Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS.

BACKGROUND: The intrathecally administered antisense oligonucleotide tofersen reduces synthesis of the superoxide dismutase 1 (SOD1) protein and is being studied in patients with amyotrophic lateral sclerosis (ALS) associated with mutations in SOD1 (SOD1 ALS). METHODS: In this phase 3 trial, we randomly assigned adults with SOD1 ALS in a 2:1 ratio to receive eight doses of tofersen (100 mg) or placebo over a period of 24 weeks. The primary end point was the change from baseline to week 28 in the total score on the ALS Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) among participants predicted to have faster-progressing disease. Secondary end points included changes in the total concentration of SOD1 protein in cerebrospinal fluid (CSF), in the concentration of neurofilament light chains in plasma, in slow vital capacity, and in handheld dynamometry in 16 muscles. A combined analysis of the randomized component of the trial and its open-label extension at 52 weeks compared the results in participants who started tofersen at trial entry (early-start cohort) with those in participants who switched from placebo to the drug at week 28 (delayed-start cohort). RESULTS: A total of 72 participants received tofersen (39 predicted to have faster progression), and 36 received placebo (21 predicted to have faster progression). Tofersen led to greater reductions in concentrations of SOD1 in CSF and of neurofilament light chains in plasma than placebo. In the faster-progression subgroup (primary analysis), the change to week 28 in the ALSFRS-R score was -6.98 with tofersen and -8.14 with placebo (difference, 1.2 points; 95% confidence interval [CI], -3.2 to 5.5; P = 0.97). Results for secondary clinical end points did not differ significantly between the two groups. A total of 95 participants (88%) entered the open-label extension. At 52 weeks, the change in the ALSFRS-R score was -6.0 in the early-start cohort and -9.5 in the delayed-start cohort (difference, 3.5 points; 95% CI, 0.4 to 6.7); non-multiplicity-adjusted differences favoring early-start tofersen were seen for other end points. Lumbar puncture-related adverse events were common. Neurologic serious adverse events occurred in 7% of tofersen recipients. CONCLUSIONS: In persons with SOD1 ALS, tofersen reduced concentrations of SOD1 in CSF and of neurofilament light chains in plasma over 28 weeks but did not improve clinical end points and was associated with adverse events. The potential effects of earlier as compared with delayed initiation of tofersen are being further evaluated in the extension phase. (Funded by Biogen; VALOR and OLE ClinicalTrials.gov numbers, NCT02623699 and NCT03070119; EudraCT numbers, 2015-004098-33 and 2016-003225-41.).

Phase 1-2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS.

BACKGROUND: Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis. Intrathecal administration of tofersen is being studied for the treatment of amyotrophic lateral sclerosis (ALS) due to SOD1 mutations. METHODS: We conducted a phase 1-2 ascending-dose trial evaluating tofersen in adults with ALS due to SOD1 mutations. In each dose cohort (20, 40, 60, or 100 mg), participants were randomly assigned in a 3:1 ratio to receive five doses of tofersen or placebo, administered intrathecally for 12 weeks. The primary outcomes were safety and pharmacokinetics. The secondary outcome was the change from baseline in the cerebrospinal fluid (CSF) SOD1 concentration at day 85. Clinical function and vital capacity were measured. RESULTS: A total of 50 participants underwent randomization and were included in the analyses; 48 participants received all five planned doses. Lumbar puncture-related adverse events were observed in most participants. Elevations in CSF white-cell count and protein were reported as adverse events in 4 and 5 participants, respectively, who received tofersen. Among participants who received tofersen, one died from pulmonary embolus on day 137, and one from respiratory failure on day 152; one participant in the placebo group died from respiratory failure on day 52. The difference at day 85 in the change from baseline in the CSF SOD1 concentration between the tofersen groups and the placebo group was 2 percentage points (95% confidence interval [CI], -18 to 27) for the 20-mg dose, -25 percentage points (95% CI, -40 to -5) for the 40-mg dose, -19 percentage points (95% CI, -35 to 2) for the 60-mg dose, and -33 percentage points (95% CI, -47 to -16) for the 100-mg dose. CONCLUSIONS: In adults with ALS due to SOD1 mutations, CSF SOD1 concentrations decreased at the highest concentration of tofersen administered intrathecally over a period of 12 weeks. CSF pleocytosis occurred in some participants receiving tofersen. Lumbar puncture-related adverse events were observed in most participants. (Funded by Biogen; ClinicalTrials.gov number, NCT02623699; EudraCT number, 2015-004098-33.).

