Immediate priorities in the ICU

1. Continuous video-EEG now
   • Sedation can mask motor seizures. Establish whether seizures are ongoing and whether there is nonconvulsive status epilepticus.
   • Titrate antiseizure and anesthetic therapy to electroclinical seizure cessation, preferably under pediatric epileptologist guidance.
   • Refractory status epilepticus requires PICU-level respiratory support and continuous IV anesthetic therapy with EEG monitoring. Goldman-Cecil Medicine describes ICU respiratory support and IV sedation sufficient to suppress epileptic EEG discharges in refractory status epilepticus.
2. Clarify the vascular diagnosis urgently
   • Review MRI diffusion/ADC, FLAIR, SWI/GRE, and contrast sequences with neuroradiology.
   • Obtain MRA or CTA of head and neck, including the aortic arch to intracranial circulation. Add vessel-wall MRI if available.
   • Obtain MR venography or CT venography. A large cortical lesion extending fronto-temporo-parieto-occipitally can be arterial, but cerebral venous sinus thrombosis with venous infarction must be actively excluded.
   • Repeat imaging if the lesion appears to expand, there is unexplained deterioration, or the first angiogram is normal but suspicion for arteriopathy remains. MRI with diffusion sequences plus vascular imaging is the preferred diagnostic approach in pediatric stroke, as summarized in this pediatric stroke imaging review.
3. Prevent secondary brain injury
   • Avoid hypoxia, fever, hypotension, hypo/hyperglycemia, and major sodium disturbance.
   • Maintain euvolemia and adequate cerebral perfusion. Avoid unnecessary hyperventilation, which can worsen ischemia, unless used transiently for impending herniation.
   • Monitor for malignant hemispheric edema: serial pupils, neuro-examination whenever sedation permits, imaging, sodium/osmolality, and early neurosurgical review for possible decompressive hemicraniectomy if there is mass effect or herniation risk.
   • Screen for aspiration, infection, drug toxicity, hepatic/renal dysfunction, and metabolic triggers.
4. Antithrombotic treatment only after defining mechanism and excluding hemorrhage
   • The choice between antiplatelet treatment, anticoagulation, or neither depends on arterial dissection, cardioembolism, cerebral venous thrombosis, hemorrhagic transformation, thrombocytopenia, infection, and planned procedures.
   • Do not assume this is a simple non-cardioembolic arterial infarct. The pediatric stroke protocol cited by Texas Children’s uses aspirin, UFH, or LMWH initially depending on whether dissection and embolic causes have been excluded. Local pediatric stroke and hematology protocols should govern treatment.

Key differential diagnoses

A. Arterial ischemic stroke causes

1. Cerebral arteriopathy
   • Focal cerebral arteriopathy, often post-infectious
   • Intracranial arterial dissection, including after minor neck trauma
   • Primary CNS vasculitis or systemic vasculitis
   • Moyamoya disease/syndrome
   • Reversible cerebral vasoconstriction syndrome, less likely but possible
   • Genetic arteriopathies: ACTA2, RNF213, COL4A1/COL4A2, connective-tissue disorders

1. Cardioembolic stroke
   • Congenital heart disease or previously unrecognized structural lesion
   • Arrhythmia
   • Endocarditis or septic emboli
   • Cardiomyopathy
   • Patent foramen ovale with paradoxical embolus, if venous thrombosis is present
   • Intracardiac thrombus
2. Prothrombotic state
   • Antiphospholipid syndrome
   • Protein C, protein S, or antithrombin deficiency
   • Factor V Leiden/prothrombin variant depending on ancestry and local testing policy
   • Elevated factor VIII, lipoprotein(a), hyperhomocysteinemia
   • Dehydration, severe infection, nephrotic syndrome, inflammatory disease, malignancy
   • Iron deficiency anemia can be a contributing risk factor in children
   • Consider COVID-19 or other recent viral illness only in proper clinical context
3. Sickle cell disease or other hematologic disease
   • Hb electrophoresis if status is unknown, plus CBC/reticulocyte count and peripheral smear.
   • Sickle vasculopathy may present with infarction and seizures. Bradley and Daroff’s Neurology in Clinical Practice reports seizures and focal neurologic deficits among common neurological manifestations in sickle cell disease.
4. Infectious vasculopathy
   • Recent or active varicella, meningitis/encephalitis, tuberculosis, HIV, syphilis where epidemiologically relevant
   • Endocarditis with embolic stroke
   • Sepsis/DIC

B. Venous stroke

1. Cerebral venous sinus thrombosis or cortical vein thrombosis
   • Can cause seizures, hemorrhagic infarction, extensive cortical involvement, fluctuating consciousness, and raised intracranial pressure.
   • MRV/CTV is essential if not already performed.

