Cerebrovascular Diseases

Disease Introduction

Cerebrovascular diseases encompass a spectrum of conditions affecting blood vessels and blood supply to the brain, representing the second leading cause of death worldwide and a major cause of disability. According to Harrison’s Principles of Internal Medicine, stroke is defined as rapidly developing clinical signs of focal (or global) disturbance of cerebral function lasting more than 24 hours or leading to death, with no apparent cause other than vascular origin.

The global burden of stroke is substantial, with approximately 13.7 million new strokes annually and 80 million stroke survivors worldwide. Stroke can be ischemic (87%) or hemorrhagic (13%). Transient ischemic attacks (TIAs) are temporary episodes of neurological dysfunction without acute infarction. Rapid recognition and treatment are critical as “time is brain” – each minute of untreated large vessel ischemic stroke destroys approximately 1.9 million neurons.

Prerequisite Normal Anatomy & Physiology

Cerebral Circulation Anatomy
  • Anterior Circulation (Carotid System): Internal carotid artery → ophthalmic artery, anterior cerebral artery (ACA), middle cerebral artery (MCA). Supplies frontal, parietal, temporal lobes, basal ganglia.
  • Posterior Circulation (Vertebrobasilar System): Vertebral arteries → basilar artery → posterior cerebral arteries (PCA), superior cerebellar artery, anterior inferior cerebellar artery, posterior inferior cerebellar artery. Supplies brainstem, cerebellum, occipital lobes, thalamus.
  • Circle of Willis: Anastomotic ring connecting anterior and posterior circulations. Components: anterior communicating artery, anterior cerebral arteries, internal carotid arteries, posterior communicating arteries, posterior cerebral arteries.
  • Blood-Brain Barrier: Tight junctions between endothelial cells, astrocytes, pericytes. Protects brain from toxins, maintains homeostasis.
Cerebral Blood Flow Regulation

Cerebral blood flow (CBF) = Cerebral Perfusion Pressure (CPP) / Cerebrovascular Resistance (CVR)

  • Normal CBF: 50-55 mL/100g brain tissue/minute
  • Autoregulation: Maintains constant CBF over MAP range 60-150 mmHg
  • Ischemic Thresholds: CBF <20 mL/100g/min → neuronal dysfunction (ischemic penumbra), CBF <10 mL/100g/min → neuronal death (infarct core)
  • Cerebral Metabolism: Brain uses 20% of body’s oxygen, 25% of glucose. Neurons rely almost exclusively on aerobic glycolysis.

Ischemic Stroke

Pathophysiology
  • Energy Failure: CBF reduction → ATP depletion → failure of Na⁺/K⁺ ATPase → depolarization → glutamate release → Ca²⁺ influx → excitotoxicity
  • Ischemic Cascade: Energy failure → excitotoxicity → oxidative stress → inflammation → apoptosis/necrosis
  • Penumbra Concept: Ischemic but viable tissue surrounding infarct core, salvageable with timely reperfusion
TOAST Classification
Type Frequency Mechanism Diagnostic Features
Large Artery Atherosclerosis 20% Artery-to-artery embolism, in situ thrombosis >50% stenosis of major brain artery, cortical/subcortical infarct >1.5cm
Cardioembolism 20% Embolism from cardiac source AFib, valvular disease, recent MI, multiple vascular territories
Small Vessel Disease 25% Lipohyalinosis, microatheroma Lacunar syndrome, subcortical infarct <1.5cm, hypertension/diabetes
Other Determined Etiology 5% Dissection, vasculitis, hypercoagulable Specific cause identified
Undetermined Etiology 30% Multiple/negative workup Cryptogenic, embolic stroke of undetermined source
Clinical Presentations by Vascular Territory
Artery Clinical Features Key Findings
Middle Cerebral Artery (MCA) Contralateral hemiparesis (face/arm > leg), hemisensory loss, hemianopia, gaze palsy toward lesion, aphasia (dominant), neglect (non-dominant) Most common site, “MCA syndrome”
Anterior Cerebral Artery (ACA) Contralateral leg weakness > arm, urinary incontinence, abulia, grasp reflex, transcortical motor aphasia Leg weakness predominant
Posterior Cerebral Artery (PCA) Contralateral homonymous hemianopia, memory impairment (thalamic), visual agnosia, alexia without agraphia “Visual field stroke”
Basilar Artery Quadriparesis, bulbar signs, decreased consciousness, “locked-in” syndrome, cranial nerve deficits Crossed findings, bilateral symptoms
Lacunar Strokes Pure motor (internal capsule), pure sensory (thalamus), ataxic hemiparesis, clumsy hand-dysarthria No cortical signs, small subcortical

Acute Ischemic Stroke Management Protocol

1
Emergency Evaluation (0-10 minutes)

FAST assessment: Face drooping, Arm weakness, Speech difficulty, Time to call emergency. ABCs: Airway, Breathing, Circulation. NIH Stroke Scale: Rapid assessment of stroke severity. Time last known well: Critical for thrombolysis window.

2
Imaging & Diagnosis (10-25 minutes)

Non-contrast CT head: Rule out hemorrhage, early ischemic signs (hyperdense MCA sign, loss of gray-white differentiation). CT angiography: Identify large vessel occlusion. CT perfusion: Penumbra assessment if available. Labs: CBC, CMP, PT/PTT, glucose, troponin.

3
Reperfusion Therapy (0-4.5 hours for IV tPA, 6-24 hours for thrombectomy)

IV Alteplase (tPA): 0.9 mg/kg (max 90mg), 10% bolus over 1 minute, remainder over 1 hour. Window: 0-4.5 hours from symptom onset. Exclusions: Hemorrhage, recent surgery, INR >1.7, platelets <100k, glucose <50 or >400, severe hypertension (>185/110). Mechanical Thrombectomy: For large vessel occlusion (ICA, M1, M2), window up to 24 hours with perfusion mismatch.

4
Acute Medical Management (First 24-48 hours)

Blood Pressure: For tPA patients: maintain <185/110. Others: permissive hypertension up to 220/120 unless other indications for lowering. Antiplatelets: Aspirin 325mg load then 81-325mg daily (start 24h after tPA). Consider dual antiplatelet (aspirin + clopidogrel) for minor stroke/TIA. Statins: High-intensity (atorvastatin 80mg). Glucose Control: Target 140-180 mg/dL.

5
Secondary Prevention & Rehabilitation

Risk Factor Control: BP target <130/80, LDL <70 mg/dL, HbA1c <7%, smoking cessation. Anticoagulation: For cardioembolic stroke (AFib, mechanical valve). DOACs preferred over warfarin. Rehabilitation: Early mobilization, physical/occupational/speech therapy. Carotid Revascularization: For symptomatic carotid stenosis >70%.

Hemorrhagic Stroke

Intracerebral Hemorrhage (ICH)
  • Epidemiology: 10-15% of strokes, mortality 40% at 1 month, 54% at 1 year
  • Common Locations: Putamen (35%), thalamus (20%), lobar (20%), cerebellum (10%), pons (10%)
  • Risk Factors: Hypertension (most common), cerebral amyloid angiopathy (elderly, lobar), anticoagulation, vascular malformations, sympathomimetic drugs
  • Pathophysiology: Vessel rupture → hematoma expansion (first 3-6 hours) → mass effect → herniation, perihematomal edema (peaks 48-72 hours)
Management Protocol for ICH
1
Initial Stabilization

ABCs: Intubation if GCS ≤8, compromised airway. IV Access: Two large bore IVs. Monitoring: Continuous cardiac, BP, pulse oximetry. Reverse Anticoagulation: Vitamin K 10mg IV, PCC for warfarin, idarucizumab for dabigatran, andexanet alfa for factor Xa inhibitors.

2
Blood Pressure Management

Goal: SBP <140 mmHg. Agents: Nicardipine drip 5-15 mg/hr (first line), labetalol 10-20 mg IV q10-20min, clevidipine 1-2 mg/hr titrated. Avoid: Nitroprusside (increases ICP), hydralazine (unpredictable).

3
ICP Management

Indications for ICP monitor: GCS <8, clinical signs of herniation, intraventricular hemorrhage with hydrocephalus. Treatment: Head elevation 30°, analgesia/sedation, hyperosmolar therapy (mannitol 0.25-1 g/kg or hypertonic saline), hyperventilation (temporarily, PaCO₂ 30-35), decompressive hemicraniectomy for malignant edema.

4
Surgical Considerations

Cerebellar hemorrhage: >3cm or brainstem compression → surgical evacuation. Lobar hemorrhage: Consider if progressive neurological decline, young patient. Ventriculostomy: For intraventricular hemorrhage with hydrocephalus.

Transient Ischemic Attack (TIA)

Definition & Risk Stratification

TIA: Transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia without acute infarction. ABCD² Score: Age >60 (1), BP >140/90 (1), Clinical features (unilateral weakness=2, speech impairment without weakness=1), Duration (>60 min=2, 10-59 min=1), Diabetes (1). Score 0-3: low risk (1% 2-day stroke risk), 4-5: moderate (4%), 6-7: high (8%).