Septin-5 and -7-IgGs: Neurologic, Serologic, and Pathophysiologic Characteristics.

BACKGROUND AND OBJECTIVES: We sought to determine clinical significance of neuronal septin autoimmunity and evaluate for potential IgG effects. METHODS: Septin-IgGs were detected by indirect immunofluorescence assays (IFAs; mouse tissue and cell based) or Western blot. IgG binding to (and internalization of) extracellular septin epitopes were evaluated for by live rat hippocampal neuron assay. The impact of purified patient IgGs on murine cortical neuron function was determined by recording extracellular field potentials in a multielectrode array platform. RESULTS: Septin-IgGs were identified in 23 patients. All 8 patients with septin-5-IgG detected had cerebellar ataxia, and 7 had prominent eye movement disorders. One of 2 patients with co-existing septin-7-IgG had additional psychiatric phenotype (apathy, emotional blunting, and poor insight). Fifteen patients had septin-7 autoimmunity, without septin-5-IgG detected. Disorders included encephalopathy (11; 2 patients with accompanying myelopathy, and 2 were relapsing), myelopathy (3), and episodic ataxia (1). Psychiatric symptoms (≥1 of agitation, apathy, catatonia, disorganized thinking, and paranoia) were prominent in 6 of 11 patients with encephalopathic symptoms. Eight of 10 patients with data available (from 23 total) improved after immunotherapy, and a further 2 patients improved spontaneously. Staining of plasma membranes of live hippocampal neurons produced by patient IgGs (subclasses 1 and 2) colocalized with pre- and post-synaptic markers. Decreased spiking and bursting behavior in mixed cultures of murine glutamatergic and GABAergic cortical neurons produced by patient IgGs were attributable to neither antigenic crosslinking and internalization nor complement activation. INTERPRETATION: Septin-IgGs are predictive of distinct treatment-responsive autoimmune central nervous system (CNS) disorders. Live neuron binding and induced electrophysiologic effects by patient IgGs may support septin-specific pathophysiology. ANN NEUROL 2022;92:1090-1101.

Lumbar punctures are safe in patients with ALS and have a risk profile similar to that in the non-ALS population.

INTRODUCTION/AIMS: Analysis of biofluids, especially cerebrospinal fluid (CSF), is critically important for amyotrophic lateral sclerosis (ALS) research. Collection of CSF is typically performed by lumbar puncture (LP). Previous studies have demonstrated the safety of LPs in patients with other neurodegenerative diseases, such as Alzheimer's disease, although there are no published studies of the safety of LPs in patients with ALS. We performed a retrospective analysis of complications resulting from LPs. METHODS: This is a retrospective study of LPs performed between 2015 and 2021 on a total of 233 participants (healthy controls [n = 63], ALS [n = 154], and disease controls [n = 16]) as part of clinical research studies at the Washington University ALS Center. We used bivariate logistical analyses looking for associations between participant characteristics and adverse events (AEs), and likelihood ratio tests were used for significance testing. RESULTS: We found an overall AE rate of 21.03%. AEs included headache, back pain, vasovagal syncope, and severe headache requiring epidural blood patch. Participants with ALS were not more likely to experience post-LP AEs compared to controls (odds ratio [OR] 0.61 [0.32-1.18]). Post-LP headaches were significantly less likely in participants with ALS (OR 0.36 [0.15-0.83]). DISCUSSION: Our findings demonstrate that LP is a safe procedure for participants with ALS, with a similar or lower rate of AEs than in participants without ALS.

Real-time quaking-induced conversion assays for prions: Applying a sensitive but imperfect test in clinical practice.

