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Data are lacking on correlations between changes in nerve conduction (NC) studies and treatment response in chronic inflammatory demyelinating polyneuropathy (CIDP). This report examined data from a randomized, double-blind trial of immune globulin intravenous, 10% caprylate/chromatography purified (IGIV-C [Gamunex]; n = 59) versus placebo (n = 58) every 3 weeks for up to 24 weeks in CIDP. Motor NC results and clinical measures were assessed at baseline and endpoint/week 24. Improvement from baseline in adjusted inflammatory neuropathy cause and treatment score correlated with improvement in proximally evoked compound muscle action potential (CMAP) amplitudes (r = -0.53; P < 0.001) of all nerves tested and with improvement in CMAP amplitude of the most severely affected motor nerve (r = -0.36; P < 0.001). Correlations were observed between improvement in averaged CMAP amplitudes and dominant-hand grip strength (r = 0.44; P < 0.001) and Medical Research Council sum score (r = 0.38; P < 0.001). Overall, the change in electrophysiologic measures of NC in CIDP correlated with clinical response to treatment.

Background: Myasthenia Gravis ( MG) is an autoimmune disease that affects the neuromuscular junction. It typically presents with fluctuating muscle weakness which can affect respiratory muscles. Data about the prevalence of sleep disordered breathing in children with MG and the benefits of non-invasive ventilation outside the setting of MG crisis has not been studied so far. Methods: Eleven children between 3 and 18 years old with confirmed MG were recruited from the The Hospital for Sick Children Neuromuscular clinic in a prospective observational study. Informed consent was obtained and patients underwent PFTs, MIP/MEP, SNIP, FVC and standard polysomnography testing’s. Results: In our study, we found that 2/11 children had abnormal Apnea Hypopnea index (AHI) and were diagnosed with obstructive sleep apnea (OSA). One of them has juvenile ocular MG with mild to moderate OSA and the second child has congenital MG with mild OSA. CPAP therapy was initiated for both patients. Conclusions: In our cohort, obstructive sleep apnea rate was significantly higher in children with MG than the known prevalence in general pediatric population ( 18% vs 2-3% ). Early diagnosis and management of OSA can have great impact on children’s health and quality of life. A larger study is needed to validate our findings.

Polyneuropathy may result in pain, numbness, and weakness, which may in turn affect driving ability. Medications used to treat neuropathic pain may alter cognition, which may further affect driving. Although such impairments have engendered questions about the driving safety in this group of patients, the rate of motor vehicle accidents (MVAs) in patients with neuropathy has not been studied rigorously. We surveyed patients with neuropathy from three medical centers for reported accident rate, and we analyzed variables related to increased risk for accidents compared to National Highway Traffic Safety Administration data. Surveys from 260 subjects demonstrated that 40.6% were involved in traffic accidents (0.11 accidents/year). Their accident rate was 10.8 MVAs per million vehicle miles traveled (MVA/MVMT), compared to 3.71 MVA/MVMT in 55-59-year-old drivers and 3.72 in 60-64-year-olds (National Highway Traffic Safety Administration data). In all, 72.4% cited their neuropathy and 55.2% cited their medications as playing a role in their accidents, and 51.6% changed their driving habits after developing neuropathy. Independently, elevated levels of pain, motor weakness, and ambulation difficulty met statistical significance for increased MVA frequency. We conclude that accident frequency and discomfort with driving are higher in neuropathy patients compared to age-matched national statistics. However, most patients seem to change habits according to their ability to drive; as such, driving issues should be addressed with caution and on a case-by-case basis.

The role of screening laboratory tests in chronic inflammatory demyelinating polyneuropathy (CIDP) is currently unknown. The objectives of this study are to explore common laboratory test abnormalities in CIDP patients.CIDP subjects attending the Neuromuscular Clinic between 01/2013 and 12/2014 were evaluated. Demographic data, clinical history, physical examination, and laboratory test results were extracted from their charts.Seventy-nine charts were reviewed. Mean age was 61 ± 11 years. Most (84%) CIDP patients had laboratory test abnormalities; the most frequent were paraproteinemia (29%) and elevated HbA1C (28%) and creatine kinase (27%). Additional abnormalities included anemia in 19%, and elevated anti-neutrophil cytoplasmic antibody, erythrocyte sedimentation rate, and urate in 17%, elevated antinuclear antibodies, rheumatoid factor, and thyroid-stimulating hormone in 11%, and abnormal C3 in 10%.Laboratory test abnormalities were found in most CIDP patients. The most common were paraproteinemia, higher than expected frequency of diabetes, and unexpected CK elevation. Additional abnormalities included anemia, high urate levels, and common biomarkers for vasculitic neuropathies. Muscle Nerve 53: 862-865, 2016.

