Systems-Based Internal Medicine Course Objectives: Neurologic PA 607 Internal Medicine

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Diffuse Lewy Body Disease

•Progressive dementia characterized by the diffuse presence of Lewy bodies (abnormal neuronal protein deposits) in comparison to Parkinson disease, where the Lewy bodies are localized. •Histology: Cortical Lewy bodies (abnormal deposition of alpha-synuclein proteins). CLINICAL MANIFESTATIONS •Core features that occur early: recurrent visual hallucinations, episodic delirium (cognitive fluctuations), Parkinsonism (bradykinesia, rest tremor, rigidity, and/or gait disorder), & rapid eye movement (REM) sleep behavioral disorder. Delusions, sensitivity to antipsychotic drugs, autonomic dysfunction (eg, orthostatic hypotension, constipation, incontinence, erectile issues). •Dementia is a late finding (characterized by deficits in attention & visuospatial function), MANAGEMENT •Treatment of the Parkinsonian symptoms may worsen the neuropsychiatric symptoms and vice versa. •Neuroleptics, Donepezil, Selegiline

For each of the following conditions, students should describe the underlying pathophysiology, presenting signs and symptoms, basic epidemiology, differential diagnosis, associated systemic disorders (if indicated), appropriate diagnostic studies, clinical intervention, pharmaceutical therapies, and health maintenance concerns Intracranial tumors

ASTROCYTOMA •Derived from astrocytes (astrocytes are star-shaped glial cells of the brain & spinal cord that support the endothelial cells of the blood-brain barrier, provide nutrients for cells, maintain extracellular ion balance, and also repair the brain after injury). •Can appear in any part of the brain. Most often infratentorial in children (supratentorial in adults). TYPES OF ASTROCYTOMAS •PILOCYTIC ASTROCYTOMA (GRADE I): (Juvenile Astrocytoma) typically localized. Considered the "most benign" (noncancerous) of all the Astrocytomas. Most common in children & young adults. Other grade I Astrocytomas include cerebellar Astrocytoma & desmoplastic infantile. •DIFFUSE ASTROCYTOMA (Grade II or Low-grade) Types: Fibrillary, Gemistocytic & Protoplasmic. They tend to invade surrounding tissues but grow at a relatively slow pace. May present with seizures. •ANAPLASTIC ASTROCYTOMA: (Grade III). Rare but aggressive. •GRADE IV: Glioblastoma multiforme is the most common primary CNS tumors in adults. •Subependymal Giant cell Astrocytoma - ventricular tumors associated with tuberculous sclerosis. CLINICAL MANIFESTATIONS 1. Focal deficits: most common. Depends on the location of the lesion. MC in frontal & temporal areas of the cerebral hemisphere. -General symptoms: headaches (may be worse in the morning, may wake patients up at night, may be positional), cranial nerve deficits, altered mental status changes, neurological deficits, ataxia, vision changes, weakness. 2. Increased intracranial pressure: due to mass effect - headache, nausea, vomiting, papilledema, ataxia, drowsiness, stupor. DIAGNOSIS 1. CT scan or MRI with contrast: Grade I & II non-enhancing. Grade III & IV are enhancing. 2. Brain biopsy: usually guided by imaging studies. Histologic appearance includes: -Pilocytic Astrocytomas (Grade I) generally form sacs of fluid (cystic), or may be enclosed within a cyst. Although they are usually slow-growing, these tumors can become very large. Rosenthal fibers (eosinophilic corkscrew fibers). -Diffuse Astrocytomas tend to contain microcysts and mucus-like fluid. They are grouped by the appearance and behavior of the cells for which they are named. -Anaplastic Astrocytomas tend to have tentacle-like projections that grow into surrounding tissue, making them difficult to completely remove during surgery. -Astrocytoma Grade IV (glioblastoma) may contain cystic material, calcium deposits, blood vessels, and/or a mixed grade of cells. MANAGEMENT 1. Pilocytic Astrocytoma: Surgical excision. In adults and older children, radiation may follow surgery if the tumor cannot be completely removed. 2. Diffuse Astrocytoma: Surgery if the tumor is accessible & can be completely removed. Radiation may be adjunctive to surgery or for unresectable tumors. 3. Anaplastic Astrocytoma: Surgery -> XRT. +/- Chemotherapy after radiation or for tumor recurrence. 4. Astrocytoma Grade IV: Surgery -> XRT (radiation therapy) + Chemotherapy.

ISCHEMIC STROKES*********** •Acute onset of neurological deficits due to death of brain tissue from ischemia. Ischemic most common type of stroke (80%). Causes include thrombotic and embolic. •Thrombotic most common (2/3). •Embolic 1/3. Embolic commonly come from the heart, aortic arch or large cerebral arteries. Sources include: atrial fibrillation, valvular disease, or patent foramen ovale (paradoxical venous emboli). Risk factors: •Hypertension is the most significant & modifiable risk factor. •Dyslipidemia, diabetes, atrial fibrillation, cigarette smoking. •Nonmodifiable risk factors: males, increasing age, ethnicity, and family history. Anterior circulation symptoms (eg, Anterior cerebral artery, Middle cerebral) •Contralateral arm or leg weakness and contralateral sensory deficits. •Visual changes: contralateral homonymous hemianopsia (on opposite side of the stroke). •Middle cerebral artery: unilateral weakness and/or numbness (upper extremity > lower), facial droop (with forehead sparing), forced gaze deviation towards the side of the lesion, visual field cuts, and, if in the dominant hemisphere, speech deficits (eg, dysarthria, aphasia). •Anterior cerebral artery most commonly, patients will present with motor deficits characteristically involving the lower extremity contralateral to the infarct site. Abulia, agitation, motor perseveration, memory impairments, emotional lability, or incontinence, as well as anosognosia, are some of the classic neuropsychologic features associated with ACA Posterior circulation symptoms: •V's: vomiting, visual changes (diplopia), vertigo; Nystagmus, nausea, coma, drop attacks, ataxia. •Contralateral arm/leg weakness and contralateral sensory deficits. DIAGNOSIS •CT head without contrast best initial test to rule out hemorrhagic stroke. CT may be normal in the first 6-24 hours. MRI is most accurate to diagnose a stroke. •Neurovascular imaging: CT or MR angiography, carotid Doppler ultrasound, transcranial US. Performed to (1) diagnose large-vessel occlusion amenable to thrombectomy, & (2) asses for atherosclerosis as the cause for stroke. Conventional angiography rarely needed. •Ancillary testing: ECG, echocardiography, & cardiac monitoring to rule out embolic causes. IMMEDIATE MANAGEMENT •Within 3 hours of symptom onset: Alteplase (thrombolytic) if no contraindications. Contraindications include blood pressure ≥185/110, recent bleeding/anticoagulated, bleeding disorder, IN > 1.7, & recent trauma or surgery. Thrombolytics can be used within 4.5 hours in some patients: < 80 years old + < 25 on NIH stroke scale (not maximally severe) + not a diabetic with a previous stroke. •Mechanical thrombectomy can be performed within 24 hours of symptom onset of large artery occlusion in the anterior circulation. Compared to Alteplase alone, thrombectomy is associated with improved reperfusion, early neurological recovery, and functional outcome. •> 3 - 4.5 hours of symptom onset: Conservative (Aspirin and long-term management). •Blood pressure should only be lowered IF blood pressure >185/110 mmHg if thrombolytics are to be used or ≥220/120 mmHg if no plan to use thrombolytics. •IV labetalol 20mg if BP control needed •NPO for airway and remember ABCs LONG-TERM (OUTPATIENT) MANAGEMENT •Antiplatelet therapy: Aspirin therapy should not be initiated until 24 hours after the time of thrombolytic therapy. If patient was already on Aspirin prior to stroke, either add Dipyridamole or switch to Clopidogrel. Aspirin when administered within 48 hours of ischemic stroke onset modestly reduces the risk of early stroke recurrence and long-term disability. Clopidogrel, Dipyridamole, and other antiplatelet agents are other long-term options. •Statin therapy should be initiated regardless of LDL level (Stroke = Statin)! MIDDLE CEREBRAL ARTERY ISCHEMIC STROKE •Most common type of ischemic stroke. Think MCA is the Most Common Artery involved. CLINICAL MANIFESTATIONS •Neurological deficits: Contralateral sensory & motor deficits greater in face & arm > leg > foot. •Facial involvement: facial droop only involves the lower half of the face (patient will be able to raise forehead). •Visual: contralateral homonymous hemianopsia (loss of visual fields on the opposite side of the stroke). This leads to gaze preference towards the side of the lesion initially. Dominant (left in 90%) hemisphere: •Aphasia (Broca - expressive or Wernicke's - sensory). Broca is an output problem - partial ability to produce language (spoken, manual, or written) with intact comprehension. Wernicke's (sensory) aphasia is an input problem - they have difficulty understanding incoming language, so they produce large amounts (fluent) speech that lack content & meaning. •Math comprehension deficits, & agraphia. Nondominant (usually right) hemisphere: •Spatial deficits, dysarthria, neglect of the other side, anosognosia, apraxia, flat affect, impaired judgment, & impulsivity. ANTERIOR CEREBRAL ARTERY STROKE CLINICAL MANIFESTATIONS •Contralateral sensory & motor deficits (hemiparesis, sensory loss, & facial paralysis) greater in the lower extremity > upper extremity. The upper extremity and the face are usually spared. •Left-sided lesions presented with more transcortical motor aphasia, in which patients have difficulty responding spontaneously with speech, but repetition is preserved. •Right-sided lesions presented with more acute confusional state and motor hemineglect (unilateral motor function is lost). •Urinary incontinence. •Contralateral homonymous hemianopsia (leads to gaze preference towards the side of the lesion initially). •Personality/cognitive deficits (eg, confusion, flat affect, impaired judgment). POSTERIOR CEREBRAL ARTERY STROKE Think of the Vs for vertebral: vertigo (including nystagmus), vomiting, visual changes (eg, diplopia) Posterior cerebral artery: •Homonymous hemianopsia (may spare the macula); alexia without agraphia (if dominant hemisphere - left PCA); visual hallucinations, sensory loss, coma, limb ataxia, nystagmus, cerebellar signs, nausea, vomiting & drop attacks. •Deep segments of the PCA: symptoms may include hypersomnolence, cognitive deficits, ocular findings, hypoesthesia, and ataxia. Ocular findings may include homonymous hemianopsia (visual field deficits in one half of their visual field) that may spare the macula. •Larger infarcts that involve the deep structures can lead to hemisensory loss and hemiparesis due to the involvement of the thalamus and the internal capsule. •Superficial infarcts present with visual and somatosensory deficits, impairment of stereognosis, tactile sensation, and proprioception. Vertebrobasilar artery: •"Crossed symptoms": ipsilateral cranial nerve deficits; contralateral motor/sensory deficits. •Diplopia, dizziness, nausea, vomiting, vertigo, limb and gait ataxia, coma, cerebellar dysfunction. •Asymmetric but bilateral deficits are the rule in basilar infarcts (eg, hemiparesis with motor or reflex abnormalities on the nonhemiparetic side). Cerebellar Infarction •Ataxia, nausea, vomiting, headache, dysarthria, and vertigo symptoms. •Edema and rapid clinical deterioration may complicate cerebellar infarction.

Electrocardiography (ECG) is indicated in all patients undergoing evaluation for syncope and is the best initial diagnostic study. Syncope is an atraumatic, sudden-onset, transient loss of consciousness that resolves within seconds or minutes. The incidence and prevalence increase with age. Common causes of syncope include cardiogenic syncope, orthostatic (postural) hypotension, and reflex (neurally mediated) syncope. Reflex mediated syncope is due to excess vagal tone or impaired peripheral circulation, resulting in hypotension. Vasovagal syncope is the most common type of syncope and occurs in the presence of stress (e.g., pain, claustrophobia, emotional distress). Patients with vasovagal syncope may experience premonitory symptoms including nausea, diaphoresis, tachycardia, and pallor. Orthostatic hypotension occurs with sudden changes in posture when the body is unable to compensate for an abrupt decrease in venous return. Orthostatic hypotension is more common in elderly patients, diabetic patients, or patients on diuretics, vasodilators, or adrenergic-blocking agents. A systolic decline of ≥ 20 mm Hg or a diastolic decline of ≥ 10 mm Hg immediately upon changing from supine to standing is indicative of orthostatic hypotension. Cardiogenic syncope results from dysrhythmias (e.g., sick sinus syndrome, AV block, ventricular tachycardia, supraventricular tachycardia with rapid ventricular rate) or mechanical causes (e.g., aortic stenosis, pulmonary stenosis, hypertrophic cardiomyopathy, right-to-left shunting, left atrial myxoma, heart failure). Cardiogenic syncope is not associated with premonitory symptoms, and patients are at increased risk for fall injuries. A careful history and physical examination is essential in the evaluation of syncope. A resting ECG, orthostatic BP evaluation, auscultation of carotid arteries, and cardiac auscultation may be used to evaluate syncope. Patients with an unremarkable history, physical examination, and initial workup may not need further evaluation. If a cardiogenic etiology is suspected (e.g., abnormal ECG, carotid bruit, cardiac murmur), a referral to a cardiologist for a cardiac workup (e.g., Holter monitor, event recorder, implantable monitor, stress test, echocardiography, electrophysiologic studies) is warranted. A tilt-table test is most helpful if recurrent vasovagal syncope is suspected and the initial evaluation is inconclusive. A tilt-table test is performed by securing the patient to a table and taking serial BP measurements with incremental increases in the angle of the table. If no abnormalities are noted, IV isoproterenol is administered to stress the heart, followed by a 60° elevation of the table and serial BP measurements. Treatment for vasovagal syncope includes avoiding triggers or an alpha-agonist (e.g., midodrine) to increase peripheral sympathetic neural outflow and decrease venous pooling. A pacemaker is indicated in patients with persistent, symptomatic bradycardia, a Mobitz type II heart block, or a third-degree heart block. Standard pharmacologic treatment, electrical cardioversion, or cardiac ablation is used to treat underlying dysrhythmias. Management of heart failure, stenotic valves, or atherosclerosis is indicated to decrease syncopal episodes.

Transient Ischemic Attack RAPID REVIEW

Transient episode of neurological dysfunction without acute infarction 10% of TIA patients will have a stroke within 90 days Low-risk TIA (ABCD2 score < 4) or moderate to major ischemic stroke (National Institutes of Health Stroke Scale (NIHSS) > 3) ->Treatment with aspirin alone High-risk TIA (ABCD2 score ≥ 4) or minor ischemic stroke (NIHSS score ≤ 3) ->Begin with dual antiplatelet therapy (DAPT) for 21 days using aspirin plus clopidogrel ABCD2 score: predicts likelihood of subsequent stroke within 2 days

carotid artery stenosis

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ACUTE BACTERIAL MENINGITIS •Bacterial infection of the meninges. •25% have a recent history of otitis or sinusitis. ETIOLOGIES Streptococcus pneumoniae: •Most common cause in adults of all ages & children ages > 3 months - 10 years. Neisseria meningitidis: •Most common in older children (10y - 19y). •Second most common cause in adults. •May be associated with a petechial (purpuric) rash on the trunk, legs, and conjunctivae. Group B Streptococcus (S, agalactiae): •Most common cause in neonates < 1 month (part of the vaginal flora) & infants <3 months. Listeria monocytogenes; •Increased incidence in neonates, >50 years, immunocompromised states (eg, history of glucocorticoid use, alcoholism, pregnant, AIDS or HIV, chemotherapy). Neonates: •Group B Streptococcus, Escherichia coli, & gram-negative rods are common causes of neonatal meningitis. Listeria monocytogenes an important pathogen. •Haemophilus influenzae (reduced incidence due to Hib vaccine) CLINICAL MANIFESTATIONS •Meningeal symptoms: headache, neck stiffness, photosensitivity, fever, chills, nausea, vomiting. •May develop altered mental status changes and seizures. PHYSICAL EXAMINATION •Meningeal signs: nuchal rigidity, positive Brudzinski (neck flexion produces knee and/or hip flexion), positive Kernig sign (inability to extend the knee/leg with hip flexion). •Focal neurologic findings (30%). DIAGNOSIS •Lumbar puncture + CSF examination best initial test & definitive diagnosis decreased glucose <45, increased neutrophils, increased protein, & increased pressure. •Head CT scan best initial test prior to LP ONLY if you need to rule out mass effect if any of these are present papilledema, seizures, confusion, focal neurologic findings, >60 years, immunocompromised, or history of CNS disease. MANAGEMENT •Antibiotics, along with Dexamethasone when indicated, should be started as quickly as possible after lumbar puncture is performed, if LP is contraindicated, or prior to head CT if a head CT is to be performed prior to LP (as quickly as possible after blood cultures are obtained). •In adults, Dexamethasone has been shown to reduce mortality and sequelae of S. pneumo, H. flu & N. meningitidis. Also recommended in children if H. influenza type B is suspected (reduces incidence of CN VIII-related hearing loss). Empiric for >1 month - 50y: •Vancomycin + Ceftriaxone (or Cefotaxime or Cefepime). Empiric for >50y: •Vancomycin + Ceftriaxone + Ampicillin (for Listeria). Empiric for neonates (up to 1 month): •Ampicillin + either Gentamicin and/or Cefotaxime. Empiric for head trauma or post-neurosurgical procedure: •Vancomycin + EITHER Ceftazidime or Cefepime (to cover aerobic gram-negative organisms, eg, Pseudomonas). Additional management for N. meningitidis: •Droplet precautions: should be continued for 24 hours after the initiation of antibiotics with suspected or confirmed N. meningitidis infection. •Post-exposure prophylaxis: Ciprofloxacin (500mg oral x 1 dose) or Rifampin (600mg orally every 12 hours for 2 days). Prophylaxis only needed for "close contacts" with prolonged exposure (>8 hours) or direct exposure to respiratory secretions (eg, household contacts, roommates, kissing, sharing utensils, performing mouth to mouth resuscitation etc.). •Prophylaxis is not recommended for healthcare workers who have not had direct exposure to respiratory secretions. ASEPTIC MENINGITIS •Clinical and laboratory evidence of meningitis with negative routine bacterial cultures. ETIOLOGIES •Enteroviruses most common cause (eg, Coxsackievirus & Echovirus). •Other viruses (eg, HSV-2, VZV), mycobacteria, fungi, spirochetes, medications, and malignancies. CLINICAL MANIFESTATIONS •Classic symptoms of meningitis but may be milder. •Meningeal symptoms: headache, neck stiffness, photosensitivity, fever, chills, nausea, vomiting. PHYSICAL EXAMINATION •Meningeal signs; nuchal rigidity, positive Brudzinski (neck flexion produces knee and/or hip flexion), positive Kernig sign (inability to straighten the knee with hip flexion). •No focal deficits in aseptic meningitis helps to distinguish it from Encephalitis. DIAGNOSIS •Diagnosis of exclusion after ruling out bacterial meningitis. •Lumbar puncture best initial test and most accurate if no symptoms of mass effect. CSF: classic findings are normal glucose, lymphocyte predominance, protein count usually <200. MANAGEMENT •Supportive; eg, antipyretics, IV fluids, analgesics, and antiemetics. •Most patients have a self-limited course with resolution even without specific therapy.

ALZHEIMER DEMENTIA •Most common type of dementia. Usually a disease of older age (>65 years of age). RISK FACTORS •Increasing age, genetics, family history. PATHOPHYSIOLOGY •Unknown - 3 hypotheses: (1) Amyloid hypothesis: extracellular amyloid-beta protein deposition (senile plaques) in the brain are neurotoxic. (2) Tau hypothesis: neurofibrillary tangles (hyperphosphorylated tau proteins) are neurotoxic. (3) Cholinergic hypothesis: acetylcholine deficiency leads to memory, language, & visuospatial changes. •Histologic findings: amyloid-beta protein deposition (senile plaques) in the brain. Amyloid precursor proteins (APP) are normally degraded by alpha-cleavage. Beta cleavage of APP results in Amyloid-beta accumulation. Neurofibrillary tangles = intracellular aggregations of tau protein (an insoluble cytoskeletal microtubule element). CLINICAL MANIFESTATIONS •Short-term memory loss (often first symptom). Progresses to long-term memory loss and cognitive deficits: disorientation, behavioral & personality changes, language difficulties, loss of motor skills etc. Usually gradual in nature. DIAGNOSIS •Clinical diagnosis (no specific test). Workup to rule out other causes include MRI of the brain, CBC, CMP, renal and liver tests, alcohol levels, VDRL or RPR to rule out Syphilis, B12, and thyroid function studies. •Decline in 2+ areas of cognition in MMSE •MRI preferred neuroimaging test - cortex atrophy + ventricular enlargement (eg, medial temporal lobe atrophy), reduced hippocampal volume, white matter lesions. MEDICAL MANAGEMENT •Acetylcholinesterase inhibitors: Donepezil, Rivastigmine, Galantamine. Used to improve memory function & symptom relief for patients with newly diagnosed Alzheimer disease (AD) dementia (does not slow down the disease progression). •NMDA antagonist: Memantine - can be adjunctive or used as monotherapy in moderate to advanced dementia (eg, MMSE <18). Mechanism: blocks NMDA receptor, slowing calcium influx & nerve damage. Glutamate is an excitatory neurotransmitter of the NDMA receptor. Excitotoxicity causes cell death. NMDA antagonists reduce glutamate excitotoxicity. May be adjunctive. •Avoid anticholinergics •time to death = 5-10 years •Aducanumab is approved by the US Food and Drug Administration (FDA) for the treatment of mild AD.

