What are the neurological findings in patients with Thrombotic Thrombocytopenic Purpura (TTP)?

Neurological Findings in Thrombotic Thrombocytopenic Purpura (TTP)

Neurological manifestations are present in 39-80% of patients with TTP and range from mild headaches to severe sequelae including confusion, seizures, stroke, and coma. 1

Common Neurological Presentations

Acute Neurological Manifestations

• Headache: Often the earliest and most common neurological symptom
• Altered mental status: May include:
  • Confusion
  • Encephalopathy
  • Behavioral changes
• Focal neurological deficits:
  • Aphasia
  • Hemiparesis
  • Visual field defects
  • Cranial or peripheral motor nerve paralysis 2
• Seizures: Both convulsive and non-convulsive types
• Coma: In severe cases

Important Clinical Finding: Nonconvulsive Status Epilepticus

• Present in approximately 10% of TTP patients with altered mental status 3
• Requires EEG for diagnosis
• May be mistaken for general encephalopathy without appropriate testing

Neuroimaging Findings

MRI Findings

• Abnormal imaging found in 56% of TTP patients with neurological symptoms 4
• Higher rate of abnormalities in patients with neurological symptoms (80%) compared to those with headaches only (18%) 4
• Common findings:
  • Hyperintense white matter lesions, particularly in the frontal lobe
  • Ischemic changes due to microvascular thromboses
  • Occasionally hemorrhagic infarctions

Correlation with Cognitive Function

• Frontal lobe involvement is disproportionately associated with marked intellectual impairment (67% vs 19% in those without intellectual impairment) 4
• Abnormal MRI correlates with lower verbal IQ (85 vs 99) and performance IQ (83 vs 100) 4

Long-Term Neurological Sequelae

Persistent Cognitive Symptoms

• Reported in 27% of patients following acute TTP 4
• Specific manifestations include:
  • Impaired memory (66%)
  • Difficulty concentrating (26%)
  • Word-finding difficulties (26%)

Psychiatric Manifestations

• Depression (65% of patients)
• Anxiety (55% of patients)
• Present regardless of initial neurological presentation 4

Pathophysiology of Neurological Symptoms

TTP is caused by severe ADAMTS13 deficiency (<10% activity), leading to:

• Accumulation of large von Willebrand factor multimers
• Formation of platelet-rich microthrombi in the cerebral microvasculature
• Resulting ischemic damage to brain tissue
• Potential for hemorrhagic complications due to severe thrombocytopenia

Diagnostic Approach for Neurological Manifestations

Essential Workup

1. Complete neurological examination: Document all focal and non-focal deficits
2. Brain MRI with and without contrast: To identify ischemic or hemorrhagic lesions
3. EEG: Particularly important in patients with altered mental status to rule out nonconvulsive status epilepticus
4. CSF analysis: To exclude other causes of neurological symptoms (with caution due to thrombocytopenia)

Laboratory Correlation

• Severity of neurological symptoms often correlates with:
  • Degree of thrombocytopenia (typically <30 × 10^9/L)
  • Severity of microangiopathic hemolytic anemia
  • ADAMTS13 activity levels

Clinical Pitfalls and Caveats

1. Misdiagnosis risk: TTP may be confused with:

   • Thrombotic thrombocytopenic purpura-like syndromes
   • Primary neurological disorders
   • Idiopathic acute vasculitides 2

2. Delayed diagnosis: Neurological symptoms may be the presenting feature before hematological abnormalities are recognized, as in cases presenting as complex migraine 5

3. Nonconvulsive status epilepticus: Often overlooked cause of altered mental status in TTP patients, requiring EEG for diagnosis 3

4. Importance of CBC: Always perform complete blood count in patients with new neurological symptoms to avoid missing TTP 5

5. Differentiation from other thrombotic microangiopathies: TTP must be distinguished from hemolytic uremic syndrome, which has less prominent neurological features 2

By recognizing these neurological manifestations early and initiating prompt treatment with therapeutic plasma exchange, corticosteroids, and rituximab, survival rates have improved from almost zero to approximately 93% 1.