Two Cases of Isolated Neurofilament Heavy Chain Antibody Syndrome

Abstract

Objective Novel clinical and laboratory findings in anti-neurofilament heavy chain encephalitis Background Antibodies to mature components of neuronal intermediate filament (NIF) have been implicated in several neurological disorders, including multiple sclerosis, amyotrophic lateral sclerosis, and more recently, various autoimmune encephalitides. The components include a-internexin, light chain and heavy chain. In the largest case series of anti-NIF syndromes (McKeon et al, 2021), patients' cell-based assays revealed antibodies to one, two or all three components. Heavy chain antibodies (anti-NfH) were present in most, including three out of four patients with encephalopathy and cerebellar involvement. One was due to a paraneoplastic phenomenon. Anti-NfH was also elevated in two cases of encephalopathy with spasticity. It was the lone autoantibody in one of the six aforementioned cases. Design/Methods N/A. Results Case 1: 37-year old female with a history of ovarian carcinoma, treated in 2016. Cognitive impairment started in fall 2019, with significant worsening to the point of catatonia and coma in October 2020. Though encephalopathy improved, severe ataxia and nystagmus persisted. Two MRI brain studies and an EEG were unremarkable, and no radiological evidence of cancer recurrence. Oligoclonal bands (in both CSF and serum) and serum anti-NfH were elevated. Case 2: 59 year-old female with gradual cognitive decline since March 2018, followed by rapid cognitive deterioration in Oct 2020. There was limb weakness, severe rigidity, clonus and a witnessed seizure. EEG showed intermittent rhythmic delta activity. MRI brain indicated severe bilateral hippocampal atrophy. CSF Protein and CSF anti-NfH were elevated. Conclusions This case series contains the first reported paraneoplastic encephalopathy with cerebellar involvement from isolated anti-NfH. Also presented is the first reported case of PERMS from any NIF antibody. Further research is needed on quantitative and qualitative factors of anti-NIF syndromes. Specifically, the clinical relevance of the number of antibodies, and associations between phenotype and specific antibody combination.