridges (folia). Each folium is lined by a thin cortical ribbon lying just exterior to a core of darkly stained white matter.

Basophilic thionine stain

Stains the cortical ribbon because of its high density of neuronal cell bodies and stained nuclei and ribosomes that take up basophilic stain

Isotretinoin (Accutane)

Still #1 teratogenic Rx drug with generics available in US market Indication: cystoid acne High incidence of early spontaneous abortions and birth defects 1st trimester use increases incidence from 3-5% to ~30% iPLEDGE (electronic risk management program) Retinoic acid derivatives disrupt normal HOX gene expression pattern -> scrambled brain

Vascular brain lesions

Stroke Transient ischemic attack (TIA) Arteriovenous malformation (AVM) Dural venous sinus thrombosis

Diencephalic derivatives

Structures surround midline 3rd ventricle -thalamus - paired -hypothalamus -pineal gland -CN 2 and retina -posterior pituitary (neurohypophysis)

stroke

Sudden neurological defect, usually unilateral, due to lack of oxygen when blood flow to the CNS is impaired by blockage or rupture of an artery (flow doesn't have to stop entirely)

superior cerebral veins gross

Superficial veins drain blood from the external cerebrum and form superficial bridging veins that enter the SSS at right angles Bridging veins are prone to rupture in shaken-baby syndrome and falls of the elderly. The former is explained by system fragility. The latter is explained by brain atrophy, which puts greater tension on bridging vessels, considering they form a bridge between the brain and the skull (to which the sinus is attached via the dura). Greater tension on these relatively thin-walled vessels as the brain atrophies with advanced aging makes them especially prone to breakage when hitting the head in a backwards fall, causing the brain to swing back and forth in an anterior-posterior direction while tethered to the skull by bridging veins. Parasagittal subdural hemorrhage (Haines p. 63) is commonly associated with such falls in the elderly.

Cerebral venous sinus thrombosis

Superior sagittal sinus thrombosis is most common (60%) Symptoms include headache, blurred vision, seizures, coma Can occur in hypercoagulable states

Cingulate sulcus

Superior to the corpus callosum and separates it from the cingulate gyrus

Vertebral artery gross

Supplies 20% of the brain Provides arterial blood to the posterior circulation The paired vertebral a. arise developmentally from longitudinal connections between the 1st - 7th intersegmental arteries (7th intersegmentals = subclavian arteries). They ascend through the foramina transversaria of C1 - C6 before piercing the posterior aspect of the atlanto-occipital ligament and entering the base of the brain through the cisterna magna. Vertebral a. give rise to several important, named branches that supply blood to the spinal cord, all components of the brainstem, the cerebellum, and the medial aspects of the occipital and temporal lobes.

Internal carotid artery gross

Supplies 80% of the brain Provides arterial blood to the anterior circulation

Acute subdural hematoma surgical treatment

Surgery for 5-mm midline shift or 10 mm thickness. All pts with acute SDH and GCS</= 8 ICP monitor. Surgery for all acute SDH with decline GCS by 2 points, ICP>20, or asymmetric or fixed/dilated pupils.

Treatment of Tethered cord syndrome

Surgically transect the filum

What secondary vesicles give rise to the cerebral hemispheres

Telencephalon Note: these are separated by median longitudinal fissure

Patient present with saw blade in head What to do? 1) Pull saw blade out and see what happens. 2) Decide medicine is not for you and decide to get that Ph.D. in Mathematics from MIT. 3) Tell your surgical resident that you feel nauseous and need to leave. 4) Tell the neurosurgery attending that the patient needs: a)immediate intubation and large bore venous access. b) hypotension(SBP <90) must be avoided/corrected ASAP. c) immediate head CT and perhaps CT angiogram. d) type/cross match multiple units of blood. e)culture wound and prepare OR for craniotomy.

Tell the neurosurgery attending that the patient needs: a)immediate intubation and large bore venous access. b) hypotension(SBP <90) must be avoided/corrected ASAP. c) immediate head CT and perhaps CT angiogram. d) type/cross match multiple units of blood. e)culture wound and prepare OR for craniotomy.

Transient ischemic attacks (TIAs)

Temporary embolic occlusion and neurologic signs These are a warning for impending stroke and should prompt lifestyle changes and prophylactic medications Affecting the anterior circulation - carotid a. disease -transient numbness or weakness of extremity, confusion and/or aphasia -Amaurosis fugax: TIA specifically targets ophthamic a.>sup/inf retinal a. Affecting the posterior circulation - -vertebrobasilar disease -binocular visual field loss -cranial nerve signs, e.g. vertigo, postural imbalance -incoordination, nausea

Anterior cerebral artery (A2) gross

The ACA-A1 gives rise to ACA-A2 segment as it arcs dorsally within the interhemispheric fissure. Trace its distribution on the medial aspect of the hemisphere, and note that it supplies the ventral and medial aspects of the frontal lobe and ventral medial parietal lobe, extending only slightly onto the dorsolateral and ventrolateral surfaces of the frontal lobe. Note: portion of the ACA after the anterior communicating artery

Typical CSF content of various solutes

The CNS makes its own growth factors and hormones. An exception is leptin, which is transported from plasma into CSF across CECs by a high affinity transporter. Once in CSF, leptin diffuses to the hypothalamus, which borders the 3rd ventricle, where it acts to mediate satiety Transporters in CECs also exist for concentrating water soluble vitamins, e.g. ascorbic acid and thiamine, from plasma into CSF. CSF normally contains negligible protein and immunoglobulin, which can increase significantly to detectable levels in disease states.

Basis pontis gross

The anterior surface that is bulbous and somewhat corrugated

Characteristics of dendrites

The are relatively short and highly branched They can extend as fas as a few hundred microns from the soma

Posterior cerebellar artery (P1) gross

The basilar artery terminates at the junction of the pons and midbrain (pontomesencephalic junction) by dividing into the paired posterior cerebral arteries (PCA) These supply supply the midbrain, the medial occipital lobe (particularly along the calcarine fissure, i.e., the primary visual cortex), and the inferior and medial surfaces of the temporal lobe.

Why would hydrocephalus ensure with a subarachnoid hemorrhage?

The blood blocks arachnoid granulations

Central (Rolandic) sulcus gross

The boundary between the frontal lobe rostrally and the parietal lobe caudally

Blood brain barrier

The brain is perfused by an extremely dense microvessel network required for dispersal of oxygen and glucose to the most energy-demanding of cell types. The vast majority of the brain's capillary and venule endothelial cells form a blood-brain barrier (BBB) throughout the CNS parenchyma. This serves as a diffusion barrier to blood-borne solutes, including most drugs, across the large luminal surface area created by the intraparenchymal microvessel beds. Note: major cells at play are astrocytes

What drains into the paired superior and inferior petrosal sinuses

The carverous sinus

Obex of medulla gross

The caudal most point of the 4th ventricle

Disorders which damage (open) the BBB: Lyme disease (Borrelia) and syphillis (Treponema palladum)

The causal spirochetes breach the BBB by tunneling through vessel walls.