BACKGROUND AND PURPOSE: Real-time quaking-induced conversion (RT-QuIC) assays offer a sensitive and specific means for detection of prions, although false negative results are recognized in clinical practice. We profile the clinical, laboratory, and pathologic features associated with false negative RT-QuIC assays and extend these to frame the diagnostic approach to patients with suspected prion disease. METHODS: A total of 113 patients with probable or definite prion disease were assessed at Mayo Clinic (Rochester, MN; Jacksonville, FL; Scottsdale, AZ) or Washington University School of Medicine (Saint Louis, MO) from 2013 to 2021. RT-QuIC testing for prions was performed in cerebrospinal fluid (CSF) at the National Prion Disease Pathology Surveillance Center (Cleveland, OH). RESULTS: Initial RT-QuIC testing was negative in 13 of 113 patients (sensitivity = 88.5%). RT-QuIC negative patients were younger (median = 52.0 years vs. 66.1 years, p < 0.001). Other demographic and presenting features, and CSF cell count, protein, and glucose levels were similar in RT-QuIC negative and positive patients. Frequency of 14-3-3 positivity (4/13 vs. 77/94, p < 0.001) and median CSF total tau levels were lower in RT-QuIC negative patients (2517 vs. 4001 pg/mL, p = 0.020), and time from symptom onset to first presentation (153 vs. 47 days, p = 0.001) and symptomatic duration (710 vs. 148 days, p = 0.001) were longer. CONCLUSIONS: RT-QuIC is a sensitive yet imperfect measure necessitating incorporation of other test results when evaluating patients with suspected prion disease. Patients with negative RT-QuIC had lower markers of neuronal damage (CSF total tau and protein 14-3-3) and longer symptomatic duration of disease, suggesting that false negative RT-QuIC testing associates with a more indolent course.

Incidence of amyotrophic lateral sclerosis in older adults.

INTRODUCTION/AIMS: We investigated the age- and sex-specific incidence and survival of Medicare beneficiaries with amyotrophic lateral sclerosis (ALS) in patients 66 to 90 years of age. METHODS: We identified all incident ALS cases within a population-based sample of Medicare beneficiaries in 2009 (total: 22 000 177 person-years at risk for ALS). We calculated age- and sex-specific incidence in 2009 according to multiple, progressively more stringent case definitions. Our most inclusive definition required one ALS code, whereas the most restrictive definition required at least one additional ALS code more than 6 months after the first code, including one from a neurologist. We identified associated imaging studies and electrodiagnostic testing and followed all cases through the end of 2014 to determine survival. RESULTS: The overall incidence for our most inclusive definition was 22.84 per 100 000 person-years for men and 16.05 per 100 000 person-years for women. The overall incidence was 5.72 per 100 000 person-years for men and 3.99 per 100 000 person-years for women for our most restrictive definition. For our most inclusive definition, fewer than 39.7% of cases ever had an ALS diagnosis from a neurologist, more than 50% had an electrodiagnostic test or imaging study, and 40.1% survived less than 1 year after diagnosis, with 25.5% of these cases surviving no more than 6 months. Cases not meeting the most restrictive definition were more likely than those who did meet the restrictive definition to be older, black, or Asian. DISCUSSION: The oldest and marginalized Medicare beneficiaries diagnosed with ALS are less likely to be included in epidemiological studies with restrictive definitions, but future studies will need to assess the accuracy of diagnosis.

Interpreting Electrodiagnostic Studies for the Management of Nerve Injury.

Nerve injuries are common after trauma and can be life-altering for patients. Electrodiagnostic studies are the gold standard for diagnosing and prognosticating nerve injuries. However, most surgeons are not trained in the interpretation of these studies; rather, they rely on the interpretation provided by the electrodiagnostician, who in turn is unlikely to be trained in nerve reconstruction. This discrepancy between the interpretation of these studies and the management of nerve injuries can lead to suboptimal surgical planning and patient outcomes. This review aims to provide a framework for surgeons to take a more active role in collaborating with their colleagues in electrodiagnostic medicine in the interpretation of these studies, with an ultimate goal of improved patient care. The basics of nerve conduction studies, electromyography, and relevant terminology are reviewed. The relationship between the concepts of demyelination, axon loss, Wallerian degeneration, nerve regeneration, collateral sprouting, and clinical function are explained within the framework of the Seddon and Sunderland nerve injury classification system. The natural evolution of each degree of nerve injury over time is illustrated, and management strategies are suggested.

Biallelic ASCC1 variants including a novel intronic variant result in expanded phenotypic spectrum of spinal muscular atrophy with congenital bone fractures 2 (SMABF2).