Introduction Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is one of several chronic treatable acquired demyelinating neuropathies. Objectives To explore the association between the degree of demyelination in CIDP, and treatment responsiveness. Methods A retrospective chart review of CIDP subjects assessed between 1997 and 2013 was performed to compare treatment responsiveness using different sets of criteria. Results 99 CIDP patients were included, 34 with diabetes mellitus (DM). Treatment responsiveness was higher in CIDP-DM fulfilling 1 or more EFNS/PNS criteria, (63% vs. 31%, p = 0.03), and in CIDP+DM fulfilling 2 or more criteria (89% vs. 36%, p = 0.01). Nonetheless, treatment responsiveness in CIDP+DM had the highest odds ratio (3.73, p = 0.01). Similar results were also shown in simplified uniform study criteria, with 10% cut off values for CIDP-DM, compared to 30% for CIDP+DM. Conclusion In CIDP+DM, higher degrees of demyelination are associated with treatment responsiveness, implying the need to adjust current criteria in these patients.

Subcutaneous immunoglobulin (SCIg) has been used for treatment of immune neuropathies.We evaluated the safety and efficacy of 1.53:1 SCIg to intravenous immunoglobulin (IVIg) in individuals receiving2 g/kg IVIg per month and 1:1 in individuals receiving 2 g/kg per month for treatment of multifocal motor neuropathy (MMN) in an open-label, 6-month trial. Medical Research Council sum score, grip strength, modified Guy's Upper Limb Neurological Disability score, Health Utility Index Quality of Life score, and immunoglobulin levels were evaluated at baseline and at 3 and 6 months.Eleven men and 4 women, aged 31-82 years, were enrolled. Eleven patients completed the program with minor localized reactions and high satisfaction. Three of 6 patients receiving less than 1.53:1 replacement developed intolerable weakness by month 3, and 1 exited after developing erythema and elevated transaminase levels.Patients with MMN tolerate SCIg infusion with maintained strength, but some patients may develop increasing weakness and merit close monitoring. Muscle Nerve 54: 856-863, 2016.

Incidence and prevalence estimates in myasthenia gravis have varied widely. Recent studies based on administrative health data have large sample sizes but lack rigorous validation of MG cases, and have not examined the North American population. Our aim was to explore trends in MG incidence and prevalence for the years 1996-2013 in the province of Ontario, Canada (population 13.5 million). We employed a previously validated algorithm to identify MG cases. Linking with census data allowed for the calculation of crude- and age/sex-standardized incidence and prevalence rates for the years 1996-2013. The regional distribution of MG cases throughout the province was examined. Mean age at the first myasthenia gravis encounter was 60.2 ± 17.1 years. In 2013, there were 3611 prevalent cases in Ontario, and the crude prevalence rate was 32.0/100,000 population. Age- and sex-standardized prevalence rates rose consistently over time from 16.3/100,000 (15.4-17.1) in 1996 to 26.3/100,000 (25.4-27.3) in 2013. Standardized incidence rates remained stable between 1996 (2.7/100,000; 95% CL 2.3-3.0) and 2013 (2.3/100,000; 2.1-2.6). Incidence was highest in younger women and older men, and geographic variation was evident throughout the province. In conclusion, this large epidemiological study shows rising myasthenia gravis prevalence with stable incidence over time, which is likely reflective of patients living longer, possibly due to improved disease treatment. Our findings provide accurate information on the Canadian epidemiology of myasthenia gravis and burden for health care resources planning for the province, respectively.