Urgent Evaluation & Management
  • Immediate neuroimaging: MRI brain with DWI (30-50% show infarction)
  • Vascular imaging: Carotid ultrasound, CTA, or MRA of head/neck
  • Cardiac evaluation: ECG, telemetry, echocardiogram (TTE ± TEE)
  • Dual antiplatelet therapy: Aspirin 81mg + clopidogrel 75mg daily for 21 days then single agent (for minor stroke/TIA)
  • Carotid intervention: Endarterectomy or stenting for symptomatic stenosis >70% within 2 weeks
Key Clinical Pearls – Cerebrovascular Diseases
  • Time is brain: 1.9 million neurons lost per minute in untreated large vessel stroke.
  • Wake-up strokes: Use MRI DWI-FLAIR mismatch to identify candidates for thrombolysis.
  • Stroke mimics: Seizure (Todd’s paralysis), migraine with aura, Bell’s palsy, conversion disorder.
  • Lacunar syndromes: Pure motor (internal capsule), pure sensory (thalamus), ataxic hemiparesis.
  • Posterior circulation strokes: Often missed – vertigo, diplopia, crossed findings, bilateral symptoms.
  • Hemorrhagic transformation: Occurs in 10% of ischemic strokes, higher with anticoagulation.
  • Cerebral amyloid angiopathy: Lobar hemorrhages in elderly, MRI gradient echo shows microbleeds.
  • Reversal of anticoagulation: PCC for warfarin, idarucizumab for dabigatran, andexanet alfa for factor Xa inhibitors.
  • Dysphagia screening: All stroke patients before oral intake to prevent aspiration.
  • Stroke prevention in AFib: CHA₂DS₂-VASc ≥2 requires anticoagulation, DOACs preferred.
High-Yield Exam Points:
  • IV tPA window: 0-4.5 hours from symptom onset (0-3 hours for >80, 3-4.5 hours if <80, not diabetic, no prior stroke).
  • Mechanical thrombectomy window: Up to 24 hours with perfusion mismatch (DAWN, DEFUSE-3 trials).
  • ICH BP goal: SBP <140 mmHg (INTERACT2, ATACH-2 trials).
  • Dual antiplatelet: Aspirin + clopidogrel for 21 days for minor stroke/TIA (CHANCE, POINT trials).
  • Carotid stenosis: Surgery for symptomatic >70%, consider for asymptomatic >80%.
  • Lacunar strokes: No cortical signs, pure motor/sensory syndromes.
  • Watershed infarcts: Hypotension + carotid stenosis, “man-in-the-barrel” syndrome.
  • CADASIL: Notch3 mutation, migraine with aura, subcortical infarcts, anterior temporal lobe involvement on MRI.
  • Reversible cerebral vasoconstriction syndrome: Thunderclap headache, vasoconstriction on angiography, resolves in weeks.
  • Central pontine myelinolysis: Rapid correction of hyponatremia >8-10 mEq/L/day.
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Seizure Disorders

Disease Introduction

Seizures are transient occurrences of signs or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Epilepsy is defined as a disorder characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. According to the International League Against Epilepsy (ILAE), epilepsy diagnosis requires at least two unprovoked seizures occurring more than 24 hours apart, or one unprovoked seizure with high probability of further seizures.

Epilepsy affects approximately 50 million people worldwide, with incidence highest in childhood and after age 60. Seizures can be classified as focal (originating within networks limited to one hemisphere) or generalized (rapidly engaging bilaterally distributed networks). Status epilepticus is a neurological emergency defined as continuous seizure activity lasting >5 minutes or recurrent seizures without return to baseline.

Prerequisite Normal Neurophysiology

Neuronal Membrane Physiology
  • Resting Membrane Potential: -70 mV, maintained by Na⁺/K⁺ ATPase (3 Na⁺ out, 2 K⁺ in)
  • Action Potential: Threshold (-55 mV) → Na⁺ channels open → depolarization → K⁺ channels open → repolarization
  • Synaptic Transmission: Presynaptic depolarization → Ca²⁺ influx → vesicle fusion → neurotransmitter release
Neurotransmitter Systems
  • Glutamate: Primary excitatory neurotransmitter. Receptors: AMPA (Na⁺ influx), NMDA (Ca²⁺ influx), kainate.
  • GABA: Primary inhibitory neurotransmitter. GABA-A receptor: Cl⁻ influx, hyperpolarization. GABA-B receptor: K⁺ efflux, presynaptic inhibition.
  • Balance Theory: Seizures result from imbalance between excitation (glutamate) and inhibition (GABA).

ILAE 2017 Classification

Seizure Type Subtypes Clinical Features EEG Findings
Focal Onset Without impaired awareness Aura (sensory, psychic, autonomic), preserved consciousness Focal spikes/sharp waves
With impaired awareness Automatisms (lip smacking, fumbling), confusion, amnesia Temporal or frontal spikes
Generalized Onset Tonic-clonic, absence, myoclonic, atonic, tonic, clonic Bilateral symmetric, impaired awareness Generalized spike-wave
Unknown Onset Tonic-clonic, epileptic spasms Insufficient information Unclassified

Focal Seizures

Clinical Features by Lobe
Lobe Aura/Initial Symptoms Ictal Manifestations Post-ictal Features
Temporal Epigastric rising, déjà vu, fear, olfactory/gustatory hallucinations Staring, automatisms (lip smacking, fumbling), dystonic posturing Confusion, amnesia, Todd’s paralysis
Frontal Brief, no aura, nocturnal Hypermotor (bicycling, thrashing), vocalizations, version (head/eye turning) Minimal or none
Parietal Somatosensory (tingling, numbness), vertigo Sensory disturbances, neglect, apraxia Todd’s sensory phenomena
Occipital Visual (flashing lights, colors, scotomas) Eye deviation, blinking, visual loss Headache, visual disturbances

Generalized Seizures

Types & Characteristics
Type Clinical Features EEG Pattern Age of Onset
Tonic-Clonic Tonic stiffening (10-20s) → clonic jerking (30-40s), cyanosis, tongue biting, incontinence Generalized spikes/polyspikes Any age
Absence Brief staring spells (5-10s), no post-ictal confusion, may have eyelid fluttering 3 Hz generalized spike-wave Childhood (4-12 years)
Myoclonic Brief, shock-like jerks, often after awakening, consciousness preserved Polyspike-wave Adolescence
Atonic Sudden loss of muscle tone (head drops, falls), brief (<2 min) Generalized spike-wave/polyspike Childhood
Tonic Sustained muscle contraction, often in sleep, flexion/extension Generalized fast activity Childhood, Lennox-Gastaut

Diagnostic Evaluation

Comprehensive Workup
  • History: Detailed description from witness, aura, post-ictal state, frequency, triggers (sleep deprivation, alcohol, stress)
  • EEG: Routine (30 min), sleep-deprived, prolonged monitoring. Activation procedures: hyperventilation (absence), photic stimulation
  • Neuroimaging: MRI brain with epilepsy protocol (thin-cut coronal T2, FLAIR, hippocampal volumes)
  • Labs: CBC, CMP, Mg²⁺, Ca²⁺, glucose, toxicology, AED levels if on treatment
  • Video-EEG Monitoring: Gold standard for diagnosis, classification, presurgical evaluation

Epilepsy Management Protocol

1
Diagnosis & Classification

Confirm epileptic seizures vs mimics (syncope, psychogenic non-epileptic seizures, migraine, movement disorders). Classify as focal vs generalized using ILAE 2017 criteria. Identify epilepsy syndrome if possible (childhood absence, JME, etc.).

2
First Seizure Management

Consider treatment if: abnormal EEG, abnormal neuroimaging, nocturnal seizure, Todd’s paralysis, patient preference. 30-50% recurrence after first unprovoked seizure. Risk factors: remote symptomatic cause, abnormal EEG, nocturnal seizure.

3
Antiepileptic Drug Selection

Focal seizures: Lamotrigine, levetiracetam, carbamazepine, oxcarbazepine, lacosamide. Generalized seizures: Valproate (first-line for generalized), lamotrigine, levetiracetam, topiramate. Avoid: Carbamazepine, oxcarbazepine, phenytoin, gabapentin in generalized epilepsy (may worsen).

4
Monitoring & Titration

Start low, go slow. Titrate to therapeutic dose or seizure freedom. Monitor side effects, labs (CBC, LFTs for specific AEDs). Therapeutic drug monitoring for phenytoin, carbamazepine, valproate. Assess adherence, consider causes of breakthrough seizures.

5
Refractory Epilepsy Evaluation

Failure of ≥2 appropriate AEDs at therapeutic doses. Refer to epilepsy center for: video-EEG monitoring, advanced imaging (PET, SPECT), neuropsychological testing, surgical evaluation (temporal lobectomy, corpus callosotomy, VNS, RNS).

Antiepileptic Drug Guide

Drug Mechanism Indications Dosing Key Side Effects Monitoring
Levetiracetam SV2A modulation Focal, generalized 500-1500mg BID Irritability, depression, fatigue CBC, behavioral changes
Lamotrigine Na⁺ channel blocker, glutamate inhibition Focal, generalized, absence 25-200mg BID (slow titration) Rash (SJS risk), dizziness, diplopia Watch for rash
Valproate Multiple: Na⁺ channels, GABA, T-type Ca²⁺ Generalized, focal, migraine 250-1000mg BID Weight gain, tremor, alopecia, teratogenic, pancreatitis LFTs, CBC, ammonia, drug levels
Carbamazepine Na⁺ channel blocker Focal, tonic-clonic 200-400mg TID Dizziness, diplopia, hyponatremia, rash, bone marrow suppression CBC, Na⁺, LFTs, drug levels
Oxcarbazepine Na⁺ channel blocker Focal 300-600mg BID Hyponatremia, dizziness, rash Na⁺
Topiramate Multiple: Na⁺ channels, GABA, carbonic anhydrase Focal, generalized, migraine 25-100mg BID Cognitive slowing, paresthesias, weight loss, kidney stones, glaucoma HCO₃⁻, creatinine
Lacosamide Enhances slow Na⁺ channel inactivation Focal 50-200mg BID Dizziness, diplopia, PR prolongation ECG if cardiac disease
Phenytoin Na⁺ channel blocker Focal, tonic-clonic, status Loading: 20mg/kg IV, Maintenance: 300-400mg daily Gingival hyperplasia, hirsutism, ataxia, megaloblastic anemia, osteomalacia Drug levels, CBC, LFTs
Zonisamide Na⁺/T-type Ca²⁺ channel blocker Focal, generalized 100-400mg daily Cognitive slowing, kidney stones, oligohidrosis HCO₃⁻, creatinine
Levetiracetam
500-1500mg BID. Broad spectrum, well-tolerated. Side effects: irritability, depression. No drug monitoring needed.
Lamotrigine
25-200mg BID. Slow titration (risk of SJS). Good for focal and generalized. Monitor for rash.
Valproate
250-1000mg BID. First-line for generalized. Side effects: weight gain, tremor, teratogenic. Monitor LFTs, CBC, ammonia.
Carbamazepine
200-400mg TID. For focal seizures. Side effects: dizziness, hyponatremia, rash. Monitor CBC, Na⁺, LFTs.