Spinal muscular atrophy with congenital bone fractures 2 (SMABF2), a type of arthrogryposis multiplex congenita (AMC), is characterized by congenital joint contractures, prenatal fractures of long bones, and respiratory distress and results from biallelic variants in ASCC1. Here, we describe an infant with severe, diffuse hypotonia, congenital contractures, and pulmonary hypoplasia characteristic of SMABF2, with the unique features of cleft palate, small spleen, transverse liver, and pulmonary thromboemboli with chondroid appearance. This infant also had impaired coagulation with diffuse petechiae and ecchymoses which has only been reported in one other infant with AMC. Using trio whole genome sequencing, our proband was identified to have biallelic variants in ASCC1. Using deep next generation sequencing of parental cDNA, we characterized alteration of splicing encoded by the novel, maternally inherited ASCC1 variant (c.297-8 T > G) which provides a mechanism for functional pathogenicity. The paternally inherited ASCC1 variant is a rare nonsense variant (c.466C > T; p.Arg156*) that has been previously identified in one other infant with AMC. This report extends the phenotypic characteristics of ASCC1-associated AMC (SMABF2) and describes a novel intronic variant that partially disrupts RNA splicing.

Testing for N-methyl-d-aspartate Receptor Autoantibodies in Clinical Practice.

BACKGROUND: The diagnosis of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis relies on the detection of NMDAR IgG autoantibodies in the serum or cerebrospinal fluid (CSF) of symptomatic patients. Commercial kits are available that allow NMDAR IgG autoantibodies to be measured in local laboratories. However, the performance of these tests outside of reference laboratories is unknown. OBJECTIVES: To report an unexpectedly low rate of NMDAR autoantibody detection in serum from patients with anti-NMDAR encephalitis tested using a commercially available diagnostic kit in an exemplar clinical laboratory. METHODS: Paired CSF and serum samples from seven patients with definite anti-NMDAR encephalitis were tested for NMDAR IgG autoantibodies using commercially available cell-based assays run according to manufacturer's recommendations. Rates of autoantibody detection in serum tested at our center were compared with those derived from systematic review and meta-analyses incorporating studies published during or before March 2019. RESULTS: NMDAR IgG autoantibodies were detected in the CSF of all patients tested at our clinical laboratory but not in paired serum samples. Rates of the detection were lower than those previously reported. A similar association was recognized through meta-analyses, with lower odds of NMDAR IgG autoantibody detection associated with serum testing performed in nonreference laboratories. CONCLUSIONS: Commercial kits may yield lower-than-expected rates of NMDAR IgG autoantibody detection in serum when run in exemplar clinical (nonreference) laboratories. Additional studies are needed to decipher the factors that contribute to lower-than-expected rates of serum positivity. CSF testing is recommended in patients with suspected anti-NMDAR encephalitis.

Effectuer en pratique clinique des tests visant à mesurer les anticorps anti-récepteurs NMDA. Contexte: Le diagnostic de l'encéphalite limbique avec anticorps anti-récepteurs NMDA repose sur la détection d'autoanticorps de classe IgG dans le sérum ou le liquide céphalo-rachidien des patients symptomatiques. Il existe certes des trousses commerciales qui permettent de mesurer ces autoanticorps dans des laboratoires locaux. Cependant, l'efficacité de ces tests en dehors de laboratoires homologués demeure inconnue. Objectif: Signaler un taux d'autoanticorps étonnamment faible dans le sérum de patients atteints d'encéphalite limbique avec anticorps anti-récepteurs NMDA, et ce, au moyen d'une trousse diagnostique commerciale utilisée dans un laboratoire clinique de haut niveau. Méthodes: En suivant les recommandations d'un fabricant, nous avons testé les échantillons appariés de liquide céphalo-rachidien et de sérum de sept patients atteints d'encéphalite limbique avec anticorps anti-récepteurs NMDA. À l'aide d'un bio-essai cellulaire, l'objectif était alors de détecter dans notre centre des autoanticorps de classe IgG et de comparer nos résultats à ceux obtenus à la suite d'une synthèse systématique et de méta-analyses incluant des études publiées au cours du mois de mars 2019 ou avant cette période. Résultats:Des autoanticorps de classe IgG en lien avec des anticorps anti-récepteurs NMDA ont été détectés dans le liquide céphalo-rachidien de tous les patients qui ont fait l'objet d'un test dans notre laboratoire clinique mais non pas dans les échantillons de sérum appariés. Les taux de détection se sont révélés plus faibles que ceux signalés précédemment. Nous avons observé une association similaire lors de méta-analyses, la probabilité de détecter des autoanticorps de classe IgG en lien avec des anticorps anti-récepteurs NMDA étant plus faible lorsqu'associée à des tests de sérum réalisés dans des laboratoires non homologués. Conclusions: Il est donc possible que les trousses commerciales ne débouchent sur des taux de détection d'autoanticorps de classe IgG plus faibles dans les sérums lorsqu'elles sont utilisées dans des laboratoires cliniques de haut niveau qui ne sont pas homologués. Des études complémentaires sont nécessaires pour mieux comprendre les facteurs qui contribuent à ces taux de positivité sérique plus bas que prévus. Enfin, des tests du liquide céphalo-rachidien sont recommandés chez des patients dont on soupçonne qu'ils sont atteints d'encéphalite limbique avec anticorps anti-récepteurs NMDA.