Migraine medications

5-HT 1B/1D RECEPTOR AGONISTS (TRIPTANS) Oral; Rizatriptan & Eletriptan tend to be the most effective, Almotriptan. Sumatriptan (oral, subcutaneous, or nasal spray); Zolmitriptan (nasal, oral). •Mechanism of action: serotonin (5HT-1b/d) agonists can stop Migraine attacks via vasoconstriction & blockage of nociceptive (pain) pathways in the brainstem & trigeminovascular system •Indications: moderate to severe migraines or no response to analgesics in mild disease. •Adverse effects: often mild and transient - chest tightness from vasoconstriction, nausea, vomiting, abdominal cramps, flushing, malaise. •Contraindications: Because of their vasoconstricting properties, they are contraindicated in individuals with a history, symptoms, or signs of ischemic cardiac, cerebrovascular, or peripheral vascular syndromes (Ischemic stroke or ischemic heart disease, uncontrolled hypertension, angina, pregnancy; hemiplegic or basilar migraines). Not used within 24 hours of the use of Ergotamines. 5-HT 1B/1D RECEPTOR AGONISTS (ERGOTAMINES) Ergotamine (oral), Dihydroergotamine (IM, IV, SQ, and intranasal) •Mechanism of action: Nonselective serotonin (5HT-1) receptor agonists that stop Migraines via cranial vasoconstriction & blockage of nociceptive (pain) pathways in the brainstem & trigeminovascular system (eg, trigeminal nucleus caudalis and trigeminal sensory thalamus). •Indications: Reserved use due to its adverse effects & contraindications (Triptans are associated with lower occurrence of adverse effects compared to Ergotamines). •Adverse effects: Rebound headache. Ergotism: Excessive Dihydroergotamine use can cause ergotism, [seizures, spasticity, irritability, numbness, and psychiatric changes (including psychosis)]. •Contraindications: Because of their vasoconstricting properties, they are contraindicated in individuals with a history, symptoms, or signs of ischemic cardiac, cerebrovascular, or peripheral vascular syndromes (eg, Ischemic stroke or ischemic heart disease, uncontrolled hypertension, angina, pregnancy; hemiplegic or basilar migraines). Hepatic or renal disease. ABORTIVE MIGRAINE THERAPY - ANTIEMETICS •IV Metoclopramide, Chlorpromazine (IV or IM), Prochlorperazine (IV or IM). •Mechanism of action: Dopamine receptor antagonists. May also reduce headache pain intensity. •Indications: Nausea &/or vomiting in patients with Migraine. •Adverse effects: Extrapyramidal symptoms - acute dystonic reactions (dyskinesias characterized by intermittent spasmodic or sustained contractions of muscles in the face, neck, trunk, etc.). IV Diphenhydramine can be given to prevent or treat dystonic reactions. QT prolongation. CGRP RECEPTOR ANTAGONISTS: Gepants: Oral gepants: Rimegepant, Ubrogepant •Mechanism of action: Calcitonin gene-related peptide receptor antagonist that inhibits pain transmission, reduces neurogenic inflammation, and minimizes artery dilatation without active vasoconstriction. •Indications: Effective in the acute treatment of Migraine with relief from pain, other symptoms, and functional disability (associated with pain- and symptom-free state at 2 hours). Oral options for the acute treatment of Migraine in patients with either insufficient response or contraindication (eg, coronary artery disease) to treatment with triptans. •Adverse effects: Gepants are extremely well tolerated with only a few percent of patients reporting troublesome side effects, such as mild nausea. Rare effects include rash, dyspnea, and hypersensitivity. 5-HT 1F RECEPTOR AGONISTS (DITANS) Lasmiditan (oral) •Mechanism of action: Highly selective 5-HT 1F receptor agonist that aborts Migraine attacks via inhibition of neuropeptide and neurotransmitter release and inhibition of PNS trigeminovascular and CNS pain signaling pathways. •Indications: Acute management of Migraine attacks. Safe in patients with cardiovascular or cerebrovascular disease - Ditans have no vascular effects because the 5-HT 1F receptor is located in the central and peripheral nervous system but not vasculature. •Adverse effects: The major side effect is dizziness. Other adverse effects include somnolence, paresthesia, fatigue, and nausea. Patients are advised not to drive for 8 hours after treatment.

Intracranial Tumors overview

50% are malignant and associated with high mortality Glial tumors (30% of all primary tumors) --80% are malignant Meningiomas (35%), schwannomas (10%), CNS lymphomas (2%) Brain metastases are 3x more common than all primary brain tumors RF: exposure to ionizing radiation (meningiomas, gliomas, schwannomas), immunosuppression (primary CNS lymphoma) Diagnosis Cranial MRI (preferred) with gadolinium contrast CT if unable to undergo MRI - PET- useful in determining the metabolic activity of the lesions seen on MRI Labs are rarely useful, although mets may have elevated tumor markers reflecting presence of brain met (B-hCG) from testicular cancer Also, rarely indicated or helpful- cerebral angiography, EEG. LP

Acetylcholinesterase inhibitors

ACETYLCHOLINESTERASE INHIBITORS: Pyridostigmine, Neostigmine •Mechanism: Acetylcholinesterase inhibitors prevent acetylcholine breakdown in the synapse). Indications: •First-line medical management of Myasthenia gravis. •Pyridostigmine usually preferred over Neostigmine due to longer duration of action. Adverse effects: •Cholinergic adverse effects; muscarinic - abdominal cramping, diarrhea, increased salivation and bronchial secretions, nausea, vomiting, sweating, and bradycardia. Acetylcholine causes SLUDD-C (salivation, lacrimation, urination, digestion, defecation and pupillary constriction). •Nicotinic adverse effects - fasciculations and muscle cramping. •Glycopyrrolate & Hyoscyamine are anticholinergic drugs with little to no effect on the nicotinic receptors. They are used to help control some adverse effects of acetylcholinesterase inhibitors. •Cholinergic crisis - excessive anticholinesterase medication, leading to paradoxical weakness, nausea, vomiting, pallor, sweating, salivation, diarrhea, miosis, bradycardia, & respiratory failure.

Acute period of cognitive dysfunction due to a medical disturbance or condition. Elderly very prone Causes include those of coma (SMASHED) plus (P. DIMM WIT) P = postoperative state (pain meds) D= dehydration I = infection (sepsis, meningitis, encephalitis, UTI) M= Meds (TCAs, steroids, anticholinergics, hallucinogens, cocaine) M= Metals (heavy metal exposure) W= Withdrawal state (ETOH, benzos) I= inflammation, fever T= trauma, burns SMASHED •Structural brain pathology: stroke, subdural or epidural hematoma, tumor, hydrocephalus, herniation, abscess •Meningitis, mental illness •Alcohol, acidosis •Seizures (postictal), substrate deficiency (thiamine) •Hypercapnia, hyperglycemia; hyponatremia, hypoglycemia, hypoxia, hypotension, hypothermia •Endocrine (Addisonian crisis, thyrotoxicosis, hypothyroidism); encephalitis, encephalopathy •Drugs (opiates, barbiturates, benzos)

Alzheimer disease is the most common cause of dementia and is characterized by cognitive decline.

Alzheimer disease is the most common cause of dementia and is characterized by cognitive decline. Risk factors include family history, genetic mutations affecting amyloid in the brain, the presence of the apolipoprotein E epsilon 4 allele, hypertension, obesity, and diabetes. Definitive diagnosis requires a brain biopsy, which is rarely performed. Histopathologic findings indicative of Alzheimer disease include amyloid plaques and the accumulation of hyperphosphorylated tau protein in neurofibrillary tangles within the brain. Current hypotheses suggest these amyloid plaques and tau proteins are toxic to the neurons in the brain, resulting in progressive cognitive decline. Older patients with a clinical presentation of progressive memory impairment may be screened with the Mini-Mental Status Examination or the Montreal Cognitive Assessment. Participation in social, mental, and physical activities may decrease the risk of developing Alzheimer disease and other forms of dementia. While there is no cure for Alzheimer disease, cholinesterase inhibitors, such as donepezil, galantamine, and rivastigmine, are used to treat symptoms of cognition and global functioning. Alzheimer Disease Patient's family will report short-term memory loss, confusion about the location of familiar places, difficulty completing daily tasks that would normally take less time to do, poor judgment that can lead to bad decision-making, changes in mood or personality (e.g., increased anxiety) Diagnosis is confirmed by microscopy of the brain that shows amyloid plaques and neurofibrillary tangles Mini-Mental State Examination is used to monitor the progression Treatment is cholinesterase inhibitors (e.g., donepezil), NMDA antagonists (e.g., memantine)Does not cure, only aims to slow progression

Question: What sign seen in Parkinson disease is characterized by a sustained blink response to repetitive tapping over the bridge of the nose?

Answer: Myerson sign.

Myasthenia Gravis RAPID REVIEW

Autoantibodies to nicotinic acetylcholine receptors resulting in impaired transmission at the neuromuscular junction Sx: ocular or generalized muscle weakness, bulbar weakness (dysarthria, dysphagia), ptosis and diplopia that is worse at the end of the day or following exertion PE: applying ice pack to eyelid improves diplopia Dx: -->Serologic testing for autoantibodies: anti-nAChR, anti-MuSK -->Electrophysiologic studies: repetitive nerve stimulation, single-fiber electromyography Tx: acetylcholinesterase inhibitors (pyridostigmine) -->Acute myasthenic crisis: plasmapheresis, IVIG Comments: associated with thymoma, thyroid disease, autoimmune disorders

Seizure meds

CARBAMAZEPINE Mechanism of action: •Prolongs inactivation of voltage gated sodium channels (blocks sodium channels), decreasing seizure spread by increasing the refractory period of the channels, decreased synapse transmission, & inhibition of action potentials. •Exact mechanism in Trigeminal neuralgia & Bipolar disorder unknown. Indications: •Epilepsy: Generalized tonic-clonic & focal seizures (simple & complex) •Trigeminal neuralgia first-line therapy. •Bipolar disorder: (1) Sodium valproate and Carbamazepine are alternative mood stabilizers to Lithium and (2) are useful for rapid cycling or mixed features. •Central diabetes insipidus (2nd-line after Desmopressin). Adverse effects: •The most common side effects of Carbamazepine are dizziness, drowsiness, ataxia, nausea, & vomiting. •Gastrointestinal: Nausea, vomiting, anorexia, hepatotoxicity (increased LFTs). •Hyponatremia (causes SIADH) - Hyponatremia is usually mild, transient, and reversible. •Stevens-Johnson syndrome (test for HLA-B*1502 - genetic susceptibility marker in Asians associated with an increased risk of developing Stevens-Johnson syndrome). •Diplopia, nausea, vomiting, arrhythmias. •Blood dyscrasias: agranulocytosis, aplastic anemia, thrombocytopenia. Rare occurrence. •Teratogenic potential: craniofacial anomalies (eg, cleft lip & palate), spina bifida, cardiovascular and cutaneous malformation, hypospadias, and developmental delays. •Cardiac: Arrhythmias. Carbamazepine can exacerbate heart failure patients or even lead to cardiac dysfunction in healthy patients due to its tendency to cause homocysteinemia. Medication interactions: •Inducer of the CP450 system (CYP450 3A4) and can reduce the levels of other medications. • Drug-induced lupus. •Contraindications: Not used in Absence (petit mal) seizures - can worsen absence seizures. ETHOSUXIMIDE Mechanism of action: •Blocks calcium channels, leading to motor cortex depression. Elevates the stimulation threshold, decreasing neuronal firing. Indications: •Drug of choice for Absence (Petit mal) seizures. Can only be used in Absence seizures. Adverse effects: •Drowsiness, ataxia, dizziness, headache, rash (Stevens-Johnson syndrome), GI upset (nausea, vomiting & diarrhea), weight gain. •Caution: renal or hepatic failure. •Monitoring: UA, CBC, LFTs. PHENOBARBITAL Mechanism of action: •Barbiturate that binds to GABA receptors & potentates GABA-mediated CNS inhibition as a result of increased duration of chloride ion channel openings. •Can be used in pregnant women and children. Indications: •Partial (simplex & complex) or generalized (tonic-clonic) seizures. •Status epileptics after Phenytoin administration. Adverse effects: •Sedation (toxicity), alteration of sleep wake cycle, cognitive dysfunction, tolerance, dependence •Inducer of P450 system - induction of hepatic drug metabolism •Psychological: suicidality, depression, hyperactivity in pediatric patients, dependence. •Stevens-Johnson syndrome. •Permanent neurologic deficit if injected into or near peripheral nerves. BENZODIAZEPINES • Lorazepam, Diazepam, Midazolam Mechanism of action: •Potentates GABA-mediated CNS inhibition - Benzodiazepines interact with postsynaptic GABA A receptor-chloride ion channel macromolecular complex at several sites within the CNS. In the presence of Benzodiazepines, the frequency of chloride ion channel openings is increased, facilitating the inhibitory effects of GABA (decreased rate of neuronal discharge). •Functions as an anxiolytic, sedative-hypnotic, anticonvulsant and muscle relaxant. •Lorazepam is the most effective Benzodiazepine for seizures & has a shorter half-life (but longer "seizure' half-life) compared to Diazepam. Indications: •Generalized and absence seizures, anxiety, sedation, muscle spasm. •First-line for acute generalized (tonic-clonic) seizures & status epileptics (usually followed by phenytoin loading to prevent seizure recurrence), alcohol withdrawal, delirium tremens, & eclampsia (recurrent seizures after magnesium sulfate administration). •Seizure prevention: during Alcohol withdrawal, Delirium tremens, & Eclampsia (recurrent seizures after IV Magnesium sulfate administration). Adverse effects: •Sedation, tolerance, dependence, ataxia, paradoxical reaction increased suicide. •Monitor blood pressure after IV administration. •Contraindications or caution: suicide risk. •Overdose: Flumazenil antagonizes the Benzodiazepine receptors. It is used for benzodiazepine sedation reversal and Benzodiazepine overdose. VALPROIC ACID, DIVALPROEX SODIUM Mechanism of action: •Multiple mechanisms - potentates GABA-mediated CNS inhibition, inhibits glutamate & NMDA receptors, increases refractory period of voltage-gated sodium channels. •Divalproex sodium is the stable, coordinated compound of sodium Valproate and Valproic acid. Indications: •Valproic acid is an anticonvulsive and mood stabilizer medication. •Seizures: Partial (simple and complex), generalized (tonic-clonic & absence). First-line for myoclonic seizures. •Headaches: Migraine prophylaxis. •Bipolar disorder: (1) Sodium valproate and Carbamazepine are alternative mood stabilizers to Lithium and (2) are useful for rapid cycling or mixed features. Adverse effects: •Common adverse effects include drowsiness (sedation), nausea, tremor, hair loss (alopecia), weight gain, hepatotoxicity, and inhibition of hepatic drug metabolism. •GI: Pancreatitis, hepatotoxicity, nausea, vomiting, weight changes (anorexia and weight gain). •Teratogenic Valproate has the highest risk of birth defects of any of the commonly used antiepileptic drugs - though multiple fetal malformations are possible, neural tube defects (eg, spina bifida) are the most common abnormalities seen after Valproate use. Valproate should be avoided if patient is not already on it prior to pregnancy or only used in very select cases. •Inhibitor of the CP450 system leading to drug-drug interactions. Thrombocytopenia. •Neurological: headache, sedation, tremor, ataxia, tinnitus, blurred vision, nystagmus, photosensitivity. Increased suicidality. Hyponatremia due to SIADH. TOPIRAMATE Mechanism of action: •Multiple actions: blocks sodium channels, increases GABA activity, glutamate receptor antagonist. Indications: •Generalized (tonic-clonic) seizures, partial (simple & complex) seizures. •Migraine prophylaxis. Adverse effects: •Nephrolithiasis: Treatment with Topiramate causes systemic metabolic acidosis, markedly lower urinary citrate excretion, and increased urinary pH. These changes increase the propensity to form calcium phosphate stones. •CNS symptoms: sedation, drowsiness, headache, dizziness, ataxia, psychomotor slowing, memory impairment, paresthesias. Hyperthermia. •Weight loss. Acute myopia, glaucoma. GABAPENTIN Mechanism of action: •Inhibits voltage-gated calcium channels (structurally similar to GABA). Indications: •Partial (simple & complex) seizures. •Neuropathy: Peripheral neuropathy & neuropathic pain, Fibromyalgia, post-herpetic neuralgia. Adverse effects: •CNS symptoms: dizziness, sedation, ataxia, nystagmus. •Can worsen Absence seizures.

cerebral aneurysm pathophysiology

Causes damage to arterial vessel wall, likely due to aberrant blood flow and genetic and modifiable risk factors (such as smoking or hypertension) Pathogenesis formation of saccular intracranial aneurysm is a gradual process which is not fully understood, but likely involves disruption of structural composition and physiological homeostasis of cerebral artery wall2aberrant blood flow and/or decreased vessel wall integrity, possibly caused or exacerbated by risk factors such as smoking and hypertension, leads to mechanical overload and shift in tensile forces acting on arterial wall at bifurcation point, which can affect vessel wall, includingdisruption of internal elastic lamina of arterial wallreconstitution and degradation of extracellular matrixmodulation of arterial smooth muscle cellsdisruption of endothelial cellssubsequent influx of macrophages and activation of other cellular and humoral inflammatory responses can further damage arterial wallstructurally defective arterial wall exposed to high shear stress from impinged blood flow, result in outward bulging (aneurysm sac formation)aneurysm sac continues growth until ongoing vessel wall repair and extracellular matrix degradation reach equilibriumaneurysm may have long-term stability before undergoing episodes of rapid growth (rupture more likely during periods of growth) about 85% of intracranial aneurysms occur in anterior circulation of circle of Willis; anatomical variations in this area that result in altered hemodynamic flow conditions (such as hypoplastic branching arteries or bifurcations with very sharp angles) reported to be risk factors for aneurysm development

Concussion (ROSH)

Concussion is also referred to as mild traumatic brain injury and occurs as a result of head injury. It is often seen in adolescents and young adults in the context of playing sports, such as American football, soccer, and ice hockey. It is most often defined by a Glasgow Coma Scale score of 13 to 15 assessed at 30 minutes postinjury. Factors that increase the risk of concussion include male sex, type of sport, headgear use, body mass index greater than 27 kg/m2, and training less than 3 hours weekly. A licensed health care provider should counsel participants in sports and their families about the risks of concussion prior to beginning any training program to make an informed decision about participation. Once an injury occurs, a number of diagnostic tools may be used along with thorough medical, neurological, or neuropsychological examinations to help confirm the diagnosis. An athletic trainer or trained medical provider may administer standardized, validated sideline assessment tools to guide management. The player should be immediately removed from play when there is suspicion of a concussion to reduce the risk of further injury. Imaging with computed tomography is obtained to rule out more serious injuries in players with a suspected concussion who also have severe symptoms, such as loss of consciousness, altered mental status, post-traumatic amnesia, focal neurologic deficits, concern for skull fracture, or signs of clinical deterioration. A stepwise return to activity once the athlete is asymptomatic and under close supervision of medical providers, coaches, family, and athletic trainers will help to prevent any complications of the injury. Postconcussive syndrome is a sequelae of concussion, with symptoms including headache, dizziness, cognitive impairment, and neuropsychiatric symptoms. Most cases occur within the first 10 days after the injury with the majority being completely resolved within 3 months. Concussion Brief LOC, amnesia No focal neurologic deficits Negative CT scan (if indicated)

Dementia (ROSH)

