LETTER TO THE EDITOR

REMISSION WITH FINGOLIMOD IN A CASEOF DEMYELINATING POLYNEUROPATHY

It has recently been shown that fingolimod, asphingosine-1-phosphate receptor modulator approvedfor relapsing2remitting multiple sclerosis (MS), can beeffective in experimental autoimmune neuritis.1,2

Because there have been no previous reports on its clini-cal use in autoimmune peripheral neuropathies, we pres-ent our successful experience with this drug in a case ofMS and autoimmune demyelinating polyneuropathy.

An 18-year-old man presented with a history of 3attacks of optic neuritis in the last 3 years. He was diag-nosed with MS based on his history, positive oligoclonalbands, and typical magnetic resonance imaging (MRI)findings. He had been receiving interferon-b-1B treat-ment since his initial attack. On presentation, hyperac-tive deep tendon reflexes (DTRs) were detected, andthere were no other pathological findings. The followingyear, he had numbness in the distal extremities withwalking difficulty that progressed within a few weeks. Atthis time, depressed tendon reflexes, bilateral facial pare-sis, and mild quadriparesis were found, along withdecreased proprioception and vibration sense in thelower extremities.

Brain MRI showed contrast enhancement in multiplecranial nerves in addition to active demyelinating pla-ques (refer to Fig. S1A2D in Supplementary Material,available online at http://www.mrw.interscience.wiley.com/suppmat/0148-639X/suppmat/). There was alsoprominent diffuse thickening and contrast enhancementbilaterally in the brachial plexi and cauda equina, con-sistent with inflammation in these structures (Fig.S1E2H in Supplementary Material online). Cerebrospi-nal fluid protein was elevated (237 mg/dl) with no cells.Nerve conduction studies (NCS) demonstrated severedemyelinating polyneuropathy associated with axonalloss in motor and sensory fibers (Fig. 1A2D, and TableS1 in Supplementary Material online). There was no evi-dence of other autoimmune, granulomatous, or infec-tious cause. Plasmapheresis was initiated to treat thepolyneuropathy. After 5 sessions, the patient describedmild relief in sensory symptoms, and bilateral hypoactive

patellar reflexes could be elicited. He then received a5-day course of 0.4 g/kg/day of intravenous immunoglob-ulin (IVIg) followed by intermittent doses every 3 weeks.

After 3 months, while still receiving interferon-b-1Band IVIg, he developed severe ataxia, diplopia, and wor-sening extremity numbness. Horizontal gaze-evoked nys-tagmus, mild interosseous atrophy, bilateral foot drop,and extensor plantar signs were evident. Contrastenhancement in the brain lesions and cauda equinawere persistent. He was readmitted and given intrave-nous steroids and another session of plasmapheresis.There was initial mild improvement in his symptoms,and maintenance plasmapheresis sessions were contin-ued (2 times weekly) for the next 6 months. Ataxia anddistal weakness of the lower extremities worsened, how-ever, and he remained dependent on foot drop splintsand a single cane for ambulation. Meanwhile, there wascontinued contrast enhancement in the brain. Becausehe had clinical and radiological disease activity in bothcentral and peripheral compartments with no satisfactoryimprovement in disability, we changed the therapy frominterferon-b to fingolimod, and plasmapheresis wasterminated.

The patient was followed for 22 months while takingfingolimod 0.5 mg/day. During this time not only thecentral but also the peripheral nervous system2relatedsymptoms and MRI activity diminished gradually, and heregained independence. On follow-up, despite the pres-ence of hypoactive deep tendon reflexes, his distal mus-cle bulk, distal muscle strength, and vibration andposition senses were nearly normal. There has been norelapse or progression since that time. Repeat NCS 15months after fingolimod showed partial but prominentimprovement in motor and sensory nerve conductionfindings (Fig. 1E2H, and Table S1 in SupplementaryMaterial online).

This case demonstrates the potential efficacy of fin-golimod in demyelinating polyneuropathy that is alsoobserved occasionally in patients with MS.3,4 Althoughour experience involved a single patient, the significantbenefit of fingolimod on both the central and periph-eral nervous system abnormalities suggests that this drugmay be a reasonable alternative in such patients. Toprove its efficacy, systematic trials in MS-associateddemyelinating neuropathy or in isolated polyneuropathycases are warranted.VC 2014 Wiley Periodicals, Inc.

Letters to The Editor MUSCLE & NERVE Month 2014 1

Sefik E Erdener, MD, PhD1

G€ulay Nurlu, MD1

Rahsan G€ocmen, MD2

Sevim Erdem-€Ozdamar, MD1

Aslı Kurne, MD1

1 Department of Neurology, Hacettepe University Faculty ofMedicine, Ankara, Turkey2 Department of Radiology, Hacettepe University Faculty ofMedicine, Ankara, Turkey

1. Kim HJ, Jung CG, Dukala D, Bae H, Kakazu R, Wollmann R, et al.Fingolimod and related compounds in a spontaneous autoimmunepolyneuropathy. J Neuroimmunol 2009;214:93–100.

FIGURE 1. Nerve conduction studies before (A2D) and after (E2H) initiation of fingolimod treatment. Compound muscle action poten-

tials of the right median nerve had prolonged distal latency, reduction in amplitudes with temporal dispersion, and excessively slow

conduction velocity (A). F waves could not be elicited with stimulation of right median nerve (B). No CMAP could be recorded with

right tibial nerve stimulation (C). Sensory nerve action potentials were absent in right median nerve (D). After approximately 15 months

of fingolimod therapy, although distal latency and conduction velocity were still above the normal limits in the right median nerve (E),

there was prominent improvement in those parameters, and CMAP amplitudes were normalized. Despite prolonged latencies, F waves

could be recorded with right median nerve stimulation (F). Right tibial CMAPs with reduced amplitudes and low conduction velocity

could be elicited at this time (G), along with a low-amplitude sensory nerve action potential in the right median nerve (H).

2 Letters to The Editor MUSCLE & NERVE Month 2014

2. Zhang ZY, Zhang Z, Zug C, Nuesslein-Hildesheim B, Leppert D,Schluesener HJ. AUY954, a selective S1P(1) modulator, preventsexperimental autoimmune neuritis. J Neuroimmunol 2009;216:59–65.

3. Di Trapani G, Carnevale A, Cioffi RP, Massaro AR, Profice P. Multi-ple sclerosis associated with peripheral demyelinating neuropathy.Clin Neuropathol 1996;15:135–138.

4. Zephir H, Stojkovic T, Latour P, Lacour A, de Seze J, Outteryck O, et al.Relapsing demyelinating disease affecting both the central and periph-eral nervous systems. J Neurol Neurosurg Psychiatry 2008;79:1032–1039.

Published online 00 Month 2014 in Wiley Online Library(wileyonlinelibrary.com). DOI 10.1002/mus.24311

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Letters to The Editor MUSCLE & NERVE Month 2014 3