Nerve ultrasound reliability of upper limbs: Effects of examiner training.

INTRODUCTION: Duration of training to reliably measure nerve cross-sectional area with ultrasound is unknown. METHODS: A retrospective review was performed of ultrasound data, acquired and recorded by 2 examiners-an expert and either a trainee with 2 months (novice) or a trainee with 12 months (experienced) of experience. Data on median, ulnar, and radial nerves were reviewed for 42 patients. RESULTS: Interrater reliability was good and varied most with nerve site but little with experience. Coefficient of variation (CoV) range was 9.33%-22.5%. Intraclass correlation coefficient (ICC) was good to excellent (0.65-95) except ulnar nerve-wrist/forearm and radial nerve-humerus (ICC = 0.39-0.59). Interrater differences did not vary with nerve size or body mass index. Expert-novice and expert-experienced interrater differences and CoV were similar. The ulnar nerve-wrist expert-novice interrater difference decreased with time (rs = -0.68, P = 0.001). DISCUSSION: A trainee with at least 2 months of experience can reliably measure upper limb nerves. Reliability varies by nerve and location and slightly improves with time. Muscle Nerve 57: 189-192, 2018.

Hereditary Motor Neuropathies and Amyotrophic Lateral Sclerosis: a Molecular and Clinical Update.

PURPOSE OF REVIEW: This article provides an overview of recent advancements in the fields of hereditary motor neuropathies and ALS. RECENT FINDINGS: There has been a robust growth in our knowledge and understanding of hereditary and degenerative motor neuronopathies/neuropathies over the last decade. Many breakthroughs in the field of hereditary motor neuropathies (HMN) have been associated with identification and characterization of the genes and molecular mechanisms underlying these disorders. Similar recent breakthroughs on the genetic and molecular underpinnings of the degenerative motor neuronopathy, amyotrophic lateral sclerosis (ALS), have been accompanied by advancements in biomarker research and the development and FDA approval of novel therapies. There is a reasonable hope that the marked and continued growth in our understanding of the molecular pathophysiology of the HMNs will translate into novel therapeutic approaches in the decade to come. Such breakthroughs have already begun in ALS, where novel biomarkers and treatment strategies have translated into a new FDA-approved therapy with a number of promising agents in development and/or in definitive phase 2/3 trials.

JC virus granule cell neuronopathy in the setting of chronic lymphopenia treated with recombinant interleukin-7.

JC virus (JCV) is a human polyomavirus that infects the central nervous system (CNS) of immunocompromised patients. JCV granule cell neuronopathy (JCV-GCN) is caused by infection of cerebellar granule cells, causing ataxia. A 77-year-old man with iatrogenic lymphopenia presented with severe ataxia and was diagnosed with JCV-GCN. His ataxia and cerebrospinal fluid (CSF) improved with intravenous immunoglobulin, high-dose intravenous methylprednisolone, mirtazapine, and mefloquine. Interleukin-7 (IL-7) therapy reconstituted his lymphocytes and reduced his CSF JCV load. One month after IL-7 therapy, he developed worsening ataxia and CSF inflammation, which raised suspicion for immune reconstitution inflammatory syndrome. Steroids were restarted and his ataxia stabilized.