Diabetic sensorimotor polyneuropathy (DSP) affects 50% of diabetes patients and is painful in about 26%. Although disease-modifying therapies are not available for DSP, symptomatic treatments for painful diabetic neuropathy (PDN) are effective.We performed a MEDLINE search on PubMed using the search terms: treatment diabetic neuropathy and treatment PDN. This review outlines the problem posed by DSP, the clinical presentation and the characterization of PDN. A discussion of disease-modifying interventions, including the benefits of strict glycemic control, is followed by a focus on interventions for PDN including antidepressants, anticonvulsants and other treatments.Disease modification in DSP remains an unmet need in clinical medicine affecting a large percentage of the population with concomitant healthcare costs. Strict glycemic control and attention to potential risk factors such as hypertension, hyperlipidemia and obesity may minimize DSP. Many patients benefit from treatment of their painful symptoms with anticonvulsants or antidepressants, but all are associated with significant side effects that limit their usefulness. There is a need for treatments of PDN with fewer side effects and more effective pain relief.

SUMMARY Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and its variants can be challenging to diagnose and treat. A combination of clinical, electrophysiological and laboratory features is often required to reach a diagnosis. New data are emerging about potential biomarkers and factors that may indicate treatment needs in individual patients. High-quality evidence exists for the efficacy of intravenous immunoglobulin (IVIG) in the treatment of CIDP, including quality of life (QoL) benefits. Besides pharmacological treatment, psychological factors must also be addressed to improve patients' QoL. Home-based IVIG infusion therapy is currently a well-established approach in some countries. A 6-month pilot study conducted in Ontario, Canada, provided proof of safety and patient acceptance of home-based IVIG therapy, although some logistical issues emerged.

Muscle cramps are sustained, painful contractions of muscle and are prevalent in patients with and without medical conditions. The objective of this review is to present updates on the mechanism, investigation and treatment of neurogenic muscle cramps. PubMed and Embase databases were queried between January 1980 and July 2014 for English-language human studies. The American Academy of Neurology classification of studies (classes I-IV) was used to assess levels of evidence. Mechanical disruption, ephaptic transmission, disruption of sensory afferents and persistent inward currents have been implicated in the pathogenesis of neurogenic cramps. Investigations are directed toward identifying physiological triggers or medical conditions predisposing to cramps. Although cramps can be self-limiting, disabling or sustained muscle cramps should prompt investigation for underlying medical conditions. Lifestyle modifications, treatment of underlying conditions, stretching, B-complex vitamins, diltiezam, mexiletine, carbamazepine, tetrahydrocannabinoid, leveteracitam and quinine sulfate have shown evidence for treatment.

Introduction: The relationship between sleep and neuromuscular fatigue is understood poorly. The goal of this study was to evaluate the effects of napping on quantitative measures of neuromuscular fatigue in patients with myasthenia gravis (MG). Methods: Eight patients with mild to moderate MG were recruited. Patients underwent maintenance of wakefulness tests (MWT) and multiple sleep latency tests (MSLT). The Quantitative Myasthenia Gravis Score (QMGS) was measured before nap and after each nap to examine the effects of napping and sleep on neuromuscular weakness. Results: Results showed that QMGS improves only after naps where patients slept more than 5 min but not where patients did not sleep or slept less than 5 min. Conclusions: Daytime napping mitigates neuromuscular fatigue in patients with MG, especially if patients slept for more than 5 min. Muscle Nerve 48:816–818, 2013

Background The efficacy of thymectomy in patients with non-thymomatous Myasthenia Gravis (MG) is still unclear. Main limitations have been variable outcome definitions, lack of a control group and adjustment for confounding. Objective To study the efficacy of thymectomy in achieving remission or minimal manifestation (R/MM) status in patients with non-thymomatous MG. Methods Patients with generalized MG and minimum follow-up of 6 months were included. Demographic data and treatments were recorded, as well as the MGFA post-intervention status at the last visit. Propensity scores were used to create a matched cohort of treated and untreated patients. Standard and Bayesian Cox models were used to study treatment effects. Results Of 395 patients included, 183(46%) had a thymectomy. Thymectomy patients were younger (p 1) of 96% using a non-informative prior, and 79% using a skeptical prior. Discussion When controlling for potential confounders, thymectomized patients had a higher probability of achieving R/MM status through time compared to controls. This study provides class III evidence of the efficacy of thymectomy in non-thymomatous myasthenia gravis.

