ADVANCED PATHOPHYSIOLOGY: NEUROLOGY

Ischemic stroke (80-85%)

1 in 4 adults --> ischemic stroke (cause: thromboembolic arterial occlusion) in their lifetime... >80M stroke survivors --> inc. risk, focus on secondary prevention Cause: Arterial occlusion (thromboembolic) occluding perfusion of the brain, may result from: -Large artery atherosclerosis and CVD (i.e. afib) --> resulting in inflammation and ulceration of vasculature (aortic arch neck OR intracranial vessels in brain) -Small vessel disease (uncontrolled HTN, DM) --> may also result in lacunar stroke- which are occlusion of small arteries penetrating deep brain areas -Arterial dissection (artery ruptures) --> initiated by trauma/sneeze, vasculitis, patent foramen ovale (L-R aria), hematologic disorders (thrombocytosis, polycythemia vera- overload of RBCs which can occlude vessels in the brain), endocarditis Modifiable risk factors: BP (>160/90 mm/Hg particularly high risk) CVD (a-fib, previous MI) DM, dec. physical activity, high waist:hip ratio Lifestyle such as smoking, ETOH, diet, psychosocial stress

TBI: Classification

Classifying TBI... TBI is acute onset or worsening of at least one of the following clinical signs: -loss of (or dec.) consciousness immediately following event (ex. inability to recall events) -loss of memory immediately preceding injury -altered mental status (dazed, confused) -difficulty thinking clearly or responding to mental status questions -neurological deficits (weakness, loss of balance) not from pre-existing intracranial lesion Mild TBI: Normal brain imaging Short LoC duration (0-30 mins) <24 hours altered mental state Post-trauma amnesia <1 day GCS score 13-15 Moderate TBI: Normal/abnormal brain imaging LoC 30 min to 24 hrs AMS >24 hours Post-trauma amnesia 1-7 days CS score 9-12 Severe TBI: Normal/abnormal brain imaging LoC >24 hours AMS >24 hours Post-trauma amnesia >7 days GCS <9 GCS, lower the number the more severe the neurologic deficit!

Encephalopathy

Encephalopathy is any condition that alters brain function or structure.... (such as fine motor functions or frontal lobe functions- controls emotions and social behaviors). Types include reversible or irreversible. Reversible -hepatic encephalopathy (such as cirrhosis from ESRD, acetaminophen OD) -Hashimoto's encephalopathy (autoimmune thyroid condition) -metabolic encephalopathy (uncontrolled DM, renal failure, CHF) -infectious encephalopathy (inflammation such as encephalitis, meningitis, sepsis, post-herpetic, HIV) -brain tumors (compression) -status epilepticus (prolonged seizures) -toxin exposure (solvents, industrial chemicals heavy metals, radiation)- potent dose response effect (ex. infant more suscpetible/affected than adult with same dose) Irreversible -chronic traumatic encephalopathy (CTE- retired NFL players Muhammed Ali) (repeated concussions, tau bodies post-mortem- characteristic protein in neurons post-mortem) -hypoxic-ischemic encephalopathy (HIE- extreme hypoxia of the brain) (MI, drug overdose, near-drowning)

Ischemic stroke: Mechanisms

Ischemia is impaired blood flow and decreased oxygenation of the tissues Infarction is resulting neuronal cell death (infarct = lack of perfusion --> neurons deprived of o2 --> result in cell death) 1. Clotting risk (i.e. AF) --> inc. clotting risk (inc. clotting bc blood isn't moving effectively through heart --> blood is apt to form small clots, and when it exits left ventricle, those clots can be sent to the brain) 2. clot occludes cerebral artery 3. cerebral blood flow changes results in: - dec. perfusion -collateral circulation (collateral shunting is when blood is shunted to other vasculature and you get a hyperperfusion of that area surrounding the ischemic area) O2 depletion --> will cause hypoxia (degree of impaired flow = severity) and will affect... -neuronal and glial function (glial cells support/protect the neurons) -vascular changes -inflammation in the vasculature Intracerebral steal: paradoxical vessel dilation at margins of the ischemic area --> dec. circulation/o2 to ischemic tissue. That further decreases perfusion of that area but shunts the blood to other parts of the brain. Sequelae of ischemic stroke: Cerebral HTN, arrhythmias, bradycardia, contribute to pulmonary edema

MDD monoamine deficiency theory

Monoamine deficiency theory We don't know cause of depression but we know that when we give certain meds, depression gets better. Serotonin: -obsessions -compulsions Meds: Selective serotonin reuptake inhibitors- inc. serotonin in synapse Noradrenaline -attention -anxiety Meds: Venlafaxine and buproprion Dopamine: -attention -motivation -pleasure *So a deficiency of any of these monoamines in the synapse may contribute to depression. We tx by giving meds that inc. these neurotransmitters in the brain's synapses.

