History.
Mr. Ho was a 50-year-old chronic smoker and non-drinker who presented with a 6-month history of progressive forgetfulness (steps of repairing water pipes and electrical wires as a plumber), unsteady gait, slurred speech, and unintentional weight loss.
He had a history of rheumatoid arthritis on isoniazid (started after symptom onset, prophylaxis in preparation for biologics due to IGRA positivity), leflunomide, methotrexate, and P20.
There was no family history of gait disturbances or cognitive impairment.
Physical examination.
Dysarthria, normal limb power, bilateral limb ataxia (right > left), broad-based gait, failed tandem walking.
No signs of posterior column or peripheral nerve dysfunction.
MOCA 18 (<65yo).
Investigations.
Mild normocytic anemia. ESR 80.
LP: OP not documented, WCC 15 polymorphs, protein 0.6, glucose not low, atypical cells present
Contrast MRI brain: no evidence of demyelination, thiamine deficiency, midbrain or cerebellar atrophy, or leptomeningeal enhancement.
EEG: no focal abnormality.
Thought process.
Syndrome:
- Subacute onset progressive cognitive impairment, bilateral cerebellar ataxia, and constitutional symptoms in an immunocompromised host
Localization:
- Bilateral cerebellum.
- Less likely cord (posterior column), peripheral nerve.
Etiology:
- Infective: indolent infections including syphilis, HIV, HTLV-1, TB, cryptococcus, fungus
- Inflammatory: autoimmune cerebellitis
- Neoplastic / paraneoplastic: leptomeningeal metastasis, paraneoplastic cerebellitis
- Less likely toxic or metabolic etiology (unable to account for the CSF pleocytosis)
Progress.
Rapidly deteriorating bilateral cerebellar ataxia and cognitive impairment rendering the patient chair-bound and dependent in 9 months from symptom onset.
Paraneoplastic antibody panel negative. Microbiological work up negative.
Serial LP: OP not elevated, WCC 8, protein 0.54, glucose not low, no abnormal cells
Serial MRI brain: no brain metastases, leptomeningeal enhancement, or cerebellar atrophy.
CT TAP: multiple subpleural lung nodules, mediastinal and hilar lymphadenopath, left pleural effusion
EBUS: atypical cells on lymph node biopsy
Next steps.
Pending FDG PETCT brain, mediastinoscopy.
Serial PETCT whole body, focused CT thorax, paraneoplastic antibody panel indicated.