Dementia is defined as one or more progressive, age-related deficits in cognition and memory that cause difficulty in daily activities and are not the result of delirium or another treatable medical condition. Areas of cognition that may be affected by dementia include learning, memory, language, attention, social cognition, perceptual motor skills, and executive function. These deficits must represent a significant decline from previous functioning. The majority of patients with dementia have Alzheimer disease, but other forms of progressive dementia exist, such as Lewy body dementia, frontotemporal dementia, and Parkinson disease. The largest risk factors for the development of dementia are advanced age and cerebrovascular disease. Diagnosis of dementia is largely clinical. A detailed history should be elicited from both the patient and close relatives regarding the patient's former functioning, decline in function, velocity of decline, and limitations in daily functioning as the next step. Close relatives should be questioned separately from the patient for more honest answers. Red flags in the history that should cause the clinician to consider delirium rather than dementia include rapid symptom onset, clouded sensorium, fluctuations in level of consciousness, and decreased concentration. Symptoms of major depression, including anhedonia, sadness, feelings of guilt, expressions of worthlessness, or suicidal ideation, should prompt the clinician toward a diagnosis of depression rather than dementia, as cognition and memory can be affected in patients with major depressive disorder. A small panel of laboratory tests may be run to rule out treatable causes of cognitive decline, such as vitamin B12 deficiency and hypothyroidism. A thorough physical exam should be performed to rule out Parkinson disease and stroke. Treatment of dementia is multimodal, including pharmacotherapy, exercise therapy, cognitive rehabilitation, and risk factor control. Two main classes of drugs used in the treatment of dementia are cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. Current treatments for dementia, whether pharmaceutical or nonpharmaceutical, are not meant to be curative but rather promote an extension of independent living and improve quality of life.

cerebral aneurysm review

Etiology, Prevalence, Risk Factors •Develops from normal hemodynamic stress or HTN •Develops at junction of communicating branch with main cerebral artery (Ant Comm + Ant Cerebral) AV malformation 1. Ruptured berry (saccular) aneurysm (MC, 80%)-most located in anterior circulation 2. Fusiform (large) 3. Mycotic (bacterial endocarditis) Associated: polycystic kidney disease, Marfan syndrome Clinical Symptoms and Signs -May manifest as compression as cranial nerves (CN III, IV, VI) -Causes of rupture = strenuous activity (exercise, coltus, physical work) Diagnostics 1. Noncontrast CT head-if normal, do LP •Contrast CT or MRI for aneurysms >5 mm or AV malformations 2. Lumbar puncture 3. Cerebral angiography (gold standard) Therapy, Prognosis, and Health Maintenance 1. Open surgical clipping 2. Endovascular coiling (preferred) Complication: -Subarachnoid hemorrhage -Of patients with aneurysms that rupture, 33% die before reaching the hospital, 20% die in the hospital, 30% recover without disability

Distal symmetric polyneuropathy is the most common form of diabetic peripheral neuropathy. Patients with poorly controlled diabetes are at higher risk of developing diabetic neuropathy. Diabetic neuropathy symptoms are typically bilateral and symmetric. Damage to the large myelinated fibers responsible for pressure and balance will result in symptoms of numbness, paresthesias, and ataxia. Damage to the small myelinated fibers responsible for nociception will result in painful sensations of burning, stabbing, or electrical shock. Peripheral nerves are more vulnerable to damage, and symptoms will originate distally and progress from the toes to the calves. The upper extremities are also affected in a stocking-glove pattern. A decrease or loss of sensation increases the risk of unperceived neuropathic injuries (e.g., ulcers, infections). Neuropathy affecting the foot musculature may result in clawing of the toes and displacement of the submetatarsal fat pads anteriorly. This displacement results in altered gait and biomechanics that further increase the risk of ulcers over the metatarsal heads, joint subluxation, and periarticular fractures. Decreased or absent ankle jerk reflexes may also be seen on physical examination. All patients diagnosed with type 2 diabetes should be screened for neuropathy at the time of diagnosis. Patients with type 1 diabetes should be screened five years after their diagnosis. Screening is also recommended for patients with prediabetes who have symptoms of neuropathy. Screening for diabetic neuropathy includes a careful history, evaluation of small myelinated fiber function with pinprick testing, and evaluation of large myelinated fiber function with vibration sense, joint position sense, light touch perception, and deep tendon reflex testing. Simple screening tests such as the Michigan neuropathy screening instrument, Utah early neuropathy scale, and United Kingdom screening test may also be used. Treatment for diabetic neuropathy includes improving vascular supply, mechanical unloading, and proper wound care. Infections should be treated with antibiotics and debridement. Wound healing is delayed in patients with diabetes due to impaired circulation. Topical platelet-derived growth factor (e.g., becaplermin) may be used to improve wound healing. Therapeutic footwear (e.g., custom-molded shoes, insoles) are useful for mechanical unloading. Referral to a podiatrist is essential in cases with deformities or recurrent infections. Patient education regarding foot care is important. Pharmacologic agents for painful diabetic neuropathy include nortriptyline, desipramine, amitriptyline, gabapentin, pregabalin, duloxetine, and capsaicin cream. Symmetric distal sensory loss, burning pain, weakness •Slow onset: stocking glove -> DM, uremia • Fast onset: drugs • Ascending: Guillain barre •Hereditary: motor and sensory loss, loss of reflexes, hammer toes -> stork leg deformity -> charcot-marie-tooth •Dx: clinical; aided by electromyography / nerve conduction studies •Tx: gabapentin, amitriptyline, topiramate, tramadol, NSAIDs ->May use low dose narcotics sparingly for breakthrough pain

Dementia progression

Early stages- mild forgetfulness, impaired ability to learn new material, poor performance at work, poor concentration, changes in personality, impaired judgment (inappropriate humor) Intermediate--memory is progressively impaired; aware of condition, yet denial present; visuospatial disturbances are common (getting lost in familiar place and difficulty following directions), repeat questions over and over Late--assistance needed for ADLs, difficulty remembering names of relatives/friends or major aspects of lives, paranoid delusions (victim of theft) and hallucinations common Advanced--complete debilitation and dependence on others, incontinence, forgets own name Death--secondary to infection or other complications of debilitated state

Delirium presentation

Etiology, Prevalence, Risk Factors "Waxing and waning," rapid onset "Sundowning" = worse at night Clinical Symptoms and Signs 1. Rapid deterioration in mental status (hours-days), a fluctuating level of awareness, disorientation, abnormal vitals 2. May be accompanied by acute abnormalities of perception, such as visual hallucinations 3, May not necessarily be agitated, but may have slow, blunted responsiveness 4 Tremor sometimes (asterixis) Diagnostics 1. Mental status examination (MMSE) 2. Labs (chemistry, B12/folate) 3. LP in febrile, delirious patient (cerebral edema) Therapy, Prognosis, and Health Maintenance Almost always reversible 1. Treat underlying cause 2. Haloperidol for agitation/psychosis 3. Supportive

FOCAL (PARTIAL) SEIZURE •Abnormal neuronal discharge from one discrete section (focus) of one brain hemisphere. •With retained awareness (simple): consciousness fully maintained. •With impaired awareness (complex): consciousness impaired. CLINICAL MANIFESTATIONS •Focal sensory, motor, or autonomic symptoms depending on the lobe affected. •Motor: jerky rhythmic movements. May start in one area (focal) and then spread to other parts of the affected limb or body (Jacksonian march). Tonic (muscular rigidity) or tonic (rhythmic jerking). May be followed by a neurologic deficit (Todd's paralysis) lasting up to 24 hours. •Sensory: paresthesias, numbness, pain, heat, cold, sensation of movement, olfactory, flashing lights. •Autonomic: abdominal (pain, nausea, vomiting, hunger), cardiovascular (sinus tachycardia), blood pressure changes, bronchoconstriction. Psychologic: fear, déjà vu, hallucinations. •Auras: may precede, accompany of follow the seizure onset. Additional findings with impaired awareness (complex): •Seizure: behavioral arrest & staring and last between 30 and 120 seconds (<3 minutes). The patients are generally unaware and unresponsive during this period. •Automatisms; repetitive behaviors (eg, lip smacking, facial grimacing, chewing, manual picking, patting, coordinated movements or repeating words or phrases). •Post ictal phase: symptoms after the seizure characterized by somnolence, confusion, and headache usually resolving within minutes but may last for up to several hours. DIAGNOSIS •Initial workup to rule out reversible causes (CBC, electrolytes, liver & renal function, & RPR). MRI. Electroencephalogram •Simple partial - focal discharge at the onset of the seizure. •Complex partial - interictal spikes or with slow waves in the temporal or frontotemporal area. ABSENCE (PETIT MAL) SEIZURE •Generalized seizure (involving both hemispheres). May occur tens of times daily. •Most commonly seen in childhood - age at onset usually 4 - 10 years (often ceases by early puberty or 20 years of age in most patients). CLINICAL MANIFESTATIONS •Pause/stare: sudden, marked impairment of consciousness & loss of awareness without loss of body tone (patient remains upright), blank staring episodes with pauses (behavioral arrest) with unresponsiveness. Episodes typically last between 5-10 seconds (rarely >30 seconds). If prolonged > 10 seconds, it can be associated with eyelid twitching & automatisms (lip smacking). •Prompt return to baseline after the spells - no postictal phase & no auras. •Triggers: may be provoked by hyperventilation or by emotions (eg, anger, fear). DIAGNOSIS •EEG main diagnostic tool for the evaluation of Absence - bilaterally synchronous & symmetrical 3 Hertz (3 cycles per second) spike and wave discharges (2.5 - 5 Hz) that start and end abruptly. MANAGEMENT •Ethosuximide first-line medical management. •Second-line: Valproic acid. Lamotrigine or Topiramate. •Medications to avoid: some sodium channel blockers (eg, Carbamazepine, Gabapentin, Phenytoin, Pregabalin) can exacerbate Absence seizures. GENERALIZED (GRAND MAL) SEIZURE •Simultaneous neuronal discharge of both hemispheres (diffuse brain involvement). •Generalized tonic conic (Grand mal) most common type. CLINICAL MANIFESTATIONS •Tonic-clonic (Grand Mal): sudden loss of consciousness with tonic activity (contraction & rigidity) that may be associated with respiratory arrest followed by 1-2 minutes of clonic activity (repetitive, rhythmic, symmetric jerking usually lasting <3 minutes) followed by postictal confusion phase. Cyanosis, tongue-biting, & urinary incontinence can occur. •Clonic; repetitive rhythmic jerking (usually lasting < 2-3 minutes) often associated with postictal state. •Myoclonic; sudden, brief, sporadic involuntary twitching of one muscle or a group of muscles, usually without loss of consciousness. •Tonic: loss of consciousness followed by rigidity. •Atonic; sudden partial or complete loss of muscle and postural tone ("drop attacks") may cause injury. DIAGNOSIS •Initial workup is to rule out reversible causes (CBC, electrolytes, liver and renal function, and RPR). •Increased prolactin & lactic acid immediately after seizures may be helpful to rule out pseudo seizures. MRI to rule out focal mass. •EEG: main diagnostic tool for the evaluation and characterization of seizures - generalized high-amplitude rapid spiking during active episodes of tonic-clonic seizures. MANAGEMENT •Treat the underlying cause if known. •Long-term options for epilepsy include Levetiracetam, Phenytoin, Valproic acid, Carbamazepine, Lamotrigine, Phenobarbital, Topiramate. Levetiracetam & Lamotrigine safest in pregnancy. •Ethosuximide first-line for Absence; Valproic acid second-line for Absence. Valproic for Myoclonic.

General vs focal symptoms intracranial tumors

General •Headache-worse in morning and improves throughout the day •Often holocephalic, but can be ipsilateral to side of the tumor Can present as 'migraine' with unilateral throbbing pain associated with visual scotoma • +/- Nausea or vomiting •Cognitive difficulties •Personality changes-apathy, withdrawal from social circumstances, mimicking depression •Gait disorder Focal •Subacute, progressive •Hemiparesis •Aphasia •Visual field defect-noticed by patient and revealed after it leads to injury (automobile accident in blind visual field) •Language difficulties-mistaken for confusion •Seizures (common)

Giant cell arteritis (ROSH)

Giant cell arteritis, also known as temporal arteritis, is a systemic, inflammatory syndrome that affects the medium and large vessels, particularly the temporal artery. It is most common in patients > 50 years of age. Presenting symptoms include a tender, inflamed, or pulsatile temporal artery; scalp tenderness; jaw claudication; throat pain; amaurosis fugax; diplopia; fatigue; fever; and symptoms of polymyalgia rheumatica. Polymyalgia rheumatica is a condition that frequently coexists with giant cell arteritis and is characterized by neck, shoulder, torso, or pelvic girdle pain and stiffness. Erythrocyte sedimentation rate and C-reactive protein are elevated in patients with giant cell arteritis. CBC will reveal a normochromic, normocytic anemia and thrombocytosis. A temporal artery biopsy is used for definitive diagnosis and should be performed promptly because untreated giant cell arteritis can result in blindness. Treatment is high-dose corticosteroid therapy (e.g., prednisone 40-60 mg/day) and should be administered immediately in all patients with suspected giant cell arteritis even before biopsy results are finalized. Patients with vision loss should receive IV methylprednisolone. Low-dose aspirin is also recommended to decrease the risk of cerebrovascular accidents and vision loss. Symptoms resolve within three days of starting corticosteroid therapy. High-dose corticosteroids will also treat coexisting polymyalgia rheumatica. Polymyalgia rheumatica in the absence of giant cell arteritis is treated with low-dose corticosteroids (e.g., prednisone 10-20 mg/day).

Bell Palsy RAPID REVIEW

History of viral prodrome Waking up with unilateral facial nerve paralysis, hyperacusis, and taste disturbance PE will show CN VII palsy that does NOT spare the forehead Most commonly caused by HSV Treatment is prednisone, artificial tears, tape eyelid shut, antivirals (for severe cases) Bilateral: Lyme disease, infectious mononucleosis

Parkinson's meds

LEVODOPA Mechanism of action: •Levodopa is converted to dopamine once it crosses the blood brain barrier. •Carbidopa reduces amount of Levodopa needed & also reduces the peripheral conversion of levodopa into dopamine, reducing the adverse effects of Levodopa. Indications: •Most effective treatment for the cardinal motor symptoms of PD. Adverse effects: •Gastrointestinal: anorexia, nausea, & vomiting (can be reduced by taking in divided doses). •Orthostatic (postural) hypotension common. CNS: somnolence, headache. •Psychosis & hallucinations upon initiation of therapy. •Behavioral: anxiety, agitation, confusion, depression. Psychosis & hallucinations upon initiation. •Dyskinesia (involuntary movements especially the lower extremities) & akinesia. •On-off phenomena: off periods of akinesia may alternate over a few hours with on periods of improved mobility. In some cases, off periods may respond to Apomorphine or Istradefylline. •Levodopa should be used at the minimum dose of clinical efficacy to reduce wearing off effect. If Levodopa is stopped abruptly, a syndrome similar to neuroleptic malignant syndrome can occur. DOPAMINE AGONISTS - BROMOCRIPTINE, PRAMIPEXOLE, ROPINIROLE, APOMORPHINE Mechanism of action: •Directly stimulates dopamine receptors, increasing dopamine levels (less motor adverse effects). •Less motor adverse effects than Levodopa but not as effective as Levodopa. Indications: •Can be used as first-line agents in younger patients (<65y) to delay the use of Levodopa. If patient is not sensitive to Levodopa, they will often be insensitive to dopamine agonists. Adverse effects: •Similar to Levodopa: hypotension, headache, dizziness, hallucinations, confusion, anorexia, N/V. •More frequent nonmotor side effects compared to Levodopa (g, sleep disturbances, somnolence, dizziness, impulse control such as compulsive shopping or gambling, hypersexuality from dopamine reward effect). Pramipexole is contraindicated in patients with active peptic ulcer disease. ANTICHOLINERGICS - TRIHEXYPHENIDYL, BENZTROPINE, BIPERIDEN, ORPHENADRINE Mechanism of action: •Anticholinergic (antimuscarinic) that blocks the excitatory effects of acetylcholine. Indications: •Most useful as monotherapy in younger patients (<70y) with tremor as the predominant symptom (without significant bradykinesia or gait disturbance). Does not improve bradykinesia. •Adjunctive treatment for severe tremor despite Levodopa or dopamine agonists. Adverse effects: •Anticholinergic - constipation, dry mouth, blurred vision, tachycardia, urinary retention. •May worsen glaucoma and benign prostatic hypertrophy. CNS toxicity. AMANTADINE Mechanism of action: •Increases presynaptic dopamine release & inhibits dopamine reuptake. Indications: •Low-potency antiparkinsonian therapy that can help early on with mild symptoms. •Improves long-term levodopa-induced dyskinesia. Adverse effects: •Livedo reticularis and ankle edema. •Rare - restlessness, agitation, confusion, psychosis, & hallucinations (more likely in older patients). SELECTIVE MAO-B INHIBITORS - SELEGILINE, RASAGILINE, SAFINAMIDE Mechanism of action: •Increases dopamine in the striatum (MAO-B normally breaks down dopamine). Indications: •Can be used as early therapy in patients with very mild sign and symptoms. •May have neuroprotective properties in PD. Adverse effects: •Nausea, headache, confusion, hallucinations. COMT INHIBITORS - ENTACAPONE, TOLCAPONE •Mechanism of action: Catechol-O-methyltransferase inhibition prevents dopamine breakdown. Indications: •Adjunctive treatment with Levodopa (prolongs the therapeutic dose of Levodopa) in patients experiencing wearing "off" periods. •Not used as monotherapy. Adverse effects: •Nausea, orthostatic hypotension, hallucination, orthostatic hypotension, Gl symptoms, brown discoloration of the urine. •Tolcapone associated with hepatotoxicity.

Lewy bodies in the substantia nigra and a decrease in dopaminergic neurons in the substantia nigra are postmortem findings in patients with Parkinson disease.

Lewy bodies in the substantia nigra and a decrease in dopaminergic neurons in the substantia nigra are postmortem findings in patients with Parkinson disease. Parkinson disease is the second most common neurodegenerative disorder after Alzheimer disease and is characterized by resting tremor, cogwheel rigidity, bradykinesia, shuffling gait, masked facies, micrographia, and postural instability. Cognitive impairment, depression, difficulty speaking or swallowing, balance problems, and sleep disturbances may also be present. Parkinson disease is more common in men and is mostly seen in adults > 50 years old. Exposure to pesticides and herbicides has been associated with an increased risk of developing Parkinson disease. A diagnosis is made based on clinical findings. Definitive diagnosis is made on autopsy by the identification of Lewy bodies in the substantia nigra and loss of dopaminergic neurons in the nigrostriatal system. The decrease in dopamine levels results in an imbalance of dopamine and acetylcholine. Higher levels of acetylcholine are associated with the uncontrolled, involuntary movements seen with Parkinson disease, whereas deficits in dopamine result in bradykinesia, difficulty initiating movement, and other signs of parkinsonism. There is no cure for Parkinson disease. Management is targeted at blocking acetylcholine with anticholinergic drugs or increasing dopamine levels to improve motor symptoms. These medications include amantadine, levodopa (the precursor of dopamine), dopamine agonists (e.g., pramipexole, ropinirole), catecholamine-O-methyltransferase inhibitors (e.g., entacapone, tolcapone), monoamine oxidase inhibitors (e.g., rasagiline), anticholinergics, and antipsychotics. Physical therapy, speech therapy, or electrical brain stimulation may benefit certain patients but has no effect on the disease course.

MRI is more sensitive than CT scan in detecting acute ischemic stroke. Cerebrovascular accidents, or strokes, are the result of a neurovascular injury from brain ischemia or hemorrhage.

MRI is more sensitive than CT scan in detecting acute ischemic stroke. Cerebrovascular accidents, or strokes, are the result of a neurovascular injury from brain ischemia or hemorrhage. Ischemic strokes are the most common cause, occurring secondary to thrombus, embolus, or systemic hypoperfusion (such as in the setting of massive blood loss or obstructive shock). Hemorrhagic strokes can occur due to either intracerebral hemorrhage or subarachnoid hemorrhage. Underlying conditions that increase the risk of stroke include hypertension, hyperlipidemia, diabetes mellitus, atrial fibrillation, atherosclerosis, valvular disease, hypercoagulable disorders, and vasculitis. Cigarette smoking and cocaine use are also risk factors for stroke. The clinical presentation is dependent on the area of the brain involved. Commonly, facial droop, slurred speech, and contralateral limb weakness are reported. Patients may additionally present with dizziness, vision loss (homonymous hemianopia), and difficulty walking. MRI of the brain is more sensitive in detecting an acute infarction. However, it is not often the initial test performed in the emergency setting, as it is time consuming, expensive, and less readily available than CT scan. A noncontrast CT scan of the head is performed initially in the emergency setting in all patients presenting with symptoms concerning for stroke, as it can effectively rule out hemorrhagic causes of stroke. Angiography can be helpful in establishing evidence of significant stenosis or vascular occlusion. Intervention is determined by whether the stroke is hemorrhagic or ischemic. For a patient presenting within 3-4.5 hours of symptom onset, intravenous thrombolytic therapy with alteplase (recombinant tissue-type plasminogen activator) should be administered as long as no thrombolytic exclusion criteria are present. For patients with large artery occlusions within proximal anterior circulation, intra-arterial mechanical thrombectomy is an appropriate intervention. Further diagnostic evaluation to rule out an embolic etiology should be considered in patients with large infarcts, hemorrhagic conversion, multiple areas of infarcts, or infarcts involving different vascular territories. Additionally, a cardiac workup should be performed in patients younger than 45 years with a suspected embolic stroke. This workup should include cardiac monitoring and a transesophageal echocardiogram to rule out atrial fibrillation, valvular disease, and patent foramen ovale. A workup for hypercoagulable disorders should be considered in patients with a personal or family history of systemic thrombosis, young patients without clear etiology for stroke, or patients with clinical findings suggestive of lupus or antiphospholipid antibody syndrome. For patients presenting with an acute stroke, high-dose statin therapy and antiplatelet therapy, such as aspirin, should be started within 48 hours, as soon as oral medications can be safely started.