Multiple Sclerosis (MS)

Multiple Sclerosis is an immune-mediated condition which causes demyelination of the CNS. -Cause = unknown -Widespread/vague clinical manifestations: muscle weakness, sensory deficits, cognitive impairment and fatigue (significant morbidity and dec. QoL). -Early in MS: You have a pattern of cyclical, relapse/remitting flares (immune cells start to attack and degrade the insulin myelin sheaths along the axon)- flares where there's active activity in the nervous system -Late in MS: Immune cells actually infiltrate the CNS --> inflammation and ROS which cause progressive demyelination --> neurodegeneration --> progressive loss of neural function Treatment: Unfortunately only slows disease progression, no cure. Risk Factors: -Low vit. D levels, tobacco use, Epstein-Barr virus -Genetic (immune: HLA, IL2, IL7R) Pathological hallmarks: -demyelinating lesions (in the brain, spinal cord, optic nerve) -disruption of the blood-brain barrier and presence of inflammatory cells in the brain

Neural tube defects (NTD)

Neural tube defects can be caused by a variety of things and take many different forms. Maternal nutrition --> risk is low folate intake!!! Craniorachischisis: Completely open brain and spinal cord- inability to form the surrounding materials around the spinal cord and brain. Anencephaly: Open brain and lack of skull vault. Failure of head and brain to develop. Encephalocele: Herniation of the meninges (and brain)- you'll see external outpouching on back of head. Iniencephaly: Occipital skull and spine defects with extreme retroflexion of the head. Spina bifidas... Spina bifida occulta: Closed asymptomatic NTD in which some of the vertebrae are not completely closed Closed spinal dysraphism: Deficiency of at least two vertebral arches, here covered with a lipoma. Meningocele: Protrusion of the meninges (filled with CSF) through a defect in the skull or spine, but it's encased Myelomeningocele: Open spinal cord (with a meningeal cyst)

Posturing

Posturing- another form if ICP Decorticate (flexor) posturing: -lesion/compression of thalamus -ominous sign of severe brain damage Decerebrate (extensor) posturing: -midbrain or lower brainstem lesion -more ominous (body loses ability to protect)

Spina Bifida

Spina Bifida is the most common NTD = 1/2500 births -Genetic factors (+ FH, mutation in MTHFR), diet (folate deficiency), environment Meningocele: Herniation of meninges and CSF, covered by skin Myelomeningocele: Meninges/neural tissue are exposed Mild --> severe: Spina bifida occulta, meningocele, myelomeningocele Potential sequelae: -meningitis (infection/inflammation of meninges) -hydrocephalus -impaired mobility -orthopedic problems -bowel/bladder incontinence -disrupted skin -sleep apnea/sleep disruption

Stroke: Cerebrovascular accident (CVA)

Stroke (CVA) is the 2nd leading cause of death globally. Stroke types include ischemic (80-85%) and hemorrhagic (15-20%). 1) Ischemic stroke: Due to: Large artery thrombosis (20% related to atherosclerotic dx) OR Small penetrating artery thrombosis (25%)- these are lacunar strokes (white matter or deep in the brain) Embolic/cardiogenic (20%)- ex. when someone has afib and throw a clot to the brain Cryptogenic (30%)- transient and of unknown etiology 2) Hemorrhagic stroke: Subarachnoid (due to aneurisms in 80% of cases) Intracerebral/intraparenchymal (20%, most fatal)

Stroke: Presentation

Think about the presentation related to where the occlusion is: LEFT hemisphere is characterized by: Language deficits: -expressive aphasia --> inability to find words or communicate (Broca's) -receptive aphasia --> inability to process and receive verbal communication (Wernicke's) -global deficits Intellectual/cognitive impairment Slow, cautious behavior Have R visual field deficits RIGHT hemisphere is characterized by: Spatial-perceptual deficits Distractibility Impulse behavior: unaware of deficits Poor judgment L visual field deficits

TBI Infographic:

Traumatic brain injuries are clinically divided into mild, mod, and severe forms. Mild TBI is known as concussion and accounts for 80-90% of cases. Mechanisms: Brain damage in TBIs is caused by rotational and/or linear acceleration forces, or blunt trauma with impact deceleration, which generate forces that stretch and damage axons. Axonal injury is considered a key mechanism of damage following TBIs, as the severity of axonal injury correlates with the extent of disability.

CVA: Secondary stroke prevention

When we think about CVA, the main focus is on early identification and secondary stroke prevention. CVA presentation: Sudden focal neuro deficit: hemiparesis (one-sided weakness), aphasia (inability to express speech), hemianopia (blindness over half field of vision, hemispatial inattention (reduced awareness of space) BE FAST: Balance --> loss of balance/dizzy Eyes --> blurred vision Face --> unilateral drooping/sagging of face Arms --> unilateral weakness in an arm or leg Speech --> receptive or expressive difficulty Time --> respond quickly! Differential diagnoses: Migraine/headache, seizure, vestibular disturbance Dx and Tx: CT (without contrast) Thrombolytic therapy (within <4.5 hrs of symptom onset) Endovascular thrombectomy- remove clot/re-perfuse brain (if longer but <6 hours) Secondary prevention: -control BP! -lifestyle (smoking, diet, salt, activity) -antiplatelet tx -high-dose statin tx (bc often underlying atherosclerotic dx)

Neurologic disorders in adult life

3 main adult neurologic disorders: 1) Multiple sclerosis (MS) Destruction in lining of myelin sheath which lines the axons, which causes neurodegeneration. 2) Alzheimer disease Characteristic form of Alzheimer's dementia which causes a diminished size of the brain. 3) Parkinson disease A loss of dopamine-secreting neurons in the brain.

