A case series describing clinical presentation and diagnostic workup in 3 patients with anti-Neurofascin-155 (NF155)

A CIDP variant associated with NF155 antibody, presents with distinct clinical features of peripheral and central demyelination.

First, a 27-year-old woman presented with progressive numbness and allodynia limiting gait. She relapsed every few months and subsequently developed hypoesthesia, postural and kinetic hand tremor, nystagmus, bilateral optic edema with peripapillary hemorrhages. Treatment included immunoglobulin, plasmapheresis and eventually rituximab.

Second, is a 75-year-old man with history of restless leg syndrome and melanoma on immunotherapy (ipilimumab and nivolumab) who presented with rapid progressive lower extremity weakness (distal more than proximal), hyporeflexia and hypoesthesia. His symptoms improved after immunoglobulin treatment and discontinuation of immunotherapy.

Third, is a 26-year-old man who presented with distal more than proximal lower extremity weakness, hyporeflexia, hyperesthesia and postural hand tremor. He improved with rituximab after failed trials of immunoglobulin and plasmapheresis.

Electrodiagnostic study in all patients showed demyelinating sensorimotor polyradiculoneuropathy with mild axonal involvement. Spinal fluid was either normal or had albuminocytological dissociation or neutrophilic pleocytosis. Nerve biopsy in one patient showed axonal degeneration with myelin loss in large fibers with relative sparing of small diameter fibers without any inflammation. Brain and spine imaging were normal, except for nerve root enhancement in third patient. Anti-NF155 antibodies were IgM in two patients and IgG in one patient.

NF155 is a protein which interacts with contactin1 and CASPR 1 proteins on axons at the paranodal regions in both central and peripheral nervous system. IgG4 is the predominant antibody subclass although rare cases of IgM have been reported. Characteristics include prominent neuropathic pain and tremor on exam, with high percentage of subclinical/clinical central demyelination. We noticed better response to rituximab than to immunoglobulin and/or plasmapheresis. Periodic imaging should be considered if CNS involvement is suspected.