✅ Model Answer:
• Diagnosis: Episodic ataxia type 2 (EA2) — CACNA1A gene mutation causing recurrent episodes of ataxia, vertigo, and nystagmus lasting 2-6 hours. Episodes triggered by stress and exercise. Interictal exam is normal. Mild cerebellar vermian atrophy on MRI is a classic finding.
• Any other test: Genetic testing for CACNA1A mutation (confirmatory), EEG (if seizures suspected), acetazolamide trial (diagnostic and therapeutic), family history for episodic ataxia, migraine, or epilepsy.
• What to do next: Start acetazolamide (5-10 mg/kg/day) — reduces frequency and severity of episodes. Avoid triggers (stress, exercise). Consider 4-aminopyridine (dalfampridine) or flunarizine if acetazolamide is ineffective.
• Follow-up plan: Monitor response to acetazolamide. Genetic counseling for family. Prognosis: good response to treatment, but may develop progressive cerebellar atrophy over time.

✅ Model Answer:
• Episodic ataxia type 2 (EA2) is an autosomal dominant channelopathy characterized by recurrent episodes of ataxia, vertigo, and nystagmus lasting hours (usually 2-6 hours).
• Gene: CACNA1A gene located on chromosome 19p13.
• Protein: P/Q-type calcium channel α1A subunit (CaV2.1) — expressed in cerebellar Purkinje cells.
• Mutation: Over 50 mutations identified (mostly missense, nonsense, or truncating).
• Inheritance: Autosomal dominant (familial) or sporadic (de novo).
• Prevalence: Rare; approximately 1 in 100,000.
• Key features: Episodic ataxia + vertigo + nystagmus + normal interictal exam + acetazolamide responsive.

✅ Model Answer:
• Episodes (duration 2-6 hours):
- Ataxia: Gait ataxia, truncal ataxia, limb dysmetria.
- Vertigo: Dizziness, imbalance.
- Nystagmus: Usually horizontal, gaze-evoked.
- Dysarthria: Slurred speech (may occur).
- Vomiting: May occur.
- Headache: Sometimes migrainous (associated with familial hemiplegic migraine).
- Weakness: Rare.
• Triggers:
- Stress: Emotional stress, anxiety.
- Exercise: Physical exertion.
- Fatigue: Sleep deprivation.
- Fever: Intercurrent infections.
• Interictal exam: Normal (between episodes).
• Progressive: Some patients develop progressive cerebellar atrophy and ataxia over time.

✅ Model Answer:
• Differential diagnoses:
- Episodic ataxia type 1 (EA1): Shorter episodes (seconds-minutes), myokymia (muscle rippling), KCNA1 gene mutation.
- Episodic ataxia type 2 (EA2): Longer episodes (hours), nystagmus, CACNA1A mutation, acetazolamide responsive.
- Episodic ataxia type 3: Episodes with vertigo, tinnitus, hearing loss.
- Episodic ataxia type 4: Episodic ataxia with myokymia.
- Familial hemiplegic migraine (FHM): Migraine with hemiplegia, ataxia, CACNA1A mutations (overlap with EA2).
- GLUT1 deficiency syndrome: Episodic ataxia, seizures, developmental delay, low CSF glucose, ketogenic diet responsive.
- Basilar-type migraine: Ataxia, vertigo, dysarthria, visual disturbances.
- Paroxysmal torticollis: Head tilt, ataxia, benign.
- Drug intoxication: Alcohol, anticonvulsants.
- Metabolic disorders: Mitochondrial disorders (MELAS), maple syrup urine disease.

✅ Model Answer:
• Acetazolamide: A carbonic anhydrase inhibitor that reduces the frequency and severity of episodes in EA2.
• Mechanism: Not fully understood — may stabilize neuronal membrane excitability or alter pH.
• Dosing: 5-10 mg/kg/day (start low, titrate up).
• Response: 70-80% of patients respond to acetazolamide (episodes reduced or resolved).
• Timing: Improvement usually seen within days to weeks.
• Side effects: Paresthesias (tingling in extremities), nephrolithiasis (kidney stones), metabolic acidosis, drowsiness.
• Alternatives: 4-aminopyridine (dalfampridine) — a potassium channel blocker — may be effective if acetazolamide fails. Flunarizine (calcium channel blocker) may also be used.
• Diagnostic: A positive response to acetazolamide supports the diagnosis of EA2.

✅ Model Answer:
• MRI Brain findings:
- Mild cerebellar vermian atrophy: Most common finding (in 50-70% of patients).
- Cerebellar atrophy: May be progressive over time.
- Normal MRI: In some patients (especially early in the disease).
- No other specific findings: White matter usually normal.
• Progression: Cerebellar atrophy may progress with age, correlating with worsening interictal ataxia.
• Differentiation: EA2 is associated with cerebellar atrophy (unlike EA1, which has normal MRI).
• Role of MRI: Supports diagnosis but is not diagnostic (genetic testing is required).

✅ Model Answer:
• Same gene: Both EA2 and Familial Hemiplegic Migraine Type 1 (FHM1) are caused by CACNA1A gene mutations.
• Overlap: Some patients with EA2 also have migraines, and some FHM patients have ataxia.
• Clinical features:
- EA2: Episodic ataxia, vertigo, nystagmus (no hemiplegia).
- FHM1: Migraine with aura, hemiplegia (weakness on one side), ataxia, visual disturbances.
• Acetazolamide: Effective for EA2 but not for FHM1.
• Genetic testing: Identifies the same CACNA1A mutations in both conditions (overlapping phenotypes).
• Clinical pearl: A patient with episodic ataxia and a family history of migraine should be evaluated for CACNA1A mutations.

✅ Model Answer:
• Prognosis:
- Good: With acetazolamide or other medications, episodes can be significantly reduced or eliminated.
- Progressive cerebellar atrophy: Some patients develop progressive interictal ataxia and cerebellar atrophy over time (especially with aging).
- Quality of life: Can be significantly improved with early diagnosis and treatment.
- Life expectancy: Normal.
• Long-term follow-up:
- Medication monitoring: Monitor for acetazolamide side effects (paresthesias, kidney stones, metabolic acidosis).
- Neurology: Annual neurologic exams (monitor for development of interictal ataxia).
- MRI: Serial MRI to monitor for cerebellar atrophy progression.
- Genetic counseling: Autosomal dominant — 50% recurrence risk for children.
- Avoid triggers: Stress, exercise, fatigue.
- Education: Educate patient and family about triggers, medication compliance, and when to seek care.