Headaches: comparison

3 types of headaches: migraine, tension, and cluster Migraine: Location is unilateral (common) or bi-frontal or global Crescendo (building effect) Pts want to be in cool, quiet, dark room Duration 4-72 hrs Sx: N/V, photophobia, aura (variable) Tension: Location is bilateral "Band-like" squeezed around head, waxes and wanes May be able to continue daily activities Duration variable No associated sx Cluster: Location is always unilateral (typically around one temple/eye) Excruciating, explosive pain, peaks within minutes Appearance variable Duration 30-90 mins (up to 3 hr) Sx: tearing, eyes red, injected schlera, rhinorrhea, may be triggered by ETOH

Seizures: Pathophysiology

A seizure is essentially an uncontrolled neural firing... about 10% of people will have a seizure in their lifetime It's really a CNS imbalance in these ion channels in the synapse of a neuron (imbalance b/w inhibitory and excitatory firing in the synapse), and that relates to calcium and chloride (Ca+/Cl-). Inhibitory mechanism: GABA and GABA receptor --> stimulates Cl- in to "close the gate" Excitatory mechanism: Glutamate and NMDA receptor --> releases Ca+ to "open the gate" --> that opening of the gate causes that firing *If you don't have inhibition of GABA and GABA receptor and over-excitation from glutamate and stimulation of the NDMA receptor, you'll have excessive neural firing.

Acute brain injury: Complications

Acute brain injury complications may include... Cranial nerve (CN) palsies: Any CN, often CN I (anosmia) secondary to olfactory nerve damage Stress ulcer: Also known as Cushing's ulcer (secondary to head trauma/brain injury) causing increase in ICP which causes an excessive vagus nerve stimulation which stimulates a parasympathetic response, which inc. gastric secretion of acids and promote gastric ulcer formation, duodenal ulcer, or distal esophagus erosions. Diabetes Insipidus/or Syndrome of inappropriate ADH (SIADH): Caused by hypothalamic pituitary trauma (in the neurohypophysis) DI = dec. in antidiuretic hormone (ADH) --> increased urine output (this hypotonic urine can cause dehydration) SIADH = inc. in ADH --> dec. urine output (very concentrated) Coagulopathies: 18% of head injuries --> coagulopathies (May be secondary to an inc. in thromboplastin as well as arachidonic acid metabolites --> coagulopathies on CBC following brain injury)

Main things contributing to neural tube defects (NTD)

Alcohol use during pregnancy Caffeine use during pregnancy FOLATE DEFICIENCY during pregnancy

Alzheimer disease

Alzheimer disease is a neurodegenerative disorder and the most common cause of dementia -Significant morbidity (patient and caregiver) -Frequent comorbidities: Hearing loss, sleep disorders, pain, depression and anxiety. Risk factors: -Age (>65 yo) -Metab: DM, HTN, obesity, low HDL -neuro: prior TBI, hearing loss -inc. alcohol consumption/abuse -genetic Clinical hallmarks: -short-term memory deficits and cognitive impairment -speech, visuospatial and executive function deficits -limited treatments (only slow disease progression) Causes and hallmark pathology: -accumulation of extracellular B-amlyoid-containing plaques and intracellular tau-containing neurofibrillary tangles. TBIs can cause inc. B-amyloid plaques as well as tau-bodies (sign for chronic traumatic encephalopathy- repeated concussions). -these protein deposits cause progressive neuron damage neurons --> and eventually cell death --> progressive brain atrophy (if you do MRI of individual w/ Alzheimer, their brain volume actually shrinks significantly).

CNS herniation

CNS herniation is another risk factor for ICP Inc. ICP --> brain tries to "escape" = herniation (when it is forced out). Types include subfalcine (highest, mid-brain), transtentorial, and tonsillar (brain stem location). Subfalcine (common): this section is pushed downward and compressed -headache -contralateral weakness (depending on affected side) Transtentorial (lower down in brain): -oculomotor changes (cranial nerve III [CNIII]) -ipsilateral dilated pupil (diff. pupil sizes on exam), abnormal EOMs (extra ocular movements) -contralateral hemiparesis (muscle weakness on one side of body occurring opposite side of body to which a structure or condition occurs) Tonsillar (lowest form- where brain stem is actually herniated, so quite severe): -obtunded -stuporous These warrant immediate imaging to try to evacuate that brain and relieve the pressure. Children less vulnerable (plates have not fused in brain- gives leeway) Elderly may tolerate in setting of age-related brain atrophy (brain shrinks with age, so more space for inc. ICP to accumulate before some form of herniation)

Take home points

CVA: understand difference b/w ischemic vs. hemorrhagic Know how to intervene to prevent sequelae (TIAs and secondary prevention) TBI = know guidelines and document, watch for long-term effects (>3 months) HAs: differentiate b/w migraine, cluster, tension-type Epilepsy = 4 steps to workup (simple or complex? focal or generalized?) Disrupted embryologic development --> NTD (folic acid) Parkinson dx = progressive movement disorder secondary to loss of dopaminergic neurons (tremor, rigidity, postural instability) Depression = monoamine deficiency theory (bc ppl response to SSRIs, must be an underlying mechanism in MDD)