Cluster Headache RAPID REVIEW

More common in men (male to female ratio is 4.3:1) Sudden onset, unilateral, and repetitive brief HAs PE will show ipsilateral conjunctival injection, lacrimation, and rhinorrhea Acute treatment: high-flow O2 and subcutaneous sumatriptan Prophylaxis: verapamil

Multiple sclerosis (ROSH)

Multiple sclerosis is a disorder of the central nervous system that results from demyelination of the white matter in the brain and spinal cord, degeneration of axons and neurons, and astrocytic sclerosis. The most common age group affected is between 20-50 years old, and women are affected more than men. An increase in distance from the equator is associated with an increased risk of multiple sclerosis. There is a genetic association between HLA-DR2 and multiple sclerosis. Additionally, patients with a first-degree relative with multiple sclerosis have a seven-fold increase in risk. The most common signs and symptoms associated with multiple sclerosis include optic neuritis, monocular vision loss, bilateral internuclear ophthalmoplegia, fatigue, ataxia, tremor, and spasticity. The most common subtype of multiple sclerosis is relapsing-remitting. Other subtypes include primary progressive, secondary progressive, and progressive-relapsing. The Uhthoff phenomenon is a worsening of symptoms with high temperatures and is associated with multiple sclerosis. Symptoms typically associated with high temperatures include fatigue, concentration problems, urinary urgency, and Lhermitte sign (an electrical sensation from the neck that radiates down the spine and into the extremities that occurs with neck flexion). The McDonald criteria (based on MRI evidence of lesion dissemination in space and time) are useful in guiding the diagnostic process and reduce unnecessary imaging. Magnetic resonance imaging (MRI) is the single most useful test for diagnosing multiple sclerosis. White matter plaques are most commonly seen in the ventricles as perpendicular projections (Dawson fingers) or ovoid lesions. Lesions in the dorsal column of the cervical spine are also commonly seen. Protein analysis of CSF fluid demonstrating oligoclonal bands is the most sensitive laboratory test and may be used to support the diagnosis. Elevated immunoglobulin G index and increased myelin basic protein are also indicative of multiple sclerosis. Visual-evoked potentials, auditory-evoked potentials, and somatosensory-evoked potentials may be used to assess nerve transmission. Acute exacerbations of multiple sclerosis may be treated with high-dose intravenous corticosteroids (e.g., methylprednisolone), and plasma exchange may be used if the patient fails corticosteroid therapy. Symptomatic management includes gamma-aminobutyric acid agonists (e.g., baclofen) or benzodiazepines (e.g., diazepam) for spasticity and anticholinergics (e.g., oxybutynin) for urologic dysfunction. Disease-modifying agents such as beta-interferons and glatiramer acetate injections are used for long-term therapy.

Myasthenia gravis (ROSH)

Myasthenia gravis is a chronic autoimmune neuromuscular disorder caused by antibodies against acetylcholine receptors and muscle-specific tyrosine kinase. It is characterized by proximal muscle weakness (e.g., shoulders, thighs) and fatigability that improves with rest. Common initial symptoms include ptosis, diplopia, blurred vision, difficulty in chewing or swallowing, and respiratory muscle weakness. Sensation and reflexes are normal. A relapsing-remitting pattern is common. Young women who are HLA-DR3 positive and older men with a thymoma (as seen on the CT scan above) are at an increased risk of myasthenia gravis. A CT scan or MRI is useful for the detection of a thymoma. The presence of acetylcholine receptor antibodies is present in 80-90% of patients with myasthenia gravis. In the absence of acetylcholine receptor antibodies, clinicians should test for muscle-specific tyrosine kinase antibodies. A diagnosis of myasthenia gravis was historically made with a positive edrophonium (Tensilon) challenge. Edrophonium is a short-acting anticholinesterase that will transiently improve muscle weakness symptoms in patients with myasthenia gravis it is however no longer used in the United States. Electrophysiologic studies (e.g., repetitive nerve stimulation, single-fiber electromyography) may also be used to establish a diagnosis. Cholinesterase inhibitors (e.g., neostigmine, pyridostigmine) are the mainstay of treatment. In patients with a thymoma who are < 65 years old, thymectomy is indicated unless muscle weakness is limited to the extraocular muscles. Corticosteroids, immunosuppressive agents, intravenous immunoglobulins, and plasmapheresis may be used in refractory disease or in patients with major disability. Life-threatening complications of myasthenia gravis are most often associated with respiratory difficulties and include aspiration pneumonia and myasthenic crisis. Myasthenic crisis is the most serious complication of myasthenia gravis and is characterized by extreme weakness of the respiratory muscles. Myasthenic crisis may be caused by pharmacologic noncompliance, respiratory infection, surgeries, or stress. Intravenous immunoglobulins and plasmapheresis are used to treat myasthenic crisis due to rapid treatment response.

Subarachnoid Hemorrhage RAPID REVIEW

Patient presents with abrupt onset of "worst headache of life" or thunderclap headache Diagnosis is made by noncontrast CT scan, blood will appear white on the CT -->If CT negative and performed within 6 hours of symptom onset, subarachnoid hemorrhage effectively ruled out -->If CT negative and suspicion high, lumbar puncture or CT angiography Most commonly caused by a ruptured aneurysm Hunt & Hess classifies severity of subarachnoid hemorrhage to predict mortality Treatment is supportive and nimodipine (decreases vasospasm)

Parkinson Disease RAPID REVIEW

Patient presents with rigidity, bradykinesia, postural instability, micrographia PE will show a resting pill-rolling tremor, mask-like facies, cog-wheeling of extremities, shuffling gait Most commonly caused by dopamine depletion in basal ganglia Treatment is levodopa-carbidopa

Primary headaches are divided into three categories: tension, migraine, and cluster. Cluster headaches are severe, unilateral, periorbital headaches

Primary headaches are divided into three categories: tension, migraine, and cluster. Cluster headaches are severe, unilateral, periorbital headaches that last between 15-180 minutes. They may occur multiple times per day for several weeks or months. Middle-aged men are most commonly affected. A family history of headaches or migraines is often absent. During a cluster headache attack, patients may be restless or aggressive. Ipsilateral lacrimation, conjunctival injection, rhinorrhea, miosis, ptosis, or eyelid edema may be present. The diagnosis for primary headaches is clinical. It is important to rule out other etiologies that may manifest as a secondary headache (e.g., subarachnoid hemorrhage, meningitis, giant cell arteritis, tumor). Red flags that warrant further investigation (e.g., brain MRI, CT scan, temporal biopsy) include age < 5 years or > 50 years, increasing frequency or intensity of headache, jaw claudication, motor or cognitive changes, the "worst headache ever," and a combination of stiff neck, fever, and malaise. The abortive treatment of choice for a cluster headache is 100% oxygen via nasal cannula. If 100% oxygen is not readily available, triptan medications (e.g., sumatriptan) or dihydroergotamine mesylate may be administered subcutaneously or intramuscularly as abortive treatment. For prophylactic treatment of cluster headaches, a short-term corticosteroid along with a calcium channel blocker (e.g., verapamil) may be given. The corticosteroid is then tapered as the calcium channel blocker takes full effect.

Guillain-Barré Syndrome RAPID REVIEW

Risk Factors: recent minor respiratory or GI illness Sx: Symmetric, progressive ascending muscle weakness, can lead to respiratory failure PE: lack of deep tendon reflexes, symmetric weakness Lumbar puncture: increased CSF protein but a normal cell count Most commonly caused by Campylobacter jejuni Treatment is supportive, plasmapheresis, or IVIG

Temporal Arteritis (Giant Cell Arteritis) RAPID REVIEW

Risk factors: age > 50, female sex Sx: new headache, jaw claudication, monocular visual loss PE: tender temporal artery Labs: ESR > 50 mm/hour, ↑CRP Dx: temporal artery biopsy Treatment is high-dose steroids, do not wait for bx if strong suspicion Associated with polymyalgia rheumatica

Symptomatic treatment of intracranial tumors

Symptomatic treatment Edema (neurologic disability, high intracranial pressure) -steroids (dexamethasone 12 to 16 mg/d in divided doses PO or IV) with taper Seizures- antiepileptic drug therapy (levetiracetam, topiramate, lamotrigine, valproic acid, lacosamide) VTE-prophylactic anticoagulants during hospitalization and nonambulatory patients Definitive treatment--based on tumor type Surgery, radiotherapy, chemotherapy

Transient ischemic attack (ROSH)

Transient ischemic attack (TIA) is a temporary period of focal brain, spinal cord, or retinal ischemia resulting in neurologic dysfunction in the absence of acute infarction. There are several different conditions that can cause a TIA. Cardioembolic sources include atrial fibrillation, subtherapeutic anticoagulation, and intracardiac thrombi. Extracranial internal carotid artery stenosis, intracranial large artery atherosclerosis, sickle cell disease, antiphospholipid syndrome, and nonbacterial thrombotic endocarditis can also cause a TIA. Recognition of TIA symptoms and prompt referral to a stroke center are important because initial TIA symptoms and ischemic stroke symptoms are indistinguishable. TIA symptoms typically resolve within an hour but can last up to 24 hours. While previous guidelines classified TIAs based on symptom resolvement in 24 hours, current guidelines classify a TIA as an ischemic attack in which permanent tissue injury has not occurred. Patients are at high risk for ischemic stroke if they have had a TIA in the past three months. Standard stroke protocol includes a noncontrast CT of the head (to differentiate between ischemic stroke, hemorrhagic stroke, and intracranial mass), complete blood count, complete metabolic panel, urinalysis, coagulation profile (PT, PTT), ECG monitoring, and serial cardiac enzymes. In the vignette above, the patient's symptoms resolved in less than one hour on her way to the ED, her noncontrast CT showed no evidence of cerebral infarction, and her metabolic, cardiac, and neurologic tests were normal other than a left-sided carotid bruit. The American Stroke Association recommends the use of the ABCD2 score to predict future stroke risk and determine the need for hospitalization. The score is composed of the following components: age ≥ 60 years (1 point); systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg (1 point); clinical features, including unilateral weakness with or without speech impairment (2 points) or speech impairment without unilateral weakness (1 point); duration of TIA ≥ 60 minutes (2 points), 10-59 minutes (1 point), or less than 10 minutes (0 points); and diabetes mellitus (1 point). Patients presenting within 72 hours of TIA should be admitted if their ABCD2 score is greater than or equal to 4, if their ABCD2 score is less than 4 and there is uncertainty that outpatient evaluation can be completed within 48-72 hours, or if their ABCD2 score is less than 3 and there is evidence of cerebral infarction. The patient in the vignette above has an ABCD2 score of 6 (1 point for age, 1 point for BP, 2 points for unilateral weakness, 1 point for symptoms lasting 10-59 minute, and 1 point for diabetes mellitus) and should be admitted and further assessed with a diffusion-weighted MRI. A diffusion-weighted MRI is better than standard CT and MRI tests for evaluating ischemic damage and subsequent stroke risk after a TIA. An abnormal diffusion-weighted MRI is associated with a higher risk of ischemic stroke. Other cerebrovascular imaging tests include brain MRI, CT angiography, magnetic resonance angiography, carotid ultrasound, and cerebral angiography. A carotid bruit warrants a carotid ultrasound. Urgent carotid endarterectomy is indicated for symptomatic stenosis > 70%. In the absence of identified vascular etiologies, echocardiography should be ordered to investigate cardioembolic causes (e.g., atrial fibrillation, patent foramen ovale). Hypertension, hyperlipidemia, and glycemic management are important in the management of TIA patients to reduce stroke risk. Antiplatelet therapy should be initiated (e.g., aspirin and dipyridamole). Patients with atrial fibrillation should be on long-term oral anticoagulation (e.g., warfarin, apixaban, dabigatran, rivaroxaban).

Tension-type headache is the most common headache

Tension-type headache is the most common headache. Patients typically present with complaints of a mild to moderate, nonthrobbing headache that is bilateral, with pain in the frontal and occipital regions. The pathophysiology is poorly understood, but it is hypothesized that, for patients with episodic headache, there is peripheral activation or sensitization of myofascial nociceptors, and for patients with chronic tension-type headache, there is sensitization of pain pathways in the nervous system due to the prolonged stimuli from the pericranial myofascial tissues. Physical exam findings are typically vague and include tenderness of pericranial myofascial tissues and increased myofascial trigger points. Patients do not present with nausea or vomiting but may have photophobia or phonophobia. Patients may also report increased stress or mental tension as well as migraine precipitating or aggravating tension-type headaches in patients who have both. Other precipitating factors include fatigue, loud noise, glare, and stress. Diagnostic criteria for chronic tension-type headache include at least 15 episodes of headache per month lasting 30 minutes to 7 days over 3 months, no nausea or vomiting, either photophobia or phonophobia but not both, and at least two of the following symptoms: bilateral location, pressing or tightening quality, mild to moderate intensity, and not aggravated by routine physical activity. Diagnosis is made clinically. Further evaluation with neuroimaging is only warranted in patients with an abnormal neurological exam or atypical headache features. Initial recommended acute treatment is with nonsteroidal anti-inflammatory drugs and aspirin. Acetaminophen is also an option. Triptans are typically not an effective treatment. Prophylactic treatment is recommended for patients with frequent, long-lasting, or disabling headaches. It is recommended for patients with chronic tension-type headache and should be considered in any other patients with frequent, long-lasting, or disabling headaches and when acute treatment fails. Amitriptyline is the recommended first-line treatment to prevent tension-type headache. It is important for patients to identify and avoid headache triggers. Cognitive behavioral therapy, stress management, focused relaxation techniques, and behavioral treatments such as regulation of sleep, exercise, and meals are beneficial for many patients.

The patient experienced a seizure. The two primary seizure types are focal (partial) onset seizures and generalized onset seizures. Focal onset seizures

The patient experienced a seizure. The two primary seizure types are focal (partial) onset seizures and generalized onset seizures. Focal onset seizures affect a portion of one cerebral hemisphere and can be further characterized by whether or not consciousness is affected. Simple partial seizures are focal seizures in which there is no impairment of consciousness. Complex partial seizures are a type of focal seizure in which consciousness is impaired. They are associated with a postictal state, in which confusion or memory loss is present after the seizure subsides. Generalized seizures are characterized by widespread seizure activity in both cerebral hemispheres and typically originate in the midbrain or brainstem before spreading to the cortices. There are several different types of generalized seizures. Absence seizures, also known as petit mal seizures, are usually seen in 5- to 10-year-old children and are characterized by a brief impairment of consciousness, typically without involuntary movements. These episodes may happen multiple times throughout the day. Patients appear to be staring into space while having an absence seizure, but these episodes are often missed. There is no postictal state of confusion, and the patient does not realize they have had an absence seizure. Tonic-clonic seizures, also known as grand mal seizures, present with rigidity and an abrupt loss of consciousness (tonic phase) followed by a period of generalized convulsions (clonic phase). The clonic phase is then followed by a postictal phase. Clonic seizures do not have a tonic phase and are characterized by regular convulsions every 2-3 seconds, followed by a postictal phase. Rigidity and loss of consciousness without convulsions are indicative of tonic seizures, while syncope and loss of muscle tone are indicative of atonic seizures. There is no rigidity associated with atonic seizures. Myoclonic seizures are characterized by brief muscular contractions lasting < 1 second and tend to occur in the morning. These contractions may occur only once or several times in a row and, unlike clonic seizures, do not occur with any regular pattern. Adults > 20 years of age who present with a new-onset seizure should undergo magnetic resonance imaging of the head. Laboratory studies should include electrolytes, glucose, and a pregnancy test, and an electrocardiogram (ECG) and electroencephalogram (EEG) should also be ordered. An EEG with brief 3 Hz spike-and-wave discharges is characteristic of an absence seizure, while focal or lateralized sharp spikes and slow waves are characteristic of a complex partial seizure. Focal seizures may be treated with phenytoin, valproic acid, phenobarbital, or lamotrigine. Absence seizures are treated with ethosuximide or valproic acid. Tonic-clonic seizures can be treated with carbamazepine, phenobarbital, levetiracetam, or phenytoin. Status epilepticus is a medical emergency. The airway should be protected, and intravenous dextrose administered if hypoglycemia is present. Intravenous lorazepam, intravenous diazepam, or intramuscular midazolam should be given first line, followed by intravenous phenytoin or fosphenytoin.

The patient has signs of delirium from taking hydrocodone. The fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders

The patient has signs of delirium from taking hydrocodone. The fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-5) associates the following five features with delirium: a disturbance in attention and awareness, a change in baseline over hours or days that fluctuates during the course of the day, an additional disturbance in cognition (e.g., memory deficit, disorientation, language, visuospatial ability, perception), a disturbance that is not better explained by a preexisting neurocognitive disorder, and evidence the disturbance is caused by a medical condition, substance overdose or withdrawal, or medication side effect. Common medical conditions that can cause delirium include infection, dehydration, kidney or liver failure, head trauma, and brain tumors. Medications associated with a risk of delirium include sedatives, anticholinergics, opioids, benzodiazepines, and antihistamines. The hallmark feature that distinguishes delirium from dementia is inattention. Patients with delirium are unable to focus on a single topic or task. Unlike delirium, dementia has an insidious course and is not reversible. Most cases of delirium are reversible if the underlying cause is treated. Diagnosis of delirium begins with obtaining a history from relatives or caretakers to determine the patient's baseline. The confusion assessment method is a quick screening test for delirium and evaluates for the presence of an acute onset and fluctuating course, inattention, disorganized thinking, or altered level of consciousness. After delirium is suspected, physical examination, review of past medical history and medication list, and laboratory testing are performed to identify potential underlying causes.

Bell palsy (ROSH)

The patient in the vignette above has Bell palsy. Bell palsy is an idiopathic facial paralysis, most commonly caused by herpes simplex virus activation in the geniculate ganglion. Herpes simplex virus is responsible for the patient's recurrent fever blisters. Bell palsy is more common in pregnant women and patients with diabetes mellitus. It is typically unilateral and most commonly occurs in patients between 15-60 years of age. Inflammation or swelling of the facial nerve (cranial nerve VII) typically results in ipsilateral symptoms, including facial muscle weakness and drooping (e.g., inability to close the eye, raise the eyebrow, or smile), impairment of taste (due to the involvement of chorda tympani fibers), increased lacrimation, ear pain, and hyperacusis. These symptoms may begin abruptly or progress over a period of days. Most patients will experience an improvement in symptoms within a few weeks and will achieve complete recovery within six months. Patients with severe pain, complete palsy, hyperacusis, or advanced age have a poorer prognosis. Bell palsy is a clinical diagnosis. Diagnostic testing is only indicated in cases of atypical presentation or to rule out other conditions such as stroke, tumor, AIDS, Guillain-Barré syndrome, Lyme disease, multiple sclerosis, sarcoidosis, or meningitis. An important differentiating factor between Bell palsy and a stroke is that stroke patients will be able to raise their eyebrows and wrinkle their forehead. Remember, "if a patient can raise their eyebrows, so should you." The treatment of Bell palsy includes protecting the affected eye with lubricating eye drops or patching and corticosteroids (e.g., prednisone 25 mg PO bid for 10 days). Corticosteroids increase the chance of complete recovery at 9-12 months and are especially important in patients who have signs or symptoms associated with a poor prognosis. Physical therapy may improve facial function. Physical examination of the external ear canal and the face for the presence of herpetic vesicles or blisters is important to rule out Ramsay Hunt syndrome. Ramsay Hunt syndrome is caused by the herpes zoster virus and should be treated with antiviral medication in addition to corticosteroids. The patient in the vignette above has a normal external ear canal.

