Thanks to Katie for presenting the interesting case of a young man with history of disseminated TB with TB meningitis and hydrocephalus requiring VP shunts, admitted for acute LUE weakness, L homonymous hemianopsia, and memory impairment, found to have acute strokes in multiple vascular territories due to TB related CNS vasculitis!

Clinical Pearls

• Remember that arterial dissection is the most common cause of stroke in a young patient.
• CNS vasculitis can be primary or secondary to a systemic illness.  It typically presents with infarcts in multiple vascular territories.  Treatment involves immunosuppression with high dose steroids + cytoxan/rituxan.
• CNS vasculitis is the most common cause of severe neurologic deficit in patients with TB meningitis.
• Vasculitis in CNS TB is the result of a hypersensitivity reaction to proteins released from the bacteria.
• TB meningitis requires an extended course of anti-TB treatment, generally up to 1 year or more.  Serial LPs are obtained to monitor adequate response to therapy.

Etiologies of stroke in a young adult

1. Coagulopathy (think of conditions that cause both arterial and venous thrombosis)
   • APLS
   • HIT
   • DIC
   • TTP/HUS
   • Hyperviscosity states
     • Waldenstrom’s
     • Leukostasis in setting of leukemia
     • Sickle cell
   • Myeloproliferative disorders (PV, ET, CML)
   • Paroxysmal nocturnal hemoglobinuria 
2. Vasculopathy
   • Noninflammatory
     • Dissection (most common cause of stroke in a young person)
     • Trauma
     • Malformations (AVMs, aneurysms, moyamoya)
     • Cerebral venous sinus thrombosis
     • Trauma
   • Inflammatory
     • Primary vasculitis
       • Large vessel: Takayasu, GCS
       • Small to medium: Kawasaki, PAN, ANCA-associated
     • Secondary vasculitis
       • Bacterial meningitis
       • HIV
       • Varicella
       • Syphilis
       • TB
       • Fungi (esp cocci)
       • Collagen vascular disease (i.e. lupus)
3. Metabolic
   • CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)
   • Fabry
   • Homocystinuria 
   • Menke’s
   • MELAS
   • Organic acid disorders
4. Drugs
   • Cocaine and meth
5. Cardiac
   • Congenital
   • Rheumatic valve disease
   • Mitral valve prolapse
   • PFO
   • ASD
   • Endocarditis with septic emboli
   • Atrial myxoma
   • Fibroelastoma
   • Arrhythmias
   • Cardiac surgery

CNS TB:

Three main manifestations:

1. TB meningitis (most common presentation in low incidence settings like the US)
2. Intracranial tuberculoma
3. Spinal tuberculous arachnoiditis

Spillage of tubercular protein into the subarachnoid space results in an intense hypersensitivity reaction and inflammation resulting in

• Proliferative arachnoiditis (fibrous mass encasing cranial nerves and vessels adjacent to it)
• Vasculitis with resultant aneurysm, thrombosis, and infarction
• Communicating hydrocephalus 

TB Meningitis

• 1% of all TB cases, 5% of all extrapulmonary TB cases
• 15-40% mortality rate
• Clinical manifestations
  • 3 stages:
    • Prodromal phase: malaise, headache, low grade fever, personality changes
    • Meningitic phase: meningismus, headache, vomiting, lethargy, confusion, CNS signs, some motor deficits
    • Paralytic phase: stupor, coma, seizures, hemiparesis (death within 5-8 weeks)
• Diagnosis:
  • Characteristic CSF findings of low glucose, elevated protein, lymphocytic pleocytosis 
  • CSF AFB smear and culture: in general, a minimum of 3 serial LPs should be performed, as diagnostic yield increases f
  • Nucleic acid tests: Xpert MTB/RIF assay should be submitted in the setting of high clinical suspicion and negative AFB staining.

• Treatment
  • Intensive phase (2 months): four drugs RIPE. Ethambutol has poor CNS penetration so some use fluoroquinolones instead.
  • Continuation phase (7-10 months)
  • Steroids
    • A review of 9 trials on 1337 patients found that use of steroids reduced death and disability by ~25%.
    • Benefit higher if started earlier in disease process.
    • Treat for 8 weeks, slow taper.
  • Stroke
    • A retrospective study in Stroke 2018 on patients with TB meningitis found that those >40, with concurrent HTN, dysplipidemia, and DM were more likely to have this complication. Some small case series showing benefit in reducing future strokes with the use of Aspirin.
    • No role for tPA.