Status Epilepticus

Definition & Classification

Status epilepticus: Continuous seizure activity >5 minutes or recurrent seizures without return to baseline. Convulsive: Tonic-clonic movements with impaired consciousness. Non-convulsive: Altered consciousness without motor activity, diagnosed by EEG.

Management Protocol
1
Stabilization (0-5 minutes)

ABCs: Airway (consider intubation if GCS ≤8), Breathing (supplemental O₂), Circulation (IV access). Monitoring: Continuous EEG if available. Labs: Glucose, CBC, CMP, Mg²⁺, Ca²⁺, AED levels, toxicology. Treat hypoglycemia: 50mL D50 if glucose <60.

2
First-line Therapy (5-20 minutes)

Benzodiazepines: Lorazepam 4mg IV (0.1 mg/kg) over 2 minutes, repeat once if needed. Alternative: Midazolam 10mg IM, Diazepam 10mg IV/PR. Goal: Seizure termination within 20 minutes.

3
Second-line Therapy (20-40 minutes)

IV AEDs: Fosphenytoin 20mg PE/kg IV at 150mg PE/min (max 1500mg). Alternative: Valproate 40mg/kg IV, Levetiracetam 60mg/kg IV. Consider continuous EEG to monitor for non-convulsive status.

4
Third-line Therapy (Refractory Status, >40 minutes)

Anesthetic agents: Midazolam drip: 0.2mg/kg bolus then 0.05-2 mg/kg/hr. Propofol: 1-2mg/kg bolus then 2-10 mg/kg/hr (caution: propofol infusion syndrome). Pentobarbital: 5-15mg/kg load then 0.5-5 mg/kg/hr. Goal: Burst suppression on EEG.

5
Identify & Treat Underlying Cause

Causes: Non-adherence to AEDs, CNS infection, stroke, metabolic (Na⁺, Ca²⁺, glucose), toxic (theophylline, TCAs), tumor, trauma. Workup: CT/MRI brain, LP if infection suspected, EEG monitoring.

Key Clinical Pearls – Seizure Disorders
  • First unprovoked seizure: 30-50% recurrence risk. Higher risk with abnormal EEG, nocturnal seizure, remote symptomatic cause.
  • Juvenile myoclonic epilepsy: Myoclonic jerks on awakening, generalized tonic-clonic seizures, EEG: 4-6 Hz polyspike-wave. Lifelong treatment needed.
  • Childhood absence epilepsy: 3 Hz spike-wave, hyperventilation precipitates, 70% remit by adolescence. Ethosuximide first-line.
  • Lennox-Gastaut syndrome: Multiple seizure types (tonic, atonic, atypical absence), cognitive impairment, EEG: slow spike-wave (<2.5 Hz).
  • Temporal lobe epilepsy: Mesial temporal sclerosis on MRI (hippocampal atrophy, T2 hyperintensity). Surgical cure rate 60-70%.
  • Non-epileptic seizures: Preserved awareness during “unconsciousness,” eye closure, asynchronous movements, pelvic thrusting.
  • Photosensitive epilepsy: Seizures triggered by flashing lights, pattern sensitivity. Avoid triggers, use blue lenses.
  • Catamenial epilepsy: Seizure exacerbation around menstruation. Consider hormonal therapy, acetazolamide.
  • SUDEP: Sudden unexpected death in epilepsy. Risk factors: frequent tonic-clonic seizures, nocturnal seizures, non-adherence.
  • Driving restrictions: Vary by state, typically 3-12 months seizure-free. Discuss with all patients.
High-Yield Exam Points:
  • Status epilepticus definition: >5 minutes continuous seizure or recurrent without return to baseline.
  • First-line for status: Lorazepam 4mg IV (0.1 mg/kg).
  • Absence seizures: 3 Hz spike-wave on EEG, hyperventilation precipitates, ethosuximide first-line.
  • Juvenile myoclonic epilepsy: Myoclonic jerks on awakening, valproate first-line.
  • Temporal lobe epilepsy: Déjà vu aura, automatisms, hippocampal sclerosis on MRI.
  • Carbamazepine/oxcarbazepine: Avoid in generalized epilepsy (may worsen).
  • Valproate: Teratogenic (neural tube defects), avoid in women of childbearing potential if possible.
  • Lamotrigine: Slow titration to prevent SJS, especially with valproate co-administration.
  • Phenytoin: Zero-order kinetics, small dose changes cause large level changes.
  • Non-convulsive status: Consider in altered mental status without explanation, EEG diagnosis.
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Neurodegenerative Diseases

Disease Introduction

Neurodegenerative diseases are characterized by progressive loss of structure or function of neurons, often including neuronal death. These disorders are increasingly prevalent with aging populations and represent a major cause of disability and dependency worldwide. According to Harrison’s Principles of Internal Medicine, the common pathological features include protein misfolding and aggregation, oxidative stress, mitochondrial dysfunction, and neuroinflammation.

Alzheimer’s disease is the most common cause of dementia, accounting for 60-80% of cases, followed by vascular dementia, Lewy body dementia, and frontotemporal dementia. Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s, with prevalence increasing with age. These conditions have substantial socioeconomic impact due to long disease courses and need for chronic care.

Alzheimer’s Disease

Pathophysiology
  • Amyloid Cascade Hypothesis: Aβ accumulation → oligomer formation → synaptic dysfunction → tau hyperphosphorylation → neurofibrillary tangles → neuronal death
  • Aβ Metabolism: Amyloid precursor protein (APP) cleavage: α-secretase (non-amyloidogenic) vs β- and γ-secretase (amyloidogenic, producing Aβ42)
  • Tau Pathology: Hyperphosphorylated tau → paired helical filaments → neurofibrillary tangles → disruption of microtubules → impaired axonal transport
  • Genetic Factors: APOE ε4 allele (3-fold increased risk with one allele, 15-fold with two), APP, PSEN1, PSEN2 mutations (autosomal dominant early-onset)
Clinical Features & Diagnosis
  • Early Stage: Memory impairment (especially episodic), anomia, visuospatial deficits, executive dysfunction
  • Middle Stage: Worsening memory, language deficits, apraxia, agitation, wandering, sleep disturbances
  • Late Stage: Mutism, incontinence, inability to walk, dependence for all ADLs
  • NIA-AA Criteria: Probable AD dementia: cognitive decline in ≥2 domains, progressive worsening, not due to other causes
  • Biomarkers: CSF: low Aβ42, high phosphorylated tau. PET: amyloid positivity, FDG-PET (temporoparietal hypometabolism)

Parkinson’s Disease

Pathophysiology
  • Dopamine Depletion: Loss of dopaminergic neurons in substantia nigra pars compacta → striatal dopamine deficiency
  • Lewy Bodies: Intracellular inclusions containing α-synuclein, ubiquitin, neurofilaments
  • Braak Staging: Stage 1-2: olfactory bulb, medulla; Stage 3-4: midbrain (substantia nigra), basal forebrain; Stage 5-6: neocortex
  • Genetic Forms: 10-15% familial, mutations in LRRK2 (most common), PARKIN, PINK1, DJ-1, SNCA
Clinical Features

Motor Features (TRAP): Tremor (resting, 4-6 Hz, pill-rolling), Rigidity (cogwheel, lead-pipe), Akinesia/Bradykinesia (slow movements, decreased amplitude), Postural instability (late feature). Non-motor Features: Depression, anxiety, REM sleep behavior disorder, anosmia, constipation, orthostatic hypotension, cognitive impairment.

Diagnostic Criteria (MDS 2015)
  • Absolute exclusion criteria: Cerebellar signs, downward vertical supranuclear gaze palsy, frontotemporal dementia within first year, parkinsonism restricted to lower limbs >3 years, treatment with dopamine blockers
  • Supportive criteria: Clear beneficial response to dopaminergic therapy, levodopa-induced dyskinesias, rest tremor, olfactory loss, cardiac sympathetic denervation on MIBG
  • Red flags: Rapid progression, early bulbar dysfunction, inspiratory respiratory dysfunction, severe autonomic failure

Neurodegenerative Disease Management

1
Alzheimer’s Disease Treatment

Cholinesterase inhibitors: Donepezil 5-10mg daily (start 5mg, increase after 4-6 weeks), Rivastigmine 1.5-6mg BID (patch 4.6-13.3 mg/24h), Galantamine 4-12mg BID. NMDA antagonist: Memantine 5-20mg daily (titrate weekly). Disease-modifying: Aducanumab, lecanemab, donanemab (monoclonal antibodies targeting Aβ). Non-pharmacologic: Cognitive stimulation, physical activity, caregiver support.