The patient in the vignette above has a presentation concerning for a spontaneous subarachnoid hemorrhage. Patients with subarachnoid hemorrhage may report a sudden "thunderclap" headache

The patient in the vignette above has a presentation concerning for a spontaneous subarachnoid hemorrhage. Patients with subarachnoid hemorrhage may report a sudden "thunderclap" headache that is described as "the worst headache of their life." Nausea, vomiting, and loss of consciousness may occur after the initial headache. The patient may regain consciousness or may progress to a coma. Patients who regain consciousness may present with altered mental status or signs of meningeal irritation (e.g., nuchal rigidity). The most common cause of nontraumatic subarachnoid hemorrhage is a ruptured saccular aneurysm. Arteriovenous malformations are a less common cause of nontraumatic subarachnoid hemorrhage. Nonmodifiable risk factors of subarachnoid hemorrhage include older age, female sex, non-Caucasian ethnicity, posterior circulation aneurysms, and larger aneurysms. Modifiable risk factors include hypertension, tobacco use, and excessive alcohol use. Cerebral aneurysms are typically asymptomatic until they rupture, however, larger aneurysms that compress adjacent structures may cause focal neurologic deficits. A noncontrast head CT scan is the initial diagnostic test for suspected subarachnoid hemorrhage and is much faster and more sensitive than MRI in the first 24 hours. In patients with a normal CT scan (as seen above), a lumbar puncture for cerebrospinal fluid (CSF) evaluation should be performed. Four CSF tubes are obtained, and an elevated red blood cell count that does not clear from the first to the fourth tube is indicative of a subarachnoid hemorrhage. Clearing of the red blood cell count from the first to the fourth tube indicates a traumatic tap. The presence of xanthochromia indicates red blood cell hemolysis that is at least two hours old and is consistent with subarachnoid hemorrhage. The primary goal of treatment is to prevent further hemorrhage. Patients should be hospitalized and seen by a neurologist. Acute hydrocephalus should be treated with placement of an intraventricular CSF shunt. Renal salt wasting may be detected by daily serum sodium levels and is treated with oral sodium chloride or intravenous hyperosmotic sodium solution. Nimodipine is indicated within the first four days of symptom onset to reduce the incidence of ischemic deficits from arterial vasospasm and should be continued for 21 days. Digital subtraction angiography of bilateral carotid and vertebral arteries allows for definitive evaluation of the vasculature and is useful for detecting the presence, size, and location of other cerebral aneurysms. Definitive treatment includes surgical clipping or endovascular coil embolization of the aneurysm.

essential tremor (ROSH)

The patient in the vignette above has an essential tremor, which is also known as benign essential tremor or essential familial tremor. The cause of essential tremor is unknown, however, some studies show it as an autosomal dominant inherited disorder. There are two peaks of onset for essential tremor: during teenage years or in the sixth decade of life. Essential tremors are slow progressing and typically affect the upper extremities and head. An action tremor typically worsens in times of stress or high emotions and is present against gravity. This tremor improves with alcohol consumption. On a finger-to-nose test, the patient's tremor increases as the target approaches. Otherwise, the patient's neurological exam will have no other significant findings. Prior to starting treatment, it is important to rule out any other causes of a tremor such as Parkinson disorder, thyroid disease, or electrolyte disturbances. Labs to be ordered include a TSH, TT4, and BMP. Before starting treatment, the patient should try to eliminate all unnecessary medications or stimulants and also try to make behavior changes prior to starting medication therapy. If no improvement, then medications can be used. The first-line medical treatment for an essential tremor is propranolol or primidone. If either propranolol or primidone alone fails, a trial of both medications combined may be effective. The third-line treatment involves using either gabapentin, topiramate, or alprazolam. Essential Tremor History of a family member with similar symptoms Hand tremor that is exacerbated by action and improved after alcohol consumption Most commonly caused by autosomal dominant gene Treatment is propanolol

complex regional pain syndrome (ROSH)

The patient in the vignette above has complex regional pain syndrome. Complex regional pain syndrome is a diagnosis of exclusion characterized by localized pain of more than six months' duration. The pain is typically unilateral, severe, and out of proportion to any physical examination or diagnostic findings. A previous history of a fracture, sprain or strain, soft tissue injury, or surgery is common. Patients may present with sensations of burning, tingling, or myalgias. Complex regional pain syndrome is more common in women and has a peak incidence at 40 years old. The Budapest criteria are used to diagnose complex regional pain syndrome after other causes (e.g., fracture, compartment syndrome, infection, cancer) have been ruled out. The Budapest criteria require the presence of at least one symptom in three of the following categories and one sign in two of the following categories: sensory, vasomotor, edema or sudomotor, and motor or trophic. Sensory signs and symptoms include hyperesthesia or allodynia. Vasomotor signs and symptoms include changes in skin color, temperature, or symmetry. Edema or sudomotor signs and symptoms include changes in edema or sweating. Motor or trophic signs and symptoms include decreased motor function, decreased range of motion, or trophic changes. The treatment of complex regional pain syndrome includes a combination of psychological therapy, physical therapy, and pharmacologic treatments (e.g., nonsteroidal anti-inflammatory drugs, gabapentin, corticosteroids, antidepressants, bisphosphonates, topical lidocaine, capsaicin cream). Referral to a pain clinic may be necessary for patients who do not respond to initial treatments.

The patient in the vignette above presents with sudden-onset, rapidly progressing, bilateral ascending weakness that is characteristic of Guillain-Barré syndrome.

The patient in the vignette above presents with sudden-onset, rapidly progressing, bilateral ascending weakness that is characteristic of Guillain-Barré syndrome. Decreased or absent deep tendon reflexes is a characteristic finding on physical examination. Patients may experience muscle aches or cramping, cardiac dysrhythmias, BP instability, facial diparesis, or respiratory failure. Symptoms typically peak one month after onset. Campylobacter jejuni is a causative agent of gastroenteritis and is treated with erythromycin or azithromycin. C. jejuni causes 30-35% of Guillain-Barré cases. C. jejuni lipooligosaccharides are similar to human gangliosides, and infection with C. jejuni may result in antiganglioside antibodies that attack and destroy the myelin sheath and neurons due to molecular mimicry. Less common causes of Guillain-Barré syndrome include other gastrointestinal and respiratory infections such as Epstein-Barr virus, cytomegalovirus, Mycoplasma pneumoniae, and influenza virus. Guillain-Barré is slightly more common in men and is mostly seen in patients > 40 years of age. The three subtypes of Guillain-Barré are acute inflammatory demyelinating polyneuropathy (most common), axonal neuropathy (acute motor and acute motor sensory), and Miller Fisher syndrome. Guillain-Barré syndrome is a clinical diagnosis based on progressive, bilateral weakness of the extremities and areflexia. Autonomic symptoms, including diarrhea, constipation, hyponatremia, bradycardia, tachycardia, and urinary retention, may be present. In severe cases, respiratory muscles are affected, and breathing becomes difficult or impossible without respiratory support. Albuminocytologic dissociation (elevated protein levels with normal WBC count in the cerebral spinal fluid) is a classic finding in Guillain-Barré syndrome but may be absent in the first few days of symptom onset. MRI of the lumbosacral spine will show gadolinium enhancement of the nerve roots and is useful in ruling out other diagnoses. Hospitalization is required for treatment. Intravenous immunoglobulin and plasmapheresis are the most effective treatments. Supportive care is needed in the presence of respiratory, cardiac, or electrolyte abnormalities and includes intubation, mechanical ventilation, or electrolyte correction. Corticosteroids are not indicated and may delay recovery. Most patients fully recover within 12 months. About 3-5% of patients will die from Guillain-Barré complications (e.g., autonomic dysfunction, respiratory distress, pulmonary embolism, infection) even with treatment.

bacterial meningitis (ROSH)

This patient has bacterial meningitis. The most common pathogens of bacterial meningitis depend on the age of the patient. Group B Streptococcus and Listeria monocytogenes are the most common pathogens in infants less than 1 month old. Neisseria meningitidis and Streptococcus pneumoniae are the most common pathogens from 1 month to 50 years of age. Streptococcus pneumoniae and Listeria monocytogenes are the most common pathogens in patients greater than 50 years old. Patients will present with the classic triad of fever, headache, and altered mental status. They may also report nausea, vomiting, and symptoms of meningeal irritation. The physical exam will reveal fever, altered mental status, Kernig sign (the inability to straighten the knee with hip flexion), and Brudzinski sign (flexion of the neck produces hip and knee flexion). A lumbar puncture is the gold standard for definitive diagnosis. Evaluation of cerebrospinal fluid will reveal elevated polymorphic neutrophils, decreased glucose, increased protein, and elevated cerebrospinal fluid opening pressure. If the patient has focal neurologic findings, papilledema, or a history of other central nervous system diseases, then a CT scan should be considered prior to lumbar puncture to assess for midline shift, which increases the risk of herniation when lumbar puncture is performed. Antibiotics are the mainstay of treatment for bacterial meningitis and should not be delayed if there is a high clinical suspicion of meningitis. The specific antibiotic depends on the suspected pathogen. Patients less than 1 month old are treated with ampicillin and cefotaxime, those 1 month to 50 years old are treated with ceftriaxone and vancomycin, and patients greater than 50 years old are treated with ampicillin and ceftriaxone. Dexamethasone is an adjunctive therapy with limited benefit. It is not routine to administer dexamethasone for streptococcal or meningococcal meningitis. When administering dexamethasone, it must be given prior to the initiation of antibiotics. Dexamethasone should not be administered to patients less than six weeks old or patients with aseptic meningitis. Bacterial meningitis can be fatal if untreated. Patients with altered levels of consciousness are known to have worse outcomes. Streptococcus pneumoniae meningitis can be prevented with the pneumococcal vaccine.

Topiramate is an appropriate first-line therapy for patients with episodic migraine who would benefit from prophylaxis.

Topiramate is an appropriate first-line therapy for patients with episodic migraine who would benefit from prophylaxis. Migraine headache occurs due to primary neuronal dysfunction, which results in cortical spreading depression, activation of the trigeminovascular system, and increased neuronal sensitivity. Individuals with migraine headaches often have a positive family history of the disorder, particularly in those with familial hemiplegic migraine. Women are more affected than men. Patients with migraine have a history of recurrent migraine attacks. Migraines have four distinct phases: prodrome, aura, headache, and postdrome. The prodrome occurs 24-48 hours prior to the onset of headache and can include an increase in yawning, food cravings, neck stiffness, or changes in mood (euphoria, depression, and irritability). Approximately one-fourth of patients with migraine will experience the aura phase (classic migraine), and those who do not experience the aura are diagnosed with common migraine. Migraine aura is characterized by one or more focal neurological symptoms of gradual development occurring for no more than 1 hour and with complete reversibility. Common aura symptoms are visual (bright lines, scintillating scotoma), auditory (tinnitus, hearing loss), language (aphasia, paraphasia, dysarthria), somatosensory (burning, paresthesia, numbness), or motor (jerking, repetitive movements, paralysis). The headache in a migraine is often unilateral and is described as throbbing or pulsatile. Severity increases over hours. Phonophobia, photophobia, and osmophobia are common. Additionally, nausea is frequent and may be accompanied by vomiting. The duration of a migraine can be from 4 hours to several days. Often, migraines can resolve with sleep or be improved by lying down in a dark and quiet room. In the postdrome phase, sudden head movement may result in pain, and the patient may feel fatigued. Triggers for migraine include stress, menstruation, barometric pressure changes, dehydration, fasting, and wine. Neuroimaging is not indicated in a patient presenting with typical migraine features and a normal neurological examination. Acute migraine treatment is dependent on the severity of attacks and accompanying features (nausea, vomiting). Simple analgesics, such as naproxen or acetaminophen, are often first-line agents. Patients should be cautioned on the risk of medication-overuse headache. For moderate to severe attacks, a combination of antiemetics and oral, subcutaneous, or nasal triptans may be used. Migraine prophylaxis should be considered in patients with more than four headaches per month or more than seven days per month with a headache. Appropriate first-line options include beta-blockers, such as metoprolol or propranolol, and anticonvulsants, such as topiramate or valproate. Other therapies often employed are antidepressants, including tricyclic antidepressants (amitriptyline), and selective serotonin and norepinephrine reuptake inhibitors (venlafaxine). Calcitonin gene-related peptide antagonists, such as erenumab, are options for individuals with frequent migraines who have not benefited from alternative therapies. Small-molecule calcitonin gene-related peptide antagonists (CGRP) are emerging as an additional treatment for the prevention of episodic migraines.

West Nile encephalitis

West Nile encephalitis is characterized by the viral infiltration of the central nervous system, resulting in acute neurologic symptoms. Almost all cases of West Nile virus infection are caused by the virus being transmitted through a mosquito bite. West Nile can be transmitted in utero and through breast milk as well. West Nile virus is the most common cause of encephalitis in the United States. Other causes of viral encephalitis include arbovirus, herpes simplex virus type 1, varicella-zoster, Epstein-Barr virus, and HIV. Risk factors for West Nile encephalitis are being exposed to infected mosquitos, advanced age, immunsuppression, and infrequently blood transfusions from an infected donor. Most patients infected with West Nile virus are asymptomatic, however, symptoms of West Nile encephalitis include altered mental status ranging from subtle deficits to complete unresponsiveness. Focal neurologic deficits such as flaccid paralysis, coarse tremor, rigidity, postural instability, and bradykinesia can also be observed. Diagnosis is made via cerebrospinal fluid (CSF) examination using enzyme-linked immunosorbent assay (ELISA). Treatment of West Nile encephalitis is mainly supportive, with many patients regaining their baseline motor function in six to eight weeks after symptom onset. Some therapies that have been suggested for the treatment of West NIle encephalitis are interferon, ribavirin, and IVIG, however, none of these therapies have been shown to improve patient outcomes and, in some cases, have been harmful to the patient.

saccular unruptured intracranial aneurysms are most common type of aneurysm (accounting for about 90% of all aneurysms) and characterized by pathological dilation at cerebral artery bifurcation and a distinct neck attaching to parent vessel(s) rupture of intracranial aneurysm leads to subarachnoid hemorrhage Who is Most Affected adults aged 35-60 years Incidence/Prevalence aneurysms generally more prevalent in women, but men and women equally affected prior to age 40 years < 5% of patients with unruptured intracranial aneurysm are children (20%-30% of unruptured intracranial aneurysms in children are saccular unruptured intracranial aneurysms) Modifiable Risk Factors smoking uncontrolled hypertension alcohol use disorder nonmodifiable risk factors associated with increased risk of unruptured intracranial aneurysms in adults include -family history of intracranial aneurysms or subarachnoid hemorrhage (in ≥ 2 relatives) -female sex -older age At-risk Conditions aortic aneurysm bicuspid aortic valve coarctation of aorta intracranial arteriovenous malformations fibromuscular dysplasia neurofibromatosis pheochromocytoma genetic disorders including autosomal dominant polycystic kidney disease Ehlers-Danlos syndrome Marfan disease Clinical Presentation most (85%-90%) unruptured intracranial aneurysms are asymptomatic and may be found incidentally in work-up for other conditions clinical presentation of symptomatic unruptured intracranial aneurysms (typically larger aneurysms) may include -headache presenting as either of the following -->nonspecific chronic headache -->sudden, intense "thunderclap" headache (typically described as "worst headache of my life") with peak intensity and resolution within 72 hours; may reflect acute aneurysm expansion, daughter sac formation, or thrombosis (or rupture, leading to subarachnoid hemorrhage) -dizziness -facial pain -eye pain -dilated pupil -visual disturbances, such as abrupt unilateral visual loss -focal neurological deficits including -->pyramidal tract signs -->cranial nerve palsies, such as third-nerve palsy (posterior communicating artery aneurysm) signs and/or symptoms of transient ischemic attack or infarction (such as motor weakness, diminished speech or vision, and decreased sensation) due to ischemic lesion in vascular distribution distal to unruptured aneurysm Seizure or other undefined neurological symptoms ("spells") Diagnosis -most unruptured intracranial aneurysms are asymptomatic and found incidentally or via screening of high-risk populations -consider symptomatic unruptured intracranial aneurysms in patients presenting with headache, dizziness, cranial neuropathies, or other neurological symptoms -noninvasive methods (useful for first-line detection, screening, and follow-up) including computed tomography angiography and magnetic resonance angiography -digital subtraction angiography******************** -->most sensitive modality for diagnosis, but carries small risks of adverse events -->useful (compared with noninvasive imaging) for identification and evaluation of cerebral aneurysms if surgical or endovascular treatment being considered other causes of thunderclap headache -subarachnoid hemorrhage and other types of intracranial hemorrhage -reversible cerebral vasoconstriction syndrome -posterior reversible leukoencephalopathy syndrome -headache due to serotonin-enhancing drugs -primary benign thunderclap headache imaging studies for detection of unruptured intracranial aneurysms include computed tomography angiography magnetic resonance angiography digital subtraction angiography (most sensitive, but carries small risks of adverse events)********************* -->risks of DSA are small but include cerebral infarction, aneurysmal rupture, arterial dissection, contrast related events, and radiation side-effects (noninvasive imaging may be preferred for patients with renal insufficiency or Ehlers-Danlos syndrome due to higher risks with catheter angiography) consider conservative management of aneurysms as alternative to aneurysm repair for small asymptomatic unruptured intracranial aneurysms with low risk of hemorrhage (determined by aneurysm characteristics, family history, and other relevant factors) in... -older patients (> 65 years old) -patients with associated medical comorbidities for conservative management -counsel patient on importance of smoking cessation -monitor patient blood pressure and treat hypertension -follow-up -->perform follow-up for aneurysm growth with magnetic resonance angiography or computed tomography angiography at regular intervals; optimal interval and duration of follow-up is uncertain -->consider performing first radiographic follow-up 6-12 months after initial aneurysm discovery with subsequent follow-up every year or every other year -->consider using time-of-flight magnetic resonance angiography as reasonable alternative to computed tomography angiography for repeated long-term follow-up in patients without contraindications to magnetic resonance imaging Management for aneurysm repair -perform repair of unruptured intracranial aneurysms at treatment centers that perform > 20 cases/year -surgical clipping and endovascular coiling are effective for repair of unruptured intracranial aneurysms considerations when choosing method of aneurysm repair -surgical clipping is associated with more durable protection against aneurysm regrowth compared to endovascular therapy -endovascular therapy is associated with reduced procedural morbidity and mortality compared to surgical clipping -consider endovascular therapy over surgical clipping particularly in cases with high risk of surgical morbidity, such as in elderly patients or with aneurysms located in basilar apex -counsel patient on procedural risk of radiation exposure when offering endovascular procedures risk factors for intracranial aneurysm rupture include -hypertension -heavy alcohol use (≥ 150 g/week) -smoking (current and former smoking) -family history of subarachnoid hemorrhage in ≥ 2 first-degree relatives -aneurysm growth on serial imaging -irregular aneurysm morphology or presence of daughter sac -multiple aneurysms -aneurysm diameter ≥ 7 mm -aneurysm location in anterior cerebral arteries, posterior cerebral arteries, or posterior communicating artery -Japanese or Finnish ancestry

trigeminal neuralgia

• Pathophysiology: compression of the trigeminal nerve (cranial nerve 5) root by the superior cerebellar artery or on occasion a tortuous vein (90%). Idiopathic (10%). • Most common in middle-aged women (60%). • In younger patients (<40 years) or bilateral TN, consider Multiple sclerosis as a cause. CLINICAL MANIFESTATIONS • Headache: sudden, usually unilateral, brief, episodic, severe, stabbing, sharp, lancinating, shock- like pain in the 2nd or 3rd division of CN5, maximal in onset, lasting a few seconds (up to 2 minutes). • Radiation: Pain starts near mouth & shoots to the eye, ear & nostril on the ipsilateral side and often occurs many times throughout the day. May be associated with facial spasm. • Trigger zones: worse with washing the face, brushing the teeth, touching those areas, shaving, talking, chewing, grimacing, or exposure to a draft of air may generate excruciating pain. Physical examination; • Usually normal but light palpation of "trigger zones" of the affected CN5 division may trigger attack. DIAGNOSIS • Usually a clinical diagnosis in the absence of history or physical findings suggestive of other cause. • MRI of the brain with and without contrast is recommended in patients < 40 years or bilateral TN (to rule out Multiple sclerosis) or if structural brain lesions are suspected MANAGEMENT • Carbamazepine or Oxcarbazepine first-line therapy for Trigeminal neuralgia. • Alternative agents: Gabapentin, Baclofen, Lamotrigine, and Pimozide. Valproic acid. Botox. • Surgical decompression or gamma knife surgery may be needed in severe or recalcitrant cases.