CSF function overview

The composition of electrolytes and other solutes needed to develop and maintain the CNS is achieved by bathing the parenchym with CSF, which derives from plasma with important changes that match its composition to the extracellular fluid surrounding brain cells. CSF freely diffuses from its collection sites in the ventricles and subarachnoid space into CNS parenchyma. CSF is produced by choroid plexuses present in every ventricle. CSF circulates to remove potentially toxic solutes from the CNS and deliver nutrients, hormones and other signals to the CNS and from one CNS structure to another. Desired drugs are removed if their structure recognizes the normal pumps used for solute removal. This can counteract therapeutic efforts to manage disorders such as meningitis. The volume of CSF increases during sleep and provides a nightly flushing of toxic metabolites, e.g. beta-amyloid, away from neurons and into the lymphatic system. CSF forms a protective water jacket surrounding the soft CNS, serving to reduce the buoyant density of the brain, and its vulnerability to acceleration-deceleration injury.

Cortical ribbon

The cortex of each cerebral hemisphere, provides a 4-6mm thick outer lining of each gyrus (ridge) and sulcus (furrow)

Monroe-Kelly doctrine

The cranial compartment is not compressible, and the intracranial volume is fixed Increasing the volume of one compartment is compensated by decreasing the volume of another As ICP rises: (1) some CSF diverts into spinal sac (2) venous blood partially extruded from brain (3-4) When compensatory steps are exhausted ,ICP rapidly rises, CPP plummets (MAP-ICP=CPP)

Cuneate gyrus gross

The cuneate gyrus and lingual gyrus specifically parallel the calcarine sulcus. These gyri together with their surfaces of cortex buried within the calcarine sulcus comprise the primary visual cortex

Lingual gyrus gross

The cuneate gyrus and lingual gyrus specifically parallel the calcarine sulcus. These gyri together with their surfaces of cortex buried within the calcarine sulcus comprise the primary visual cortex

Postcentral gyrus (primary somatosensory cortex) gross

The gyrus immediately caudal to the central sulcus This is the rostal most gyrus of the parietal lobe and is where cortical decoding occurs for all somatosensory information (cutaneous and proprioception) coming the body and structures of the head, excluding viscera. The postcentral gyrus functions as the primary somatosensory cortex. The term "primary" is applied to any sensory cortex where the arriving information in the brain is initially decoded before its cortically processed in nearby association cortices where what is sensed is actually interpreted

Precentral gyrus (primary motor cortex) gross

The gyrus immediately rostral to the central sulcus This is the caudal most gyrus of the frontal lobe viewed from its lateral aspect

precentral gyrus

The gyrus just rostral to the central sulcus and caudal to the precentral sulcus

Inferior parietal lobule gross

The inferior parietal lobule is further divided into the more rostral supramarginal gyrus and its caudal partner, the angular gyrus

Superior cerebellar artery gross

The last branch before the basilar artery branches to form the PCA Supplies the lateral regions of the middle and rostral pons and superior aspect of the cerebellum.

Posterior inferior cerebellar artery (PICA) gross

The last major branch before the fusion of the vertebral arteries to form the basilar artery PICA provide blood to the dorsolateral aspect of the medulla, choroid plexus of the fourth ventricle, and posterior inferior surface of the cerebellum. Often PICA is disconnected from the vertebral a. during brain removal. Even so, the looping arteries found on the posterior inferior surface of the cerebellum derive from PICA. This "looping" appearance is easily see on arteriograms (Atlas, p. 247, compare with drawing in p. 33) and is easily displaced by a mass-occupying lesion

Uncus gross

The medial most protuberance of the medial inferior temporal lobe This structure is most prone to herniation from its normal position above the tentorial notch, to just below it. The result is compression of the midbrain and traction of the 3rd cranial nerve. if unchecked, brainstem displacement and death result.

Spina bifida aperta (myeloschisis)

The most debilitating open cord because it is the least repairable Presents with open cord/roots splayed without sac or skin

Anterior inferior cerebellar artery (AICA) gross

The most inferior branches off the basilar artery These vessels supply lateral regions of the caudal pons and anterior and inferior surfaces of the cerebellum Note: these are the first major branches once the basilar artery is formed

Medulla pyramids gross

The most prominent features of the anterior surface of the medulla Oriented along the longitudinal axis of the medulla and bracket the midline anterior median fissure

Pineal body gross

The pineal gland (syn. epithalamus), extends caudally from the dorsal thalamus below the splenium of the corpus callosum and overlies the tectum. It produces the hormone, melatonin. When synchronized by retinal projections of light information to a hypothalamic relay nucleus, it drives our circadian rhythms.

Pars orbitalis gross

The portion that lies above the eyes

What drains into the internal jugular veins

The sigmoidal sinuses

What drains in the Confluence of sinuses (torcula)

The superior sagittal sinus and the straight sinus

Polymicrogyria

The surface of the cortex appears to form microgyri Often found in vascular territories or watershed areas suggesting they arise from a hypoxic/ischemic event

When staining the spinal cord with basophilic stain, why does the white matter stain lightly?

The surrounding WM is lightly stained because ribosomes do not enter axons coursing through it, and glial cells there don't cluster together as much as neurons do in gray matter to accumulate stain

Brain tumors and symptoms

The tumors can localized to specific brain functions Causes increase intracranial pressure Symptoms: Cerebrum -Headaches -Seizures -Cognitive change -Personality change -Motor/sensory functions -Memory changes -Visual changes Cerebellum -Voluntary movement -Balance (ataxia) Brain stem -Vomiting -Alertness -Blood pressure -Breathing -Heart rate -Digestion and swallowing

Parahippocampal gyrus gross

The uncus is a medial extension of the parahippocampal gyrus, named for the deeper hippocampus situated superior to it.

Basilar artery

The vertebral arteries fuse together at the pontomedullary junction to form the basilar artery, which follows the basilar sulcus in the basis pontis

Why do meta-analyses provide the highest level of evidence?

There are several elements of meta-analysis methodology that lend high credibility to meta-analysis results: Accuracy of the information is high because a systematic review of studies is conducted and only studies of proven quality are included. Precision of the effect size estimate is increased by pooling data across studies -Each study included provides an estimate of the true effect, and depending on the sample size, the estimate will be more or less imprecise -A meta-analysis will combine all the data from the individual studies to obtain a single summarized estimate or "effect size" -Because data from all the studies is included, the sample size is increased and the precision of the pooled estimate increases. -The pooled estimate is not a simple average. Each study has a "weight" that is directly related to its sample size.

Side effects of alteplase

There is an increase in the incidence of Intracranial Hemorrhage, and it is unlikely that this study result is due to chance The incidence of death is actually a bit reduced with Alteplase, although looking at the 95% CI it is possible that it could be increased too

Flocculus of cerebellum gross

These are portions of the flocculonodular lobe visible along the ventral surface of the cerebellum and positioned on either side of the brainstem, lateral to the rostral medulla. They appear as small circumscribed buttons of cerebellar tissue.

