Trigeminal Nerve Involvement in Bulbar-Onset Anti-IgLON5 Disease

Abstract

Objectives: Anti-IgLON5 disease (IgLON5-D) may present with a bulbar-onset motor neuron disease-like phenotype, mimicking bulbar-onset amyotrophic lateral sclerosis. Recognition of their distinctive clinical and paraclinical features may help for differential diagnosis. We report 2 cases of atypical trigeminal neuropathy in bulbar-onset IgLON5-D.

Methods: Trigeminal nerve involvement was assessed using comprehensive clinical, laboratory, electrophysiologic, and MRI workup.

Results: Both patients were referred for progressive dysphagia, sialorrhea, and hoarseness. They were treated with bilevel positive airway pressure for nocturnal hypoventilation. Patient 1 complained of continuous facial burning pain with allodynia, exacerbated by mastication and prolonged speech. Patient 2 reported no facial pain. Anti-IgLON5 autoantibodies (IgLON5-Abs) were positive in serum for both patients and CSF for patient 1. Cerebral MRI revealed bilateral T2 fluid-attenuated inversion recovery (FLAIR) hyperintensity and enlargement of trigeminal nerves without gadolinium enhancement in both patients. Needle myography showed fasciculations in masseter muscles. Blink-reflex study confirmed bilateral trigeminal neuropathy only in patient 2. Cortical laser-evoked potentials showed a bilateral small-fiber dysfunction in the trigeminal nerve ophthalmic branch in patient 1.

Discussion: In case of progressive atypical bulbar symptoms, the presence of a trigeminal neuropathy or trigeminal nerve abnormalities on MRI should encourage the testing of IgLON5-Abs in serum and CSF.

Figure 1. Trigeminal Nerve Abnormalities on MRI of the Brain

Axial T2 FLAIR sequences showing hyperintensity and slight nerve enlargement of both trigeminal nerves in patients 1 (A, B) and 2 (C, D) (red arrows), including the intra-axial portion of the right trigeminal nerve in patient 1 (A). In patient 2, the right temporal pole abnormalities were attributed to coincidental opercular enlargement of perivascular space with peripheral gliosis.

Figure 2. Bilateral Trigeminal Neuropathy on Blink-Reflex Study in Patient 2: Baseline and 6-Month Follow-up Evaluations

At baseline evaluation (A, B), after stimulation of the right supraorbital nerve (A), R1 and ipsilateral and contralateral R2 latencies were all prolonged (R1 latency: 15.3 ms, normal value: 8–13 ms; ipsilateral R2 latency: 48.6 ms, normal value 29–41 ms; contralateral R2 latency: 48.5 ms, normal value ≤44 ms), suggesting right trigeminal neuropathy according to previously described normative values. After stimulation of the left supraorbital nerve (B), R1 and ipsilateral and contralateral R2 responses were all absent, indicating a severe left trigeminal neuropathy. After 6 months of immunotherapy (C, D), normal latency responses were recorded after right side stimulation (R1 latency: 12.8 ms, ipsilateral R2 latency: 38.3 ms, contralateral R2 latency: 39.5 ms) (C). After left side stimulation (D), R1 and ipsilateral and bilateral R2 responses were obtained but with slightly prolonged latencies (R1 latency: 14.8 ms, ipsilateral R2 latency: 43.0 ms, contralateral R2 latency: 44.9 ms) (red arrows), indicating a clear improvement of both left and right trigeminal neuropathy. L = latency; N = normal value.