Normal pressure hydrocephalus

•(1) Dilation of the cerebral ventricles with (2) normal opening pressures on lumbar puncture. Pathophysiology: •Unknown but thought to be a local pressure effect due to impaired CSF absorption after a CNS injury (eg, Subarachnoid hemorrhage, chronic meningitis, tumors, inflammatory disease, head injury etc.). CLINICAL MANIFESTATIONS •Triad 1. gait disturbance, 2. urinary incontinence, & 3. dementia/cognitive dysfunction "wobbly, wet, & wacky" •Gait disturbances: wide-based, shuffling gait - described as gait apraxia or "magnetic" gait (as if the feet are stuck to the floor). May be associated with postural instability, especially when attempting to turn. Gait disturbance is the most prominent and often the earliest feature. •Urinary incontinence may present as urinary urgency early in the disease. •Dementia: includes impaired executive function, psychomotor depression, & apathy. •Other: weakness, lethargy, malaise, rigidity, hyperreflexia, & spasticity. DIAGNOSIS •Neuroimaging: Ventriculomegaly (ventricular enlargement) in the absence of or out of proportion to sulcal dilation. MRI is superior to CT scan. •Lumbar puncture: CSF pressure is usually normal (<200 mm H20). Positive lumbar tap test: Removing fluid during LP may be therapeutic, causing improvement of symptoms. MANAGEMENT •Ventriculoperitoneal shunt treatment of choice. Gait abnormalities usually the most improved.

status epilepticus

•A single, continuous epileptic seizure (1) lasting 5 minutes or greater, or (2) > 1 seizure within a 5 minute period without recovery in between the episodes. Considered a neurologic emergency. ETIOLOGIES •Structural abnormalities, infections (eg, meningitis, encephalitis), metabolic abnormalities, medications, toxins. DIAGNOSIS: Neuroimaging: once stabilized to determine if intracranial mass or hemorrhage is present. MANAGEMENT •Benzodiazepines are the preferred initial agents (Lorazepam usually preferred). They are associated with rapid control of seizure. Additional doses can be given. Midazolam (IM, nasal, buccal) can be used as initial therapy if an IV access cannot be established. Rectal Diazepam if no IV. •Second-line: Levetiracetam, Fosphenytoin, Phenytoin, or Valproate if no response to Benzodiazepine &/or to prevent seizure recurrence. Lacosamide or Phenobarbital. •Third-line: Phenobarbital if no response to Phenytoin or other second-line agent (refractory) Lacosamide is an alternative. •General anesthesia: Midazolam and Propofol can be used. COMPLICATIONS •Hypoxia, aspiration, respiratory failure, cardiac arrhythmias.

vascular dementia

•Any dementia that is primarily caused by cerebrovascular disease or impaired cerebral blood flow, or in which cerebrovascular disease or impaired cerebral blood flow is a contributing causative factor. •Hypertension most important risk factor. Diabetes mellitus, history of CVA, Atrial fibrillation CLINICAL MANIFESTATIONS •Sudden decline in functions with a stepwise progression of symptoms - random infarct then decline -> stable then another infarct -> decline etc. •Cortical manifestations: depends on areas affected. Medial frontal: executive dysfunction, apathy, abulia. Left parietal: apraxia aphasia or agnosia. Right parietal: hemineglect, confusion, visuospatial abnormalities. •Subcortical manifestations: focal motor deficits, gait abnormalities, urinary difficulties, personality changes. DIAGNOSIS •Clinical diagnosis. Workup similar to Alzheimer disease - rule out other causes of symptoms (eg, B12 and folate levels, RPR, etc.). Vascular dementia is the second most common cause of Dementia. •MRI: white matter lesions, cortical or subcortical infarcts. CT scan may show lacunar infarcts. PREVENTION: strict blood pressure control.

•Autoimmune peripheral nerve disorder of the neuromuscular junction due to autoantibodies against the acetylcholine receptor on the muscles, leading to weakness. EPIDEMIOLOGY: •Bimodal distribution: Most common in young women <40 and older men >50y, •Strong association with an abnormal thymus gland (hyperplasia or thymoma), HLA B8 & DR3 PATHOPHYSIOLOGY: •Type II hypersensitivity: Autoantibodies against acetylcholine (nicotinic) postsynaptic receptor at the neuromuscular junction. This prevents ACh from exciting the postsynaptic muscle & decreases skeletal muscle neuromuscular transmission. leading to weakness. Autoantibodies vs. receptor-associated protein, muscle-specific tyrosine kinase also seen. T cell-dependent T cells stimulate B-cell antibody production. •Transient worsening of myasthenic symptoms can be precipitated by concurrent infection, surgery, pregnancy, childbirth, and medications. CLINICAL MANIFESTATIONS •2 main manifestations: 1. Ocular weakness & 2. Generalized weakness worsened with repeated use. •Ocular weakness: diplopia & ptosis usually first presenting symptoms. Pupils are spared. •Skeletal muscle weakness: fluctuating skeletal muscle weakness worsened with repeated muscle use & throughout the day, often with true muscle fatigue, is the hallmark cardinal feature of Myasthenia gravis. Fatigue is manifest by contractile force of the muscle, not tiredness. •Bulbar (oropharyngeal) weakness; weakness with prolonged chewing, dysphagia, dysphonia, & dysarthria. Respiratory muscle weakness may lead to respiratory failure = Myasthenic crisis. •Sensation and deep tendon reflexes are usually preserved. •Bedside ice pack test: can be used to support the diagnosis of Myasthenia gravis in patients with ptosis, but it is not helpful for those with extraocular muscle weakness. Application of ice for 10 minutes improve ocular symptoms of MG. DIAGNOSIS: •Serologic antibody testing: Acetylcholine receptor antibodies initial test of choice (positive in 85%). Thymic hyperplasia is frequent in AChR-Ab positive MG. •MuSK antibodies obtained if ACR antibodies negative (often negative in isolated ocular MG). •Anti-striated muscle antibodies: useful marker for Thymoma in early onset MG. •Electrophysiology testing: Repetitive nerve stimulation (RNS) and single-fiber electromyography (SFEMG) are the most accurate test for MG. Repetitive nerve stimulation - most frequently used electrodiagnostic test for MG. RNS positive for MG if the decrement is >10% (not specific). RNS is usually performed first, followed by SFEMG, if the diagnosis is still uncertain. SFEMG - positive for MG if there is increased jitter due to decreased neuromuscular junction transmission (nonspecific). The variability in time of the second action potential relative to the first is called "jitter." •Chest imaging: (eg, chest CT or MRI) should be done in all patients diagnosed with MG to detect thymus gland abnormalities (eg, hyperplasia, thymoma). MANAGEMENT •Myasthenic crisis or severe: Plasmapheresis or IV immunoglobulin. •Long-term: acetylcholinesterase inhibitors (eg, Pyridostigmine or Neostigmine) first-line treatment of symptoms. Glucocorticoid. Azathioprine, or Mycophenolate are steroid alternatives. •Thymectomy, even if thymus gland is normal, can improve symptoms and removes the source of antibodies. Useful if no improvement with medical management. Glucocorticoids if > 60 years. •Avoid medications known to exacerbate MG (eg, fluoroquinolones, aminoglycosides, beta blockers).

•Autoimmune, inflammatory demyelinating disease of the CNS of idiopathic origin associated with axon degeneration of white matter (brain & spinal cord). •Most common in women & young adults 20-40y, colder climates. Associated with HLA-DR2 3 MAIN TYPES: •Relapsing-remitting disease most common - episodic exacerbations. •Progressive disease: progressive decline without acute exacerbations. •Secondary progressive: relapsing-remitting pattern that becomes progressive. CLINICAL MANIFESTATIONS •Sensory disturbances followed by weakness & visual disturbances are the most common presenting symptoms. Sensory deficits (pain, paresthesias), motor deficits (weakness, gait, and balance problems). Visual disturbances (diplopia, Optic neuritis), fatigue. Trigeminal neuralgia. •Uhthoff's phenomenon: worsening of symptoms with heat (eg, exercise, fever, hot tubs, weather etc.). •Spinal cord symptoms: bladder or bowel dysfunction. PHYSICAL EXAMINATION •Upper motor neuron signs: spasticity, upward Babinski, hyperreflexia, muscle rigidity. •Lhermitte's sign; neck flexion causes lightning-shock type pain radiating from the spine down the leg. •Marcus-Gunn pupil with Optic neuritis - during swinging-flashlight test from the unaffected eye into the affected eye, the pupils appear to dilate (due to less than normal pupillary constriction). This response is due to the brain perceiving the delayed conduction of affected optic nerve as if light was reduced. •Internuclear ophthalmoplegia - inability to adduct the eye on the side of the lesion with nystagmus in the other eye. •Cerebellar: Charcot's neurologic triad (nystagmus, staccato speech, and intentional tremor). Ataxia. •Spinal cord symptoms: bladder, bowel, or sexual dysfunction. DIAGNOSIS Mainly clinical (at least 2 distinct episode of CNS deficits). •MRI with gadolinium best initial & most accurate test - hyperintense white matter plaques hallmark finding. There should be proof at least 2 areas of white matter involvement before the diagnosis is made. •Lumbar puncture indicated if negative MRI: increased IgG & oligoclonal bands - small discrete bands in the gamma globulin region seen on electrophoresis, which reflects inflammatory cells penetrating the blood brain barrier. MANAGEMENT - ACUTE EXACERBATION •IV high-dose Glucocorticoids first-line treatment of exacerbations of MS. •Plasmapheresis if not responsive to glucocorticoids. PREVENTION OF RELAPSE & PROGRESSION: •Escalation therapy: Beta-interferon or Glatiramer first-line. If ineffective or partially effective second-line drugs are used for escalation of therapy (eg, Ocrelizumab, Natalizumab, Fingolimod, Alemtuzumab, Teriflunomide). •Amantadine helpful for fatigue symptoms. Baclofen & Diazepam for spasticity. •Induction therapy used in aggressive MS - more potent immunosuppressant agents early in the course of the disease (eg, Mitoxantrone, Fingolimod, Natalizumab, Alemtuzumab, Ocrelizumab).

•Autosomal dominant inherited disorder (30-70%). Incidence increases with age. CLINICAL MANIFESTATIONS •Intentional tremor - postural bilateral action tremor, most commonly affecting the upper extremities & head (hands, forearms, head, neck, or voice). •Tremor worsened with action & intentional movement, postural eg, holding affected body part against gravity (eg, arms held outstretched), adrenergic activity (eg, emotional stress, anxiety). •Tremor improved with alcohol ingestion, when the body part is supported, and with rest. PHYSICAL EXAMINATION •Tremor is more pronounced with (1) with the arms suspended against gravity in a fixed posture (eg, outstretched arms) and (2) during goal-directed activity (eg, on finger to nose testing, the tremor increases at the end of approaching the target or holding a position against gravity). •Besides the tremor, no other significant neurologic findings seen, other than cogwheel phenomenon. DIAGNOSIS •Diagnosis of exclusion based on history, family history, physical after ruling out other causes. MANAGEMENT: •Medical treatment not usually needed if mild. Less impaired patients may opt not to be treated. Reduction of tremors with weighting the limb, non-medical relaxation techniques, and biofeedback. Medical: •First-line; Propranolol &/or Primidone (barbiturate) if no relief with Propranolol. Propranolol is often the first-line therapy of choice in most cases, unless contraindicated [eg, heart block, Asthma, or type 1 Diabetes mellitus, CHF, bradycardia]. Primidone used if contraindications to Beta blockers. Adverse effects of Primidone: sedation, drowsiness, fatigue, depression, nausea, vomiting, ataxia, malaise, dizziness, unsteadiness, confusion, vertigo. •Second line: Alprazolam (benzodiazepine if intermittent), Gabapentin, Pregabalin, or Topiramate. Interventional therapy: •For patients who fail or tolerate adverse effects of medication treatment, surgical options include deep brain stimulation, focused ultrasound, thalamotomy, or Botulinum toxin injections.

•Autosomal dominant neurodegenerative disorder characterized by involuntary choreatic movements with cognitive and behavioral disturbances. PATHOPHYSIOLOGY: •Inheritance of trinucleotide repeats of cytosine, adenine, and guanine (CAG/glutamine) on the Huntingtin gene (chromosome 4). •This leads to neurotoxicity as well as cerebral, putamen & caudate nucleus atrophy. The disease predominantly affects the striatum but progresses to involve the cerebral cortex and other brain regions. EPIDEMIOLOGY: •Both sexes are affected equally. •Symptoms usually begins between ages 30-50 years of age, but may begin as early as infancy (juvenile HD if age of onset < 20), or in older age. CLINICAL MANIFESTATIONS: •Symptoms usually appear 30-50y of age. •3 hallmark manifestations: 3 Ms: Mood, Movement, & Memory - behavioral & mood changes, chorea (rapid involuntary movements), & dementia. •Behavioral changes: personality, cognitive, intellectual, & psychiatric including irritability. •Chorea: brief, abrupt, involuntary or arrhythmic movements of the face, neck, trunk, & limbs initially. Chorea worsened with voluntary movements & stress (may disappear with sleep). •Dementia: most develop dementia before 50y (primarily executive dysfunction). •Gait abnormalities, ataxia (often irregular & unsteady), incontinence, & facial grimacing. •Psychiatric dysfunction: depression, suicidal ideation, irritability, anxiety. Psychosis, sleep disturbances. PHYSICAL EXAMINATION: •Restlessness, fragility. •Quick, involuntary hand movements. •Brisk deep tendon reflexes. DIAGNOSIS: •Clinical symptoms + family history (if known) + genetic confirmation. Neuroimaging: •CT or MRI: cerebral & striatal (caudate nucleus & putamen) atrophy with subsequent widening in the frontal horns of the lateral ventricle (boxcar ventricle sign). •PET scan: decreased glucose metabolism in the caudate nucleus & putamen. Genetic testing: •Trinucleotide CAG, expansion repeats on the short arm of chromosome 4 in the Huntingtin gene. MANAGEMENT: •No cure. Usually fatal within 15-20 years after presentation (due to disease progression). •No medication stops the disease progression. •Tetrabenazine for dyskinesia or chorea. •Antidopaminergics: typical & atypical antipsychotics. •Benzodiazepine use intermittently may help with chorea & sleep, especially during stressful situations.

Acoustic Neuroma (Vestibular Schwannoma)

•Benign tumor involving Schwann cells, which produce myelin sheath that arises in the cerebellopontine angle & can compress structures (eg, Cranial nerves VIII, VII, & V). •Bilateral vestibular schwannomas may be seen with neurofibromatosis type 2 (NF2). CLINICAL MANIFESTATIONS •Slowly progressive unilateral sensorineural hearing loss & vestibular hypofunction (eg, tinnitus). •Unsteadiness with walking, ataxia, headache, facial numbness (CN V), or facial paresis (CN VII). DIAGNOSIS •MRI imaging test of choice: well-circumscribed enhancing lesion in the middle ear with extension into the cerebellopontine angle with an "ice cream on cone" appearance •Audiometry is the laboratory test of choice: asymmetric sensorineural hearing loss most common. MANAGEMENT •Surgery or focused radiation therapy (depending on age, tumor location, size, etc.).

subarachnoid hemorrhage

•Bleeding between the arachnoid membranes & the pia mater. ETIOLOGIES: •Most commonly due to a ruptured saccular (berry) aneurysm at the anterior communicating artery (Circle of Willis). •Arteriovenous malformation, stroke or trauma. RISK FACTORS: •Cigarette smoking and Hypertension most important. •Polycystic kidney disease, atherosclerotic disease, smoking, excessive alcohol intake, Ehlers-Danlos syndrome, Marfan syndrome, family history. CLINICAL MANIFESTATIONS: •Headache: most common symptom sudden or rapid onset of an intense thunderclap headache (severe, rapidly progressing with maximal intensity at its onset) that is often unilateral in the occipital area. Often described as "the worst headache of my life". •May be associated with delirium, seizures, nausea, vomiting, & meningeal symptoms (photophobia, neck stiffness, fever), decreased level of consciousness, hemiparesis, and occasionally, seizures. •May have loss of consciousness initially. •Prodromal symptoms: May have a history of a prior, milder headache (sentinel leak). PHYSICAL EXAMINATION: •Hypertension is often present on physical examination. •Meningeal signs: may be present, such as nuchal rigidity, positive Brudzinski and Kernig signs. •Usually not associated with focal neurologic deficits but may have a CN III palsy (fixed, dilated, "blown" pupil). •Terson syndrome: preretinal hemorrhages may be seen and are associated with a poorer prognosis (higher association with abrupt increase in intracranial pressure). DIAGNOSIS •CT scan without contrast initial study of choice subarachnoid bleeding, blood most commonly found in the basal cisterns. May also be seen in the Sylvian fissures, interhemispheric fissure, and suprasellar, ambient, and quadrigeminal cisterns. Most are picked up on Head CT performed within 6 hours of symptom onset. •Lumbar puncture: performed if CT is negative + no papilledema or focal signs - xanthochromia (yellow to pink color of the CSF fluid due to breakdown of RBCs in the CSF, increased CSF protein from bilirubin, and increased CSF pressure). May not develop until 6 hours or longer after event. •4-vessel CT or MR angiography usually performed after confirmed SAH (on neuroimaging or LP) to identify source of bleeding & other aneurysms. Digital subtraction angiography may also be used. MANAGEMENT •Supportive management: bed rest, analgesia, stool softeners, lower intracranial pressure, and venous thromboembolism prophylaxis. Nimodipine reduces cerebral vasospasms, improving neurologic outcomes in aneurysmal SAH (eg, 60mg orally every 4 hours). •Blood pressure should be titrated to a target systolic blood pressure (SBP) <160 mmHg or mean arterial pressure (MAP) <110 mmHg for most patients with SAH. Lowering blood pressure may decrease the risk of rebleeding but may also increase the risk of infarction. If needed, Labetalol. Nicardipine and Enalapril are preferred antihypertensives. •Ventriculostomy may be needed if SAH is associated with hydrocephalus. •Prevention of rebleeding: endovascular coiling or surgical clipping of aneurysm or AVM used to prevent rebleeding (coiling often preferred over clipping). •Acute complications: rebleeding, hydrocephalus, Hyponatremia, and cerebral vasospasms.

Epidural hematoma

•Bleeding in the potential space between the skull and the dura, usually resulting from trauma. PATHOPHYSIOLOGY •Most common due to rupture of the middle meningeal artery, often associated with a temporal bone fracture. May lead to hemorrhagic stroke & brain herniation. Mean age 20-30 years of age. CLINICAL MANIFESTATIONS •3 classic phases - (1) brief loss of consciousness followed by (2) a lucid interval (patient regains consciousness and seems fine) followed by (3) neurologic deterioration (mental status changes to coma as a result of increased intracranial pressure). •During the deterioration phase, headache, vomiting, aphasia, hemiparesis, & seizures may occur. •Uncal herniation: cranial nerve III palsy fixed, dilated "blown" pupil can be seen on the ipsilateral side of the injury (tentorial herniation compressing CN Ill). Cushing reflex: triad of hypertension, bradycardia, & respiratory irregularity. DIAGNOSIS •Head CT without contrast initial test of choice "bulging" biconvex (lens-shaped) hyperdensity usually in the temporal area that does not cross suture lines (because the collection is limited by firm attachments of the dura to the cranial sutures). MANAGEMENT •Hematoma evacuation & craniotomy treatment of choice in most symptomatic acute EDH, hematoma volume > 30 ml regardless of Glasgow coma score, GCS <9 with pupillary abnormalities. •May be observed closely with serial imaging every 6-8h if small and the patient is in good condition. •Increased intracranial pressure: head elevation, short-term hyperventilation, & hyperosmolar therapy (IV Mannitol or hypertonic saline).

Oligodendroglioma

•Oligodendrocyte - a type of cell that makes up the supportive (glial) tissue of the brain. These tumors can be found anywhere within the cerebral hemispheres (especially the frontal & temporal lobes). CLINICAL MANIFESTATIONS •May be asymptomatic. May be incidental finding (tumor grows slowly). •Focal deficits: includes seizures, headaches & personality changes (depends on the tumor location). DIAGNOSIS •CT scan or MRI with contrast. •Brain biopsy: usually guided by imaging studies. Codeletion of 1p/19q and have IDH mutations. •Histologic appearance: soft, grayish-pink calcified tumors, areas of hemorrhage &/ or cystic. Chicken-wire capillary pattern with perinuclear clearing ("fried-egg" appearance) seen on microscopy. MANAGEMENT •Surgical resection, & in if residual disease or aged >40 years, radiation &/or chemotherapy.

intracerebral hemorrhage

•Bleeding within the brain parenchyma. •May compress the brain, ventricles, and sulci. RISK FACTORS •Hypertension most common overall cause of spontaneous ICH. •Cerebral amyloid angiopathy is the most common cause of nontraumatic ICH in the elderly. •Arteriovenous malformation is the most common cause in children. •Trauma, older age, high alcohol intake, and coagulopathy. CLINICAL MANIFESTATIONS •Neurologic symptoms usually increase within minutes to hours - headache, nausea, vomiting, syncope, focal neurologic symptoms (hemiplegia, hemiparesis, seizures), altered mental status (lethargy, obtundation, etc.). PHYSICAL EXAMINATION •May have focal motor and sensory deficits. DIAGNOSIS: •CT scan of the head without contrast: initial neuroimaging of choice. MANAGEMENT •Supportive: gradual blood pressure reduction. •Prevention of increased intracranial pressure - raising the head of the bed 30 degrees, limiting IV fluids, blood pressure management, analgesia & sedation. •Reduction of increased intracranial pressure if present: IV mannitol, temporary hyperventilation. •Blood pressure reduction: IV Labetalol, Nicardipine, Esmolol, Hydralazine, Nitroprusside and Nitroglycerin. Aggressive reduction only if systolic BP (SBP) >220 mmHg to <220 then gradual reduction (over a period of hours) to a target range of 140-160 mmHg if the patient remains stable.