Cerebral hemorrage: intraparenchymal

Cerebral hemorrage (intraparenchymal) is most fatal (40% have 1 year survival) due to deep bleeding in brain. Primary --> rupture of small arteries or arterioles (due to uncontrolled HTN) Secondary --> ruptured arteriovenous malformation (AVM), or cerebral venous thrombosis, or hemorrhagic conversion of ischemic stroke (you have ischemic stroke and as a result, there is hemorrhage in a vessel in the brain which is a secondary sequelae of an occlusive stroke), tumor, vasculitis, coagulopathy. Risk factors: HTN, smoking, ETOH, sympathomimetic drugs (anything that constricts vasculature) Presentation: Acute-onset headache, seizure and/or focal neurologic deficit with N/V. Seizure and N/V are due to the increased INCP caused by the blood flooding into the brain and putting pressure on it bc there's no where for blood to escape to. Tx: CT and surgical intervention

Chiari malformation

Chiari malformation is a hindbrain malformation which occurs in the back: cerebellum forced through the foramen magnum so lower brain stem is herniated --> hydrocephalus is common (CSF fluid doesn't communicate) --> development manifests as inc. ICP --> papilledema! Different levels of malformation: Type I -Neural tube defect in herniation of the medulla -milder, sometimes asymptomatic, not identified unless imaging Type II -almost exclusively with myelomeningocele -herniation of cerebellum, medulla, pons, and 4th ventricle Type III -herniation of cerebellum and brain stem -very serious occlusion of the ventricles --> paralysis and severe neurologic problems Type IV -underdeveloped/incompletely developed cerebellum (cerebellar hypoplasia)

Cluster HA

Cluster headaches are excruciating, strictly unilateral pain syndrome... -attacks last 15-180 min -marked ipsilateral cranial autonomic symptoms- one side of head affected (significant tearing or lacrimation and conjunctival injection- eyes very red) -severe pain (F --> "worse than childbirth") Diagnostic criteria for cluster headache: Meeting at least 5 attacks that meat criteria... -severe unilateral pain lasting 15-180 mins Either or both of following: -ipsilateral to the HA -conjunctival injection -lacrimation -nasal congestion and/or rhinorrhea -sense of restlessness or agitation May have frequency b/w one every other day and 8 per day for more than half the time the disorder is active (flares) Pathogenesis: unclear Thought to. be related to some hypothalamic input, as well as stimulation of the trigeminovascular system (like migraine), and involves the parasympathetic nervous system (evidenced by rhinorrhea, nasal congestion, and tearing). Diagnosis: Based on S/S, R/O other primary HAs or secondary HA causes Treatment: Preventive pharmacologics and neuromodulation

Seizure: Classification

Consciousness: simple (patient maintains conscious) vs. complex (patient becomes unconscious) Affected area: Focal onset: -1 hemisphere affected -Aware w/ or w/o impaired awareness -Motor onset or non-motor onset -May have focal to bilateral tonic-clonic seizures Generalized onset: -2/both hemispheres of the brain are affected Motor: -Tonic-clonic or -Other motor or non-motor (absent) seizure Terminology: When we talk about what types of seizure activity are... Tonic: is about flexion Atonic: is about relaxation Myoclonus: is about twitching Clonic: is convulsive Absence: blank stare, like someone's spacing out Tonic-clonic: flexion and convulsing convulsion (stiff and then convulse) Status epilecticus: a seizure that lasts >5 min (a potential risk for inc. ICP) "Jacksonian March": seizure activity that begins in one muscle group --> spreads (as that excitation moves to a more proximal muscle group).

Traumatic brain injury (TBI)

Definition of TBI: trauma/injury that disrupts brain function, usually blunt, non-penetrating trauma (closed head injury). May manifest as some intracranial bleeding (such as subdural or epidural hematoma). Mild TMI = is what we call a concussion Types of TBI focal injuries: -epidural hematoma -subdural hematoma -intracerebral hematomas (bleeding within the brain) S/S = variable (some routine neuro exams may be unremarkable) Physical: N/V, dizziness, headache Cognitive: poor concentration, memory problems Behavioral: irritability, emotional lability, impulsiveness, LoC For most mild TBIs, symptoms resolve in 7-10 days in 80-90% of cases. Most symptoms resolve <3 months. However, post-concussive syndrome (PCS) = symptoms > 3 months or 12 weeks

Comorbid depression

Depression is a common comorbidity in many chronic diseases --> sig. psychosocial burden and dec. QoL. Contributing factors: -shared genetic factors -converging biological pathways -social factors -health behaviors -psychological factors Dx and tx challenging due to overlaps. Tx can be difficult bc: -med adjustments due to comorbid dx -comorbid dx sx/tx may interfere with depression tx -depressive sx may dec. adherence for both conditions

Migraine diagnosis and red flags

Diagnostic criteria for migraine (at least 5 of the following): Headache lasts 4-72 hr Has at last 2 of the following: Unilateral location Pulsating quality Moderate or severe pain intensity Aggravation by or causing avoidance of routine physical activity During headache, at least one of following: N/V Photophobia and phonophobia Features suggestive of secondary headache: Now onset of headache (in persons >50 years) Headache lasting >72 hr or 3 days Vision, sensory, and language sx lasting >1 hr (so not aura, as that lasts under 1 hr) Very sudden onset of headache or neurologic sx Abnormal neurologic examination Associated fever, systemic illness (which may suggest meningitis)

Phenotype and TBI recovery

Different types of TBIs and recovery Linear acceleration (translational) --> forward moving Rotational acceleration (angular) --> punched in the jaw, neck twisted to the side Impact deceleration --> fall and hit back of head on ground, slamming of brain Headache post-TBI is an important marker of how people will recover... JAMA study: People who didn't have a post-traumatic headache at the initial visit returned to recovery much faster than those who presented with a headache. Furthermore, those who had a migraine phenotype had a prolonged recovery. So best case scenario is no headache TBI, second best is no migraine headache, post TBI.