Muscle cramps are common in the general population and can be disabling for patients, but there is little evidence comprehensively evaluating cramp characteristics in patients with polyneuropathy. This study describes the prevalence and characteristics of muscle cramps in this patient group. Patients over 18 diagnosed with polyneuropathy were invited to join the study. Patients completed nerve conduction studies, the Toronto Clinical Neuropathy score, neuropathy-specific Vickrey's Quality of Life Assessment and a self-administered questionnaire examining demographics, neuropathy symptoms and cramp characteristics. Two hundred and twenty-five participants were enrolled (28.0% female). Sixty-three percent of patients experienced cramps, occurring on average 6 times per week, lasting 10.5 min and scoring 6 out of 10 on a pain scale and described as disabling by 43.6% of patients. No significant difference was found in cramp prevalence according to underlying pathophysiology (p = 0.52) or fiber type (p = 0.41). Patients with disabling cramps rated their physical (p0.0001) and mental (p = 0.04) quality of life lower than patients without disabling cramps. This study confirms that muscle cramps are common, disabling and associated with reduced quality of life in patients with polyneuropathy. Similar prevalence of cramps across predominant nerve fiber type suggests a role of sensory afferents in cramp generation, although this needs to be confirmed in larger cohorts.

Background:Patient registries represent an important method of organizing “real world” patient information for clinical and research purposes. Registries can facilitate clinical trial planning and recruitment and are particularly useful in this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are individually rare but in aggregate have a significant prevalence. In Canada, information on NMDs is lacking. Barriers to performing Canadian multicentre NMD research exist which can be overcome by a comprehensive and collaborative NMD registry.Methods:We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR).Results:The CNDR is a clinic-based registry which launched nationally in June 2011, incorporates paediatric and adult neuromuscular clinics in British Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of December 2012, has recruited 1161 patients from 12 provinces and territories. Complete medical datasets have been captured on 460 “index disease” patients. Another 618 “non-index” patients have been recruited with capture of physician-confirmed diagnosis and contact information. We have demonstrated the feasibility of blended clinic and central office-based recruitment. “Index disease” patients recruited at the time of writing include 253 with Duchenne and Becker muscular dystrophy, 161 with myotonic dystrophy, and 71 with ALS.Conclusions:The CNDR is a new nationwide registry of patients with NMDs that represents an important advance in Canadian neuromuscular disease research capacity. It provides an innovative platform for organizing patient information to facilitate clinical research and to expedite translation of recent laboratory findings into human studies.

The minimal clinically important difference (MCID) is the smallest outcome change that has clinical significance. Its use has not been established in the study of myasthenia gravis (MG).Patients from a published intravenous immunoglobulin (IVIg) vs. placebo study were studied. One anchor-based and 3 distribution-based techniques were used to identify quantitative myasthenia gravis score (QMGS), repetitive nerve stimulation (RNS), and single-fiber electromyography (SFEMG) MCID cut-offs. Patients with a change-score exceeding MCID cut-offs were compared.MCID cut-offs were below a QMGS change of 3.0. Anchor-based and 1 × SEM cut-offs showed 58.3% vs. 30.7% responders (P = 0.017), ½ SD 54.2% vs. 19.2% responders (P = 0.018), and effect size 0.519 vs. 0.164 (P = 0.011) in IVIg vs. placebo. Anchor-based (P = 0.73) and effect-size (P = 0.41) MCID cut-offs did not show a difference between IVIg and placebo. MCID methods did not produce meaningful RNS cut-offs.QMGS MCID values provide clinically relevant information and are recommended in MG trials. MCID analysis shows that improvement in MG patients treated with IVIg reflects clinically meaningful changes.

The relationship between sleep and neuromuscular fatigue is understood poorly. The goal of this study was to evaluate the effects of napping on quantitative measures of neuromuscular fatigue in patients with myasthenia gravis (MG).Eight patients with mild to moderate MG were recruited. Patients underwent maintenance of wakefulness tests (MWT) and multiple sleep latency tests (MSLT). The Quantitative Myasthenia Gravis Score (QMGS) was measured before nap and after each nap to examine the effects of napping and sleep on neuromuscular weakness.Results showed that QMGS improves only after naps where patients slept more than 5 min but not where patients did not sleep or slept less than 5 min.Daytime napping mitigates neuromuscular fatigue in patients with MG, especially if patients slept for more than 5 min.