•Cluster headache is characterized by hypothalamic activation with secondary activation of the trigeminal-autonomic reflex, probably via a trigeminal-hypothalamic pathway. RISK FACTORS: •Male gender: men are 3 times more affected •Age of more than 30 (young & middle-aged males) •Consumption of alcohol, tobacco use, Prior brain surgery or trauma, Family history. TRIGGERS •Worse at night (onset of attacks is nocturnal in about 50% of patients), alcohol, stress, or ingestion of specific foods, hot weather, stress, watching TV, use of Nitroglycerin, sexual activity, glare. CLINICAL MANIFESTATIONS •Headache: Severe, unilateral, periorbital, deep (retroorbital), or temporal pain that is sharp, lancinating, and excruciating. Headaches usually last <2 hours with spontaneous remission. •Bouts occur several times a day. May have one or two cluster periods per year (each lasting weeks to months). PHYSICAL EXAMINATION: Ipsilateral autonomic symptoms: •Partial Horner's syndrome: ptosis &/or miosis. •Nasal congestion or rhinorrhea, conjunctival injection or lacrimation, and eyelid edema or forehead/facial sweating, occurring only during the pain attack. •Autonomic symptoms are indicative of both parasympathetic hyperactivity and sympathetic impairment. Sweating and cutaneous blood flow may also increase on the painful side. DIAGNOSIS: •Clinical diagnosis. Neuroimaging •Neuroimaging is suggested to exclude a cranial lesion in patients with suspected Cluster headache. •MRI performed with and without contrast or a noncontrast Computed tomography (CT) scan to exclude abnormalities of the brain and pituitary gland. ACUTE MANAGEMENT: •100% Oxygen first-line (6-12L for 15-20 minutes). Most patients respond to oxygen therapy, and it is effective in less than 10 minutes. Oxygen use carries no risks or adverse effects. •Anti-migraine medications help during attack: fast-acting Triptans - eg, SQ Sumatriptan (preferred) or Zolmitriptan intranasal spray; Ergotamines (vasoconstriction). •Noninvasive vagus nerve stimulation is FDA approved for the acute treatment of attacks in episodic Cluster headache using three 2-min stimulation cycles applied consecutively at the onset of headache on the side of pain. •For patients with relatively short bouts, limited courses of oral glucocorticoids can be very useful. A 10-day course of Prednisone, beginning at 60 mg daily for 7 days and followed by a rapid taper, may interrupt the pain bout for many patients. PROPHYLAXIS: •Verapamil first-line medical therapy. •Corticosteroids, Ergotamines, Valproic acid, Lithium. •Suboccipital blockade. Adverse events are nonserious, including transient injection site pain and low-level headache.

•Formerly known as reflex sympathetic dystrophy (RSD). •Autonomic dysfunction following bone or soft tissue injuries (eg, wrist fracture or post-surgery). 30% have no history of injury. •Most commonly affects the upper extremities, women & >30 years. CLINICAL MANIFESTATIONS •Characterized by 4 main symptoms after an initiating event: •Sensory - pain, hyperalgesia often out of proportion to the initial injury. •Motor/trophic changes: decreased range of motion & motor dysfunction with trophic changes (increased hair & nail growth initially followed by decreased growth). •Edema or sweating changes •Vasomotor: temperature & skin color asymmetry with autonomic dysfunction. DIAGNOSIS: •Mainly a clinical diagnosis •Radiographs: may show patchy osteoporosis. Bone scintigraphy: increased uptake/activity. Diagnostic criteria: •An initiating event, or immobilization •Persistent pain, allodynia, or hyperalgesia out of proportion to the initiating event •Symptoms of edema, changes in skin blood flow, or abnormal sudomotor activity •No other obvious diagnosis that could explain the symptoms MANAGEMENT •NSAIDs, physical & occupational therapy are initial management. •Cognitive behavioral therapy is a necessary component in the management. •Anesthetic blocks, antidepressants - eg, Duloxetine, tricyclic antidepressants (eg, Amitriptyline or Nortriptyline), anticonvulsants (eg, Gabapentin), transdermal Lidocaine, transcutaneous electric nerve stimulation, etc.

•Group of conditions due to acquired autoimmune-mediated demyelinating polyradiculopathy of the peripheral nervous system, characterized by rapidly evolving muscular weakness. ETIOLOGIES •Increased incidence with Campylobacter jejuni (most common) or other antecedent GI or respiratory infections. Influenza A and B. •CMV, Epstein-Barr virus, HIV, Mycoplasma infections, immunizations, & postsurgical. PATHOPHYSIOLOGY: •Molecular mimicry: Inflammatory neuropathy triggered when an immune response to an antecedent event produces antibodies that cross react with shared epitopes on peripheral nerve (neural antigens). C. jejuni expresses lipooligosaccharides in the bacterial wall similar to gangliosides on peripheral nerves. This molecular mimicry creates antiganglioside antibodies that attack nerves. •Demyelination: These autoantibodies and macrophages attack the myelin sheath of the peripheral nerves (Schwann cells); breakdown of the blood-nerve barrier at the dural attachment allows transudation of plasma proteins into the cerebrospinal fluid (high CSF protein with normal cell count). Demyelination causes conduction slowing and leads to muscle weakness. CLINICAL MANIFESTATIONS •Symmetric, ascending, progressive, flaccid muscle weakness & sensory changes (paresthesias, pain) hours to days - distal lower extremities first. Often 2-4 weeks after antecedent infection. •Cranial nerve & bulbar symptoms - Cranial nerves III, IV, & VI may lead to ophthalmoplegia (oculomotor weakness); involvement of the glossopharyngeal, vagus, & hypoglossal cranial nerves may lead to bulbar symptoms (oropharyngeal weakness with swallowing difficulties). •May develop weakness of the respiratory muscles necessitating ventilatory support. •Sensory involvement: paresthesias (hands & feet), pain, cramps. Dysautonomia (ileus, wide fluctuations in blood pressure, fever, tachycardia or bradycardia), urinary retention. PHYSICAL EXAMINATION •Lower motor neuron signs: decreased deep tendon reflexes, flaccid paralysis, muscle weakness. •Sensory deficits & Cranial nerve palsies (eg, CN VII, III, IV, and VI). •Autonomic dysfunction; tachycardia, arrhythmias, hypotension, hypertension, breathing difficulties DIAGNOSIS •Electrophysiologic studies: Nerve conduction studies (most specific test) & needle electromyography - decreased motor nerve conduction velocities & amplitude. Nerve conduction reveals features of demyelination (absent or prolonged H reflexes &/or F wave latencies. •CSF analysis: high protein with a normal WBC count (usually seen 1-3 weeks after symptom onset). •Autoantibody testing - Antiganglioside antibody testing may be useful in clinical practice to help identify patients with atypical symptoms (eg, anti-GM1, anti-GD1A, anti-GT1A, and anti-GQ1B). •Pulmonary function test: important to assess peak inspiratory pressure and forced vital capacity (FVC) - - both decrease with GBS. Most important to determine the need for intubation. MANAGEMENT •Plasmapheresis or IV immune globulin (IVIG) are first-line for antibody removal and neutralization. They are equally effective for typical GBS & best within 4 weeks of symptom onset. •Mechanical ventilation if respiratory failure or decreased FVC on PFTs. •Prednisone not indicated as they show no benefit in GBS and may even delay long-term recovery. •Prognosis: by 4 weeks after onset, > 90% of patients have reached the nadir of the disease. > 80% achieve independent ambulation after 6 months.

Hemangiomas

•Hemangioma: abnormal buildup of blood vessels in the skin or internal organs. 2% of all 1ry brain tumors. Von Hippel-Lindau syndrome 10% - (hemangiomas, tumors of the liver, pancreas & kidney). •Hemangioblastoma: arises from the blood vessel lining. Benign, slow growing well-defined tumors. MC found in the posterior fossa (brainstem & cerebellum). Often >40y. May occur in the cerebral hemispheres or spinal cord. Retinal hemangiomas associated with von Hippel-Lindau syndrome. •Hemangiopericytoma: originate from the cells surrounding the blood vessels & the meninges. May spread to the lung & liver. CLINICAL MANIFESTATIONS •Hemangioblastoma: headache, nausea, vomiting, gait abnormalities, poor coordination of the limbs. May produce erythropoietin (secondary polycythemia). Hemangiopericytoma: depends on tumor location. DIAGNOSIS •CT scan or MRI. Biopsy: well-defined borders, usually does not invade surrounding healthy tissue. Foam cells with high vascularity. MANAGEMENT: surgical resection. Radiation may be used in tumors attached to the brainstem.

Idiopathic Intracranial Hypertension

•Idiopathic increased intracranial (CSF) pressure on CF examination with no clear identifiable cause evident on neuroimaging (eg, MRI or CT). •AKA Pseudotumor cerebri (mimics a brain tumor with nausea, vomiting, and visual disturbances). Pathophysiology: •Symptoms of increased intracranial pressure occur due to reduced cerebrospinal fluid absorption. ETIOLOGIES: •Idiopathic no specific cause found in most cases. Most commonly among overweight women of childbearing age (20-44 years). •Meds: withdrawal of long-term corticosteroids, growth hormone, thyroid replacement, oral contraceptives, long-term tetracycline use, & vitamin A toxicity. •Thrombosis of the transverse venous sinus as a complication of otitis media or chronic mastoiditis. •Endocrine disturbances: hypoparathyroidism, hypothyroidism, thyroid replacement therapy, or Addison disease. Chronic pulmonary disease, Systemic lupus erythematosus, uremia. CLINICAL MANIFESTATIONS: Signs & symptoms of increased intracranial pressure: •Headache; most common presenting symptom often lateralized, pulsatile, or throbbing, worse with straining or changes in posture. •Retrobulbar pain that may be worse with eye movements. •Nausea, vomiting. Pulsatile tinnitus (patients often describe hearing rushing water or wind). •Visual changes eg, transient visual obscurations that may last seconds at a time, photopsia, horizontal diplopia. May lead to blindness if not treated. Ocular examination: •Funduscopic exam: papilledema hallmark (usually bilateral & symmetric, but may be unilateral and/or asymmetric) - blurred optic discs and engorged retinal veins. •Visual field loss may be seen. •Cranial nerve VI palsy: may have CN VI (abducens nerve) palsy, which may cause diplopia. DIAGNOSIS •CT scan: performed prior to LP to rule out intracranial mass. •Lumbar puncture: increased CSF pressure (250 mmH20 or greater) + otherwise normal CSF. •MRI with MR venography ideal neuroimaging. MANAGEMENT •Acetazolamide first-line (decreases CSF production) & weight loss recommended. •Furosemide or other diuretics may be adjunct if symptoms worsen while on Acetazolamide. •Short-course of systemic corticosteroids may be indicated if acute visual loss as a temporizing measure prior to surgical intervention. Repeat lumbar puncture reduces intracranial pressure. •Refractory: CSF shunting (ventriculoperitoneal shunt or optic nerve sheath fenestration).

•Idiopathic, unilateral CN VII/facial nerve palsy leading to hemifacial weakness & paralysis due to inflammation or compression. Lower motor neuron disorder. •Although idiopathic, reactivation of this virus Herpes simplex virus (HSV) type 1 DNA in the geniculate ganglion may be responsible for most cases. •Risk factors: Diabetes mellitus, pregnancy (especially the 3rd trimester), post URI, dental nerve block. CLINICAL MANIFESTATIONS: •Prodrome: Sudden onset of ipsilateral hyperacusis (ear pain) 24-48 hours followed by weakness. •Unilateral facial weakness or paralysis (forehead included) - unable to lift the affected eyebrow, wrinkle forehead, smile, loss of the nasolabial fold, drooping of the corner of mouth, biting the inner cheek, eye irritation (decreased lacrimation & inability to fully close eyelid). Bell phenomenon: eye on the affected side moves laterally & superiorly when eye closure is attempted. The weakness & paralysis ONLY affects the face. •Sensory dysfunction: Taste disturbance involving the anterior 2/3 of the tongue. DIAGNOSIS: •Diagnosis of exclusion. MANAGEMENT: •No treatment is required (>85% of cases resolve within 1 month) - supportive: artificial tears (replaces lacrimation, reduces vision problems). Eye patches worn during sleep if severe to prevent corneal ulceration. Massage of the weakened muscles. •Prednisone (especially if started within the first 72 hours of symptom onset) reduces the time to full recovery & increases the likelihood of complete recuperation at 9-12 months (12-15%). •Acyclovir in combination with glucocorticoids in severe cases has been shown to improve symptoms & recovery timing. The presence of incomplete paralysis in week 1 most favorable prognostic sign.

•Immune-mediated large- & medium-vessel granulomatous vasculitis of the extracranial branches of the carotid artery (eg, temporal, occipital, ophthalmic, & posterior ciliary arteries). PATHOPHYSIOLOGY: T-cells and monocytes are recruited to the vessel wall and result in an inflammatory response. •If not recognized & treated early, ischemic complications may cause permanent vision loss (15-25%). EPIDEMIOLOGY: •Same clinical spectrum as Polymyalgia Rheumatica - PMR & GCA frequently overlap; 20% of patients with PMR will get diagnosed with GCA later; In GCA, PM features are present in up to 50%. RISK FACTORS: •Women, >50 years of age - incidence rises steadily thereafter, peaking between the ages of 70 - 79 (80% of patients are 70 years and older). Northeastern Europeans and Caucasians. Smoking. CLINICAL MANIFESTATIONS: •Headache - new-onset headaches or change in baseline headaches is the most common systemic symptom (75%). Headache is usually temporal but can be occipital, periorbital, or non-focal as well. Headaches have an insidious onset and gradually progress over time, although they may spontaneously resolve rarely, even in the absence of treatment. Scalp tenderness while combing or brushing hair is frequent and can be focal in the temporal areas or diffuse. •Jaw claudication - mandibular pain, discomfort, or fatigue brought on by chewing, talking, or using the jaw, relieved by stopping (exertional ischemia) seen in ~50%. Jaw Claudication occurs secondary to ischemia of the masseter muscle, which is supplied by the maxillary artery. •Visual changes: ocular involvement may include eye pain, monocular (rarely binocular) vision loss, diplopia, & Amaurosis fugax (transient monocular vision loss). •Abnormal superficial temporal artery: absent or decreased pulsation, local tenderness to palpation (including scalp tenderness), localized erythema, beading (nodularity), or thickening. A clinically normal temporal artery does not rule out GCA. •Constitutional symptoms: fever (usually low-grade), fatigue, weight loss, anorexia, malaise. DIAGNOSIS: •Elevated ESR & CRP •Temporal artery biopsy: Criterion standard - histopathology reveals inflammatory infiltrate surrounding a fragmented internal elastic lamina within the media of an arterial wall. The infiltrate consists predominantly of mononuclear cell infiltration or granulomatous inflammation, or multinucleated giant cells. Biopsy may be normal as there may be skip lesions of normal tissue. •Scheduling of temporal artery biopsy should never interfere with or delay initiation of treatment in a patient with a high likelihood of GCA, since delay can put the patient at risk for complications (eg, vision loss). The yield of biopsy is still very high up to 2 weeks after initiation of corticosteroids. MANAGEMENT: •High-dose systemic glucocorticoids; initiated once GA is suspected to prevent blindness and suppress disease activity (do not delay treatment to biopsy or for biopsy results). IV Methylprednisolone pulses for 3-5 days prior to oral may be used in some with visual changes. •Low-dose Aspirin: Helps to reduce the risk of vision loss, transient ischemic attacks, & Strokes in GCA and can be considered as adjuvant therapy if no contraindications exist. •IL-6 inhibitors: Tocilizumab, an IL-6 inhibitor, may be an alternative in patients who are intolerant to corticosteroids. IL-6 levels are significantly elevated in patients with GA, and IL-6 is thought to play a pathogenic role in GCA by activating the T-cells and promote IFN-gamma release from the T-cells.

CNS lymphoma

•Primary: seen without evidence of systemic disease. Variant of extranodal Non-Hodgkin lymphoma (NHL). Secondary is more common. •Secondary: METS from another site (eg, NHL in the neck, chest, groin, abdomen) especially diffuse large B cell lymphoma (90%). Burkitt's lymphoma (10%). Risk factors: •Epstein-Barr virus positive in 90% of these patients, immunosuppression (eg, AIDS, post-transplant, receiving immunosuppressant treatment). CLINICAL MANIFESTATIONS •Focal deficits; depends on the location. Visual changes, steroid-refractory posterior uveitis. DIAGNOSIS •CT scan or MRI with contrast: hypointense ring-enhancing lesion in the deep white matter on CT. •Biopsy: usually guided by imaging study. •Workup includes CT of abdomen/ pelvis, PET scan, bone marrow biopsy, slit lamp examination. MANAGEMENT •Chemotherapy: Methotrexate most effective chemotherapy (given with Folinic acid/leucovorin) may be given with other chemotherapeutics (eg, Cytarabine). Chemotherapy not usually given at the same time as radiation therapy (increased risk of leukoencephalopathy). RT, corticosteroids. •Secondary: when an aggressive approach is feasible, induction therapy (eg, R-CHOP) plus high-dose Methotrexate-based regimen followed by consideration of consolidative therapy with high-dose chemotherapy and autologous hematopoietic cell transplantation (HT) in eligible patients.

•Infection of the brain parenchyma. ETIOLOGIES •Herpes simplex virus-1 most common identified virus. •Varicella zoster virus, Epstein-Barr virus, measles, mumps, rubella, HIV, St. Louis virus. CLINICAL MANIFESTATIONS •Meningeal symptoms: headache, neck stiffness, photosensitivity, fever, chills, nausea, vomiting, seizures. •Focal deficits: The presence of altered mental status, changes in personality, speech, & movement distinguishes Encephalitis from Aseptic meningitis. PHYSICAL EXAMINATION •Focal neurologic deficits (eg, hemiparesis, sensory deficits, cranial nerve palsies). DIAGNOSIS •CT scan of the head must be performed first to rule out space-occupying lesions (these patients often have altered mental status, requiring imaging before LP). •Lumbar puncture criterion standard & performed after CT - normal glucose, increased lymphocytes (similar to Aseptic meningitis). •MRI: preferred modality for Encephalitis - temporal lobe involvement characteristic of HSV. •PCR testing of CSF fluid is the most accurate test for Herpes encephalitis. MANAGEMENT •IV Acyclovir: early empiric treatment for HSV Encephalitis should be initiated as soon as possible if the patient has encephalitis with no obvious cause. Supportive management

Frontotemporal Dementia

•Localized brain degeneration of the frontotemporal lobes. May progress globally. •Histology: Pick bodies (round or oval aggregates of Tau protein) seen on silver-staining of the cortex. CLINICAL MANIFESTATIONS •Marked changes in social behavior, personality, and language (aphasia) are early signs of FTD with eventual executive and memory dysfunction (dementia with advanced disease). The onset of dementia is earlier than Alzheimer disease (usually presents in the 6th decade). •Behavioral changes: disinhibition or socially inappropriate behaviors, apathy, hyperorality (binge-eating, changes in food preferences, putting large amounts of food in their mouth), compulsive ritualistic behaviors, loss of sympathy & empathy. May have deficits in executive control. PHYSICAL EXAMINATION •Preserved visuospatial. In advanced disease, they may have positive primitive reflexes (palmomental & palmar grasp). May have Parkinsonism. May have nonfluent aphasia.

•Mild traumatic brain injury leading to alteration in mental status, with or without loss of consciousness. •May result after blunt force or an acceleration/deceleration head injury. CLINICAL MANIFESTATIONS •Headache, dizziness, psychological symptoms, and cognitive impairment. •Confusion: confused or blank expression, blunted affect. •Amnesia: pretraumatic (retrograde) or posttraumatic (antegrade) amnesia. The duration of retrograde amnesia is usually brief. Headache, dizziness, visual disturbances: blurred or double vision. •Delayed responses & emotional changes: emotional instability. •Signs of increased intracranial pressure: persistent vomiting, worsening headache, increasing disorientation, changing levels of consciousness. •CT head without contrast is the study of choice for evaluating most acute head injuries. •MRI study of choice if prolonged symptoms >7-14 days or with worsening of symptoms not explained by concussion syndrome. •CT angiography of the head or neck if vascular injury is suspected. MANAGEMENT •Cognitive & physical rest is the main management of patients with concussion. •Some form of observation is recommended for a minimum of 24 hours (outpatient or inpatient). •Patients may resume strenuous activity after resolution of symptoms & recovery of memory as well as cognitive functions. •Neurosurgical or neurologic consult if CT scan shows mass effect, substantial hematomas (epidural, subdural, cerebral), subarachnoid hemorrhage, pneumocephalus, depressed skull fracture, cerebral edema.

