Autoimmune GFAP Astrocytopathy

Autoimmune glial fibrillary acidic protein astrocytopathy is a steroid responsive meningoencephalomyelitis with IgG antibodies to GFAP (alpha isoform), seen in adults at a median age of about 45 to 50 years. A viral prodrome occurs in a third. Cancer, mostly ovarian teratoma, is found in up to 20 to 40%, and other autoimmune disease (type 1 diabetes, thyroid disease) may coexist.

Pathophysiology. Antibodies against an intracellular astrocyte antigen are likely markers of a T-cell mediated astrocytic injury.

Subacute fever, headache and meningism, encephalopathy, seizures, tremor, myoclonus, ataxia, visual blurring from optic disc oedema, myelitis (often with bladder dysfunction) and autonomic dysfunction. Many have hyponatraemia.

Red flags.

• Febrile subacute encephalopathy with optic disc swelling.
• Myelitis with brain involvement.
• Severe encephalopathy or status epilepticus.

CSF GFAP-IgG by cell based assay (more sensitive than serum). CSF shows lymphocytic pleocytosis (median 30 to 50 cells), raised protein, and sometimes low glucose. MRI shows linear perivascular radial enhancement in the white matter perpendicular to the ventricles (characteristic), brainstem, longitudinally extensive cord lesions with central canal enhancement, and leptomeningeal enhancement. Search for tumour (CT chest, abdomen and pelvis, pelvic ultrasound or MRI, testicular ultrasound) and repeat if negative. Exclude infection.

Differential diagnosis.

• Infectious meningoencephalitis (herpes, tuberculosis), neurosarcoidosis and lymphoma.
• Neuromyelitis optica spectrum disorder, MOG antibody disease and autoimmune encephalitis.
• CNS vasculitis and Susac syndrome.

Exclude infection, give empirical aciclovir 10 mg/kg IV every 8 hours while awaiting PCR, and start immunotherapy early.

First line.

• Methylprednisolone 1 g IV daily for 3 to 5 days, then prednisolone 1 mg/kg daily (maximum 60 mg), tapered slowly over 6 to 12 months.
• Intravenous immunoglobulin 0.4 g/kg daily for 5 days, or plasma exchange (5 sessions) for poor response.

Steroid sparing and refractory. Rituximab 1 g IV twice, 2 weeks apart (screen for hepatitis B), mycophenolate mofetil 1 g twice daily, or azathioprine 2 to 3 mg/kg daily (check thiopurine methyltransferase).

Tumour. Remove ovarian teratoma and other tumours.

Supportive care. Seizure control (levetiracetam 500 to 1500 mg twice daily), correction of sodium, bladder care and rehabilitation.

Monitoring. Clinical and MRI response, antibody titres where used, relapses (about 10 to 20%), and tumour surveillance for 2 to 4 years.

Referral and escalation. Refer urgently to neurology.