2
Parkinson’s Disease: Early Stage

Levodopa/carbidopa: 25/100mg TID, increase gradually. Most effective but risk of motor complications. Dopamine agonists: Pramipexole 0.125-1.5mg TID, Ropinirole 0.25-8mg TID. MAO-B inhibitors: Rasagiline 1mg daily, Selegiline 5mg BID. Anticholinergics: Benztropine 0.5-2mg BID (mainly for tremor, avoid in elderly). Amantadine: 100mg BID-TID for tremor or dyskinesias.

3
Parkinson’s Disease: Advanced Stage

Motor fluctuations: Wearing off → shorten dosing interval, add COMT inhibitor (entacapone 200mg with each levodopa), add MAO-B inhibitor. Dyskinesias: Reduce individual levodopa dose, add amantadine. Device-aided therapies: Deep brain stimulation (STN or GPi), levodopa-carbidopa intestinal gel, apomorphine pump.

4
Non-motor Symptom Management

Depression: SSRIs (sertraline, citalopram), SNRIs (venlafaxine). Psychosis: Reduce/stop anticholinergics, amantadine, dopamine agonists first. If needed: quetiapine 12.5-50mg HS, clozapine 6.25-50mg daily (requires weekly CBC). Sleep: REM sleep behavior disorder: clonazepam 0.5-1mg HS, melatonin 3-12mg HS. Autonomic: Orthostatic hypotension: fludrocortisone 0.1-0.3mg daily, midodrine 2.5-10mg TID.

5
Other Dementias

Vascular dementia: Control vascular risk factors, cholinesterase inhibitors may help. Lewy body dementia: Extreme sensitivity to antipsychotics (avoid typical antipsychotics), cholinesterase inhibitors first-line. Frontotemporal dementia: SSRIs for behavioral symptoms, speech therapy for primary progressive aphasia.

Parkinson’s Medication Guide

Drug Class Examples Mechanism Dosing Key Side Effects Special Considerations
Levodopa/Carbidopa Sinemet, Rytary Dopamine precursor + DDC inhibitor 25/100mg TID, titrate to effect Nausea, dyskinesias, hallucinations, wearing off, on-off Take 30 min before meals, protein interferes with absorption
Dopamine Agonists Pramipexole, Ropinirole, Rotigotine Direct D2 receptor stimulation Pramipexole: 0.125-1.5mg TID
Ropinirole: 0.25-8mg TID
Rotigotine patch: 2-8 mg/24h		 Sleep attacks, impulse control disorders, edema, nausea, hallucinations Start low, titrate slowly over weeks. Higher risk of ICDs than levodopa.
MAO-B Inhibitors Rasagiline, Selegiline, Safinamide Inhibit dopamine breakdown Rasagiline: 1mg daily
Selegiline: 5mg BID
Safinamide: 50-100mg daily		 Insomnia (selegiline), hypertension with tyramine (rare with selective MAO-B) Mild symptomatic benefit, may delay need for levodopa
COMT Inhibitors Entacapone, Tolcapone Inhibit peripheral levodopa metabolism Entacapone: 200mg with each levodopa dose
Tolcapone: 100-200mg TID		 Diarrhea, orange urine, dyskinesias, hepatotoxicity (tolcapone) Extend levodopa effect, reduce wearing off. Monitor LFTs with tolcapone.
Anticholinergics Benztropine, Trihexyphenidyl Antagonize muscarinic receptors Benztropine: 0.5-2mg BID
Trihexyphenidyl: 1-2mg TID		 Confusion, dry mouth, constipation, urinary retention, glaucoma exacerbation Mainly for tremor in young patients. Avoid in elderly.
Amantadine Amantadine NMDA antagonist, anticholinergic, dopamine release 100mg BID-TID, ER 274mg daily Livedo reticularis, edema, confusion, hallucinations Useful for dyskinesias, tremor. Reduce dose in renal impairment.
Levodopa/Carbidopa
25/100mg TID, most effective. Side effects: dyskinesias, hallucinations, wearing off. Take 30 min before meals.
Dopamine Agonists
Pramipexole 0.125-1.5mg TID. Risk of impulse control disorders, sleep attacks. Start low, titrate slowly.
MAO-B Inhibitors
Rasagiline 1mg daily. Mild benefit, may delay levodopa. Generally well-tolerated.
COMT Inhibitors
Entacapone 200mg with each levodopa. Reduces wearing off. Side effect: diarrhea, orange urine.

Dementia Differential Diagnosis

Type Clinical Features Imaging Findings Pathology Treatment
Alzheimer’s Disease Memory loss first, gradual onset, aphasia/apraxia later Medial temporal atrophy, parietal hypometabolism (FDG-PET), amyloid PET positive Amyloid plaques, neurofibrillary tangles Cholinesterase inhibitors, memantine, anti-amyloid antibodies
Vascular Dementia Stepwise decline, focal signs, executive dysfunction early Multiple infarcts, white matter disease, strategic infarcts Infarcts, small vessel disease Vascular risk factor control, cholinesterase inhibitors may help
Lewy Body Dementia Fluctuating cognition, visual hallucinations, parkinsonism, REM sleep behavior disorder Occipital hypometabolism, normal medial temporal lobes Lewy bodies (α-synuclein) Cholinesterase inhibitors, avoid antipsychotics
Frontotemporal Dementia Behavior/personality change (bvFTD) or language impairment (PPA), relative sparing of memory Frontal/temporal atrophy, asymmetric Tau or TDP-43 inclusions SSRIs for behavior, speech therapy
Normal Pressure Hydrocephalus Triad: gait apraxia, urinary incontinence, cognitive impairment Ventricular enlargement out of proportion to atrophy CSF absorption impairment Ventriculoperitoneal shunt, lumbar puncture trial
Key Clinical Pearls – Neurodegenerative Diseases
  • Alzheimer’s vs normal aging: Forgetting entire experiences vs forgetting details, getting lost in familiar places vs temporarily forgetting way.
  • MCI (mild cognitive impairment): Objective cognitive impairment with preserved function. 10-15% progress to dementia annually.
  • Parkinson’s plus syndromes: Poor response to levodopa, early falls, vertical gaze palsy, autonomic failure, cerebellar signs.
  • Multiple system atrophy: Parkinsonism + autonomic failure + cerebellar signs. Hot cross bun sign on MRI pons.
  • Progressive supranuclear palsy: Vertical supranuclear gaze palsy, axial rigidity, early falls, cognitive/behavioral changes.
  • Corticobasal degeneration: Asymmetric parkinsonism, alien limb phenomenon, cortical sensory loss, apraxia.
  • Dementia with Lewy bodies: One-year rule: dementia before or within one year of parkinsonism. Extreme neuroleptic sensitivity.
  • Frontotemporal dementia subtypes: Behavioral variant (disinhibition, apathy), semantic variant (anomia, loss of word meaning), nonfluent variant (agrammatism, apraxia of speech).
  • REM sleep behavior disorder: Often precedes synucleinopathies (PD, DLB, MSA) by years. Treat with clonazepam or melatonin.
  • Impulse control disorders in PD: Gambling, shopping, eating, hypersexuality. Associated with dopamine agonists.
High-Yield Exam Points:
  • Alzheimer’s biomarkers: Low Aβ42, high phosphorylated tau in CSF; amyloid PET positive.
  • Cholinesterase inhibitors: Donepezil, rivastigmine, galantamine. Common side effect: bradycardia.
  • Parkinson’s motor features: TRAP (Tremor, Rigidity, Akinesia, Postural instability).
  • Levodopa complications: Motor fluctuations (wearing off, on-off), dyskinesias (peak dose, diphasic).
  • Dopamine agonists: Higher risk of impulse control disorders than levodopa.
  • Multiple system atrophy: Parkinsonism + autonomic failure + cerebellar signs. Hot cross bun sign.
  • Progressive supranuclear palsy: Vertical gaze palsy, axial rigidity, early falls backwards.
  • Lewy body dementia: Fluctuating cognition, visual hallucinations, parkinsonism, REM sleep behavior disorder.
  • Normal pressure hydrocephalus: Triad of gait apraxia, urinary incontinence, dementia. Treat with shunt.
  • Frontotemporal dementia: Behavioral/personality changes or progressive aphasia with relative memory sparing.
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Meningitis & Encephalitis

Disease Introduction

Central nervous system infections represent medical emergencies requiring prompt recognition and treatment to prevent mortality and significant morbidity. Meningitis is inflammation of the meninges, while encephalitis involves inflammation of the brain parenchyma. According to Harrison’s Principles of Internal Medicine, acute bacterial meningitis has mortality rates of 15-25% even with appropriate antibiotic therapy, with neurological sequelae in 25-50% of survivors.

The clinical presentation can vary from subtle symptoms in immunocompromised patients to fulminant illness with rapid neurological deterioration. The differential diagnosis is broad and includes infectious and non-infectious causes. Lumbar puncture with cerebrospinal fluid analysis remains the cornerstone of diagnosis, with neuroimaging often performed first to rule out contraindications.