Concussion and screen time

Effect of screen time on recovery from concussion... Those who were permitted to screen time had a slower recovery compared to those who were not allowed screen time.. flickering of screen is a visual stimuli which is quite difficult on the brain. Limit screen time post TBI or concussion!

Intracranial pressure (ICP)

Either a hemorrhagic stroke or occlusive stroke will result in an increase in intracranial pressure. When you have a bleed, the blood puts inc. pressure on brain tissue and CSF. Imbalance: between Central Perfusion pressure (CPP- perfusing pressure of the blood in the brain) and intracranial pressure (ICP) caused by the hemorrhage or cerebrovascular accident. When ICP > CPP --> you develop hypoxia and hypercapnia (a natural response to the hypoxia) --> start breathing rapidly, inc. CO2 --> vasodilation --> inc. pressure in the brain --> brain damage (eventual loss of autoregulation of respiratory drive and oxygenation) Causes: edema, hemorrhage, tumor, or excess CSF Cardinal signs of ICP is Cushing's triad (unlike shock: tachycardia + hypotension) Cushing's triad: HTN (widened pulse pressure), bradycardia, irregular respirations

Epilepsy

Epilepsy is a seizure disorder where there's a normal and excessive or asynchronous neural activity: -one of the most common, disabling neurologic disorders (65 M) -Epilepsy affects ALL age groups -Prevalence: lowest in infants/children --> increased during adolescence-early adulthood --> decreases later in life -Epileptogenesis aka onset is what causes an epileptic seizure, it is multifactorial Errors in dx common (no lab set, EEG is the mainstay of diagnosing epilepsy): -cognitive, psychological and social consequences -1/3 patients have uncontrolled seizures -can be fatal (primary and secondary- indirect i.e. swimming w/ seizure --> drowning, MVA) Treatment goals: 1. Control seizures 2. Avoid tx side effects 3. Maintain or restore quality of life (peds may be controlled with a strict ketogenic diet)

Epilepsy cont.

Epilepsy is more than 2 unprovoked/or reflex seizures more than 24 hours apart. 1. Differentiate epileptic seizure vs. mimics (e.g. migraine, daydreaming, vertigo, TIA) 2. Discern unprovoked, reflex, or acute symptomatic 3. Ascertain index seizure (23-57% have prior seizure)- when was the last time last seizure occurred? Was there a structural component? 4. Classify (below) Seizure types: -Focal -Generalized -Unknown Epilepsy types: -Focal -Generalized -Combined generalized and focal -Unknown

Altered Consciousness

Glasgow Coma Scale for altered consciousness... Order: Obeys commands --> "make a fist", "grip my finger" Localizes pain --> trapezius squeeze or supraorbital pressure Flexion/withdrawal to pain --> flexion of limbs Abnormal flexion to pain --> adduction/internal rotation of upper limbers or extension of lower limbs Extension to pain --> extension of upper and lower limbs No response --> no motor response Coma (Glasgow Coma Scale): -no eye-opening -unable to follow instructions -no speech/communication -no purposeful movement Persistent vegetative state: -sleep/awake cycles return -BP, resp. and digestion normalize -eyes may open (but no tracking, no sustained fixation) Minimally conscious state: -inconsistent evidence of perception and communication -eyes open sometimes

Glasgow coma scale (GCS)

Glasgow coma scale: Minor Brain Injury (concussion or traumatic brain injury): 13-15 points Moderate Brain Injury: 9-12 points Severe Brain Injury: 3-8 points Lower the score, the more severe!

Cluster HA: trigeminal-PSA pathway

How do these cluster headaches form? PSA pathway 1. Trigeminal nerve activation (innervates of the face/neck) of trigeminocervical complex (TCC): --> activates the trigeminal nucleus caudalis (TNC) and cervical nerves Basically, you're sending nerve inputs from this mechanical nociceptive input from face or neck, routing it through this trigeminal cervical complex (TCC), and then sending those messages on to higher brain centers. 2. Activation of Peripheral Nervous System (PNS) efferents --> this trigeminal nerve activation will also activate the PNS, which will result in activation of autonomic symptoms (next) --> 3. Vasodilation --> autonomic symptoms (resulting from peripheral NS activation): -lacrimation and redness of eyes -rhinorrhea -nasal congestion

Hydrocephalus (in children)

