How to localize the lesion and manage a 1-year-old, 8kg male presenting with absence seizures, hypersalivation, bronchoconstriction, vertical nystagmus, rashes, and sunset eyeballs?

Lesion Localization and Management in a 1-Year-Old with Seizures and Vertical Nystagmus

Lesion Localization

The constellation of vertical nystagmus (particularly sunset eyeballs/downward gaze deviation), autonomic features (hypersalivation, bronchoconstriction), and seizures in this 1-year-old strongly localizes to the brainstem, specifically the dorsal midbrain/tectal region, with possible involvement of the diencephalon and thalamic structures. 1

Key Localizing Features:

• Vertical nystagmus and sunset eyeballs indicate dorsal midbrain pathology affecting the vertical gaze centers and pretectal region 1, 2
• Autonomic dysfunction (hypersalivation, bronchoconstriction) suggests involvement of brainstem autonomic nuclei or diencephalic structures 3
• Absence-like seizures in this age group with these features suggest thalamocortical circuit dysfunction, potentially from structural lesions affecting the thalamus or brainstem 1, 4
• The combination of vertical nystagmus with seizures points to central vestibular pathway involvement (brainstem vestibular nuclei to ocular motor nuclei) 1

Differential Diagnosis by Localization:

Structural lesions to consider:

• Brainstem/tectal gliomas (particularly optic pathway gliomas extending posteriorly) 1
• Malformations of cortical development (MCD) with brainstem involvement 1
• Chiari malformation (3.4% prevalence in pediatric nystagmus cases) 1
• Posterior fossa tumors affecting the cerebellum/brainstem 1
• Vascular malformations (arteriovenous malformations) 2
• Metabolic/leukodystrophies with white matter abnormalities (4% prevalence) 1

Diagnostic Approach

Immediate Neuroimaging (Priority #1):

MRI brain without and with IV contrast is the definitive initial imaging modality. 1, 2

Specific MRI protocol requirements:

• Include dedicated brainstem and posterior fossa sequences 1
• T2-weighted imaging to detect white matter abnormalities 1
• Contrast administration is essential given the high suspicion for structural lesion (vertical nystagmus is NOT isolated nystagmus) 1
• Consider MRI spine if longitudinally extensive lesions or demyelinating process suspected 1

CT has NO role in initial evaluation of pediatric nystagmus and seizures 1

Video-EEG Monitoring:

• Capture ictal events to characterize seizure semiology and distinguish epileptic from non-epileptic phenomena 5, 6
• Look for generalized spike-wave discharges (absence seizures) versus focal epileptiform activity 6, 4
• Document relationship between nystagmus and epileptic activity (epileptic nystagmus is rare but possible) 6

Additional Workup:

• Ophthalmologic examination to assess for papilledema (increased intracranial pressure), optic pathway abnormalities 1
• Metabolic screening if MRI shows white matter abnormalities (leukodystrophies, mitochondrial disorders) 1
• Genetic testing if MCD suspected 1

Management Approach

Acute Seizure Management:

Initiate valproate for absence seizures at 15 mg/kg/day (120 mg/day for this 8kg patient), divided into 2-3 doses. 7

Dosing algorithm:

• Start: 15 mg/kg/day = 120 mg/day (40 mg TID or 60 mg BID) 7
• Increase by 5-10 mg/kg/week based on seizure control 7
• Target therapeutic level: 50-100 μg/mL 7
• Maximum dose: 60 mg/kg/day (480 mg/day for this patient) 7

Critical caveat: If vertical nystagmus worsens or new episodes of tonic upgaze develop after starting valproate, consider valproate-induced paroxysmal tonic upgaze (PTU) and discontinue the medication 5

Symptomatic Management:

• Bronchodilators for bronchoconstriction during seizures (albuterol as needed)
• Antihistamines may help with rashes if related to autonomic surge during seizures
• Monitor for increased intracranial pressure signs given sunset eyeballs 8

Definitive Management Based on Imaging:

If structural lesion identified:

• Neurosurgical consultation for resectable lesions (tumors, focal cortical dysplasia) 1
• Oncology referral if brain tumor confirmed 1
• Epilepsy surgery evaluation if focal epileptogenic zone identified on FDG-PET (shows hypometabolism interictally) 1

If MCD/developmental abnormality:

• Continue antiepileptic therapy with close monitoring 1
• Consider FDG-PET to better define epileptogenic zone extent (higher sensitivity than MRI for FCD type 2) 1

If vascular malformation:

• Neurosurgical/interventional neuroradiology consultation for treatment planning 2

Common Pitfalls to Avoid:

• Do NOT assume this is benign infantile nystagmus - vertical nystagmus with seizures and autonomic features mandates neuroimaging 1, 3
• Do NOT delay MRI - 15.5% of children with nystagmus have abnormal intracranial findings 1
• Do NOT use CT as initial imaging - it has no role in pediatric nystagmus evaluation 1
• Monitor for valproate-induced PTU - can develop 2 weeks after treatment initiation 5
• Watch for thrombocytopenia with valproate levels >110 μg/mL 7
• Do NOT abruptly discontinue antiepileptic drugs - risk of status epilepticus 7

Follow-up Monitoring:

• Repeat MRI in 3-6 months if initial imaging shows suspicious but non-diagnostic findings 1
• Serial EEGs to assess seizure control 6
• Developmental assessment given the complex presentation 1
• Valproate levels 1-2 weeks after dose adjustments 7