Prerequisite Anatomy & Pathophysiology

Blood-Brain Barrier & Meninges
  • Meningeal Layers: Dura mater (outer), arachnoid mater (middle, contains CSF), pia mater (inner, adherent to brain)
  • Subarachnoid Space: Between arachnoid and pia, contains CSF, cerebral arteries, veins
  • Blood-Brain Barrier: Tight junctions between endothelial cells, astrocytes, pericytes. Protects from pathogens but limits antibiotic penetration
  • CSF Production: Choroid plexus produces 500mL/day, total volume 150mL, turns over 3-4 times daily
Pathophysiological Mechanisms
  • Bacterial Invasion: Nasopharyngeal colonization → bacteremia → crossing BBB via endothelial invasion or through choroid plexus
  • Inflammatory Cascade: Bacterial cell wall components (LPS, teichoic acid) → cytokine release (TNF-α, IL-1, IL-6) → increased BBB permeability → cerebral edema
  • Increased ICP: Vasogenic edema (BBB breakdown), cytotoxic edema (cellular injury), interstitial edema (obstructed CSF flow)

Bacterial Meningitis

Epidemiology & Common Pathogens
Age Group Common Pathogens Empirical Therapy Duration
Neonates (<1 month) Group B Strep, E. coli, Listeria Ampicillin + Cefotaxime or Gentamicin 14-21 days
Infants/Children (1-23 months) S. pneumoniae, N. meningitidis, H. influenzae Vancomycin + Ceftriaxone or Cefotaxime 7-14 days
Adults (18-50 years) S. pneumoniae, N. meningitidis Vancomycin + Ceftriaxone or Cefotaxime 10-14 days
Elderly (>50 years) or Immunocompromised S. pneumoniae, Listeria, Gram-negatives Ampicillin + Vancomycin + Ceftriaxone 14-21 days
Post-neurosurgery or CSF shunt S. aureus (including MRSA), Coagulase-negative Staph, Gram-negatives Vancomycin + Ceftazidime or Meropenem 10-14 days, often require shunt removal
Clinical Features
  • Classic Triad (present in <50%): Fever, neck stiffness, altered mental status
  • Other Symptoms: Headache (usually severe), photophobia, nausea/vomiting, seizures (20-30%)
  • Physical Exam: Nuchal rigidity, Kernig’s sign (pain with knee extension when hip flexed), Brudzinski’s sign (neck flexion causes hip/knee flexion), petechial/purpuric rash (meningococcus)
  • Complications: Cerebral edema, hydrocephalus, seizures, SIADH, hearing loss, cranial nerve deficits, cerebral venous thrombosis
Diagnostic Evaluation
1
Immediate Stabilization & Blood Cultures

ABCs: Consider intubation if GCS ≤8, compromised airway. Blood cultures: 2 sets before antibiotics. Empirical antibiotics: Do not delay for imaging/LP if clinical suspicion high. Dexamethasone: 10mg IV then 10mg q6h ×4 days (start with or before antibiotics for suspected pneumococcal meningitis).

2
Neuroimaging

CT head before LP if: Immunocompromised, history of CNS disease, new-onset seizure, papilledema, focal deficit, altered consciousness. Findings: May be normal early, leptomeningeal enhancement, hydrocephalus, cerebral edema.

3
Lumbar Puncture

Opening pressure: Normal 7-20 cm H₂O, elevated in bacterial meningitis. CSF analysis: Cell count with differential, glucose, protein, Gram stain, culture, PCR if available. Tube 1: Chemistry, Tube 2: Microbiology, Tube 3: Cell count, Tube 4: Optional (cytology, special tests).

4
CSF Interpretation
Parameter Normal Bacterial Viral Fungal/TB
Opening Pressure 7-20 cm H₂O Elevated (>25) Normal/mildly elevated Elevated
WBC count 0-5 cells/μL 100-10,000 (PMN predominant) 10-500 (lymphocytic) 10-500 (lymphocytic)
Protein 15-45 mg/dL 100-500 Normal/mildly elevated 50-500
Glucose 50-80 mg/dL (2/3 serum) Low (<40, <50% serum) Normal Low
Gram stain Negative Positive 60-90% Negative Negative (except cryptococcus)

Bacterial Meningitis Treatment Protocol

1
Immediate Empiric Therapy (0-30 minutes)

Adults 18-50: Vancomycin 15-20 mg/kg IV q8-12h + Ceftriaxone 2g IV q12h. Adults >50 or immunocompromised: Add Ampicillin 2g IV q4h for Listeria coverage. Penicillin allergy: Vancomycin + Moxifloxacin or Meropenem. Dexamethasone: 10mg IV with first antibiotic dose, then 10mg q6h ×4 days (if suspected pneumococcal).

2
Definitive Therapy Based on Culture (24-72 hours)

S. pneumoniae (PCN MIC <0.1): Penicillin G 4 million units IV q4h or Ceftriaxone. PCN-resistant (MIC ≥0.12): Ceftriaxone + Vancomycin. N. meningitidis: Penicillin G or Ceftriaxone. Listeria: Ampicillin + Gentamicin (synergy). Gram-negatives: Ceftriaxone or Meropenem.

3
Adjunctive Therapies

ICP management: Head elevation 30°, avoid hypotonic fluids, mannitol 0.25-1 g/kg for signs of herniation. Seizure prophylaxis: Not routine, treat seizures with benzodiazepines + load with AED if recurrent. Fluid/electrolytes: Monitor for SIADH, maintain euvolemia.

4
Monitoring & Duration

Repeat LP: Consider at 24-48h if no clinical improvement or drug-resistant organism. Duration: S. pneumoniae: 10-14 days; N. meningitidis: 7 days; Gram-negatives: 21 days; Listeria: 21 days. Steroid duration: 4 days total.

5
Infection Control & Prophylaxis

Droplet precautions: For N. meningitidis until 24h of antibiotics. Chemoprophylaxis: For close contacts of meningococcal meningitis: Rifampin 600mg BID ×2 days, Ciprofloxacin 500mg once, or Ceftriaxone 250mg IM once. Vaccination: PCV13, PPSV23, MenACWY, MenB for at-risk groups.

Viral Meningitis & Encephalitis

Common Viral Pathogens
Syndrome Common Pathogens Seasonality Diagnostic Tests Treatment
Aseptic Meningitis Enteroviruses (80-90%), HSV-2, VZV, HIV Summer/fall CSF PCR, viral culture Supportive, acyclovir if HSV suspected
Encephalitis HSV-1 (most common sporadic), VZV, Enteroviruses, Arboviruses (West Nile, EEE, WEE) Arboviruses: summer CSF PCR, MRI (temporal lobe for HSV) Acyclovir for HSV, supportive for others
Myelitis Enteroviruses (polio, EV-D68), HSV-2, VZV, West Nile Variable CSF PCR, MRI spine Supportive, acyclovir if HSV/VZV
Post-infectious (ADEM) Following viral infection or vaccination Variable MRI (multifocal white matter lesions) High-dose steroids, IVIG, plasmapheresis
Herpes Simplex Encephalitis (HSE)
  • Clinical Features: Fever, headache, altered mental status, focal deficits (aphasia, hemiparesis), seizures, temporal lobe signs (olfactory/gustatory hallucinations, personality changes)
  • MRI Findings: T2/FLAIR hyperintensity in medial temporal lobes, insula, cingulate gyrus (often unilateral early, becomes bilateral)
  • CSF Findings: Lymphocytic pleocytosis (10-500 WBCs), elevated protein, normal/low glucose, RBCs common, HSV PCR positive (sensitivity 98%, specificity 94%)
  • Treatment: Acyclovir 10 mg/kg IV q8h (adjusted for renal function) ×14-21 days. Start empirically if suspicion high.

Autoimmune Encephalitis

Common Antibody-Mediated Syndromes
Antibody Clinical Syndrome Tumor Association Diagnostic Clues Treatment
Anti-NMDA Psychiatric symptoms, seizures, dyskinesias, autonomic instability, decreased consciousness Ovarian teratoma (40% of women) Young women, CSF pleocytosis, oligoclonal bands Steroids, IVIG, plasmapheresis, rituximab, cyclophosphamide, tumor removal
Anti-LGI1 Limbic encephalitis, faciobrachial dystonic seizures, hyponatremia Thymoma, small cell lung cancer Older men, low sodium, FBDS characteristic Steroids, IVIG, tumor search
Anti-CASPR2 Morvan syndrome (encephalitis, neuromyotonia, autonomic dysfunction, insomnia) Thymoma Neuromyotonia on EMG Steroids, IVIG, tumor removal
Anti-GABAb Limbic encephalitis, prominent seizures Small cell lung cancer (50%) Refractory seizures, MRI temporal lobe hyperintensity Steroids, IVIG, tumor search/treatment
Anti-AMPAR Limbic encephalitis, psychiatric symptoms Thymoma, lung, breast cancer Relapsing course Steroids, IVIG, tumor removal
Key Clinical Pearls – CNS Infections
  • Partially treated meningitis: Previous antibiotics → CSF may show lymphocytic predominance, negative cultures. PCR can still identify pathogen.
  • Mollaret’s meningitis: Recurrent benign lymphocytic meningitis, often HSV-2 related. Self-limited episodes.
  • Parameningeal focus: Sinusitis, otitis, brain abscess can cause meningeal signs with sterile CSF. Need imaging to identify source.
  • Tuberculous meningitis: Subacute onset, cranial neuropathies, basal enhancement on MRI, CSF: lymphocytic, very low glucose, high protein.
  • Cryptococcal meningitis: HIV patients with CD4 <100. CSF: India ink positive, cryptococcal antigen positive, often mild symptoms.
  • Lyme neuroborreliosis: Lymphocytic meningitis, cranial neuritis (especially facial nerve), radiculoneuritis. CSF: lymphocytic pleocytosis, positive Lyme antibodies.
  • Neurosyphilis: Tabes dorsalis (lightning pains, ataxia, Argyll Robertson pupils), general paresis (dementia, personality change), meningovascular.
  • Brain abscess: Ring-enhancing lesion with edema, often from contiguous spread (sinus, ear) or hematogenous (endocarditis).
  • Varicella zoster: Can cause meningitis, encephalitis, vasculitis (especially with ophthalmic distribution).
  • HIV CNS manifestations: Primary HIV seroconversion (aseptic meningitis), AIDS dementia complex, toxoplasmosis, PML, primary CNS lymphoma.
High-Yield Exam Points:
  • Bacterial meningitis empiric therapy: Vancomycin + Ceftriaxone for adults. Add ampicillin if >50 or immunocompromised (Listeria coverage).
  • Dexamethasone: 10mg IV q6h ×4 days, start with first antibiotic dose for suspected pneumococcal meningitis.
  • HSV encephalitis: Acyclovir 10 mg/kg IV q8h ×14-21 days. Temporal lobe involvement on MRI.
  • CSF in bacterial meningitis: High WBC (PMN predominance), low glucose (<40), high protein (>100).
  • CSF in viral meningitis: Moderate WBC (lymphocytic), normal glucose, mildly elevated protein.
  • Anti-NMDA receptor encephalitis: Young women, psychiatric symptoms, seizures, dyskinesias, ovarian teratoma association.
  • Tuberculous meningitis: Basal enhancement, cranial neuropathies, very low CSF glucose.
  • Cryptococcal meningitis: India ink, cryptococcal antigen. Common in AIDS with CD4 <100.
  • Lyme meningitis: Facial nerve palsy (often bilateral), lymphocytic pleocytosis, positive Lyme serology in CSF.
  • Brain abscess: Ring-enhancing lesion with edema, often need surgical drainage in addition to antibiotics.
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Headache Disorders