Places in the brain that lack a BBB

These are referred to as circumventricular organs (due to their location around the walls of the 3rd and 4th ventricles). Their purpose is to give hydrophilic agents in blood or CSF direct and easy access to chemosensory neurons positioned within ventricular walls. Other leaky sites are neuroendocrine interfaces providing for (1) pineal gland secretion of melatonin, (2) the relay of Releasing Factors from the median eminence of the hypothalamus to the portal circulation, and (3) a site for neurohypophyseal release of oxytocin and vasopression, all into vascular beds that must be sufficiently leaky to admit these messengers that otherwise could not access microvessels bounded by tight junctions in the rest of the CNS. Note: No astrocytes surround microvessels at sites without a BBB, underscoring the concept that without a source of inducing signal the BBB does not form.

Cerebral peduncles

These are thick stalks of motor fibers that stream from each cerebral hemisphere to the brainstem and beyond. Arising from the medial walls of the interpeduncular fossa are the prominent oculomotor nerves (CN3), which course anteriorly between the posterior cerebral and superior cerebellar arteries.

Medial striate arteries gross

These are tiny thread like vessels that branch off the A1 at 90 degrees and and perforate the anterior perforated substance These are named for the deep medial gray matter structures including the striatum of the basal ganglia they perfuse. The largest of the medial striate a. is the Recurrent a. of Hübner, which arcs laterally to join the lenticulostriate a. as they penetrate the brain parenchyma. The Recurrent artery perfuses the head of the caudate nucleus. We will discuss their function later in the course.

Radial glia cells

These cells guide migrating neurons The span the neural tube wall during the first trimester as scaffolding There are then adhesion molecules interactions between these radial glial cells and the migratory neuron The radial glia cells will disappear in the cerebral cortex and cord following migration

Electrical properties of dendritic and axonal domains

They differ This renders them capable of only uni-directional signaling from the dendritic pole toward the axonal pole

Disorders which damage (open) the BBB: Progressive multifocal leukoencephalopathy (PML)

This demyelinating CNS disease is caused by reactivation of a latent JC polyomavirus infection. The virus crosses the BBB.

Functional significance of the blood brain barrier

This diffusion barrier across CNS ECs protects the brain from many microbes, immune recognition, plasma-borne signaling molecules, e.g. growth factors and xenobiotics capable of misguiding CNS development or disrupting normal brain function. The brain requires receptor-mediated signaling by many of the same peptide growth factors common to tissues and organs outside the CNS. The BBB allows the brain to develop at just the right time without interference from these outside signals. However, because the brain requires many of same growth factors, e.g. PDGF, and hormones, e.g. T3, these signals are also produced by CNS cell types inside the BBB to assure normal brain development and function.

Anencephaly gross

This is a failure of the development of the cerebral cortex, calvaria, and scalp

Anterior cerebral artery (A1) gross

This is the first branch of the ACA It is medially directed, will have to reflect the optic chiasm in order to see Note: this is the portion of ACA that is before the anterior communicating artery

Corpus callosum gross

This is the largest commissure or interhemispheric connection in the brain and is composed of association fibers that interconnect homologous structures on the two sides of the cerebral cortex. Portions of the corpus callosum include the rostrum (closest to the nose), genu (knee or bend), body, and splenium.

Diffusion-weighted MRI identifies cytotoxic edema consequent to massive dry stroke

This shows a MCA dry stroke that has progressed to cytotoxic edema

MRI-T2 reveals vasogenic edema consequent to BBB breakdown within the tumor

This shows a glioma (likely a glioblastoma) results in a loss of the BBB which can lead to vasogenic edema

Lenticulostriate arteries gross

Threadlike branches that arise from MCA-M1 These terminal vessels give rise to ischemic "lacunar" infarcts after degenerating in a process termed lipohyalinosis. As a result the vessels are prone to rupture, causing intraparenchymal hemorrhagic stroke.

Types of occlusive stroke

Thrombotic - atheroma occludes or narrows vessel Embolic (most common) - embolus dislodges from heart or carotids, moves downstream (I.e. up to the brain) and the stroke deficit depends on embolus size and perfusion territory blocked

_______ bond adjacent CECs near their apical surface

Tight junctions (zona occludens)

Treatment of Acute Ischemic Stroke

Tissue Plasminogen Activator (TPA) -Digests fibrin clot -i.v. Tx window is ≤3 hr -Intra-arterial Tx window is ≤6hrs -Contraindicated in hemorrhagic stroke - confirm by non-contrasted CT Additional neuroprotective agents co-administered with TPA are under study. Minocycline - not yet FDA approved due to conflicting clinical studies -Tetraclycine derivative crosses BBB - Inhibits apoptosis in stroke models by preventing apoptosis activation upstream of caspase activation - Prominent Anti-inflammatory effects attributed to its inhibition of chronic microglial activation following Acute Ischemic Stroke

What drains into the sigmoid sinuses

Torcula drains into the paired transverse sinuses and then into the sigmoid sinuses

Zika virus infection during brain development

Transmitted by mosquitos Children present with microcephaly Birth Defects 1st Trimester 8% 2nd trimester 5% 3rd Trimester 4 %

Traumatic parenchymal lesions surgical treatment

Treat surgically parenchymal lesions with >5mm midline shift, ICP>20 despite optimal medical management, progressive neuro decline. Decompressive procedures including bifrontal DC are treatment options.

Trichrome stain of the spinal cord

Trichrome imparts a magenta-color to the central gray matter and blue stain of surrounding WM

Notochordal signals

Triggers induction! Autocrine signaling from the ectodermal cells, mediated by bone-morphogenetic protein-4 (BMP-4), maintains ectodermal phenotype When and where BMP-4 levels decrease, ectoderm differentiates into neuroectoderm Notochord secretes various proteins such as noggin that bind BMP-4 and block its interaction with the BMP-4 receptor >> primary neurulation

Disorders which damage (open) the BBB: Astrocytomas and gliomas

Tumors are highly neovascularized but the microvessels in them do not form normal associations with the neoplastic astrocytes, and thus lack tight junctions. This can result in significant peritumoral edema. In principal it can also facilitate access of charged antineoplastic drugs to the tumor.

CT of acute subdural hematoma

Under the dura and presents with a "sawtooth" pattern

Subcortical white matter

Underlies the cortical ribbon, named for its glossy white appearance in gross tissue, and which extends into the core of each gyrus

Pyramidal decussation gross

Upper motor neuron pyramid axons crossing the midline

Meta-analysis

Uses statistical techniques to combine date form the studies and estimates the "effect size", that is, a pooled measure of the treatment effect (be it a Relative Risk, Hazard Ratio, Odds Ratio, Risk Difference, etc.). A net effect of pooling the data is a substantial increase in sample size, which results in more precise estimates of the "effect size". Effect size estimates derived from a well conducted meta-analysis are regarded as the most accurate and precise Therefore, meta-analyses can shed light over research questions that individual studies have not been able to answer definitively

