What are the incidence, diagnosis, onset times, and clinical presentation of cocaine-induced encephalopathy and vasculitis?

Cocaine-Induced Encephalopathy and Vasculitis: Incidence, Diagnosis, Onset, and Clinical Presentation

Cocaine-induced vasculitis and encephalopathy are serious neurological complications that typically develop within hours to weeks after cocaine use, with symptoms potentially persisting for weeks to months even after drug cessation, requiring prompt recognition and treatment to prevent significant morbidity and mortality.

Incidence and Epidemiology

• Exact incidence is not well established in the literature, but cocaine-induced vasculitis represents a subset of drug-induced vasculitis cases
• Cocaine-induced cerebrovascular complications are more common in:
  • Young adults (typically under 40 years of age)
  • Male gender predominance
  • Cigarette smokers
  • Users of all routes of administration (intranasal, intravenous, smoked "crack")
  • Can occur with both first-time and chronic cocaine use 1

Pathophysiology

Cocaine affects the cerebrovascular system through multiple mechanisms:

• Direct vasoconstrictor effects causing coronary and cerebral vasospasm
• Endothelial dysfunction and accelerated atherosclerosis with chronic use
• Enhanced platelet aggregation and thrombosis
• Immunological mechanisms potentially triggered by cocaine or adulterants (particularly levamisole)
• Increased blood pressure and heart rate, increasing risk of hemorrhagic complications

Diagnosis

Clinical Presentation of Cocaine-Induced Encephalopathy

• Acute presentation (hours to days after use):

  • Headache (often severe and persistent)
  • Altered mental status ranging from agitation to disorientation
  • Seizures
  • Focal neurological deficits
  • Visual disturbances including transient blindness
  • Progressive widespread cerebral dysfunction 2

• Subacute/chronic presentation:

  • Persistent headaches
  • Progressive cognitive decline
  • Focal neurological deficits that evolve over weeks

Clinical Presentation of Cocaine-Induced Vasculitis

• Sinonasal symptoms (when affecting this region):

  • Progressive nasal obstruction
  • Epistaxis (nosebleeds)
  • Nasal crusting
  • Midline destruction of nose and palate in severe cases 1

• Systemic symptoms:

  • Fever
  • Multifocal neurological events
  • Skin lesions (particularly retiform purpuric rash with levamisole-adulterated cocaine)
  • Hypertension
  • Disproportionate systemic illness 1

Laboratory Findings

• Elevated inflammatory markers (ESR, CRP) may be present but can be normal
• ANCA testing:
  • c-ANCA and PR3 can be positive in cocaine-induced vasculitis
  • Dual positivity for MPO and PR3 ANCA is more suggestive of drug-induced vasculitis
  • ANCA reacts with human neutrophil elastase (HNE) in cocaine-induced vasculitis but not in autoimmune vasculitis 1
• Cerebrospinal fluid analysis may show:
  • Increased opening pressure
  • Elevated protein values
  • Lymphocytic pleocytosis (rarely exceeding 250 cells/mm³) 1
• Toxicology screening for cocaine and metabolites

Imaging

• MRI:

  • Contrast-enhanced MRI studies are abnormal in >90% of cases
  • May show ischemic or hemorrhagic lesions
  • Edema and inflammatory changes

• Cerebral angiography:

  • May show segmental arterial narrowing
  • Vascular occlusions
  • Peripheral aneurysms
  • Vascular shifts or avascular areas
  • Can be entirely normal despite biopsy-proven vasculitis 3, 2

• CT scan:

  • May show intracerebral hemorrhage
  • Infarctions
  • Edema

Definitive Diagnosis

• Brain biopsy is the gold standard for diagnosis of cerebral vasculitis:
  • Shows vascular changes primarily involving small arteries
  • Lymphocytic infiltration
  • Endothelial thickening
  • Deposition of proteinaceous material within and around vessel walls 3
  • In cocaine-induced cases, may show massive apoptosis with abundant caspase-3 and 9 expression 1

Onset and Duration

• Onset timing:

  • Acute effects: Minutes to hours after cocaine use
  • Subacute effects: Days to weeks following use
  • Chronic effects: May develop after prolonged use

• Duration after cessation:

  • Vasculitis can persist for weeks to months even after drug cessation
  • Some cases show improvement within days to weeks after stopping cocaine
  • More severe cases may require months for resolution
  • Some patients may have permanent neurological sequelae despite drug cessation

Differential Diagnosis

• Primary CNS vasculitis
• Autoimmune vasculitides (GPA, EGPA, MPA)
• Infectious causes of vasculitis
• Other drug-induced vasculitis (amphetamines, methamphetamine)
• Reversible cerebral vasoconstriction syndrome
• Thrombotic or embolic stroke from other causes

Management Considerations

• Immediate cessation of cocaine use is essential
• Benzodiazepines may be useful for management of acute cocaine intoxication with hypertension and tachycardia 1
• Avoid beta-blockers in acute cocaine intoxication due to risk of unopposed alpha stimulation worsening coronary and cerebral vasospasm 1
• Calcium channel blockers may be beneficial for vasospasm
• Corticosteroids have shown benefit in some cases of cocaine-induced vasculitis 3, 2
• Cyclophosphamide may be considered in severe, progressive cases 2
• Supportive care and management of complications (seizures, increased intracranial pressure)

Key Pitfalls and Caveats

• Cocaine-induced vasculitis can mimic primary autoimmune vasculitis (including ANCA-positive disease)
• Normal angiography does not rule out cerebral vasculitis
• Negative biopsy results do not exclude the diagnosis due to the focal nature of vasculitis
• Cocaine use may not be volunteered by patients and should be specifically questioned
• Levamisole-adulterated cocaine is associated with a higher risk of vasculitis and can cause neutropenia
• Distinguishing between cocaine-induced vasculitis and primary CNS vasculitis is crucial as management differs