Disease Introduction

Headache disorders are among the most common neurological conditions, with lifetime prevalence of 96% for men and 99% for women. According to the International Classification of Headache Disorders (ICHD-3), headaches are classified as primary (no underlying structural cause) or secondary (due to another condition). Primary headaches include migraine, tension-type headache, and trigeminal autonomic cephalalgias (cluster headache).

Migraine affects approximately 12% of the population, with higher prevalence in women (18%) than men (6%). Chronic migraine (≥15 headache days/month for >3 months) affects 1-2% of the population and is a major cause of disability. Secondary headaches require urgent evaluation to identify and treat the underlying cause, which can range from benign conditions to life-threatening emergencies.

Prerequisite Pain Pathways & Anatomy

Pain-Sensitive Structures
  • Intracranial: Dura mater (especially near arteries), dural sinuses, cerebral arteries (proximal), venous sinuses, parts of pia-arachnoid
  • Extracranial: Skin, subcutaneous tissue, muscles, arteries, periosteum, sinuses, teeth, eyes, ears
  • Insensitive: Brain parenchyma, most of pia-arachnoid, ependyma, choroid plexus
Pain Pathways
  • Trigeminovascular System: Trigeminal nerve (V1) innervates anterior/middle fossa, V2/V3 and upper cervical roots (C1-C3) innervate posterior fossa
  • Referred Pain: Supratentorial structures → forehead/eye (V1), Infratentorial structures → occiput/nuchal (C2-C3)
  • Central Modulation: Periaqueductal gray, raphe nuclei, locus coeruleus modulate pain transmission

Migraine

Pathophysiology
  • Cortical Spreading Depression: Wave of neuronal depolarization followed by suppression, spreads at 2-3 mm/min across cortex
  • Trigeminovascular Activation: CSD activates trigeminal nerve → release of CGRP, substance P → neurogenic inflammation, vasodilation
  • Central Sensitization: Increased sensitivity in trigeminal nucleus caudalis → cutaneous allodynia (pain from non-painful stimuli)
  • Serotonin (5-HT): 5-HT1B/1D agonists (triptans) inhibit neuropeptide release, cause vasoconstriction
ICHD-3 Diagnostic Criteria for Migraine Without Aura
  • A: ≥5 attacks fulfilling criteria B-D
  • B: Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated)
  • C: Headache has ≥2 of: unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity
  • D: During headache ≥1 of: nausea and/or vomiting, photophobia and phonophobia
  • E: Not better accounted for by another ICHD-3 diagnosis
Migraine With Aura
  • Typical aura: Fully reversible visual, sensory, or speech/language symptoms, no motor weakness
  • Visual aura: Most common (90%), fortification spectra (zigzag lines), scotoma, photopsia
  • Timing: Aura develops gradually over ≥5 minutes, lasts 5-60 minutes, followed by headache within 60 minutes
  • Hemiplegic migraine: Motor weakness during aura, familial (CACNA1A, ATP1A2, SCN1A mutations) or sporadic

Tension-Type Headache

Clinical Features
  • Pain quality: Pressing/tightening (non-pulsating), mild to moderate intensity
  • Location: Bilateral, band-like distribution
  • Duration: 30 minutes to 7 days
  • Associated symptoms: No nausea/vomiting, may have photophobia OR phonophobia (but not both)
  • Exacerbating factors: Stress, poor posture, jaw clenching, lack of sleep
Frequency Classification
  • Infrequent episodic: <1 day/month
  • Frequent episodic: 1-14 days/month
  • Chronic: ≥15 days/month for >3 months

Cluster Headache

Clinical Features
  • Pain: Severe, excruciating, orbital/supraorbital/temporal, strictly unilateral
  • Duration: 15-180 minutes if untreated
  • Frequency: 1 every other day to 8 per day during cluster period
  • Autonomic features (ipsilateral): Conjunctival injection/lacrimation, nasal congestion/rhinorrhea, forehead/facial sweating, miosis/ptosis, eyelid edema
  • Behavior during attack: Restlessness or agitation (cannot sit still)
  • Pattern: Clusters last weeks to months, followed by remission months to years

Secondary Headaches – Red Flags

SNOOP4 Mnemonic for Secondary Headache
  • S – Systemic symptoms: Fever, weight loss, myalgias, jaw claudication (temporal arteritis)
  • N – Neurologic symptoms/signs: Focal deficits, seizures, confusion, papilledema
  • O – Onset sudden/thunderclap: Peak intensity within seconds to minutes (SAH, RCVS, pituitary apoplexy)
  • O – Older age onset: New headache after age 50 (temporal arteritis, malignancy)
  • P – Pattern change: Progressive worsening, different character
  • P – Precipitated by: Valsalva, exertion, position (ICP changes)
  • P – Pregnancy/postpartum: CVT, preeclampsia, pituitary apoplexy
  • P – Papilledema: Increased ICP (tumor, IIH, CVT)
Common Secondary Headaches
Cause Clinical Features Diagnostic Tests Treatment
Subarachnoid Hemorrhage Thunderclap headache, neck stiffness, photophobia, may have loss of consciousness Non-contrast CT (sensitivity 98% within 12h), LP if CT negative (xanthochromia) Neurosurgery consultation, BP control, nimodipine for vasospasm
Giant Cell Arteritis Age >50, temporal headache, jaw claudication, scalp tenderness, vision loss Elevated ESR/CRP, temporal artery biopsy (gold standard) High-dose steroids immediately if vision threatened (prednisone 1 mg/kg/day)
Idiopathic Intracranial Hypertension Obese women of childbearing age, pulsatile tinnitus, transient visual obscurations, papilledema MRI/MRV to rule out CVT, LP: elevated opening pressure (>25 cm H₂O), normal CSF Weight loss, acetazolamide, topiramate, serial LPs, shunt if vision threatened
Cerebral Venous Thrombosis Headache (most common symptom), seizures, focal deficits, papilledema MRI/MRV (empty delta sign), CTV Anticoagulation (heparin then warfarin), treat underlying cause
Meningitis/Encephalitis Fever, neck stiffness, altered mental status, photophobia LP (CSF analysis), MRI brain Empiric antibiotics/antivirals, supportive care

Headache Management Protocol

1
Acute Migraine Treatment

Mild-moderate attacks: NSAIDs (ibuprofen 400-800mg, naproxen 500mg) or acetaminophen 1000mg. Moderate-severe attacks: Triptans: sumatriptan 50-100mg PO, 20mg nasal spray, 6mg SC; rizatriptan 10mg; eletriptan 40mg. Nausea: Metoclopramide 10mg, prochlorperazine 10mg. Rescue: Dexamethasone 10mg IV/IM to prevent recurrence.

2
Migraine Preventive Therapy

Indications: ≥4 headache days/month, ≥8 days with acute medication use/month, disability despite acute treatment. First-line: Beta-blockers (propranolol 40-240mg daily, metoprolol 50-200mg daily), Topiramate 25-100mg BID, Amitriptyline 10-150mg HS. Second-line: Valproate 500-1500mg daily, Venlafaxine 75-225mg daily. CGRP mAbs: Erenumab, fremanezumab, galcanezumab for refractory cases.

3
Cluster Headache Acute Treatment

First-line: High-flow oxygen 100% via non-rebreather mask at 12-15 L/min for 15-20 minutes. Triptans: Sumatriptan 6mg SC or 20mg nasal spray, zolmitriptan 5mg nasal spray. Other: Intranasal lidocaine 4% (sphenopalatine ganglion block). Avoid: Oral medications (too slow).

4
Cluster Headache Preventive Therapy

Transitional: Prednisone 60mg daily ×5 days then taper over 2-3 weeks, greater occipital nerve block. Maintenance: Verapamil 240-960mg daily (start 80mg TID, titrate, monitor ECG), lithium 300-900mg daily (monitor levels). Other: Topiramate, melatonin 9mg HS.