Hydrocelphalus is inability to perfuse cerebrospinal fluid, either in the flow or the absorption --> CSF accumulates in ventricles in the middle of the brain. Normally: see CSF bathing the brain within the skull with this fluid and it's produced in the ventricles Hydrocephalus: when you blocked or obstructed flow (from bleeding, tumor or malformation) you have buildup of CSF in the brain causing inc. ICP. Types: Congenital (non-communicating) Meaning this is some kind of obstruction or structural lesion which is preventing that CSF from normally circulating through the spinal tract and around the brain. Acquired (communicating) CSF blocked after exiting ventricles (so it's produced in the ventricles but then is blocked from re-entering bc of some kind of hemorrhage or inflammation)... -Subarachnoid hemorrhage -Meningitis -Head injury -Neoplasia/tumor S/S: signs of inc. ICP Vomiting, sleepiness, irritability, poor feeding, seizures, eyes fixed downward ("sunsetting" of the eyes), dec. muscle tone, poor responsiveness to touch, poor growth

Ischemic stroke infographic

Ischemic stroke is responsible for 71% of strokes worldwide, and is caused when there is an interruption to brain blood flow. Most ischemic strokes are thromboembolic in origin. Mechanisms: Occur owing to presence of embolus in cerebral vasculature. Other causes include cerebral small vessel disease, which can cause narrowing of small vessels of brain. These emboli can originate from peripheral thrombi that form on atherosclerotic lesions or at sites of arterial dissection, or in people with afib or patent foramen ovale.

Meningitis: Kernig's and Brudzinski's signs

Kernig's sign: Pain elicited on resistance to extension of leg --> indicator of subarachnoid hemorrhage or meningitis (some kind of inc. ICP) Brudzinski's neck sign: Neck manipulation elicits hip and knee flexion (knees will rise up as a response bc that maneuver will inc. the pressure of CSF)

Seizure: Management

Level of risk and # of seizures: Low risk: 1 seizure: We don't think of using anti-seizure meds until medium or high risk Medium risk: 1 seizure with abnormal EEG/neurologic disorder or 2 to multiple seizures High risk: More freq. seizures

Headaches: Red flags

Look out for: Intracranial space-occupying lesions: -progressively worsening HA -HA with sneezing/coughing or exercise Secondary headache: -HA onset >50 years -focal neurologic sx -weight loss -impaired memory/altered consciousness -change in memory/personality Intracranial hyper/hypotension -HA aggravated by posture or maneuvers that inc. ICP (think Brudzinski's sign or Kernig's sign and CSF posturing lying down/sitting up) Subdural hematoma: -head trauma Subarachnoid hemorrhage: is characterized by -Nuchal rigidity (stiff neck) -"thunderclap" HA Meningitis: -Unexplained fever -Nuchal rigidity

Major depressive disorder (MDD)

MDD is a debilitating disease: -affects 6% adults/yr -2nd leading cause of dx burden worldwide (i.e. years lived with dx) -20x more likely to die of suicide Etiology unknown (complex interplay of factors): -genetic (3x inc. risk with +FH) -biological (F:M = 2:1) -psychological (such as early life trauma) -environmental (such as trauma as an adult) DSM: 5 of 9 of these criteria over a 2 week period: (Make sure you rule out mimicking biologic cause such as hypothyroidism). 1) depressed mood 2) diminished interest (anhedonia) 3) inc. or dec. appetite, weight gain or loss 4. dim ability to concentrate 5. fatigue/loss of energy 6. feelings of worthlessness/guilt 7. agitated or retardation 8. insomnia or hypersomnia 9. suicidal ideation

Tension Type Headache (TTH): Mechanisms

Mechanism of tension type HA (TTH) occurs in 2 phases... 1. Peripheral sensitization Contribution from either myofascial or vascular mechanisms! Myofascial mechanisms: Increased muscle tightness, tenderness, hardness, local inflammation, or local ischemia- may be inflammation b/w muscle and fascia Vascular mechanisms: Increased blood flow into the cerebral arteries, abnormal carotid artery blood flow, or abnormal extracranial vascular response (which provides input of peripheral sensitization of pain in brain) 2. Central mechanisms This is central sensitization... first there is peripheral input, then there's a central mechanism where the brain becomes sensitized to these inputs, then there is dysfunction in the descending pain modulation. There are some identified genetic variants associated with TTH.

Tension-type headache infographic

Mechanisms: Combination of... 1. Genetic factors 2. Central mechanisms 3. Vascular mechanisms 3. Myofascial mechanisms

Migraine HA

Migraine HA is the 7th leading cause of disability worldwide: -Highly variable in freq. and severity -May begin in childhood, prevalence increases between 10-14 y/o (around onset of puberty) -2-3x more common in W>M -Up to 1/25 (4%) women have chronic migraine >15d/month Migraine triggers: -Emotional stress (80%) -Hormones in women (65%) (fluctuations related to menstruation) -Not eating (57%) -Weather (53%) -Sleep disturbances (50%) -Odors (44%) -Neck pain (38%) Pathophysiology not well established, onset associated with triggers Some migraines are associated with a prodromal phase/aura (25% of migraines): -aura develops over 5-60 mins. = visual, sensory, motor, brainstem, retinal or speech changes (fully reversible) due to vascular changes going on in brain preceding migraines -aura is poorly understood, thought to be: nociceptor excitation (of the meninges) --> which causes rapid depolarization and repolarization/excitation (of cortical neurons in the glia) --> this hyperpolarization and inhibition causes this phenomenon of sensory changes.

How did neural tube defects form?

