A 19-year-old short-statured man presents with sudden left hemianopia, headache, vomiting, and focal seizures. His mother and maternal aunt have diabetes mellitus and sensorineural hearing loss. Serum lactate is elevated at rest (4.5 mmol/L) with disproportionate rise on exercise. MRI brain shows a T2-hyperintense lesion in the left occipital lobe that does not respect vascular territories, with restricted diffusion and elevated lactate peak on MR spectroscopy. The EEG pattern marked **B** in the diagram is recorded over the affected occipital region. Based on this clinical presentation and EEG finding, what is the most appropriate acute management for the stroke-like episode?
A. High-dose intravenous valproate to control seizures and stabilize mitochondrial function
B. Immediate thrombolytic therapy with alteplase to restore vascular patency
C. Urgent mechanical thrombectomy given the large vessel occlusion pattern
D. Intravenous L-arginine (0.5 g/kg) as substrate for nitric oxide synthesis and to improve cerebral perfusion
Explanation
Why Intravenous L-arginine is correct
The EEG pattern marked B (focal posterior slowing with epileptiform discharges) in the context of a stroke-like episode that does NOT respect vascular territories is pathognomonic for MELAS syndrome. The stroke-like episodes in MELAS represent neuronal-vascular dysfunction with hyperemia rather than true ischemic strokes. Intravenous L-arginine (0.5 g/kg) acts as a substrate for nitric oxide synthesis, improving cerebral perfusion and neuronal function during acute stroke-like episodes. This is the evidence-based acute management and is recommended both for acute episodes and chronic prevention in MELAS (Harrison's 21e, DiMauro NEJM 2003).
Why each distractor is wrong
Thrombolytic therapy with alteplase: MELAS stroke-like episodes are NOT true ischemic strokes caused by thromboembolism or vascular occlusion. The lesion does not respect vascular territories, and thrombolytics are contraindicated and ineffective in this mitochondrial disorder.
High-dose intravenous valproate: While seizure control is important, valproate is specifically contraindicated in MELAS and other mitochondrial disorders because it is a mitochondrial toxin and can precipitate metabolic decompensation and worsening of the condition.
Mechanical thrombectomy: This intervention is reserved for acute ischemic stroke with large vessel occlusion. MELAS does not present with true vascular occlusion; the lesion reflects mitochondrial dysfunction and hyperemia, not thromboembolism.
High-YieldNEET PG
MELAS stroke-like episodes are NOT true ischemic strokes—they represent mitochondrial neuronal-vascular dysfunction and respond to L-arginine, not thrombolytics. Always avoid valproate in mitochondrial disorders.