Objective:To determine the safety and tolerability of home-based intravenous immunoglobulin (IVIG) (Gamunex) as maintenance treatment in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in Canada.Methods:We enrolled ten subjects with CIDP who had previously received IVIG in the hospital setting to receive the comparable IVIG dose (1-2 g/kg/month) in the home for six months. The patients were evaluated in the clinic at three months and at six months to evaluate their clinical status as well as the safety and tolerability of IVIG.Results:All subjects tolerated home-based IVIG treatment as maintenance treatment of CIDP. There were no serious adverse events related to IVIG. Subjects did experience “anticipated” IVIG events post-infusion such as headache and fatigue, which were managed with analgesics and supportive counseling. One subject withdrew consent at end of study due to hospitalization. This event was not related to the IVIG. Another subject experienced a “flare” of CIDP symptoms near the end of the study, however, completed all visits as per protocol. All subjects expressed excellent satisfaction with the individualized therapy, and almost all (nine out of ten) patients preferred home-infusion to hospital-infusion.Conclusion:Intravenous immunoglobulin can be delivered safely and is well tolerated outside the hospital setting in Canada in patients with chronic, stable neuromuscular conditions such as CIDP who have previously tolerated IVIG in the hospital medical day Care Unit.

The objective was to study the effects on noninvasive ventilation on sleep outcomes in patient with ALS, specifically oxygenation and overall sleep quality.Patients with ALS who met criteria for initiation of NIV were studied with a series of 2 home PSG studies, one without NIV and a follow-up study while using NIV. Primary outcome was a change in the maximum overnight oxygen saturation; secondary outcomes included change in mean overnight oxygen saturation, apnea and hypopnea indexes, sleep latency, sleep efficiency, sleep arousals, and sleep architecture.A total of 94 patients with ALS were screened for eligibility; 15 were enrolled; and 12 completed study procedures. Maximum overnight oxygen saturation improved by 7.0% (p = 0.01) and by 6.7% during REM sleep (p = 0.02) with NIV. Time spent below 90% oxygen saturation was also significant-ly better with NIV (30% vs 19%, p0.01), and there was trend for improvement in mean overnight saturation (1.5%, p = 0.06). Apnea index (3.7 to 0.7), hypopnea index (6.2 to 5.7), and apnea hypopnea index (9.8 to 6.3) did not significantly improve after introducing NIV. NIV had no effect on sleep efficiency (mean change 10%), arousal index (7 to 12), or sleep stage distribution (Friedman chi-squared = 0.40).NIV improved oxygenation but showed no significant effects on sleep efficiency, sleep arousals, restful sleep, or sleep architecture. The net impact of these changes for patients deserves further study in a larger group of ALS patients.

Intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) are used to treat myasthenia gravis (MG) but with little trial evidence. While a class I study provided evidence for the efficacy of IVIG treatment, the empirical support for PLEX has been less convincing until recently. In a randomized controlled single-masked study of 84 MG patients with moderate to severe disease, IVIG and PLEX had comparable efficacy as demonstrated by reduction in the Quantitative Myasthenia Gravis Score (QMGS) for disease severity, percentage of responders, persistence of treatment effect, and tolerability, which were similar in both treatment arms. The change in QMGS was accompanied by improved disease-specific quality of life. The only factor predicting response to treatment was baseline severity. FcR polymorphisms did not predict response to IVIG therapy, but an inhibitory polymorphism was associated with baseline disease severity. These studies support the choice of either IVIG or PLEX as comparable treatments in adult patients with moderate to severe MG.

Introduction Small fiber neuropathy might be a part of typical mixed small and large fiber neuropathy, or a distinct entity, affecting exclusively small nerve fibers. Objectives Explore the utility of small nerve fiber testing in patients with clinical presentation suggesting small fiber neuropathy, with and without evidence for concomitant large fiber neuropathy. Methods Patients attending the neuromuscular clinic from 2012 to 2015 with a clinical presentation suggesting small nerve fiber impairment, who had Laser Doppler flare imaging (LDIFlare) and quantitative thermal testing (QTT) were evaluated for this study. Patients with clinical or electrophysiological evidence for concomitant large fiber neuropathy were not excluded. Results The sensitivities of LDIFlare, cooling and heat threshold testing were 64%, 36%, and 0% respectively for clinically highly suggestive small fiber neuropathy, 64%, 56%, and 19% respectively for mixed fiber neuropathy, and 86%, 79%, and 29% respectively for diabetic mixed fiber neuropathy. Discussion LDIFlare and cooling thresholds testing are non-invasive small nerve fiber testing modalities, with moderate performance in patients with small and mixed fiber neuropathy, and excellent performance in diabetic mixed fiber neuropathy.