Vasogenic edema vs cytotoxic edema

Vasogenic - e.g. HACE - There is a separation of the tight junctions or tear in the vessel leading to a leakage of blood plasma into the interstitial space Cytotoxic - during ischemia there is not enough glucose and oxygen going to the tissues causing ATP production to plummet. Na/K ATPase is then unable to excrete 3Na+ from the neuron. There is a buildup of cations in the neuron. H2O and Cl- will travel into these neurons producing edematous neurons. - Also present with edematous astrocytes via H2O entering through aquaporins - If we are moving most of the cations and Cl- into these neurons then the concentration will be greater than the interstitial space. This generates a Transcapillary diffusion gradient that moves H2O from the vascular compartment into the brain parenchyma (cerebral edema)

3 types of cerebral edema that increase in brain water content over 80% (normal)

Vasogenic (leak in the plumbing such as hemorrhage) Cytotoxic (those seen in dry stroke which causes an ischemic territory) Interstitial (reserved for distinct hydrocephalus and when the CSF pressure in the ventricles is so great that there is movement across the ependymal border)

Inferior parietal lobule

Ventral to the superior parietal lobule separated by the intraparietal sulcus Contains the supramarginal gyrus and the angular gyrus

Transverse temporal gyrus gross

Viewed on the superior surface of the superior temporal gyri deep to temporal operculum (must pry open the lateral fissure The gyri appears to be going back to the occipital lobe This is the location of primary auditory cortex, where auditory sensory information is cortically decoded in both cerebral hemispheres. It is located on both sides of the brain

Zika virus teratogen effect

Virus infects pluripotent neural stem cells (NSCs) and radial glia Uses AXL surface receptor protein to gain entry Inhibits NSC division/increases apoptosis Depletes developing brain of migratory neurons Microencephaly>microcephaly Incidence has plummeted over past 3 yrs

BBB transport of water

Water moves freely across the BBB as plasma osmolarity changes. This allows an intravenous infusion of a osmotic diuretic, e.g. mannitol or hypertonic saline, to rapidly draw water from brain interstitial fluid (ECF) into the vascular lumen in an attempt to reduce cerebral edema and the potential for brain herniation.

Primary auditory cortex

Where all auditory information goes to the brain and decoded Located on the superior surface of the superior temporal gyrus Note: located near the Wernicke's area

Cerebral aqueduct gross

Where the 3rd ventricle narrows, and passes through the midbrain The most common cause of non-communicating hydrocephalus (defined by a blockage within the ventricular system or at the exiting apertures of the 4th ventricle) in the newborn occurs at the aqueduct, due either to stenosis, a narrowing commonly as the result of cytomegalovirus infection or toxoplasmosis, or atresia(congenitally unformed).

Acute Meningitis histology

Will see a lot of neutrophils within the subarachnoid space Note: the amount of neutrophils or bacteria can actually lead to occlusion of blood vessels and lead to stroke

CT of acute infarct of the anterior cerebral artery

Will see a thin strip of the cortex that is hypodense

CT of acute middle cerebral artery

Will see a wedge shaped structure that is hypodense

Diffuse Axonal Injury (DAI) histology

Will see axonal spheroids are axons that have been stretched and whose function stops their (like a traffic jam) often seen within the white matter. These can also be IHC stained with APP Note: you will have see blood around the eyes with these type of injuries

Subdural hematoma histology

Will see blood (dark pink/red) under the dura About a 1 wk, you will have granulation tissue With time, will develop "old membrane" which is fibrotic with siderophages

Contusion histology

Will see free blood within the brain parenchyma and dead neurons (red and dead)

Berry aneurysm histology

Will show loss of muscles, elastic fibers, and collagen Note: these tend to occur at branch points Note: the anterior circulation is also where most of these occur

angular gyrus

Within the inferior parietal lobule Follow the superior temporal sulcus up, where it looks like it ends in a loop. This is the angular gyrus This is the where all the words we know are stored

Supramarginal gyrus gross

Within the inferior parietal lobule If you follow the lateral fissure, where it loops at the end is this structure

Pyramidal neuron histology

Within the inner pyramidal layer (Layer V) Notice their apical dendrites and now they orient in one direction, which is towards the pial surface These axons tend to aggregate in places (look for the blue streaks stained for myelin as they traverse the cortex toward the subcortical white matter. May be able to see Nissl bodies which are basophilic which contains nissl substance which is a maker for big neurons and reflects a concentration of rough endoplasmic reticulum, polyribosomes, and free ribosomes All the space around the neurons are interconnections

Middle cerebral artery (M2) gross

Within the lateral fissure, MCA-M1 forms the M2 segment as it perfuses the insula and typically bifurcates into the superior and inferior divisions. As these divisions emerge from the lateral fissure they perfuse the lateral convexities of the frontal lobe (superior division) and parietal/temporal (inferior division) lobes, respectively

Postcentral gyrus

Within the parietal lobe just caudal to the central sulcus

Are CN2 or CN3 signs possible for circle lesions?

YES

Are anterior horn cells of the cord multipolar?

YES

Do individual gyration patterns differ but have stereotyped features?

YES

Does each folium have a white matter core extending into them?

YES

Does low glucose decrease cognitive performance and increase meta-ignorance?

YES

Does somatosensory pathways also cross midline to carry info from one side of the body to opposite side of the brain (postcentral g)?

YES

Are compensatory mechanisms lost as ICP increases too much?

YES 7-15 = normal supine adult 20 = drowsy & confused >25 = brain swelling -> HERNIATION

Do the fluid and solutes of the CSF equilibrate with and provides interstitial fluid for brain tissue.

YES Any solute, including a drug, that makes it into CSF can in turn freely diffuse into brain across the ependymal lining from the ventricular side or across the pial surface from the SAS side

Can hemorrhaged lenticulostriates include effects to the internal capsule posterior limb which is supplied by the anterior choroidal artery?

YES Blood released by hemorrhaged lenticulostriates into the interstitial space vasoconstricts neighboring vessels, thereby expanding the ischemic territory beyond their actual perfusion territory to include the Internal capsule posterior limb

Is the human brain critically dependent on a continuous supply of blood?

YES Deprivation - 10s -> unconscious - 20s -> electrically inactive - few mins -> irreversible damage

Does the motor cortex on one side control the opposite side of the body?

YES Descending two-neuron motor pathway -Upper motor neuron (1) in precentral g. descends, crosses midline, descends further, and synapses on an α-motor neuron (2) in ventral horn of cord (or brainstem). -Lower motor neuron (2) projects through spinal nerve to motor unit.

Is the spinal cord functionally polarized?

YES Dorsal half tends to be committed to sensory neurons Ventral half tends to be committed to motor neurons

Can epileptic foci lead to glutamate excitotoxicity?

YES Glu released by repeatedly depolarizing neurons [GLU]o exceeds glial uptake capacity during status epilepticus Leads to excitotoxic neuronal death by apoptosis

Does the cerebellum stain darker with the basophilic thionine stain?

YES The extremely high density of neuronal cell bodies in GM of the cerebral cortex imparts an even darker blue thionine stain also observed in this midsagittal section through the cerebellum (arrow). Approximately 50% of all neuronal cell bodies in the brain are packed in the cerebellar cortex!!!

Are deep penetrating arteries vulnerable to rupture?

YES (these include penetrators off the Circle via ACA, MCA, and PCA; and paramedian branches off the basilar artery) Most vulnerable structures if this occurs is the basal ganglia, thalamus, internal capsule, and pons

Is the most common brain tumor a metastasis?