5
Tension-Type Headache Management

Acute: NSAIDs, acetaminophen, caffeine combinations. Limit use to <15 days/month to prevent medication overuse headache. Preventive: Amitriptyline 10-75mg HS (first-line), venlafaxine, mirtazapine. Non-pharmacologic: Physical therapy, stress management, biofeedback, acupuncture.

Medication Overuse Headache (MOH)
  • Definition: Headache occurring on ≥15 days/month in patient with pre-existing headache disorder, developing as consequence of regular overuse of acute headache medication for >3 months
  • Risk: Simple analgesics ≥15 days/month, triptans/ergots/opioids ≥10 days/month, combination analgesics ≥10 days/month
  • Management: Abrupt withdrawal of overused medication (may need bridge therapy with prednisone, NSAIDs, antiemetics), start preventive therapy, patient education, follow-up
  • Bridge therapy: Prednisone 60mg daily ×5 days then taper, naproxen 500mg BID ×2 weeks, antiemetics for withdrawal symptoms

Headache Medication Guide

Drug Class Examples Mechanism Dosing Key Side Effects Contraindications
Triptans Sumatriptan, Rizatriptan, Eletriptan, Zolmitriptan 5-HT1B/1D agonists: vasoconstriction, inhibit neuropeptide release Sumatriptan: 50-100mg PO, 6mg SC, 20mg nasal
Rizatriptan: 5-10mg PO
Eletriptan: 40mg PO		 Chest tightness, paresthesias, flushing, dizziness, fatigue CAD, PVD, uncontrolled HTN, hemiplegic/basilar migraine, within 24h of ergots/other triptans
Ergots DHE (dihydroergotamine) Non-selective 5-HT agonists, also α-adrenergic, dopaminergic DHE: 1mg IV/IM/SC, repeat hourly to max 3mg/day Nausea (pretreat with antiemetic), vasoconstriction, ergotism Same as triptans plus renal/hepatic impairment, sepsis, pregnancy
Gepants Ubrogepant, Rimegepant CGRP receptor antagonists Ubrogepant: 50-100mg PO
Rimegepant: 75mg PO		 Nausea, somnolence, dry mouth Severe hepatic impairment
Ditans Lasmiditan 5-HT1F agonist (no vasoconstriction) 50-200mg PO Dizziness, paresthesias, sedation, driving impairment Avoid with CNS depressants, do not drive for 8h after dose
CGRP mAbs Erenumab, Fremanezumab, Galcanezumab Monoclonal antibodies against CGRP or its receptor Erenumab: 70-140mg SC monthly
Fremanezumab: 225mg SC monthly or 675mg quarterly
Galcanezumab: 240mg load then 120mg monthly		 Injection site reactions, constipation None absolute
Triptans (Sumatriptan)
50-100mg PO, 6mg SC, 20mg nasal. 5-HT1B/1D agonist. Contraindicated in CAD, uncontrolled HTN, hemiplegic migraine.
CGRP mAbs (Erenumab)
70-140mg SC monthly. For migraine prevention. Injection site reactions, constipation side effects.
Gepants (Ubrogepant)
50-100mg PO. CGRP receptor antagonist for acute treatment. No vasoconstriction, safe in cardiovascular disease.
Ditans (Lasmiditan)
50-200mg PO. 5-HT1F agonist, no vasoconstriction. Causes sedation/dizziness, avoid driving for 8h.
Key Clinical Pearls – Headache Disorders
  • Thunderclap headache: Peak intensity within seconds to minutes. Differential: SAH (most common), RCVS, pituitary apoplexy, CVT, cervical artery dissection.
  • New daily persistent headache: Abrupt onset of continuous headache, remember patient’s exact day it started. Can be primary or secondary.
  • Trigeminal neuralgia: Brief, electric shock-like pain in V2/V3 distribution, triggered by light touch. First-line: carbamazepine.
  • Hemicrania continua: Unilateral continuous headache with autonomic features, absolute response to indomethacin.
  • Paroxysmal hemicrania: Brief (2-30 min) severe unilateral attacks with autonomic features, >5/day, absolute response to indomethacin.
  • SUNCT/SUNA: Short-lasting (5-240s) unilateral neuralgiform headache with conjunctival injection and tearing. Treatment resistant.
  • Hypnic headache: Older adults, awakens patient from sleep at same time nightly, responds to lithium, caffeine, indomethacin.
  • Nummular headache: Coin-shaped area of pain on scalp, constant or intermittent.
  • Primary exertional headache: Bilateral throbbing headache during or after exertion, lasts 5 min to 48h. Rule out SAH, arterial dissection.
  • Primary sexual headache: Explosive (orgasmic) or dull (pre-orgasmic). Rule out SAH.
High-Yield Exam Points:
  • Migraine with aura: Visual/sensory/speech symptoms lasting 5-60 minutes, followed by headache within 60 minutes.
  • Cluster headache: Severe unilateral orbital/temporal pain with autonomic features, restlessness, lasts 15-180 minutes.
  • Thunderclap headache differential: SAH (do CT then LP if negative), RCVS, CVT, pituitary apoplexy.
  • Temporal arteritis: Age >50, headache, jaw claudication, elevated ESR/CRP, treat with high-dose steroids to prevent blindness.
  • Idiopathic intracranial hypertension: Obese women, papilledema, pulsatile tinnitus, elevated opening pressure on LP.
  • Medication overuse headache: Headache ≥15 days/month with regular overuse of acute medications >3 months.
  • Triptan contraindications: CAD, PVD, uncontrolled HTN, hemiplegic/basilar migraine.
  • Indomethacin-responsive headaches: Hemicrania continua, paroxysmal hemicrania.
  • Trigeminal neuralgia: Brief electric shocks in V2/V3, triggered by light touch, carbamazepine first-line.
  • Red flags (SNOOP4): Systemic symptoms, Neurologic deficits, Onset sudden, Older age, Pattern change, Precipitated, Pregnancy, Papilledema.
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Dizziness & Vertigo

Disease Introduction

Dizziness is a common complaint affecting approximately 20-30% of the population at some point, with prevalence increasing with age. According to Harrison’s Principles of Internal Medicine, dizziness can be categorized into four main types: vertigo (illusion of motion), presyncope (feeling of impending faint), disequilibrium (imbalance without abnormal head sensation), and non-specific dizziness (often psychiatric). Vertigo specifically results from dysfunction of the vestibular system, either peripheral (inner ear or vestibular nerve) or central (brainstem or cerebellum).

Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo, accounting for 20-30% of cases. Acute vestibular neuritis is the most common cause of acute spontaneous vertigo. Differentiating peripheral from central causes is critical as central causes may indicate serious neurological conditions such as stroke or multiple sclerosis.

Prerequisite Vestibular Anatomy & Physiology

Vestibular System Components
  • Peripheral Apparatus: Semicircular canals (anterior, posterior, horizontal) detect angular acceleration; Otolith organs (utricle, saccule) detect linear acceleration and gravity
  • Vestibular Nerve: Superior division (anterior/horizontal canals, utricle), inferior division (posterior canal, saccule)
  • Central Connections: Vestibular nuclei (medulla/pons) → medial longitudinal fasciculus (VOR), vestibulospinal tract (posture), thalamus → cortex (perception)
  • Vestibulo-ocular Reflex (VOR): Stabilizes gaze during head movement. Head rotation → vestibular signal → eye movement in opposite direction
Nystagmus Physiology
  • Definition: Rhythmic oscillation of the eyes with slow phase (pathologic drift) and fast phase (corrective movement)
  • Peripheral nystagmus: Unidirectional, horizontal-torsional, suppressed by fixation, fatigue with repeated testing
  • Central nystagmus: May be bidirectional, pure vertical/torsional, not suppressed by fixation, no fatigue
Four-Type Classification Approach
Type Description Key Questions Exam Findings Common Causes
Vertigo Illusion of motion (spinning, tilting) “Does the room spin?” “Is it worse with head movement?” Nystagmus, positive head impulse test, difficulty with tandem gait BPPV, vestibular neuritis, Meniere’s, vestibular migraine
Presyncope Feeling of impending faint “Do you feel lightheaded?” “Does it happen when you stand up?” Orthostatic hypotension, carotid sinus hypersensitivity, arrhythmias Orthostatic hypotension, vasovagal, arrhythmia, medication side effect
Disequilibrium Imbalance without abnormal head sensation “Do you feel unsteady on your feet?” “Is it worse in the dark?” Wide-based gait, positive Romberg, proprioceptive loss Peripheral neuropathy, cerebellar degeneration, Parkinson’s, sensory deficits
Non-specific Vague lightheadedness, floating, dissociation “Does it feel like you’re disconnected?” “Is it constant?” Often normal exam, hyperventilation may reproduce Anxiety/panic, hyperventilation, depression, somatization

Benign Paroxysmal Positional Vertigo (BPPV)

Pathophysiology & Clinical Features
  • Canalithiasis: Otoconia dislodged from utricle → float freely in semicircular canal (most common, 85-95%)
  • Cupulolithiasis: Otoconia adherent to cupula (less common, 5-15%)
  • Most common canal: Posterior (85-90%), then horizontal (5-10%), anterior (rare)
  • Triggers: Rolling over in bed, looking up, bending forward
  • Duration: Brief episodes (<1 minute) with positional changes
  • Nystagmus: Latency (1-5 seconds), fatigability (decreases with repeated maneuvers), upbeating-torsional (posterior canal), horizontal (horizontal canal)
Diagnostic Maneuvers
1
Dix-Hallpike Test (Posterior Canal)

Patient sitting, head turned 45° to one side. Rapidly lower to supine position with head hanging 20° below exam table. Observe for nystagmus: posterior canal BPPV → upbeating nystagmus with torsional component (top poles of eyes beat toward affected ear). Latency 1-5 seconds, duration <1 minute, fatigues with repetition.