We studied 63 patients with myasthenia gravis (MG) requiring treatment with intravenous immunoglobulin, to determine if polymorphisms within the FCγR2A (rs1801274), FCγR2B (rs1050501), FCγR3A (rs396991), and FCγR3B (NA1/NA2) genes are correlated with response to treatment. There was no significant difference in any of the polymorphisms studied between responders and nonresponders. Patients with the FCγR2B-232I/I polymorphism had higher disease severity measured by the quatitative myasthenia gravis score (QMGS). There was no difference in the distribution of the FCγR2B-232 polymorphisms between the patients and 90 healthy controls. The finding of greater disease severity in patients with the FCγR2B-232I/I polymorphism requires confirmation in a larger population of patients with myasthenia gravis.

Background Though intra-epidermal nerve fiber density (IENFD) is considered the gold standard for diagnosis of small fiber sensory neuropathy (SFSN), we aimed to determine if novel threshold values derived from standard tests of small or large fiber function could serve as diagnostic alternatives. Methods Seventy-four consecutive patients with painful polyneuropathy and normal nerve conduction studies (NCS) were defined as SFSN cases or controls by distal IENFD

Background Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi-randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Main results Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L-threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta-analysis of two small studies showed a statistically nonsignificant result for the amino acid L-threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. Authors' conclusions There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed.

Factors determining response to intravenous immunoglobulin (IVIg) and plasmapheresis in myasthenia gravis (MG) have not been evaluated systematically.This study included patients treated with IVIg (n = 63) or plasmapheresis (n = 42) from two trials evaluating IVIg vs. placebo or plasmapheresis in MG. Response was defined as improvement in the quantitative myasthenia gravis score (QMGS) of ≥3.5 points at day 14. Baseline clinical, electrophysiological, and immunological factors were analyzed as predictors.Baseline QMGS, acetylcholine receptor antibody (AChRAb) positivity, single-fiber electromyography (SFEMG) jitter, and percent abnormal pairs and percent blocking pairs were higher in responders than in non-responders. Using multivariate logistic regression, the odds ratio for response was 13.0 (1.01-381.5) in QMGS 11-17 and 15.3 (1.34-414.3) in QMGS17 compared with QMGS11.Baseline QMGS, AChRAb positivity, and SFEMG parameters were more abnormal in patients who responded to treatment. Using multivariate regression, baseline QMGS remained as the only significant independent predictor of response.

Analysis of continuous diaphragm electromyography (dEMG) has not been well studied. We describe a system of analyzing continuous dEMG using implanted electrodes.dEMG signal was acquired via two pairs of electrodes near the diaphragm motor points. Raw bursts of dEMG signal were compared to externally captured electrocardiogram (ECG) using adaptive filtering in order to remove cardiac contamination. Differential energy levels were used to identify each dEMG burst, and average amplitude and area values from both hemidiaphragms were aggregated and averaged for the duration of the recording.A 64-year-old patient with amyotrophic lateral sclerosis underwent three serial dEMG studies every 6 months. An average of three tracings were collected per visit, and all had excellent intertest reliability (κ0.8). Average dEMG area correlated with forced vital capacity and mean inspiratory pressure (r(2)0.9).The approach described represents a comprehensive method for capturing and analyzing continuous diaphragm EMG signal.

Life-threatening cardiomyopathy is associated with certain systemic myopathies and usually presents as an end-stage progression of the disease. However, cardiac symptoms can sometimes precede muscle weakness. The authors reviewed medical records from 2003 to 2008 on patients attending their neuromuscular clinic and identified patients who initially presented with an end-stage cardiomyopathy and were later diagnosed with a specific muscle disease through muscle biopsy. They report 5 cases of children who initially presented with cardiomyopathies without neuromuscular symptoms. The cardiac symptoms were so severe that 4 of them required cardiac transplantation and 1 died prior to transplantation. Review of muscle pathology confirmed the diagnoses of Becker muscular dystrophy, myofibrillar myopathy, mitochondrial myopathy with cytochrome oxidase deficiency, Danon disease, and glycogen storage disease. The authors conclude that cardiomyopathy can be the initial presentation of a wide spectrum of systemic myopathies. Careful evaluation of neuromuscular systems should be carried out in patients presenting with end-stage cardiomyopathies.

