What is the management approach for seizures in patients with Thrombotic Thrombocytopenic Purpura (TTP)?

Management of Seizures in Thrombotic Thrombocytopenic Purpura (TTP)

Seizures in TTP require immediate neurological consultation, antiepileptic therapy with levetiracetam, and concurrent treatment of the underlying TTP with plasma exchange and immunosuppression.

Pathophysiology and Presentation

Seizures are a common neurological manifestation in TTP patients, occurring in up to 80% of cases 1. They result from microvascular thrombi formation in cerebral vessels due to the accumulation of ultra-large von Willebrand factor multimers caused by ADAMTS13 deficiency. Neurological symptoms in TTP can range from:

• Headaches and confusion
• Focal neurological deficits
• Seizures (both convulsive and non-convulsive)
• Altered mental status
• Coma

Importantly, research has shown that altered mental status in TTP patients may be secondary to non-convulsive status epilepticus in at least 10% of cases, requiring EEG for diagnosis 2.

Diagnostic Approach for TTP Patients with Seizures

When a TTP patient presents with seizures:

1. Immediate neurological assessment:

   • Perform neurological examination
   • Assess level of consciousness using appropriate scales
   • Evaluate for focal neurological deficits

2. Diagnostic workup:

   • EEG to rule out non-convulsive status epilepticus 2
   • Brain MRI with and without contrast (CT if MRI unavailable) 3
   • Lumbar puncture with measurement of opening pressure if no contraindications 3

3. Laboratory evaluation:

   • Complete blood count with peripheral smear examination for schistocytes
   • ADAMTS13 activity level and inhibitor titer 3
   • LDH, haptoglobin, reticulocyte count, bilirubin
   • Coagulation studies (PT, PTT, fibrinogen)
   • Blood group and antibody screen 3

Treatment Algorithm for Seizures in TTP

Step 1: Immediate Management of Seizures

• For active seizures:

  • Administer benzodiazepines (lorazepam 0.05 mg/kg IV, max 1 mg per dose) 3
  • If seizures persist, repeat benzodiazepine dose
  • For status epilepticus, follow standard status epilepticus protocols 3

• Antiepileptic therapy:

  • Initiate levetiracetam (10 mg/kg, up to 500 mg per dose) every 12 hours 3
  • Avoid antiepileptic drugs with unfavorable cardiotoxicity profiles (lacosamide, phenytoin) 3
  • Continue antiepileptic therapy throughout the acute phase of TTP

Step 2: Concurrent Treatment of Underlying TTP

• Plasma exchange (PEX):

  • Initiate immediately while awaiting ADAMTS13 results 4
  • Continue daily until clinical improvement and platelet count normalization

• Immunosuppressive therapy:

  • Methylprednisolone 1 g IV daily for 3 days, with first dose administered immediately after first PEX 3
  • Consider rituximab (375 mg/m² weekly for 4 weeks) for refractory cases 3, 4
  • For cases unresponsive to standard therapy, consider cyclosporine 5

Step 3: Supportive Care

• Maintain fluid balance and electrolyte correction
• Provide folic acid 1 mg daily supplementation 4
• Avoid medications that cause CNS depression 3
• Implement aspiration precautions and IV hydration 3
• Consider ICU admission for patients with severe neurological manifestations

Monitoring and Follow-up

• Perform frequent neurological assessments (at least twice daily) 3
• Monitor platelet count, hemolysis markers, and renal function daily
• Repeat EEG if neurological status deteriorates
• Continue antiepileptic therapy for at least 30 days after resolution of acute TTP 3
• Monitor ADAMTS13 activity during remission to detect early relapses 4, 1

Special Considerations

• Refractory seizures: In cases unresponsive to standard antiepileptic therapy, consider:

  • Additional immunosuppression with cyclosporine 5
  • Splenectomy in extremely refractory cases 6

• Non-convulsive status epilepticus: Maintain high suspicion in TTP patients with altered mental status and obtain EEG promptly 2

• Cerebral edema: If present, consider hyperosmolar therapy and neurosurgical consultation 3

Prognosis

With prompt recognition and appropriate treatment, survival rates for TTP have improved from nearly zero to approximately 93% 1. Early recognition of seizures as a manifestation of TTP and appropriate management with both antiepileptic therapy and TTP-specific treatments is critical for improving neurological outcomes and reducing mortality.

Pitfalls to Avoid

• Delaying plasma exchange: Each 12-hour delay in treatment increases morbidity and mortality
• Failing to obtain EEG: Non-convulsive status epilepticus can be missed without EEG monitoring
• Using antiepileptic drugs that interfere with recovery: Some antiepileptic drugs may dampen neural plasticity mechanisms 3
• Misdiagnosing TTP as primary seizure disorder: Consider TTP in patients with new-onset seizures and unexplained thrombocytopenia 7