C. Stroke mimics or mechanisms that can coexist with true infarction

1. Peri-ictal MRI abnormality from focal status epilepticus
   • Prolonged focal seizures may produce cortical diffusion restriction, swelling, and perfusion changes. This can mimic infarction.
   • However, a true infarct can also trigger status epilepticus. MRI lesion distribution, ADC evolution, perfusion, vascular imaging, and serial scans distinguish them.
2. MELAS or another mitochondrial cytopathy
   • Consider especially if lesions cross arterial territories or migrate, and there is lactic acidosis, hearing loss, migraine/vomiting, diabetes, short stature, myopathy, maternal family history, or recurrent “stroke-like” episodes.
   • MELAS commonly involves seizures and stroke-like episodes, but lesions characteristically do not respect a vascular distribution. Miller’s Anesthesia, 10e notes that MELAS lesions are inconsistent with vascular territories and that seizures are common.
   • Send lactate, pyruvate, blood gas, CK, glucose, liver profile, plasma amino acids/acylcarnitines as indicated, urine organic acids, and arrange mitochondrial/genetic testing. Interpret lactate cautiously, because seizures, shock, and beta-agonists can elevate it.
   • If POLG-related disease is plausible, discuss antiseizure drug selection urgently with neurology. Valproate can cause catastrophic hepatic failure in POLG disease.
3. Metabolic and inflammatory mimics
   • Hypoglycemia/hyperglycemia, hyperammonemia, severe electrolyte disorders
   • Urea-cycle disorder or organic acidemia, if clinical/lab pattern supports it
   • PRES, particularly with hypertension, renal failure, immunosuppressants, or posterior-predominant vasogenic edema
   • Autoimmune encephalitis or infectious encephalitis, if there is encephalopathy, fever, CSF inflammation, or new psychiatric/movement symptoms

Syndromes specifically worth considering

Focused investigations once stabilized

Neurovascular

• MRI brain with DWI/ADC, FLAIR, SWI/GRE, contrast as appropriate
• MRA/CTA head and neck
• MRV/CTV
• Vessel-wall MRI if vasculitis, dissection, or focal cerebral arteriopathy suspected
• Catheter angiography if noninvasive imaging is inconclusive or moyamoya/revascularization is being considered
• Repeat vascular imaging, because pediatric arteriopathy may evolve

Cardiac and embolic source

• ECG and telemetry
• Transthoracic echocardiography with bubble study when appropriate
• Transesophageal echo if there is high suspicion for endocarditis, thrombus, or unclear embolic source
• Blood cultures before antibiotics if fever/endocarditis suspected

Hematology and thrombosis

• CBC with smear, platelets, reticulocyte count
• PT/INR, aPTT, fibrinogen, D-dimer
• Sickle screen/Hb electrophoresis where relevant
• Thrombophilia testing in coordination with hematology. Some results are distorted by acute thrombosis, sepsis, liver dysfunction, transfusion, anticoagulants, and critical illness, so a normal or abnormal acute-phase result may need confirmation later.
• Antiphospholipid antibody testing
• Lipoprotein(a), fasting lipids, homocysteine

Infection, inflammation, metabolic, genetic

• ESR, CRP, renal/liver profile, urinalysis, CK, glucose, thyroid function if indicated
• Lactate, pyruvate, ammonia, blood gas, serum/urine metabolic studies if a mitochondrial/metabolic disorder is plausible
• CSF only if safe and if infection/vasculitis/autoimmune encephalitis is suspected. It should not delay vascular evaluation or be performed with unsafe raised intracranial pressure.
• Genetics consultation and targeted panel/exome/genome testing after phenotype review.

Seizure management considerations

• Determine the current antiseizure medication list, adherence, serum levels where measurable, recent changes, and drug interactions.
• Check glucose, sodium, calcium, magnesium, phosphate, renal and liver function, ammonia, infection markers, and antiseizure drug concentrations.
• Treat electrographic seizures promptly, but distinguish refractory status epilepticus from sedation-related EEG suppression or periodic patterns.
• Because this infarct has major cortical involvement, the risk of continued acute seizures and future epilepsy is high. A 2025 systematic review found pooled pediatric post-stroke epilepsy risk of 27.6%; cortical involvement, MCA involvement, acute symptomatic seizures, and prolonged acute seizures increased risk (Alqahtani and Makke, 2025, PMID 41674782).
• Post-stabilization, reassess drug burden and choose a maintenance regimen based on seizure type, renal/hepatic function, stroke mechanism, behavioral adverse effects, and possible mitochondrial/genetic diagnosis.

A practical working formulation

Acute pediatric arterial ischemic stroke or venous infarction with refractory focal/multifocal status epilepticus, with urgent exclusion of large-vessel arteriopathy/dissection/moyamoya, cerebral venous thrombosis, cardioembolism, thrombophilia, infection-associated vasculopathy, and mitochondrial stroke-like disease.

Acute left hemispheric arterial ischemic stroke with refractory focal/multifocal status epilepticus, most likely due to an underlying cerebral arteriopathy until angiography proves otherwise.

• seizures since day 2 of life,
• neurodevelopmental disorder,
• refractory multifocal seizures,
• fronto-temporo-parieto-occipital involvement, and
• possible non-single-arterial-territory lesion,

Bottom line

• If MRI/MRA shows arterial-territory infarction plus MCA/ICA stenosis or irregularity: most likely focal cerebral arteriopathy causing pediatric AIS.
• If the lesion crosses vascular territories, migrates/enlarges atypically, angiography is normal, and lactate is elevated: most likely MELAS stroke-like episode rather than thromboembolic infarction.
• Also urgently exclude cerebral venous sinus thrombosis with MRV/CTV, because extensive cortical seizure-associated infarction may be venous.

Working diagnostic probability chart

Most likely working conclusion

Acute left anterior-circulation arterial ischemic stroke, probably related to focal cerebral arteriopathy, complicated by refractory focal/multifocal status epilepticus.

The two diagnoses that must be separated urgently

1. Focal cerebral arteriopathy with true arterial ischemic infarction
2. MELAS stroke-like episode