Background: A Food and Drug Administration advisory in 2006 warned against the off-label use of quinine sulfate and its derivatives in the treatment of muscle cramps. Physicians are faced with a difficult scenario in choosing a treatment regimen for patients with muscle cramps. This American Academy of Neurology assessment systematically reviews the available evidence on the symptomatic treatment of muscle cramps. Methods: A total of 563 potential articles were reviewed, of which 24 met the inclusion criteria of prospective trials evaluating the efficacy of a particular treatment on muscle cramps as a primary or secondary outcome. Results: There are Class I studies showing the efficacy of quinine derivatives for treatment of muscle cramps. However, the benefit is modest and there are adverse effects from published prospective trials as well as case reports. There is one Class II study each to support the use of Naftidrofuryl, vitamin B complex, lidocaine, and diltiazem in the treatment of muscle cramps. Recommendations: Although likely effective (Level A), quinine derivatives should be avoided for routine use in the management of muscle cramps because of the potential of toxicity, but in select patients they can be considered for an individual therapeutic trial once potential side effects are taken into account. Vitamin B complex, Naftidrofuryl, and calcium channel blockers such as diltiazem are possibly effective and may be considered in the management of muscle cramps (Level C). Further studies are needed to identify agents that are effective and safe for the treatment of muscle cramps. Neurology ® 2010;74:691–696

There are limited epidemiological studies addressing the prevalence of muscle cramps in the general population and diseases like diabetes (1). Common long-term complications of diabetes, such as neuropathy and nephropathy, have been associated with higher rates of muscle cramps (2). We aimed to determine the prevalence and characteristics of muscle cramps in patients with diabetes compared with healthy volunteers. Frequency, severity (using visual analog scale [VAS]), duration, and disability due to muscle cramps were evaluated, as is standard in clinical trials. Information about each patient’s clinical status was collected, including patient demographics, neuropathy (diagnosed using established clinical and electrophysiological criteria and quantitated using the Toronto Clinical Neuropathy Score) (3), diabetes complications, duration and type of diabetes, concurrent cramp-inducing (β-blockers, diuretics, statins) and cramp-protecting (quinine, calcium channel blockers, antiepileptics) medications, and markers of glycemic control (HbA1c). Baseline demographics and cramp characteristics for 269 patients with diabetes (type 1 diabetes, n = …

Polyneuropathy may result in pain, numbness, and weakness, which may in turn affect driving ability. Medications used to treat neuropathic pain may alter cognition, which may further affect driving. Although such impairments have engendered questions about the driving safety in this group of patients, the rate of motor vehicle accidents (MVAs) in patients with neuropathy has not been studied rigorously. We surveyed patients with neuropathy from three medical centers for reported accident rate, and we analyzed variables related to increased risk for accidents compared to National Highway Traffic Safety Administration data. Surveys from 260 subjects demonstrated that 40.6% were involved in traffic accidents (0.11 accidents/year). Their accident rate was 10.8 MVAs per million vehicle miles traveled (MVA/MVMT), compared to 3.71 MVA/MVMT in 55-59-year-old drivers and 3.72 in 60-64-year-olds (National Highway Traffic Safety Administration data). In all, 72.4% cited their neuropathy and 55.2% cited their medications as playing a role in their accidents, and 51.6% changed their driving habits after developing neuropathy. Independently, elevated levels of pain, motor weakness, and ambulation difficulty met statistical significance for increased MVA frequency. We conclude that accident frequency and discomfort with driving are higher in neuropathy patients compared to age-matched national statistics. However, most patients seem to change habits according to their ability to drive; as such, driving issues should be addressed with caution and on a case-by-case basis.

