Objective: We report a very rare case of isolated ZIC4 associated rapidly progressive cerebellar syndrome occurring in the background of bone marrow tuberculosis.

Background: Rapidly progressive cerebellar syndrome also known as paraneoplastic cerebellar degeneration has been described with several antibodies like anti-Hu and anti-Yo in association with malignancies like small cell lung carcinoma and ovarian tumors. ZIC4 antibodies are mostly reported occurring concurrently with other more significant antibodies. Isolated ZIC4 associated rapidly progressive cerebellar syndrome is a very rare entity and usually reported to have a benign course. Reported cases were associated more commonly with tumors than not. Infections triggering antibodies leading to Autoimmune/paraneoplastic encephalitis is also a rare occurrence. Reported antibodies and associated infection include NMDA with herpes simplex, tuberculosis, varicella zoster, EBV, toxoplasma gondii and chikungunya, anti-glycine receptor and West Nile virus, GABA-B with SARS-CoV2, GABA-A with parvovirus B19. ZIC4 antibodies have been reported to be concurrently present in a case of prion disease.

Method: A 62-year-old male presented with subacute onset progressive cerebellar ataxia and dysautonomia in form of urinary incontinence and recurrent gastrointestinal symptoms for last 2 months. Evaluation for generalized weakness and weight loss 5 months back had yielded a diagnosis of bone marrow tuberculosis and chronic liver disease and was on appropriate drugs for same. He also developed focal unaware seizures, facio-brachial dystonia and multifocal myoclonus. MRI Brain with contrast was normal. CSF evaluation for infection including tuberculosis was unyielding. Serum was strongly positive for ZIC4 antibodies. Whole body PET CT did not reveal any malignancy.

Results: He developed refractory status epilepticus and was managed with anti-epileptics, anesthetic agents and IV methylprednisolone. No improvement was seen and hence IVIG was given. Seizures were controlled. Patient subsequently remained in a vegetative state.

Conclusion: This is an extremely rare case of likely tuberculosis triggered ZIC4 encephalitis causing ataxia, dystonia and seizures in absence of any malignancy. Molecular mimicry is a possible mechanism for inducing antibodies. Isolated ZIC4 encephalitis can present triggered by systemic infection and in absence of malignancy.

References: 1. Bataller L, Wade DF, Graus F, Stacey HD, Rosenfeld MR, Dalmau J. Antibodies to Zic4 in paraneoplastic neurologic disorders and small-cell lung cancer. Neurology. 2004 Mar 9;62(5):778-82. doi: 10.1212/01.wnl.0000113749.77217.01. PMID: 15007130
2. Xiaoli C, Qun W, Jing L, Huan Y, Si C. Concurrent Tuberculous Meningoencephalitis and Anti-NMDAR Encephalitis: A Case Report. Front Neurol. 2022 Jul 7;13:870607. doi: 10.3389/fneur.2022.870607. PMID: 35873772; PMCID: PMC9301103.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/isolated-zic-4-antibody-associated-cerebellar-dysfunction-triggered-by-tuberculosis/