YES!

Can lipophilic substance cross the blood brain barrier?

YES! Lipophilic substances can move from the lumen of vessels that penetrate the brain(technically outside the brain!!) across the BBB into brain parenchyma by simple transmembrane diffusion. This is the major entry mechanism into CNS for most psychoactive drugs. The rate of entry depends on their lipid solubility, which is estimated experimentally by determining the oil/water partition coefficient for the substance. Agents in the upper right of the diagram have the fastest rate of CNS access and include most drugs of abuse.

Are dendrites studded with spines?

YES!! Primary, secondary and tertiary branches of the dendritic arbor are in turn studded with tiny dendritic spines They confer huge surface area to the dendrite and form the majority of a neuron's post synaptic sites. In doing so a single large neuron receives as many as 2 x10^5 synaptic inputs from other neurons There is daily addition and removal of spines which reflect their critical, dynamic role in memory formation and extinction

Is there a greater chance for another concussion once you have one prior?

YES, and it may increase the odds of post-concussion syndrome

In children and teens, does it take longer to recover from a concussion?

YES, and they are more likely to get them

Is the optic nerve a CNS component?

YES, unlike the other cranial nerves, it is entirely CNS The optic nerve is of the utmost clinical significance to vision and to multiple sclerosis (MS), a neurologic disorder restricted to the CNS. This autoimmune disorder frequently attacks the optic nerve for this reason early on in the course of the disease.

How do you know that you are looking right in the midline on a midsagittal cut?

You can visualize the cerebral aqueduct which is the narrowest part of the CSF circulatory system

T1 MRI

Z axis parallel Looks like normal anatomic brain slices, gray matter is gray and white matter is white

Predicated sites of brain herniation from uncompensated ICP

a = subfalcine -cingulate g. slips under falx (leads to compression of of the pericallosal artery and more importantly the callosomarginal artery) b = uncal/transtentorial -uncus ± parahippocampal g. slips under tenotorial notch c = central -essentially a bilateral transtenorial e = tonsilar -tonsils displaced through f. magnum d = transcalvarial -achieved by decompressive craniectomy

anterior median fissure gross

a groove along the anterior midline of the medulla

Chronic traumatic encephalopathy (CTE)

a potential late effect of sport-related concussion and subconcussive head trauma A type of neurodegeneration many of the same histopathologic findings as Alzheimer's disease

interthalamic adhesion (intermediate mass)

a small, midline commissure connecting the right and left thalamus In about 50% of brains an interthalamic adhesion (syn. massa intermedia) of unclear function spans the midline

Cerebellopontine angle gross

a surgical landmark and depression found immediately lateral to the pontomedullary junction and medial to the flocculus. The CPA is proximal to the origins of the facial nerve (cranial nerve VII), and vestibulocochlear nerve (cranial nerve VIII). The depression of the CPA allows for growth of benign tumors of the vestibular portion of the CN VIII, termed vestibular Schwannomas. This tumor typically causes symptoms of dysequilibrium, gait disturbance and cranial nerve signs, e.g. tinnitus (ringing of the ears).

Methodological steps to a well-designed meta-analysis

a) Hypothesis formulation -the objective of the meta-analysis should be clearly stated b)Sampling strategy and the possibility of publication bias -Efforts should be made to include ALL relevant studies -The published literature may exclude information that would affect the ultimate conclusion of the meta-analysis (Publication bias) -It is necessary to search for unpublished studies too! - trial registries would provide information on trials completed but not published - Proceedings of Conferences would include abstracts of studies that were presented at the conference but might not have been followed by a publication c) Major principles behind Inclusion criteria - Study quality - Feasibility of combining the study with others d) Data to be collected e) Data abstraction and the possibility of observation (information) bias

CSF secretion by CECs is driven by:

active ion transport resulting in a net secretion of Na+ and Cl-, the main ionic components of CSF. Na+K+ATPase is the primary transporter of Na+ and found at the apical surface of the CEC. A Cl-/HCO3- exchanger localizes to the basolateral surface and drives steady state efflux of intracellular HCO3- to drive Cl- influx. The action of carbonic anhydrase (CA) maintains intracellular [HCO3-]. The CA inhibitor, acetazolamide (DiamoxTM) is administered to reduce CSF production in some medical conditions, e.g. benign intracranial hypertension, aka pseudotumor cerebri. It works to inhibits CA, which reduces [HCO3-]in and thus Cl- influx across the basolateral membrane. As a result, reduced [Cl-]in limits Cl- efflux at the apical membrane, pulling less water with it, i.e. producing less CSF.

pneumoencephalitis

air around the brain, can be caused by a cribriform plate fracture

BBB transport of non-essential amino acids

alanine, glycine, proline) and their derivatives, e.g. γ-aminobutyric acid (GABA), do not enter the brain, as their A-type transport protein is lacking on the luminal EC membrane. Their synthesis within brain is required. Glutamine transport is efficient, however, and mediated by an N-type mechanism (Na+ dependent transporter) in the luminal and abluminal EC membrane.

______ is the leading teratogen in the Western Hemisphere

alcohol

Preoccipital notch gross

along the inferior edge of the cerebral hemisphere lying just superior to the cerebellum

Teratogen

an agent or factor that causes a congenital malformation Ex: - alcohol - oral retinoids - phenytoin - varicella - Zika

Each carotid artery gives rise to ____

an ophthalmic a., posterior communicating a., and anterior choroidal a., as well as the middle cerebral a. (MCA), collectively remembered as OPAAM.

Perforators off ACA, MCA and PCA collaborate with the ______

anterior choroidal a. to perfuse deep structures in cerebrum

Neurons are represented in white matter only as _____

axons The axon modeled extends from a projection neuron (Np) and is sufficiently long to require a myelin coating for optimal signaling speed. For example, the optic nerve is a big bundle of myelinated axons of projection neurons, the cell bodies of which are located in the retina

Cryptococcal meningitis can lead to long term damage of the ______

basal ganglia

The vertebral artery eventually fuses with the ______

basilar artery

Concussion treatment

bed rest, fluids, and mild pain relievers

The ACA1-AComm juncture is frequently a site of a _______

berry aneurysm Note: Other medical conditions, i.e., hypertension, can rupture the aneurysm, causing severe and often fatal, acute-onset intracranial hemorrhage into the subarachnoid space.

