Autoimmune Cerebellitis

Autoimmune cerebellitis is immune mediated inflammation of the cerebellum causing a subacute pancerebellar syndrome. It includes paraneoplastic, post-infectious and antibody associated forms.

It is rare. Paraneoplastic forms are mostly in adults, and post-infectious forms (after varicella, Epstein-Barr virus and other viral infections) occur mainly in children.

Causes and associations.

• Paraneoplastic: anti-Yo (breast and ovarian cancer), anti-Hu, anti-Ri, anti-Tr/DNER (Hodgkin lymphoma), anti-mGluR1, anti-KLHL11 (testicular germ cell tumour), anti-CV2/CRMP5.
• Non-paraneoplastic: anti-GAD65, anti-CASPR2, anti-PCA-2, and gluten related and post-infectious disease.

Pathophysiology. Paraneoplastic forms are driven by cytotoxic T-cell loss of Purkinje cells to intracellular antigens (Yo, Hu). Surface antigen antibodies (mGluR1, DNER) act directly on Purkinje cell function and may respond to treatment.

Presentation is subacute, over days to 3 months, with gait and limb ataxia, dysarthria, nystagmus, vertigo and oscillopsia. Tremor, diplopia and nausea occur. Features of the underlying cancer or other autoimmune disease may be present.

Red flags.

• Rapid progression over days to weeks.
• Weight loss, mass or smoking history, suggesting cancer.
• Fever, headache or meningism, suggesting infective cerebellitis.

MRI brain is normal or shows early cerebellar swelling or enhancement, later atrophy. CSF shows mild pleocytosis, raised protein and oligoclonal bands. Send paired serum and CSF for neural antibodies (a full paraneoplastic panel and surface antibodies). Search for cancer with CT of chest, abdomen and pelvis, mammography, testicular or pelvic ultrasound and whole body FDG-PET if negative, and repeat after 3 to 6 months if antibodies are positive.

Differential diagnosis.

• Infective cerebellitis, acute disseminated encephalomyelitis and multiple sclerosis.
• Alcohol, drug and toxic cerebellar syndromes (phenytoin, lithium, solvents).
• Posterior circulation stroke, Wernicke encephalopathy and Creutzfeldt-Jakob disease.
• Hypothyroidism, vitamin E deficiency and gluten ataxia.

Treat early, since cerebellar neuronal loss is irreversible.

First line immunotherapy.

• Methylprednisolone 1 g IV daily for 3 to 5 days, then oral prednisolone 1 mg/kg daily (maximum 60 mg) tapered over weeks to months.
• Intravenous immunoglobulin 0.4 g/kg daily for 5 days, or plasma exchange (5 exchanges on alternate days). Check renal function and thrombosis risk with immunoglobulin.

Second line. Rituximab 1 g IV, repeated after 2 weeks (or 375 mg/m2 weekly for 4 doses), or cyclophosphamide 750 mg/m2 IV monthly for 6 months for paraneoplastic or refractory disease. Screen for hepatitis B before rituximab.

Treat the tumour. Surgery, chemotherapy or radiotherapy, which gives the best chance of stabilisation. Anti-Yo disease responds poorly.

Supportive care. Physiotherapy, occupational therapy, speech therapy and falls prevention.

Monitoring. Ataxia scale at 3 to 6 months, cancer surveillance for at least 4 years in antibody positive patients, and infection risk.

Referral and escalation. Refer urgently to neurology and oncology.

Special groups. In children, post-infectious cerebellitis is often self-limiting, with steroids or immunoglobulin for severe cases.