Tremor Associated with Chronic Inflammatory Demyelinating Polyneuropathy and Anti-Neurofascin-155 Antibodies
Background: Tremor is an underrecognized feature in certain neuropathy subtypes.
Phenomenology shown: We show a patient with a disabling neuropathic tremor and mild cerebellar syndrome associated with chronic inflammatory demyelinating polyneuropathy (CIDP) and anti-neurofascin-155 (NF155) antibodies.
Educational value: Anti-NF155 testing should be considered in patients with CIDP and disabling tremor because of therapeutic implications.
Keywords: Neuropathic tremor, neurofascin-155, chronic inflammatory demyelinating polyneuropathy
Citation: Bailly L, Mongin M, Delorme C, Apartis E, Saheb S, Viala K, et al. Tremor associated with chronic inflammatory demyelinating polyneuropathy and anti-neurofascin-155 antibodies. Tremor Other Hyperkinet Mov. 2018; 8. doi: 10.7916/D81560ZW
*To whom correspondence should be addressed. E-mail: firstname.lastname@example.org
Editor: Elan D. Louis, Yale University, USA,
Received: September 8, 2018 Accepted: October 18, 2018 Published: December 4, 2018
Copyright: © 2018 Bailly et al. This is an open-access article distributed under the terms of the Creative Commons Attribution–Noncommercial–No Derivatives License, which permits the user to copy, distribute, and transmit the work provided that the original authors and source are credited; that no commercial use is made of the work; and that the work is not altered or transformed.
Financial Disclosures: L. Bailly has nothing to disclose M. Mongin received travel support from Merz-Pharma C. Delorme received travel support from Merz-Pharma and Elivie. E. Apartis received research support from APTES S. Saheb received research support from Octapharma, CSL Bering, Terumo BCT, Amgen, and Sanofi E. Roze received research support from Merz-Pharma, Orkyn, Aguettant, Elivie, Ipsen, Ultragenix, Fondation Desmarest, AMADYS, Fonds de Dotation Brou de Lauriàre, and Agence Nationale de la Recherche; has served on scientific advisory boards for Orkyn, Aguettant, and Merz-Pharma; and has received honoraria for speeches from Orkyn, Aguettant, Merz-Pharma, and Medday-Pharma.
Conflicts of Interest: The authors report no conflict of interest.
Ethics Statement: All patients that appear on video have provided written informed consent; authorization for the videotaping and for publication of the videotape was provided.
We report the case of a 64-year-old female with type 2 diabetes and a longstanding history of bipolar disorder treated with valproate and venlafaxine on stable doses. She presented with gait ataxia and distal limb paresthesia that had gradually worsened over 2 months. She then noticed bilateral upper limb tremor and dysarthria. Clinical examination showed a mild proximal and distal quadriparesis, absent deep tendon reflexes, dysmetria, ataxic dysarthria, and mixed proprioceptive and cerebellar gait ataxia. She had a predominantly action tremor (kinetic, postural, and intentional) with proximal and distal involvement and a mild rest tremor (Video 1). Electroneuromyography showed motor and sensory demyelinating neuropathy in the upper and lower limbs with proximal and distal involvement, consistent with CIDP. Cerebrospinal fluid examination showed an increased protein level (0.67 g/L) with a normal cell count. Polymyographic recording revealed a rest and action tremor with a 5-Hz frequency intermingled with occasional subcortical myoclonus. Brain magnetic resonance imaging and dopamine transporter scan results were normal. Antibody testing was positive for anti-neurofascin-155 (NF155) antibodies. We made the diagnosis of CIDP associated with anti-NF155 antibodies causing a pronounced neuropathic tremor and cerebellar syndrome. The subacute presentation while on stable doses argues against roles of sodium valproate and venlafaxine in the tremor and myoclonic jerks, but a mild effect cannot be excluded. She did not respond to intravenous immunoglobulins (IVIg). Corticosteroids given with rituximab and plasma exchange allowed partial improvement of sensory and motor manifestations, tremor severity, and neurophysiological parameters. NF155 is an adhesion molecule expressed at paranodes at the terminal loops of myelin, where it plays a key role in promoting rapid nerve impulse propagation.1 CIDP with anti-NF155 antibodies is frequently associated with disabling neuropathic tremor. It is described as an action tremor with low frequency, high amplitude, and marked postural and intention components.2 Mild rest component and jerks could also be a feature of neuropathic tremor. In a recently described cohort, some patients with NF-155 antibodies (5/38) had an additional cerebellar syndrome with gait ataxia, dysarthria, and nystagmus. In addition, some patients also had central nervous system (CNS) demyelination (3/38), which may be related to the presence of an NF155 antigen in the CNS.2 Disabling action tremor in the context of a demyelinating neuropathy is a clue for anti-NF155 antibody-associated CIDP. This has important therapeutic implications as this condition does not usually respond to IVIg but may improve with plasmapheresis and rituximab.2
1. Querol L, Devaux J, Rojas-Garcia R, Illa I. Autoantibodies in chronic inflammatory neuropathies: diagnostic and therapeutic implications. Nat Rev Neurol 2017;13:533–47. doi: 10.1038/nrneurol.2017.84
2. Devaux JJ, Miura Y, Fukami Y, Inoue T, Manso C, Belghazi M, et al. Neurofascin-155 IgG4 in chronic inflammatory demyelinating polyneuropathy. Neurology 2016;86:800–7. doi: 10.1212/WNL.0000000000002418