Interpeduncular cistern

between cerebral peduncles

Chronic mild traumatic brain injury (MTBI) most often results from ____

blast injuries

Tegmentum of pons gross

borders the floor of the 4th ventricle

Duret hemorrhage

brainstem hemorrhages due to stretching & rupture of *Basilar A*. --> *Transtentorial Herniation* -usually fatal

Superficial structure of the cerebral hemispheres venous drainage flow sequence

bridging veins -> sup. sagittal sinus -> confluens -> transverse sinuses -> sigmoid sinuses -> int. jugulars

The basal structures of the cerebral hemispheres and most of the temporal lobe drain their venous blood in____

cavernous and petrosal sinuses -> sigmoid sinuses

During the 2nd trimester, neuronal proliferation migration has stopped except in the _____

cerebellum and hippocampus

The cerebral spinal fluid is produced by:

choroid plexus, by specialized capillaries of the Pia mater within the ventricles

Anterior choroidal artery supplies the ____

choroid plexuses of the lateral and 3rd ventricles, posterior limb of the internal capsule and hippocampus, and can be occluded to cause stroke

Choroid plexuses

coiled capillaries that protrude into the lumen of every ventricle. The fluid of blood flowing through these capillaries under high hydrostatic pressure forms the fluid of CSF, which is modified and secreted into ventricles by a layer of choroid epithelial cells (CECs), which surrounds the capillary core of the Choroid plexuses These resembles a telephone cord. The core capillary (wire) is surrounded by the CEC lining (white plastic), which has its microvillous surface facing outward into the ventricular lumen

Adult/elderly acute (bacterial) meningitis

community acquired Most common microbe, Strep. Pneumonia (pneumococcal meningitis) - Prevnar vaccination Listeria Any organism is possible with hospital-acquired infection

Cerebral aqueduct

connects the third and fourth ventricles

Sigmoid sinus

continuation of the transverse sinus which drains into the internal jugular vein

White matter also bridges the midline of the cerebrum, most prominently as the _______

corpus callosum

Each cerebral hemisphere includes:

cortex subcortical white matter, corpus callosum basal ganglia hippocampus amygdala olfactory tract and bulb and more...

Cingulate gyrus gross

curves to follow the splenium posteriorly, forming the isthmus of the cingulate gyrus anterior portion of the cingulate gyrus (blue area in the image) is the trouble spot in cases of obsessive compulsive disorder that are refractory to drug treatment. Protocols exist to electrically ablate this tissue by stereotaxic surgery

Deep structures comprised of gray matter are referred generically as ____

deep nuclei Designated here are the caudate nucleus (black arrow) and putamen (A), both components of the basal ganglia. Deep nuclei are gray matter, but do not have the histologic requirement to be called cortex (≥3 neuronal layers).

neural tube defects are due to ____

defects in neutral tube closure Apoptosis, programmed cell death Expansion of the cranial mesenchyme Neural crest emigration Contraction of subapical actin

The intellectual disability of Down's syndrome is attributed to a significantly reduced ______

dendritic arbor and spine content

Primary induction is responsible for :

development and closure of the neural tube down to and including cord level S2 neural plate -> neural folds -> neural grove -> neural tube Note: impaired closure causes neural tube defects (NTDs) - occult and asymptomatic -> lethal

Global Ischemia

diminished CBF, e.g., cardiac arrest, near drowning, sudden carotid occlusion or dissection (cerebral arteries fully patent) Watershed territories are the first affected. Located at perfusion overlap of ACA/MCA and MCA/PCA. These are brain areas normally subject to marginally adequate perfusion pressure Will see proximal limb weakness: "man-in-a-barrel" syndrome

Brain dominance

dominance, reflects the lateralization of certain brain functions to one side, and it relates to handedness. In patients, dominance is assigned to the side of the brain determined to process language. In >95% of right-handed individuals, the left side of the brain is "dominant" in this regard. This means that both output and comprehension of human language functions map to the left side of the brain. Among the majority of left-handers (~70%), the left side of the brain is also dominant. In the other 30%, language output function maps to the equivalent structures of the right inferior frontal gyrus, and comprehension maps to the right temporal and parietal lobe structures; some lefties even have speech functions distributed across both hemispheres. Bottom line: With few exceptions, the Broca's aphasics you will encounter have had stroke damage compromising the left inferior frontal gyrus

Medial striates (ACA-A1)

e.g. Recurrent artery of Hübner enter ant. perforated substance perfuse head of caudate n. and IC-anterior limb

Most large vessel infarcts are due to ____

emboli

Limbic system structures are involved in ______

emotion and memory formation -portions of other lobes -mostly medial and inferior structures -anterior insula -temporal pole

Petrosal sinus

enlarged vein that receives blood from the cavernous sinus and flows into the internal jugular vein

Thalamoperforators (PCA-P1, PComm)

enter post. perforated substance perfuse thalamus

The central canal of the spinal cord is lined by _____

ependymal cells Note: although the canal is not patent, its remnant persists

The ventricular zone is replaced with _____

ependymal cells and thin sub ventricular germinal zone (SVG)

filum terminale

fibrous extension of the pia mater; anchors the spinal cord to the coccyx

Cerebral blood flow (CBF)

flow into brain over a given time; determined by net pressure gradient driving blood flow into the brain (cerebral perfusion pressure) against cerebrovascular resistance CBF = CPP/CVR Could alternatively be determined by MAP working against ICP (resistance within rigid skull due to brain, vessels, and CSF)

Ependymoma histology

form perivascular rosettes structures similar to lining of ventricles

superior medullary velum gross

forms the superior portion of the 4th ventricle roof posterior to the pons.

4 lobes of the brain

frontal, parietal, occipital, temporal

Adult exposure to lead

generally limited to peripheral neuropathy because the cation is not very accessible to the CNS through the adult BBB.

ATP production requires a constant supply of _____

glucose

Metabolic activity in real time is measured by _____

glucose consumption This can be achieved by radioactive homolog of glucose and PET scan

95% of the brain ATP is used in the ____

gray matter for cognitive tasks! (like taking tests)

Upstream MCA-M1 "stem infarct" can cause _____

hemideficits (sensory + motor) plus profound aphasia if on the dominant side Although paracentral lobule not perfused by MCA, its axons course through subcortical WM and internal capsule Note: this is referred to as a capsular infarct which almost always involves hemorrhage of the lenticulostriate arteries

Subarachnoid hemorrhage classifies as a ________ stroke

hemorrhagic

Hippocampal or Transtentorial Herniation

herniation of medial temporal lobe and uncus through the tentorial notch

Choroid plexuses are specialized for _____

high volume secretion

Fetal alcohol affect on the brain

hippocampal atrophy (memory and intellectual impairment) microcephaly microencephaly learning disabilities attention deficits hyperactivity memory and intellectual impairment Possible: holoprosencephaly; callosal agenesis

Big neurons are most vulnerable to ______

hypoxia and oxidative damage They have a high metabolic rate and ATP demand met by large # of mitochondria. Oxyradicals are mitochondrial byproducts of oxidative phosphorylation Neurons have relatively poor antioxidant mechanisms to detoxify these radicals

Pseudotumor cerebri

idiopathic intracranial HTN. Most common in women in 20-40s Symptoms -Vision changes -Dizziness, nausea/vomiting -Stiff neck -Tinnitus -Cognitive change Causes -Oral contraceptives -Certain antibiotics -Chemotherapy -Steroids -Some ache medications -Pregnant women are at increased risk

Deep brain structures venous drainage flow sequence

inf. sagittal sinus-> straight sinus-> confluens int. cerebral veins -> great vein of Galen-> straight sinus-> confluens

______ location determines stroke signs

infarct

Herniation syndromes are often caused by______

intracranial pressure

Basilar sulcus gross

is the midline furrow formed in the anterior surface of the basis pontis to accommodate the basilar artery

Hemispheral dominance

language processing side defines "dominant" side -95% of right-handers/60% of lefties are left-dominant for total of -97% population; 1% right dominance; 2% mixed Skilled motor tasks (praxis) - ~90% population are right-handed - 1 in 1000 right-handers are right-side dominant for language

Cisterna magna

large area of cerebrospinal fluid collection between the cerebellum and the medulla

Dural venous sinuses

large veins in the dura mater that drain the cranium

Foramen of Luschka

lateral aperture that connects fourth ventricle to subarachnoid space

Occipitotemporal (fusiform) gyri gross

lateral to the collateral sulcus, these bridge the inferior surface of the temporal lobe and rostral inferior occipital lobe. Functions in storage of human faces

Medullary olive gross

lateral to the pyramids

The parahippocampal gyrus and the uncus are essential for ______

laying down new factual memories and vulnerable to degeneration early in the course of Alzheimer's dementia.