2
Supine Roll Test (Horizontal Canal)

Patient supine, rapidly turn head 90° to one side. Observe for nystagmus: horizontal canal BPPV → horizontal nystagmus beating toward ground (geotropic) or toward ceiling (apogeotropic). No latency, duration >1 minute, may not fatigue.

Treatment Maneuvers
1
Epley Maneuver (Posterior Canal)

1. Dix-Hallpike position on affected side. 2. Wait for nystagmus to stop, then wait 30 seconds. 3. Turn head 90° to opposite side. 4. Roll body onto shoulder, head now facing floor. 5. Sit up slowly. Maintain upright position for 48 hours. Success rate 80-90% with single treatment.

2
Semont Liberatory Maneuver (Posterior Canal)

1. Sitting, head turned 45° away from affected side. 2. Rapidly lie down on affected side (nose up). 3. After 1-2 minutes, rapidly swing through sitting to opposite side (nose down). 4. Return slowly to sitting. Alternative to Epley.

3
Barbeque Roll Maneuver (Horizontal Canal)

For geotropic nystagmus: 1. Supine, turn 90° toward unaffected side. 2. Continue rolling 90° (now prone). 3. Continue rolling 90° (now on affected side). 4. Continue rolling 90° to supine. Each position held until nystagmus stops or 30 seconds.

Vestibular Neuritis

Clinical Features
  • Presentation: Acute severe vertigo, nausea/vomiting, imbalance, lasting days to weeks
  • Key feature: No hearing loss or other neurological symptoms (differentiates from labyrinthitis)
  • Nystagmus: Unidirectional horizontal-torsional, fast phase away from affected ear, suppressed by fixation
  • Head Impulse Test: Positive toward affected side (corrective saccade when head rapidly turned toward affected ear)
  • Pathophysiology: Viral (HSV-1 reactivation most common) or post-viral inflammation of vestibular nerve
Diagnostic Tests
  • HINTS exam: Head Impulse test (positive = peripheral), Nystagmus (unidirectional = peripheral), Test of Skew (vertical misalignment = central). Sensitivity 100%, specificity 96% for stroke.
  • Caloric testing: Reduced response on affected side
  • MRI: Usually normal, may show enhancement of vestibular nerve; indicated if central signs or HINTS suggests central
Treatment
  • Symptomatic: Methylprednisolone 100mg daily ×3 days then taper over 2-3 weeks (improves long-term recovery)
  • Antivirals: Valacyclovir 1g TID ×7 days (added benefit debated)
  • Symptom control: Benzodiazepines (lorazepam 0.5-1mg q6-8h PRN) or antiemetics (promethazine 12.5-25mg q6h PRN) for first 24-48 hours only
  • Vestibular rehabilitation: Start as soon as tolerable (gaze stabilization, habituation, balance exercises)

Meniere’s Disease

Diagnostic Criteria (AAO-HNS 1995)
  • Definite Meniere’s: ≥2 episodes of vertigo ≥20 minutes, audiometric hearing loss on at least one occasion, tinnitus or aural fullness in affected ear, other causes excluded
  • Classic triad: Episodic vertigo, fluctuating sensorineural hearing loss (low frequency initially), tinnitus/aural fullness
  • Pathophysiology: Endolymphatic hydrops (excess endolymph in inner ear)
  • Natural history: Early: low-frequency hearing loss, vertigo prominent. Late: hearing loss across all frequencies, vertigo lessens, constant imbalance
Treatment
1
Acute Attack Management

Benzodiazepines (lorazepam 1-2mg), antiemetics (promethazine 25mg, metoclopramide 10mg), vestibular suppressants (meclizine 25-50mg). Rest in dark, quiet room.

2
Long-term Medical Management

Dietary: Low salt (<1-2g/day), avoid caffeine, chocolate, alcohol, MSG. Diuretics: Hydrochlorothiazide/triamterene 25/37.5mg daily, acetazolamide 250mg BID. Betahistine: 16-48mg TID (not FDA approved in US).

3
Refractory Cases

Intratympanic gentamicin: Chemical labyrinthectomy (20-40mg/mL, weekly injections). Intratympanic steroids: Dexamethasone (10mg/mL). Surgical: Endolymphatic sac decompression, vestibular nerve section, labyrinthectomy (last resort, causes deafness).

Diagnostic Approach to Acute Vertigo

Central vs Peripheral Vertigo
Feature Peripheral Central
Nystagmus Unidirectional, horizontal-torsional, suppressed by fixation, fatigable May be bidirectional, pure vertical/torsional, not suppressed by fixation, non-fatigable
Head Impulse Test Positive (corrective saccade) Negative (normal)
Skew Deviation Absent May be present (vertical misalignment)
Hearing May be affected (tinnitus, hearing loss) Usually normal
Other Neurologic Signs Absent Often present (dysarthria, limb ataxia, sensory loss)
Severity Severe vertigo, nausea/vomiting Vertigo may be less severe relative to other symptoms
Common Causes BPPV, vestibular neuritis, Meniere’s Stroke (PICA, AICA), MS, tumor, migraine
HINTS Exam for Acute Vestibular Syndrome
  • Head Impulse test: Rapid head turn 10-15° while patient fixates on examiner’s nose. Normal = eyes stay fixed. Abnormal (peripheral) = corrective saccade to refixate.
  • Nystagmus: Unidirectional = peripheral (fast phase away from lesion). Direction-changing or pure vertical = central.
  • Test of Skew: Alternate cover test. Vertical misalignment (skew deviation) = central (brainstem).
  • Sensitivity: HINTS has 100% sensitivity, 96% specificity for stroke in acute vestibular syndrome (better than early MRI).
Other Causes of Dizziness/Vertigo
Condition Clinical Features Diagnostic Tests Treatment
Vestibular Migraine Episodic vertigo with migraine features (headache, photophobia, phonophobia, aura), may occur without headache Clinical diagnosis, normal exam between attacks Migraine preventives (topiramate, propranolol, amitriptyline), trigger avoidance
Perilymph Fistula Vertigo/hearing loss after trauma, barotrauma, straining, may have Tullio phenomenon (vertigo with loud sounds) Clinical, fistula test (nystagmus with pressure), exploratory tympanotomy Bed rest, avoid straining, surgical repair if persistent
Superior Canal Dehiscence Vertigo with loud sounds (Tullio) or pressure (Hennebert), autophony, pulsatile tinnitus, conductive hearing loss High-resolution temporal bone CT, VEMP testing (lower thresholds) Avoid triggers, surgical repair (middle fossa approach)
Vestibular Paroxysmia Brief (seconds) vertigo attacks, multiple times daily, may respond to carbamazepine Clinical, may have neurovascular compression on MRI Carbamazepine, oxcarbazepine
Persistent Postural-Perceptual Dizziness (PPPD) Chronic non-vertiginous dizziness, exacerbation with upright posture, motion, complex visual stimuli Clinical diagnosis (≥3 months), often follows acute vertigo episode SSRIs/SNRIs, vestibular rehabilitation, CBT
Key Clinical Pearls – Dizziness & Vertigo
  • BPPV: Brief vertigo with position change, upbeating-torsional nystagmus with Dix-Hallpike, treat with Epley maneuver.
  • Vestibular neuritis: Acute severe vertigo lasting days, positive head impulse test, unidirectional nystagmus, no hearing loss.
  • Meniere’s disease: Episodic vertigo with fluctuating hearing loss, tinnitus, aural fullness. Low-salt diet, diuretics first-line.
  • Vestibular migraine: Most common cause of recurrent spontaneous vertigo. May occur without headache.
  • HINTS exam: For acute vestibular syndrome. Head Impulse (positive = peripheral), Nystagmus (unidirectional = peripheral), Test of Skew (positive = central).
  • Posterior circulation stroke: May present with isolated vertigo (especially PICA strokes affecting cerebellum). HINTS helps differentiate from peripheral.
  • Superior canal dehiscence: Vertigo with loud sounds or pressure changes, autophony, pulsatile tinnitus.
  • Vestibular paroxysmia: Brief vertigo attacks like trigeminal neuralgia of vestibular nerve, responds to carbamazepine.
  • PPPD: Chronic dizziness after acute vertigo episode, exacerbated by upright posture, motion, visual stimuli. Treat with SSRIs and vestibular rehab.
  • Drug-induced vertigo: Aminoglycosides, loop diuretics, chemotherapy (cisplatin), anticonvulsants, alcohol.
High-Yield Exam Points:
  • BPPV: Brief vertigo with position change, upbeating-torsional nystagmus, treat with Epley maneuver.
  • Vestibular neuritis: Acute severe vertigo, positive head impulse test, unidirectional nystagmus, treat with steroids.
  • Meniere’s disease: Episodic vertigo + fluctuating hearing loss + tinnitus + aural fullness.
  • HINTS exam: For acute vestibular syndrome. 3 components differentiate central from peripheral.
  • Vestibular migraine: Most common cause of recurrent spontaneous vertigo.
  • Superior canal dehiscence: Vertigo with loud sounds (Tullio) or pressure (Hennebert).
  • Perilymph fistula: Vertigo after trauma or barotrauma, may have conductive hearing loss.
  • PPPD: Chronic dizziness after acute vertigo, exacerbated by upright posture and motion.
  • Posterior circulation stroke: May present with isolated vertigo, HINTS helps identify.
  • Drugs causing ototoxicity: Aminoglycosides, loop diuretics, cisplatin, aspirin (tinnitus).
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