Neurofascin-mediated Neuropathy Mimicking Miller-Fisher Syndrome, Displaying a Broader Clinical Spectrum Inclusive of Trigeminal Autonomic Cephalalgias
Manuela Ochoa Urrea1, Ore-Ofe Adesina2, Sri Raghav Sista1
1Neurology, 2Ophthalmology, University of Texas Health Science Center at Houston
Background:
Pathogenic antibodies targeting nodopathies and para-nodopathies represent novel and distinct disorders, separate from traditional inflammatory neuropathies (such as acute and chronic immune-mediated polyradiculoneuropathies). The clinical range of these disorders continues to evolve.
Results:
A 66-year-old woman with past medical history of hypertension, atrial fibrillation, hyperlipidemia, and right Bell’s palsy presented with 6 days of progressive diplopia, unsteady gait, and severe stabbing headaches localized around her right eye. Neuroexam was notable for right sided-ptosis, left III CN palsy, bilateral VI CN palsies OS>OD with bilateral downgaze paresis, right hypoacusis, bilateral dysmetria on finger-to-nose, positive Romberg, and ataxic gait. Spinal fluid analysis, MR brain and entire spine with and without contrast, MR angiogram of head and neck were non-contributory. Intra-venous immunoglobulin was initiated for presumptive diagnosis of Miller-Fisher syndrome, without any improvement. Later was noted to be positive Neurofascin-140 and 155 IgG in the serum. Comprehensive genetic testing for hereditary neuropathies was negative. Electrodiagnostic testing performed four months from symptom onset did not demonstrate a large fiber neuropathy, but blink and facial nerve responses were impeded due to patient’s discomfort from headaches. She initiated on rituximab with improvement of gait, dysmetria, and oculomotor palsies (residual right sided-ptosis and right VI), two months after the first infusion. Her headaches were reminiscent of trigeminal autonomic cephalgia and responded to indomethacin.
Conclusions:
As demonstrated from our patient, nodal/paranodal antibody mediated polyneuropathy can present with what is traditionally considered Miller-Fisher syndrome highlighting the importance of their testing especially given that these disorders are refractory to the established immunomodulatory treatments but respond well to rituximab. Furthermore, the observed trigeminal autonomic cephalalgia in our patient represents a previously undocumented facet of nodal/paranodal antibody-related disorders.