Lateral lenticulostraites (MCA-M1) perfuse ____

lentiform nucleus and IC-genu

Superior Frontal Gyrus gross

lies superior to the cingulate gyrus as far caudal as the imaginary plane of the central sulcus extended to the medial surface, and is separated from the cingulate gyrus by the cingulate sulcus.

The parahippocampal gyrus (and underlying hippocampus) and cingulate gyrus (and underling cingulum) comprise the largest cortical components of the _____

limbic system, which also includes the fornix, mammillary bodies, and hypothalamus

Cerebellar tonsils gross

located at the inferior most and medial part of each cerebellar hemisphere, posterolateral to the caudal medulla. The tonsils reside just superior to the foramen magnum of the skull and are important clinically because they can herniate inferiorly into the foramen due to increased intracranial pressure caused by mass-occupying lesions within the posterior fossa or congenital deformation of the cerebellum. "Tonsillar herniation" is a medical emergency that can occur when a mass occupying lesion within the posterior fossa displaces the cerebellar tonsils into the foramen. Without intervention, medullary cardiovascular centers are compressed, and death can rapidly ensue.

Anterior commissure gross

located just rostral to the columns of the fornix and the lamina terminalis, the rostral wall of the third ventricle

calcarine cortex

location of the primary visual cortex

The neural tube develops ____ domains

longitudinal

Ex-vacuo hydrocephalus

loss of brain parenchyma leading to increased ventricular size Can be due to Trauma, strokes, Neurodegenerative disease

Paracentral lobule gross

lower extremity extension of the motorstrip and primary somatosensory cortex The lower extremity of the homunculus maps to the motor and sensory halves of the paracentral lobule.

Ependymal cells line the following structures:

lumens of all ventricles interventricular formina cerebral aqueduct lateral and median apertures central canal of the formative spinal cord

Glial cells include:

macroglia (astrocytes, oligodendroglia) microglia, ependymal cells, and choroid epithelial cells

Lower extremities map to the ___ side of the brain

medial

Myelencephalon becomes _____

medulla oblongata

The notochord is a derivative of _______

mesoderm

What are the 3 divisions of the brainstem

midbrain, pons, medulla

At more levels of the brain, other ventral structures supply sonic hedgehog (Shh) that drives ______ instead of motor neuron development

midline patterning essential for prosencephalization

Cell type specific markers for oligodendrocytes

myelin basic protein myelin proteolipid protein galactocerebroside

Neutral tube defects (NTDs) result from _____

neural tube closure failure 4th postnatal wk Defective neuropore closure Affect brain and/or cord development Detected by maternal serum alpha-fetoprotein levels and sonogram Neurologic consequences vary from none to fatal Preventative measures possible

Mutations causing tau to misfold due to tau hyperphosphorylation are implicated in _______

neurodegenerative diseases of aging, termed tauopathies, including Alzheimer's disease These promote microtubule disassembly

When does ionizing radiation have its peak teratogen effects

neuronal proliferation (gmo 2-4)

Antibodies raised to neurotransmitter synthetic enzymes can identify _______

neurons that use the related neurotransmitter Example: Purkinje cells (PC) in cerebellar cortex selectively label with antibodies made to glutamate decarboxylase, the rate-limiting synthetic enzyme for the inhibitory neurotransmitter, GABA, used by these neurons.

80% of encephalocele and cranial meningocele involve the _____ region

occipital

Cortical branches of ACA-A2

orbital, frontopolar, callosomarginal, and pericallosal arteries

Brainstem stroke syndromes reflect perfusion territory loss for ______

paramedian or circumferential arteries

3 arterial classes of vertebrobasilar perfusion of the brainstem

paramedian penetraters - basilar a. branches - ant. sp. a. branches short circumferential - unnamed for us long circumferential -SCA -AICA -PICA

Anterior choroidal artery (ICA)

perfuses IC-posterior limb, thalamus, chorid plexuses of lateral and 3rd ventricles

Calcarine sulcus

perpendicular to the parieto-occipital sulcus Bisects the medial side of the occipital lobe into a superior cuneus and inferior lingula

Autoregulation maintains constant CBF in response to _____

physiologic changes in MAP Works over MAP range of 50-150 Torr and when ICP is in normal range Vessels themselves regulate CBF through pressure-dependent responses of arteriolar smooth muscle Physiologic changes to know -Transient postural hypotension - > relaxation of arterial and arteriolar smooth muscle -> vasodilation increase CBF to prevent cerebral ischemia -Transient postural hypertension -> contraction of stretch-sensitive myocytes -> vasoconstriction decrease CBF to prevent cerebral edema

Infundibulum gross

pituitary stalk (infundibulum) is usually shorn off and leaves a little hole/tear at the midline of the inferior border of the hypothalamus. Clearly visible from the inferior view are the paired

Metencephalon becomes ____

pons and cerebellum

______ circulation pathology has the most lethal consequences

posterior

The basilar artery terminates as a _____

posterior cerebral artery

Extraventricular drain can both remove CSF and measure ICP with a _____

pressure transducer

When does retinoid overexposure have its peak teratogen effects

prosencephalization (gwk 5-6)

Where the search for studies HAS TO BE comprehensive to minimize the possibility of ________

publication bias, , once the inclusion and exclusion criteria are applied, only studies of good quality and reasonable degree of similarity make the final cut

Excitatory neurons migrate _____

radially (95% of ribbon)

Cerebellum anterior lobe gross

remarkable for its modulation of the lower extremity and is especially vulnerable to the neurotoxic effects of chronic alcoholism.

Exposure to exogenous retinoids disrupts _______ formation

rhombomere exogenous retinoids applied for medical use achieve nanomolar- micromolar concentrations in CNS - overwhelm endogenous signaling balance with teratogenic effects Derivatives applied topically for acne are absorbed orally or percutaneously and cross placenta into fetal CNS due to high lipophilicity

Entire neuraxis develops from neural tube and acquires dorsal-ventral polarity as far anterior as the ______

rostral midbrain Note: the notochord extends only as far as the rostral midbrain!

