What are the appropriate investigations and treatment for a 26-year-old postpartum female (post-cesarean section) who experienced a generalized tonic-clonic seizure (GTCS) followed by transient weakness of the left upper and lower limbs, with a normal plain MRI?

Post-Partum Seizure with Transient Focal Weakness: Diagnostic Approach and Management

Immediate Clinical Assessment

This presentation most likely represents a generalized tonic-clonic seizure with Todd's paralysis (post-ictal focal weakness), but cerebral venous thrombosis (CVT) must be urgently excluded given the postpartum timing and high mortality risk. 1

The key diagnostic priority is distinguishing between:

• Post-ictal (Todd's) paralysis following a primary seizure disorder
• Seizure secondary to cerebral venous thrombosis (CVT), which is life-threatening and requires immediate anticoagulation 1
• Eclampsia (though typically occurs within 48 hours postpartum, can occur up to 4 weeks post-delivery)

Essential Investigations

Immediate/Urgent Imaging

MRI with venography (MRV) is mandatory despite the normal plain MRI, as isolated cortical vein thrombosis can be missed on standard sequences. 1

• CT venography or MR venography should be performed immediately to exclude CVT, as plain MRI can miss isolated cortical vein thrombosis 1
• If venographic studies are inconclusive but clinical suspicion remains high, digital subtraction angiography (DSA) is indicated 1
• The presence of ipsilateral dural thickening and enhancement on MRI may indicate isolated cortical vein thrombosis 1

Electroencephalography

EEG should be obtained within 24 hours of the seizure, as this timing yields the highest diagnostic yield (51% vs 34% for later EEG). 2

• If the initial EEG is negative, sleep-deprived EEG should be performed 2
• EEG helps distinguish between generalized and focal epilepsy syndromes, which guides treatment selection 2
• Interictal EEGs are typically normal in syncope but abnormal in epilepsy 3

Laboratory Investigations

Comprehensive metabolic panel including ionized calcium is essential, as hypocalcemia can trigger seizures in postpartum women. 1

• Serum calcium (ionized), magnesium, glucose, sodium, and renal function 1
• Complete blood count and coagulation studies (to assess for thrombophilia if CVT suspected) 1
• Liver function tests (baseline before antiepileptic drug initiation)
• Pregnancy test (to confirm postpartum status)
• Thrombophilia workup if CVT is confirmed 1

Treatment Approach

If CVT is Confirmed

Immediate anticoagulation with heparin is indicated even in the presence of hemorrhagic transformation, as per American Heart Association/American Stroke Association guidelines. 1

• Therapeutic anticoagulation should be initiated and continued despite intracranial hemorrhage, as the benefits outweigh risks in CVT 1
• Antiepileptic therapy with levetiracetam (loading dose followed by maintenance) should be started 1
• Surgical intervention may be required if hemorrhage expands despite medical management 1

If Primary Seizure Disorder (CVT Excluded)

Levetiracetam is the preferred first-line antiepileptic drug for generalized tonic-clonic seizures in this population. 4, 5, 6

Dosing regimen:

• Initial dose: 500 mg twice daily (1000 mg/day) 4
• Can be increased by 1000 mg/day every 2 weeks to target dose of 3000 mg/day (1500 mg twice daily) 4
• This represents Class 1 evidence for efficacy in primary generalized tonic-clonic seizures 5

Alternative if levetiracetam is not tolerated:

• Valproic acid is effective but should be avoided in women of childbearing potential due to teratogenicity 6
• Lamotrigine or topiramate are alternatives with Class 1 evidence 5

Hypocalcemia-Related Seizures

If hypocalcemia is identified, calcium and vitamin D supplementation should be initiated immediately, as hypocalcemic seizures may resolve with supplementation alone. 1

• Anticonvulsant therapy may still be needed if seizures persist after calcium normalization 1
• Monitor ionized calcium, magnesium, and parathyroid hormone levels 1

Antiplatelet Therapy Decision

Antiplatelet agents are NOT indicated in this clinical scenario. 1

• Antiplatelets are used for atherosclerotic cerebrovascular disease, not for seizure disorders 1
• If CVT is confirmed, anticoagulation (not antiplatelet therapy) is required 1
• If this is a primary seizure disorder, antiepileptic drugs (not antiplatelets) are the appropriate treatment 4, 5

Critical Pitfalls to Avoid

Do not dismiss this as simple post-ictal weakness without excluding CVT, as postpartum women have 5-20 times higher risk of CVT, and delayed diagnosis carries significant mortality. 1

• Plain MRI can miss isolated cortical vein thrombosis; venographic imaging is mandatory 1
• The combination of postpartum status, seizure, and focal neurological deficit is CVT until proven otherwise 1
• Dural enhancement on MRI may be misinterpreted as post-lumbar puncture syndrome when it actually indicates CVT 1
• Do not withhold anticoagulation in CVT even if hemorrhage is present 1

Follow-Up Considerations

• If antiepileptic therapy is initiated, treatment duration is typically 2-5 years for a first unprovoked seizure 6
• Sixteen of 26 patients in one series remained seizure-free after discontinuation of antiepileptic drugs 6
• If CVT is confirmed, anticoagulation is typically continued for 6 months 1
• Repeat imaging and EEG may be needed based on clinical course 2