Nerve ultrasound identifies abnormalities in the posterior interosseous nerve in patients with proximal radial neuropathies.

INTRODUCTION: The radial nerve and posterior interosseous nerve (PIN) are prone to injury at multiple sites. Electrodiagnostic (EDx) studies may only identify the most proximal lesion. Nerve ultrasound could augment EDx by visualizing additional pathology. METHODS: This investigation was a retrospective examination of ultrasound and EDx from 26 patients evaluated for posterior cord/radial/PIN lesions. RESULTS: Eighteen of 26 patients had abnormalities on EDx (15 radial, 2 PIN, 1 posterior cord). Ultrasound identified 15 of 18 (83%) of the EDx abnormalities and provided additional diagnostic information. In 6 of 15 (40%) patients with EDx evidence of radial neuropathy, ultrasound identified both radial nerve enlargement and additional, unsuspected PIN enlargement (53% to 339% enlarged vs. unaffected side). Ultrasound also identified: nerve (dis)continuity at the trauma site (n = 8); and nerve tumor (n = 2; 1 with normal EDx). CONCLUSION: In radial neuropathy, ultrasound often augments EDx studies and identifies a second lesion in the PIN. Further studies are required to determine the etiology and significance of this additional distal pathology.

Chronic Progressive External Ophthalmoplegia in the Absence of Ptosis.

Classically defined as bilateral, symmetric, and progressive ophthalmoparesis with myopathic ptosis, chronic progressive external ophthalmoplegia (CPEO) rarely has been reported in the absence of ptosis. We describe 2 patients with CPEO and without ptosis who presented with binocular diplopia related to small-angle esodeviations, poor fusional amplitudes, and slow saccades. In both cases, hematological studies and neuroimaging ruled out alternative etiologies, whereas muscle biopsy showed findings of mitochondrial myopathy.

Criteria for reducing unnecessary testing for herpes simplex virus, varicella-zoster virus, cytomegalovirus, and enterovirus in cerebrospinal fluid samples from adults.

Excessive utilization of laboratory diagnostic testing leads to increased health care costs. We evaluated criteria to reduce unnecessary nucleic acid amplification testing (NAAT) for viral pathogens in cerebrospinal fluid (CSF) samples from adults. This is a single-center split retrospective observational study with a screening cohort from 2008 to 2012 and a validation cohort from 2013. Adults with available results for herpes simplex virus 1/2 (HSV-1/2), varicella-zoster virus (VZV), cytomegalovirus (CMV), or enterovirus (EV) NAAT with CSF samples between 2008 and 2013 were included (n = 10,917). During this study, 1.3% (n = 140) of viral NAAT studies yielded positive results. The acceptance criteria of >10 nucleated cells/µl in the CSF of immunocompetent subjects would have reduced HSV-1/2, VZV, CMV, and EV testing by 63%, 50%, 44%, and 51%, respectively, from 2008 to 2012. When these criteria were applied to the 2013 validation data set, 54% of HSV-1/2, 57% of VZV, 35% of CMV, and 56% of EV tests would have been cancelled. No clinically significant positive tests would have been cancelled in 2013 with this approach. The introduction of a computerized order entry set was associated with increased test requests, suggesting that computerized order sets may contribute to unnecessary testing. Acceptance criteria of >10 nucleated cells/µl in the CSF of immunocompetent adults for viral CSF NAAT assays would increase clinical specificity and preserve sensitivity, resulting in significant cost savings. Implementation of these acceptance criteria led to a 46% reduction in testing during a limited follow-up period.

Ocular Neuromyotonia Associated with Chronic Inflammatory Demyelinating Polyneuropathy.

Ocular neuromyotonia (ONM) is a neuro-ophthalmic disorder characterized by episodic diplopia caused by contraction of one or more ocular muscles due to spontaneous excitation of the respective ocular motor nerve. We report a patient whose ocular neuromyotonia arose in the setting of a subacute demyelinating polyneuropathy consistent with chronic inflammatory demyelinating polyneuropathy (CIDP) and subsequently resolved following the initiation of intravenous immunoglobulin (IVIg) for her neuropathy. Our patient provides additional evidence towards the role of demyelination and ephaptic neurotransmission in ocular neuromyotonia and also represents the first reported case of ocular neuromyotonia associated with a systemic neurological condition.