Optic, trigeminal, and facial neuropathy related to anti‐neurofascin 155 antibody

Abstract

Objective: To characterize the frequency and patterns of optic, trigeminal, and facial nerve involvement by neuroimaging and electrophysiology in IgG4 antineurofascin 155 antibody-positive (NF155 +) chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: Thirteen IgG4 NF155 + CIDP patients with mean onset age of 34 years (11 men) were subjected to neurological examination, blink reflex, and visual-evoked potential (VEP) testing, and axial and/ or coronal T2-weighted head magnetic resonance imaging (MRI). Results: Among 13 patients, facial sensory impairment, facial weakness, and apparent visual impairment were observed in three (23.1%), two (15.4%), and two (15.4%) patients, respectively. All 12 patients tested had blink reflex abnormalities: absent and/or delayed R1 in 11 (91.7%), and absent and/or delayed R2 in 10 (83.3%). R1 latencies had strong positive correlations with serum anti-NF155 antibody levels (r = 0.9, P ≤ 0.0001 on both sides) and distal and F wave latencies of the median and ulnar nerves. Absent and/or prolonged VEPs were observed in 10/13 (76.9%) patients and 17/26 (65.4%) eyes. On MRI, hypertrophy, and high signal intensity of trigeminal nerves were detected in 9/ 13 (69.2%) and 10/13 (76.9%) patients, respectively, whereas optic nerves were normal in all patients. The intra-orbital trigeminal nerve width on coronal sections showed a significant positive correlation with disease duration. Interpretation: Subclinical demyelination frequently occurs in the optic, trigeminal, and facial nerves in IgG4 NF155 + CIDP, suggesting that both central and peripheral myelin structures of the cranial nerves are involved in this condition, whereas nerve hypertrophy only develops in myelinated peripheral nerve fibers.

Anti-Neurofascin 155 Antibody-Positive Chronic Inflammatory Demyelinating Polyneuropathy/Combined Central and Peripheral Demyelination: Strategies for Diagnosis and Treatment Based on the Disease Mechanism

“…In NF155 + CIDP, the distal and F-wave latencies are affected more severely than the motor conduction velocities and compound muscle action potential amplitudes ( 5 ). Together with a high frequency of spinal root hypertrophy on MRI, as described in the following section ( 5 , 32 ), these findings suggest that, although all nerve segments are affected in NF155 + CIDP, the distal and proximal root segments tend to be involved more severely in NF155 + CIDP than in NF155 − CIDP. This may reflect the possibility that anti-NF155 antibodies have easy access to PNS tissue at nerve terminals and spinal roots where the blood–nerve barrier (BNB) is anatomically absent or loose.…”

“…In our NF155 + CIDP patient cohort, absent and/or prolonged visual-evoked potentials (VEPs) were observed in 10 of 13 (76.9%) patients and in 17 of 26 (65.4%) eyes ( 32 ), although clinically overt visual disturbance was infrequent. Otherwise, VEPs in CIDP were examined only in a few studies on a small series of Caucasian patients without investigating anti-NF1555 antibodies ( 37 – 39 ).…”

“…Interestingly, all the NF155 + CIDP patients we examined showed blink reflex abnormalities, including absent and/or delayed R1 in 91.7% (11/12) and absent and/or delayed R2 in 83.3% (10/12) ( 32 ). Given the infrequent overt facial or trigeminal manifestations, a very high frequency of prolonged R1 and R2 latencies in the blink reflex test indicates that subclinical demyelination of these nerves is a common feature of NF155 + CIDP.…”

“…In addition, the R1 latencies had strong positive correlations with the distal and F-wave latencies of the median and ulnar nerves ( 32 ), which indicates that somatic and cranial nerves are involved in parallel via anti-NF155 antibodies ( Figure 3 ). The fact that the distal and F-wave latencies correlated with the blink reflex abnormalities more strongly than with the motor conduction velocities and compound muscle action potential amplitudes probably indicates an antibody-mediated nerve terminal damage in the trigeminal and facial nerves, as described above for somatic nerves ( 32 ).…”

“…Devaux et al ( 6 ) also compared the clinical features of 38 NF155 + CIDP patients with those of 100 NF155 − CIDP patients and found sensory ataxia in 74%, tremor in 42%, and cerebellar ataxia associated with nystagmus in 13%. Overt cranial nerve manifestation is only occasionally seen in NF155 + CIDP, although its frequency seems to be somewhat higher in NF155 + CIDP than in NF155 − CIDP ( 5 , 32 ): visual disturbance [23.1% (3/13) vs. 7.3% (3/41)], facial sensory disturbance [23.1% (3/13) vs. 17.1% (7/41)], and facial palsy [15.4% (2/13) vs. 4.9% (2/41)] ( 5 ).…”