Inferior sagittal sinus

runs within the inferior margin of the falx cerebri

Deaths due to mass occupying lesions are usually caused ______

secondarily by cerebral edema -> herniation -> brainstem compression/ischemia

The gross appearance of neural tube defects is caused by ____

secondary deformation of overlying (dorsal) tissues - vertebral arches - calvaria - meninges - skin - muscle

Foamy microglia

seen in brain inflammatory lesions, take on their appearance in the case of multiple sclerosis due to bits of engulfed myelin and lipid droplets.

Holoprosencephaly predisposes to ______

seizure disorder Because the ganglionic eminences are malformed. MGE/LGE fail to generate inhibitory neurons that migrate into developing cortex. Malfunctional circuitry promotes seizures due to unopposed excitatory neurons Note: Inhibitory neurons normally release GABA as their neurotransmitter. Excitatory neurons release glutamate (GLU)

Cortex with >95:5 GLU:GABA active neuron ratio is prone to ________

seizures

Parieto-occipital sulcus gross

separates parietal and occipital lobes mostly seen on the medial surface

calcarine sulcus

separates the occipital lobe into superior (cuneus) and inferior (lingula) lobules

parieto-occipital sulcus

separates the parietal lobe from the occipital lobe

Superior temporal sulcus gross

separates the superior temporal gyrus from the middle temporal gyrus

Sulcus

shallow groove

Where do the inferior petrosal sinuses drain

sigmoid sinuses

Ventral prosencephalon structures secrete_________ to signal midline patterning needed for prosencephalization

sonic hedgehog (Shh) Ventral diencephalon releases Shh gradient Shh induces MGE (medial ganglionic eminence) and LGE (lateral ganglionic eminence), germinal zones that become future thalamus and basal ganglia, respectively Once induced, MGE and LGE in turn release Shh Intracerebral Shh gradient triggers formation of associated midline structures arising during prosencephalization, e.g. falx, interhemispheric fissure, septum pellicidum, fornix

Inhibitory neurons migrate ____

tangentially (5%) from the two germinal zones (MGE and LGE)

Prosencephalization forms _____

telencephalic vesicles + diencephalon

What branches off the P1 segment of the PCA?

thalamoperforator arteries

The ophthalmic arteries become the _____

the central retinal arteries, and are frequently a site for micro-occlusion of the anterior circulation which can present as transient, monocular and partial visual field loss (amaurosis fugax).

Agenesis of corpus callosum

the congenital absence of corpus callosum which may be partial or complete A midline patterning defects

Corticogenesis

the development of the cortex of the brain

Tectum

the dorsal part of the midbrain; includes the superior and inferior colliculi

Middle frontal gyrus

the frontal lobe gyrus that is located between the superior and inferior frontal gyri Separated from the superior gyrus by the superior fontal sulcus, and from the inferior frontal gyrus by the inferior frontal sulcus

Inferior frontal gyrus

the frontal lobe gyrus that is located just inferior to the middle frontal gyrus Separated from the middle frontal gyrus by the inferior frontal sulcus Contains the pars orbitalis, pars triangularis, and the pars opercularis

Superior frontal gyrus

the frontal lobe gyrus that runs horizontally along the top of the lobe Separated from the middle frontal gyrus by the superior frontal sulcus

________are the most common sites of strokes due to embolisms. In turn, the delicate ______ they give rise to are the most common site of hemorrhagic strokes.

the middle cerebral arteries lateral lenticulostriate arteries

In order of studies to be combined, _____

there must be reasonable similarities among studies regarding patient populations, treatment regimens, outcomes measured, etc.

septum pellucidum gross

thin membrane that separates lateral ventricles

Blood brain barrier endothelial cells are bonded to each other by ____

tight junctions and lack fenestrations! Within the CNS, (brain, spinal cord, optic nerve), as the vessel diameter narrows, vascular smooth muscle of the arteriole is replaced by the "endfeet" of stellate-shaped astrocytes, which line the entire abluminal surface of capillary and venule endothelium. As a result of the astroglial covering, the otherwise leaky junctions between endothelial cells (ECs) become sealed to form a diffusion barrier by tight junctions (zona occludens), which express the obligatory protein, claudin. as well as several other accessory proteins. These inter-EC junctions comprise the physical aspect of the blood-brain barrier. Understand that neither the endfeet themselves nor the EC basement membrane comprise this physical barrier. The expression of EC claudins that form the physical seal of the BBB is induced by diffusible astrocyte-derived growth factors released from the apposing endfeet and receptor-mediated mechanisms that trigger claudin expression in brain EC.

Lead toxicity for the developing CNS

toxic for immature astrocytes Stunted astrocyte endfeet -> defective BBB -> leaked albumin enters CNS to promote vasogenic edema and increased ICP Interferes with myelination Limits developmental reorganization of cortex, synaptic pruning Pb+2 at pM levels competes with or mimics the action of Ca+2 100X > affinity for Ca+2-binding proteins than Ca+2 itself Attenuates neuronal transmission underlying memory/cognition The access of drugs and toxins, e.g. Pb, to developing brain appears to reflect the more fragile state of microvessels in infants and children and not the absence of tight junctions per se in the BBB. The barrier is present early in development to allow the brain to internally control its environment but is apparently more vulnerable to breakdown at an early age than in the adult

Decussation

tract that crosses midline to a different level of the neuraxis e.g. corticospinal upper motor neuron fibers cross at the pyramidal decussation, located at the spinomedullary junction

Where do the superior petrosal sinuses drain

transverse sinuses

Forest plot

type of diagram used to present the meta-analysis results of studies with dichotomous outcomes Most common way to present results

Confluens

where straight, transverse, and superior sagittal sinuses merge

Mammillary bodies gross

which represent the caudal-most hypothalamus, and which undergo pronounced degeneration in thiamine deficiency and chronic alcoholism, leading to defective memory processing.

Cerebellum primary fissure gross

which separates the anterior lobe and posterior lobe of the cerebellum

Retrograde cargo includes _____

worn out organelles as well as endocytosed growth factor-receptor complexes, viruses, and some neurotoxins.

T2 MRI

x-y plane parallel Looks like a film negative, gray and white matter colors are switched Often better for detecting pathologic change

CSF production

~70% produced by choroid plexuses (CPs). The remainder is composed of interstitial fluid that equilibrates across the ependymal lining. Produced at rate of ~500 cc/day or approximately 20cc/hour (0.3-0.5 cc/kg/hr), i.e. one-third of the rate of urine production. About 2/3 of it circulates outside the CNS in the subarachnoid space. CSF eliminated at the same rate as production by absorption across the arachnoid villi into the dural sinuses, chiefly the superior sagittal sinus, and from there eventually into the jugular veins. Production of CSF by CPs is an active secretory process, and not directly dependent on the arterial blood pressure.

Monitor ICP for GCS ______

≤8 ICP can be monitored via an ventriculostomy (usually placed in the right side). Intraventricular catheter(IVC)= external ventricular drainage (EVD). Monitors pressure. Allows therapeutic CSF drainage. Intraparenchymal monitors usually placed at bedside. No CSF drainage. Subdural monitors usually placed after a craniotomy.

When ICP increases (due to mass occupying lesion or edema) you must maintain a CPP of ____

≥70 Torr in order to prevent ischemia due to hypoperfusion