Neural tube defects: formation Start with neural fold, neural plate, and notochord --> during development, neural folds begin to fuze --> forming of this neural plate in a sealed capacity is what forms the neural tube. When you have folate deficiency or some kind of genetic defect, the neural tube does not completely form, and you may have this occult where you may not have complete formation of this neural tube. Or you may have a meningocele where there's some outpouching or myelomeningocele bc these neural folds do not fully seal.

Subarachnoid hemorrhage: Aneurysm

On of the most severe of hemorrhagic strokes is subarachnoid hemorrhage, typically caused by an aneurysm. 80% caused by ruptured intracranial aneurysm- caused by inc. BP causing outpouching (also: malformations, vasculitis/inflammation, or secondary to vasospasm- smooth muscle spasm of vasculature). -5-10% of all strokes -Inc. lethality (25-50%) VERY HIGH -Severe long-term neurologic deficits Risk factors: +Family hx, women > men HTN Hispanic/Latinx Connective tissue disorders (Ehlers Danlos- inherited connective tissue disease caused by mutation in fibrilin gene) Polycystic kidney disease (PCKD)- cysts enlarge, decline in renal function Smoking, ETOH, sympathomimetic drugs (i.e. cocaine) --> think BP Age (peaks in 50s) S/S "Thunderclap headache" --> someone says "I have the worst headache of my life"- see blood in center of the optic disc --> Refer for immediate imaging and surgical craniotomy!

Cerebrospinal fluid (CSF) leak

One of the signs you can see from a traumatic injury to the head is a cerebrospinal fluid leak (CSF). This is a break in the integrity of meninges --> CSF leak (i.e. typically caused by a basilar skull fracture, dural tears usually heal within 7-10 days) S/S -"Raccoon eyes", CSF rhinorrhea (runny nose), periorbital edema (swelling of CSF under eyes) -CSF otorrhea (leaking out of ears), post-auricular bruising (Battle's sign- bruising posterior to ear) -positional headache (worsens when standing), photophobia, nausea, petechial rash (skin/mucous membranes- pinpoint bloody spots), nuchal rigidity (stiff neck- csf limiting mobility) -positive Kernig's or Brudzinski's signs (assess if there is CSF leak) -leakage --> "halo sign" bloody center with CSF halo (primarily filled with glucose + and salts) on white blotter paper Key signs: HA worsens when upright HA improves when lying down

Parkinson disease (PD)

PD is one of the most common neurological disorder... it is a progressive movement disorder with adult onset. Clinical hallmarks: -resting tremor (pin rolling with fingers) -rigidity (cog-wheeling- robotic movement, mask-like facies) -problems initiating movement -postural instability (shuffling gait) Cause: progressive loss of dopamine-producing neurons in the substantia nigra (black substance). Dec. in dopamine secretion manifests as movement disorders. Hallmark pathology: -diminished substantia nigra volume- this is a part of the basal gangli, deep in cerebral hemispheres, with connections to the motor cortex --> which is critical for movement -Lewy bodies- cell types seen on histological exams- this is abnormal aggregation of eosinophils and proteins that appear before neuron death

Papilledema

Papilledema- another sign of ICP... you have small outlet coming from brain leading into eye, and inc. pressure on this will compress optic nerve and optic chasm constrict/restrict blood flow to eye. Characteristics: Inc. ICP (bilateral) --> compresses optic nerve and blood vessels (in the subarachnoid space)... -blood stagnates (loss of venous pulsations) -inc. hydrostatic pressure --> plasma leaks -excess fluid absorbed by papilla/optic nerve --> changes in optic disc -Sequelae: blindness (papilla = blind spot)

Migraine HA: Pathophysiology

Pathophysiology of the migraine HA: 1. Trigeminovascular neuron sensitization This is the vasculature around the trigeminal nerve (cranial nerve that innervates face) --> stimulation of this trigeminal vascular neuron signals the trigeminal ganglion. 2. Trigeminal ganglion firing --> fires down into the brain stem (this activates the spinal trigeminal nucleus) 3. We also have messages being sent up into the brain, into the trigeminovascular neurons (in the thalamus- center of brain) --> sensory motor cortex and cortex sensitization (polarization and repolarization)--> gives sense perception of migraine pain to the meninges. 4. Trigeminal activation (when you sense that pain)--> also stimulates a parasympathetic stimulation --> which causes vasodilation of intracranial and dural arteries --> which causes pressure on dura --> intense and exquisite pain that is characteristic of a migraine HA

TBI Management

TBI Management Mild traumatic brain injury --> watchful waiting approach When should you do imaging? -Concern for life-threatening intracranial injury (such as fx or hemorrhage) -See CSF fluid (otorrhea or rhinorrhea) --> Raccoon eyes or Battle Sign - Alteration of consciousness (GCS, severe headaches, or signs of ICP such as repeated vomiting or seizures) -Or very young or very old patient <2 years or >60 years

