Pan-neurofascin autoimmune nodoparanodopathy: A case report and literature review

Abstract

Rationale: Locked-in syndrome (and its variant, completely locked-in state) generally has a high mortality rate in the acute setting; however, when induced by conditions such as acute inflammatory polyradiculoneuropathy, it may well be curable such that an attempt at cure should be systematically sought by clinicians.

Patient concerns: A 52-year-old man presented with acute tetraparesia and areflexia, initially diagnosed as Guillain-Barré syndrome. Despite appropriate treatment, his condition deteriorated, evolving into a completely locked-in state.

Diagnoses: The detection of anti-pan-neurofascin antibodies led to the correct diagnosis, acute pan-neurofascin autoimmune nodoparanodopathy.

Interventions: Immunosuppressive treatment (rituximab) and plasma exchanges were performed.

Outcomes: After several months, the patient's neurological symptoms almost completely subsided, without any major sequelae.

Lessons: In patients with locked-in syndrome (or its variant), neurologists and intensive care physicians must be aware of, and look for, the main etiologies (including pan-neurofascin autoimmune nodoparanodopathy), to allow the prompt initiation of treatment and thus a rapid recovery for these ultimately curable conditions. Despite causing major disability, pan-neurofascin autoimmune nodoparanodopathy is curable if the appropriate treatment is given.

Figure 1.

Schematic of the main clinical course and the electrophysiological parameters during the 532-day follow-up of our patient. The muscle motor assessments of the 4 limbs were evaluated by deriving the MRC scores (normal muscle force = 100). Disability was evaluated using the total overall neuropathy limitations scale (ONLS; maximum score = 12; 0, no disability; 12, total disability). In the electrophysiological context, we showed the evolution of the CMAP amplitude (an “axonal parameter”) and the duration thereof (a “demyelinating” parameter) for the right median nerve (at wrist) compared to the normal values represented by the dotted red line. CMAP = compound muscle action potential, IVIg = intravenous immunoglobulin, mg = milligram, ms = millisecond, mV = millivolt, PLEX = plasma exchange.

Figure 2.

Sera (diluted 1:100) obtained before and after treatment were incubated with cells transfected to allow NF155 and NF186 expression (A) or beads with recombinant NF155 (B). After washing, cells and beads were incubated with anti-IgG (A), anti-IgG1, anti-IgG2, anti-IgG3, or anti-IgG4 fluorescence-labeled antiserum (B). The fluorescence levels were compared to those obtained using non-transfected cells or control beads. We observed a positive result for anti-NF155 and anti-NF186 antibodies at D114, with negativity at D532 (A); these were only anti-IgG4 antibodies (B). AF-488 = Alexa FluorTM 642 (it specifically detects IgG1 antibodies), AF-642 = Alexa FluorTM 642 (it specifically detects IgG2 antibodies), AF-750 = Alexa FluorTM 750 (it specifically detects IgG3 antibodies), NF = neurofascin, PB = plasmablasts (circulating plasmablasts are elevated in active IgG4 related diseases, so it is used as a biomarker of IgG4 antibodies).