Glioblastoma Multiforme

•Most common & most aggressive primary malignant CNS tumors in adults. •Glioblastoma = Grade IV Astrocytoma (heterogenous mixture of poorly differentiated astrocytes). RISK FACTORS: •Males, >50y, HHV-6 & cytomegalovirus infections, ionizing radiation. TYPES •PRIMARY: most common (60%). Seen in adults >50y. Arises de novo (new). Most common type & most aggressive. •SECONDARY: (40%). Most common <45y. Due to malignant progression from a low-grade Astrocytoma (grade Il) or anaplastic Astrocytoma (grade Ill). May transform as early as 1 year or >10 years. VARIANTS •"Classic": 97%. Presence of extra copies of the epidermal growth factor receptor gene (EGFR). TP53 is rarely mutated in this type (note that the others are associated with TP53 mutation). •Mesenchymal: high rates of mutations & alterations including the gene encoding for neurofibromatosis type I. TP53 often mutated. An alteration of MGMT (a DNA repair enzyme). CLINICAL MANIFESTATIONS •Focal deficits depend on the location of the tumor. Most common in the frontal & temporal areas of the cerebral hemisphere. •Patients usually present in the sixth and seventh decades of life with headache, seizures, or focal neurologic deficits. •General: headache (may be worse in the morning, may wake patients up at night, may be positional), cranial nerve deficits (eg, fixed, dilated pupil from a CN III palsy), altered mental status, neurological deficits, ataxia, vision changes, weakness. DIAGNOSIS •Brain MRI with contrast initial study of choice - classic finding is heterogenous lesion with variable ring of enhancement with central necrosis, surrounded by edema & irregular (serpiginous) margins. Mass effect may cause hydrocephalus. May cross the corpus callosum ("butterfly" glioma). •Histology (usually post-surgical): malignant astrocytes + necrotizing, hemorrhagic center surrounded by pseudo palisading (tumor cells lining the area of necrosis). MANAGEMENT •Treatment involves maximal surgical excision when possible, followed by adjuvant partial-field external-beam radiotherapy (6000 cGy in thirty 200-cGy fractions) with concomitant chemotherapy with Temozolomide (alkylating agent), followed by 6 months of adjuvant Temozolomide. •Implantation of biodegradable polymers containing Carmustine chemotherapy into the tumor bed after resection of the tumor or addition of tumor treating fields (scalp electrodes delivering low-intensity electric currents) may also be used in some.

•Most common overall cause of Primary headache. Mean age of onset ~30y. •Risk factors: mental stress, sleep deprivation, eye strain, poor posture, hunger. CLINICAL MANIFESTATIONS •Bilateral, pressing, tightening "bandlike, viselike, tight-cap" non-throbbing (nonpulsatile) steady or aching, occipitonuchal or bifrontal headache, usually mild to moderate in intensity. Often described as "dull", "pressure", "head fullness" or "heavy weight on their head or shoulders". The pain often builds gradually and lasts 30 minutes - 7 days. •Exacerbating factors: worsened with stress, fatigue, noise, or glare. •Not worsened with routine activity (as in Migraines). •Usually not pulsatile & not associated with nausea, vomiting, photophobia & phonophobia (one may be present but not both), or focal neurological symptoms (auras). Physical examination: •Usually normal but may have increased pericranial muscle tenderness (head, neck, shoulders). DIAGNOSIS: Clinical - diagnosis of exclusion (there are no specific tests). MANAGEMENT •Simple analgesics - NSAIDs mainstay of treatment (eg, Ibuprofen or Naproxen) or Aspirin, Acetaminophen, Local heat. Behavioral approaches (eg, relaxation). Anti-migraine medications. •Chronic management: Tricyclic antidepressants (eg, Amitriptyline). Amitriptyline is the most studied and has the strongest evidence of efficacy. Nortriptyline. Other antidepressants: Mirtazapine, Venlafaxine. Anticonvulsants: Topiramate, Gabapentin. Cognitive behavioral therapy.

•Neurodegenerative movement disorder due to deceased dopamine resulting from idiopathic loss of dopaminergic neurons in the striatum & substantia nigra & the presence of Lewy bodies. •Onset of symptoms 45-65y most common. Usually a clinical diagnosis. PATHOPHYSIOLOGY •Idiopathic degeneration of dopamine-producing neurons within the pars compact of the substantia nigra and Norepinephrine cells of the locus coeruleus in the brainstem. •Decreased dopamine leads to imbalance of dopamine & acetylcholine, resulting in improper movement due to failure of acetylcholine inhibition in the basal ganglia (acetylcholine is an excitatory CNS neurotransmitter, dopamine is inhibitory). •It also affects dopamine's ability to initiate movement. •The pathologic hallmark of PD seen on post-mortem histology is eosinophilic cytoplasmic inclusions (Lewy bodies) & loss of pigment cells seen in the substantia nigra. CLINICAL MANIFESTATIONS •Motor triad: resting tremor, bradykinesia, & muscle rigidity (cardinal motor symptoms of PD). •Resting tremor: often the first symptom. "Pill-rolling" resting tremor of the hand. -Tremor is worse at rest, emotional stress, excitement, and walking. -Tremor improves with voluntary activity, intentional movement, and sleep. Typically, the tremor disappears with action of the involved limb & reemerges with maintained posture. -Usually confined to one limb or one side for years before it becomes generalized. •Bradykinesia: slowness of voluntary movement & decreased automatic movements (eg, lack of swinging of the arms while walking & shuffling gait). •Rigidity: sustained increased resistance to passive movement - cogwheel rigidity (ratchety pattern of resistance and relaxation as the examiner moves the limb through its full range of motion). Festination = increasing speed while walking. Freezing (inability to initiate stepping). •Dementia in 50% (usually a late finding). Many develop depression. •Postural instability, including a flexed (stooped) posture, and loss of postural reflexes is a sign of more advanced disease. Postural instability may significantly impact the quality of life. Early in the course of the disease postural reflexes are preserved. •Nonmotor symptoms: include the loss of smell (anosmia), mood disorders (especially Depression), constipation, excess salivation or drooling (sialorrhea), & sleep dysfunction. •Behavioral symptoms include personality changes, anxiety, depression occurs in up to 40% of patients with PD and is the most prevalent neurobehavioral change in PD. Physical examination: •Normal deep tendon reflexes. Usually no muscle weakness. •Face involvement; relatively immobile face (fixed facial expressions), widened palpebral fissure, Myerson's sign: tapping the bridge of nose repetitively causes a sustained blink. Decreased blinking. Seborrhea of the skin common. •Postural instability: usually a late finding. Pull test - standing behind the patient & pulling the shoulders causes the patient to fall or take steps backwards. MANAGEMENT •Levodopa-carbidopa - most effective treatment. •Dopamine agonists (eg, Bromocriptine, Pramipexole, Ropinirole) may be used as initial treatment •Anticholinergics (eg, Trihexyphenidyl, Benztropine) •Amantadine - increases dopamine. MAO-B inhibitors (eg, Selegiline, Rasagiline) •COMT inhibitors (eg, Entacapone, Tolcapone). •Deep brain stimulation is extremely effective for rigidity and tremors in select patients.

Lacunar infarcts

•Small-vessel disease of the penetrating branches of the cerebral arteries in the pons and basal ganglia. RISK FACTORS: •80% have a history of Hypertension. Diabetes mellitus 5 CLASSIC PRESENTATIONS: •(1) Pure motor; most common presentation. Hemiparesis or hemiplegia in the absence of sensory or "cortical signs" (eg, aphasia, agnosia, neglect, apraxia, or hemianopsia). •(2) Ataxic hemiparesis; ipsilateral weakness and clumsiness in the leg > arm. •(3) Pure sensory deficits - numbness, paresthesias of the arm, face, and leg on one side of the body in the absence of motor or "cortical" signs. •(4) Sensorimotor: weakness and numbness of the face, arm, and leg on one side of the body in the absence of the aforementioned "cortical" signs •(5) Dysarthria (clumsy hand syndrome): dysarthria, facial weakness, dysphagia and slight weakness and clumsiness of one hand in the absence of "cortical" signs. DIAGNOSIS: •CT scan - small punched-out hypodense areas (lacunar infarcts) usually in the central & noncortical areas (eg, basal ganglia). MANAGEMENT: •Aspirin, control of risk factors (eg, Hypertension, Diabetes mellitus). PROGNOSIS: •Good prognosis - partial or complete deficit resolution ranging from hours up to 6 weeks

Subclavian steal syndrome

•Subclavian steal syndrome refers to signs and/or symptoms that occur due to reversed (retrograde) blood flow from the vertebral artery to the ipsilateral arm as a result of decreased flow in the subclavian artery (stenosis or occlusion). •The blood flow to the arm is at the expense of the vertebrobasilar circulation. ETIOLOGIES •Atherosclerosis of the subclavian artery most common. •Takayasu arteritis, dissecting aortic aneurysm, thoracic outlet syndrome. CLINICAL MANIFESTATIONS •Most patients are asymptomatic ("subclavian steal" not syndrome), an incidental finding. •Symptoms of arm arterial insufficiency: arm claudication with exercise, paresthesias. •Symptoms of vertebrobasilar insufficiency: presyncope or syncope, dizziness, neurologic deficits, vertigo, diplopia, nystagmus, weakness, drop attacks, gait abnormalities. PHYSICAL EXAM •Blood pressure difference between the arms (reduction of brachial systolic blood pressure in the affected arm > 15 mmHg compared to the unaffected arm). •Radial pulse may diminish with arm elevation or arm exercise. DIAGNOSIS •Duplex ultrasound can reveal proximal subclavian artery stenoses and demonstrate reversal of flow in the ipsilateral vertebral artery, if present. Continuous wave Doppler US. •Magnetic resonance (MR) angiography, computed tomographic (CT) angiography, or occasionally catheter-based arteriography may be used if US nondiagnostic. MANAGEMENT •Revascularization or percutaneous transluminal angioplasty in severe cases.

•Transient acute episode of ischemic neurologic deficits caused by focal brain, spinal cord, or. retinal ischemia without acute infarction, lasting <24 hours (usually <1-2 hours). •~30% of patients with stroke have a history of TIAs and 5-10% of patients with TIAs will have a stroke within 90 days. Risk factors: Hypertension most important, cardiovascular risk factors. 3 MAIN TYPES: •Embolic: Atrial fibrillation, left ventricular thrombus, Heart failure, Endocarditis, Atrial septal defects. •Large artery (low flow): ischemia due to atherosclerosis & atherothrombosis. •Lacunar: penetrating small vessels. CLINICAL MANIFESTATIONS •Neurologic deficits lasting <24 hours, depending on the artery involved (resembles stroke pattern). Most last for a few minutes with complete resolution within 1 hour (most last a few minutes). •Amaurosis fugax - transient monocular vision loss - "temporary shade down on one eve". • Physical examination: carotid bruits may be heard. DIAGNOSIS •(1) Neuroimaging + (2) neurovascular imaging + (3) tests to rule out cardioembolic source. •Neuroimaging CT scan performed initially to rule out hemorrhage but MRI more sensitive. •Neurovascular imaging CT or MR angiography, carotid Doppler US, transcranial Doppler US. •Conventional angiography definitive diagnosis (invasive). •Ancillary testing: rule out cardioembolic source (ECG, telemetry, & echocardiogram). Rule out metabolic or hematologic cause of neurologic symptoms (eg, hypoglycemia, CBC). HIV & Syphilis. MANAGEMENT: •Place patient in the supine position to increase cerebral perfusion, avoid lowering blood pressure unless >220/120 mmH. Thrombolytics contraindicated in TIA. Noncardiogenic TIA: •Dual antiplatelet therapy - Aspirin plus Clopidogrel, followed by Aspirin only substantially reduces the risk of future TIA or strokes if high risk (ABCD2 score >4) started while evaluating the ischemic mechanism. Aspirin + extended-release Dipyridamole another option. •Aspirin monotherapy - Aspirin (162-325 mg/daily) alone for low-risk TIA (ABCD2 score <4). •Long-term: reduce modifiable risk factors (eg, DM, hyperlipidemia, hypertension control, smoking cessation, weight reduction, regular exercise), statin therapy regardless of LDL levels. •Revascularization: Carotid endarterectomy recommended if internal carotid artery stenosis 50-99% with a life expectancy of at least 5 years + Aspirin. Endovascular intervention & stenting. Cardiogenic (Nonvalvular Atrial fibrillation): •Oral anticoagulation - Warfarin or a direct oral anticoagulant (eg, Dabigatran, Rivaroxaban, Apixaban, Edoxaban). ABCD2 SCORE ASSESSMENT IN TIA The risk of stroke after a TIA is significantly increased, and the risk is highest during the days immediately following the TIA. The ABCD2 tool is designed to predict the risk of stroke in the 3 to 90 days after a TIA. Patients receive one point each for: •Age>60 •Blood pressure>140/90 •Clinical symptoms (one point for slurred speech or two points for unilateral weakness) •Duration (one point for > 10 minutes or two points for >60 minutes) •Diabetes ABCD2 SCORE •0-3 points = 3.1% 90 day stroke risk •4-5 points = 9.8% 90 day stroke risk •6-7 points = 17.8% 90 day stroke risk

Ependymoma

•Tumor arising from ependymal cells line the ventricles & parts of the spinal column. •Most common in children (mean age at diagnosis is 5 years of age). •Most commonly arise from the 4th ventricle, spinal cord, & medulla. CLINICAL MANIFESTATIONS •Infants: increased in head size, irritability, sleeplessness & vomiting. •Older children & adults: nausea, vomiting, headache. May cause Cauda equina in adults. DIAGNOSIS •CT scan or MRI with contrast; hypointense T1, hyperintense T2. Enhances with gadolinium. •Brain biopsy: perivascular pseudo rosettes (tumor cells surrounding a blood vessel). MANAGEMENT •Surgical resection -> adjuvant radiation therapy. Chemotherapy not as helpful usually.

meningioma

•Usually benign, slow-growing tumors arising from arachnoid meningothelial cells of the meninges (covering the brain & spinal cord). •Most commonly arises from the dura or sites of dura reflection (eg, venous sinuses, falx cerebri). •Meningiomas are classified by the WHO into 3 histologic grades of increasing aggressiveness: grade I (benign), grade Il (atypical), and grade III (malignant). Risk factors: •Females (estrogen receptors on tumor cells), radiation exposure, Neurofibromatosis type 2 (NF2), and history of cranial irradiation. Their incidence increases with age. CLINICAL MANIFESTATIONS •Often asymptomatic (incidental finding) or causes symptoms due to compression & displacement of the brain (usually does not invade the brain parenchyma). Headaches, seizures, or focal neurologic signs (depending on the location of the tumor). Fixed dilated pupil (CN III) common. DIAGNOSIS •MRI with contrast preferred: extra-axial intensely enhancing, well-defined lesion often attached to the dura (resembling a snowball). May have increased calcifications. •Histology: spindle-cells concentrically arranged in a whorled pattern. Psammoma bodies (concentric round calcifications). MANAGEMENT •Asymptomatic: observation if small. The lesion can be observed with serial MRI studies. •Symptomatic or large: surgical excision when possible (transarterial embolization may be performed prior to surgery). External beam Radiation therapy may be used if not a surgical candidate or as adjuvant treatment in some (eg, partially resected tumors).

subdural hematoma

•Venous bleeding in the potential space between the dura and the arachnoid membranes. •Etiology: most commonly due to rupture of the cortical bridging veins after blunt trauma. RISK FACTORS •Elderly & alcoholics (brain atrophy puts tension on the bridging veins) •Anticoagulant use. Shaken baby syndrome or child abuse. CLINICAL MANIFESTATIONS •Because the bleeding is venous, it can develop over a longer period of time compared to Epidural. •Varies but usually a gradual increase in generalized neurologic symptoms (eg, headache, dizziness, nausea, vomiting) or focal neurologic symptoms. •May be associated with Loss of consciousness. DIAGNOSIS •Head CT without contrast - concave (crescent-shaped) bleed that can cross the suture lines. If severe, midline shift may occur due to increased intracranial pressure. •CT scan may negative immediately after the injury so serial imaging may be needed. MANAGEMENT •Nonoperative management: if clinically stable with a small hematoma or no CT signs of brain herniation (eg, midline shift <5 mm) or no signs of increased intracranial pressure. •Surgical management: surgical evacuation may be indicated if ≥5mm or greater midline shift or severe. Options include burr hole trephination, craniotomy, and decompressive craniectomy.

•~75% of all persons who experience Migraines are women. Family history (80%). •Although unknown, Migraine headaches are thought to be likely secondary to numerous intra-and extracranial changes, such as activation of the trigeminovascular system (eg, trigeminal nerve afferent activation and firing, alteration of blood-brain permeability, cranial vasodilation via vasogenic peptide release, and neurogenic inflammatory changes in the pain sensitive meninges. 2 major types: •Migraine without aura - most common type (75%). Migraine with aura classic but not common. CLINICAL MANIFESTATIONS •The prodrome consists of affective or vegetative symptoms that appear 24 to 48 hours prior to the onset of headache. •Headache: Usually episodic lateralized (unilateral), throbbing (pulsatile) headache localized in the frontotemporal & ocular area usually 4-72 hours in duration, and moderate to severe in intensity. Often associated with nausea, vomiting, photophobia, &/or phonophobia. •Worsened with routine physical activity, stress, lack or excessive sleep, alcohol, specific foods (eg, chocolate, red wine), hormonal (eg, oral contraception & menstruation), dehydration etc. •Auras: focal neurologic symptoms that usually last <60 minutes (5-20 minutes common). Auras accompany or follow the headache within 60 minutes. Visual (most common type), auditory, somatosensory, or loss of function (eg, aphasia, hearing etc.). •Physical examination: Usually normal. May have aphasia, dysarthria, paresthesias, or weakness. DIAGNOSIS: •Clinical diagnosis: At least 2: unilateral pain, throbbing (pulsatile) pain, aggravated by movement, moderate or severe intensity plus at least 1: nausea/vomiting, photophobia & phonophobia. ABORTIVE (SYMPTOMATIC) MANAGEMENT •Migraine therapy must be individualized; a standard approach for all patients is not possible. •IV fluids & placing the patient in a dark & quiet room are helpful. •Mild to moderate: Simple analgesics (eg, NSAIDs, Acetaminophen or Aspirin) first-line alone or in combination with other compounds (eg, Acetaminophen, Aspirin, and caffeine). For patients unresponsive to analgesics, the combined use of an NSAID with a triptan may be effective. •Moderate to severe: Migraine-specific agents for moderate to severe Migraine attacks and in those who respond poorly to NSAIDs or combination analgesics - 5-hydroxytryptamine-1 (5-HT 1b/1D) receptor agonists - (triptans, Sumatriptan-Naproxen, Ergotamines) either alone or in combination with Dopamine receptor antagonists (eg, Metoclopramide, Prochlorperazine, Chlorpromazine); CGRP antagonists (gepants), 5-HT 1F receptor agonists (Lasmiditan). •Severe Migraine attacks in an emergency department - initial treatment with either subcutaneous Sumatriptan or a parenteral antiemetic agent rather than other migraine-specific drugs. When using intravenous (IV) Metoclopramide or Prochlorperazine for nausea/ vomiting for Migraine, adjunctive use of Diphenhydramine is recommended to prevent extrapyramidal symptoms (eg, Dystonic reactions, Akathisia). •Dexamethasone can reduce recurrence of early headaches, but doesn't provide immediate relief. PROPHYLACTIC (PREVENTATIVE) •Anti-hypertensives: Beta-blockers (eg, Propranolol) & Calcium channel blockers (eg, Verapamil, Flunarizine). Candesartan. NSAIDs, Rimegepant. Anticonvulsants eg, Topiramate, Valproate. •Antidepressants: Tricyclic antidepressants (eg, Amitriptyline, Nortriptyline). Venlafaxine. •Monoclonal antibodies: to the CRGP receptor (eg, Erenumab) or the peptide (eg, Eptinezumab, Framnezumab, Galcanezumab). •Botulinum toxin A may be beneficial in patients with intractable, chronic migraine that has failed to respond to at least three conventional preventive medications.

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