TBI: Mechanism

TBI mechanism Primary brain injury at time of trauma... -focal contusions/hematomas cause some extra-axial force (epidural, subdural, subarachnoid hemorrhage) -that pressure causes diffuse axonal injury (DAI)- multifocal shearing of white matter tracts (white matter covers/insulates nerve fibers --> disruption and leakage impair ability of axon to carry neural message) --> impaired synaptic function (may see change in consciousness/altered mental) --> cerebral edema. As a result of that, may see increase in amyloid beta production (Amyloid B --> associated with Alzheimer's) and also contributes to formation of tau bodies which is the hallmark sign of chronic traumatic encephalopathy (CTE). Secondary brain injury- cascading molecular injury that follows --> cerebral edema from trauma may lead to neuronal cell death, cerebral edema, inc. ICP (may contribute to neurologic findings such as seizures or hypoxia or hyperperfusion or hypoglycemia) --> there will be energy deficits --> cause immediate inc. in Ca+ levels --> activate molecular cascade --> cytoskeletal rearrangement Mechanisms: Neurotransmitter-mediated cytotoxicity (glutamate- an activity molecule) stimulates production of --> free-radical (ROS) cell membrane injury --> this injury causes: -electrolyte imbalances (disruption in Ca+ levels) -also triggers inflammatory response -this cascade related to electrolyte deficiency and inflammation may lead to: Apoptosis which will cause further inflammation --> which will cause ischemia (secondary to vasospasm, microvascular occlusion, and vascular injury from initial trauma itself or resulting cerebral edema and the molecular cascade) which can cause this neural filament and axonal rearrangement.

Transient ischemic attack (TIA)

TIA is a heralded event (precedes) in about 20-25% of ischemic strokes. Ischemic stroke and TIA have the same clinical manifestations (but, stroke is often evident on imaging) However, only about 60% of ischemic strokes are visible on CT within the first 6 hours- so not always helpful for differentiating CVA vs. TIA. TIA is transient, so typically some degree of recovery following the ischemia. TIA = cerebral or retinal symptoms lasting <1 hour. No evidence of ischemic stroke on imaging. Suspected TIA --> immediate evaluation (imaging) Short term tx: aspirin Secondary prevention: Anticoagulation, control BP/lipids/glycemia, smoking cessation, diet and lifestyle changes Common sx suggestive of TIA... Definite: -Focal, cerebral or retinal sx lasting <1 hr -Motor muscle weakness limbs and face -Sensory deficit in limbs and face -Visual-field defect/cuts (such as hemianopia) or monocular blindness -Aphasia or dysarthria (difficulty forming words) Suggestive: -Unsteady gait -Diplopia (seeing double) -Vertigo, dizziness -Dysphagia

Tension-Type HA (TTH)

TTH is the most prevalent neurological disorder worldwide: -recurrent, mile-moderate HA -bilateral location (both sides of head) -pressing/tightening quality (squeezing band sensation) -not aggravated by routine physical activity -+ FH is a key risk factor Pathophysiology remains unclear (next) Diagnosis: based on history, and rule-outs (that it's not migraine, secondary, or cluster) Treatment: pharmacological therapy is mainstay Acute = analgesics (ibuprofen, acetaminophen) Preventative for recurrent/debilitating TTH = antidepressants including amitryptyline, venlafaxine, mirtazapine, and selected non-pharmacological therapies

Hemorrhagic stroke: Pathophysiology

The other type of stroke is hemorrhagic, and this is due to bleeding into the brain. 1. Bleeding --> inc. inctracranial pressure (ICP) -->restricts perfusion of brain tissue, causing ischemia 2. Ischemic cellular response (due to ischemic triggering cellular responses)--> 3. Cerebral edema (innate immune response) --> 4. Dec. cerebral perfusion pressure (CPP)- due to edema + inc. ICP 5. Possible herniation (of the brain stem) --> causing really severe occlusion of blood flow

MDD: multisystem involvement

This MDD multisystem involvement includes a number of diff factors including: -altered neurotransmitters (monoamine deficiency hypothesis) -neuroinflammation -dec. neuroplasticity (ability of neurons to change and alter) -dec. neurogenesis (formation of new neurons) -dec. in regional brain volume All lead to S/S that we see that produces a variety of cascades of events: 1) Activates adrenal axis --> cortisol secretion out of cortex --> inc. cardiometabolic risk 2) Immune inflammation (inc. pro-inflammatory cytokines) 3) Stress response (inc. cortisol) 4) ANS activation (autonomic NS) --> (inc. secretion of of catecholamines in the medulla- epi and norepi) *All these contribute to the cardiovascular and metabolic risk factors associated with MDD.

Progression of motor and non-motor symptoms

This progression of parkinson's disease includes both motor function and non-motor symptoms. Early PD (only see motor sx): dec. sense of smell, anxiety or depression, slow GI motility, constipation, disordered sleep Mid-stage onset of motor sx: -Inc. daytime sleepiness -Fluctuating course of dyskinesia (involuntary movement), bradykinesia, pin rolling tremor -Axial skeletal deformities -Dysphagia (swallowing) Late stage can see the diagnosis: Classic signs of postural instability, shuffling gait, risk for falls, bradykinesia (slow movement), rigidity and tremor, progressively you'll see additional fatigue, development of pain syndromes, impaired cognition, urinary syndromes, orthostatic HTN, visual hallucinations/psychotic sx --> eventually dementia. Treatment approach = inc. dopamine

MDD: Gene-environment interaction

We have predispositions, then the environment plays an epigenetic role (of turning on genes, silencing genes through things like methylation or post-translational modification or histone modification). Things like prenatal factors, childhood trauma, stress, drug abuse, all have epigenetic signatures. Protective factors: Social support, active-coping response, exercise (almost as potent as antidepressants).