We report patients from two neuromuscular centers who were evaluated between the years 2000 and 2008 and met the following criteria: (1) proximal muscle weakness occurring during or after treatment with statins; (2) elevated serum creatine kinase (CK); (3) persistence of weakness and elevated CK despite discontinuation of the statin; (4) improvement with immunosuppressive agents; and (5) muscle biopsy showing necrotizing myopathy without significant inflammation. Twenty-five patients fulfilled our inclusion criteria. Twenty-four patients required multiple immunosuppressive agents. Fifteen patients relapsed after being tapered off immunosuppressive therapy. Exposure to statins prior to onset was significantly higher in patients with necrotizing myopathy (82%) as compared to those with dermatomyositis (18%), polymyositis (24%), and inclusion-body myositis (38%) seen in the same time period. The lack of improvement following discontinuation of statins, the need for immunosuppressive therapy, and frequent relapse when treatment was tapered suggest an immune-mediated etiology for this rare, statin-associated necrotizing myopathy.

We report two patients with myasthenia gravis (MG) who underwent thymectomy but developed thymic carcinoma years after the initial surgery. In one patient, the initial thymic pathology was normal, whereas the other had an encapsulated benign thymoma that was found only on pathological assessment. These cases demonstrate that MG may occur as part of a "new" paraneoplastic syndrome even after thymectomy. The late appearance of metastatic thymoma raises questions about monitoring for these patients.

Introduction Vibration perception threshold (VPT) examination using a neurothesiometer provides objective, sensitive and specific information, and has been utilized mainly in patients with diabetic polyneropathy. Objectives Explore the utility of VPT examination in CIDP patients. Methods CIDP subjects attending the Neuromuscular clinic between 01/2013 and 12/2014 were evaluated. Demographic data, clinical history, physical examination, VPT values, and electrophysiologic data from their charts were extracted. Results 70 charts were reviewed. 55 CIDP patients had elevated VPT, associated with higher frequency of abnormal sensory testing for various modalities (92.7% vs. 46.7%, p

Diabetes mellitus (DM) is pandemic, and is the leading global cause of polyneuropathy, most commonly, a distal symmetric sensorimotor polyneuropathy (DSP). By contrast, chronic inflammatory demyelinating polyneuropathy (CIDP) is rare, and characterized mainly by symmetrical proximal and distal muscles weakness. There are currently 15 sets of criteria using a variable combination of clinical, electrophysiologic, laboratory, and biopsy features to identify CIDP, but it is unclear if these criteria are the same in patients with and without DM. Slowed conduction velocity, a feature of demyelination, is observed in patients with type 1 DM with poor control, and the clinical characteristics of these patients differ from those who have CIDP and DM, suggesting a different pathophysiology. Treatment response rates in CIDP patients, with and without DM, are as high as 80 %, and it is recommended that treatment be started early to prevent secondary axonal loss. However, patients with type 1 DM with CIDP are far less likely to be treated than CIDP patients who do not have DM. In patients with type 1 DM with polyneuropathy who have prominent weakness or demyelination in electrophysiologic studies, a diagnosis of CIDP and a trial of therapy should be considered.

In myasthenia gravis (MG), presence of pathogenic acetylcholine receptor antibodies (AchRAb) and thymic pathology are related. Our study assesses the long-term clinical outcome of thymectomy as a function of thymic pathologies, AchRAb levels in blood and the ability of immunocytes to secrete AchRAb ex vivo. We found that those patients who have thymocytes that secrete AchRAb in vitro have a greater decrease in their need for Mestinon® over the 60 months of follow-up than the non-secretors (p=0.04). Those patients whose cultured peripheral blood mononuclear cells (PBMC) secreted AchRAb also had a greater decrease in Mestinon requirements over the 60 months of follow-up than the non-secretors (p=0.05), however, differences between the two groups at each individual assessment were not statistically significant. Serial post-op AchRAb measurements in sera of thymocyte and PBMC non-secretors showed no change from pre-op levels (

IntroductionWe aimed to determine whether the clinical characteristics and electrodiagnostic classification of nerve injury, and response to treatment differed in patients diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) with and without diabetes.MethodsCIDP patients with diabetes (CIDP+DM) (n = 67) and without diabetes (CIDP-DM) (n = 67) underwent clinical examination and nerve conduction studies (NCS). CIDP-DM patients were selected using age and gender matching with the existing CIDP+DM cohort. Patients treated with immunotherapies were classified as responders (R) (n = 46) or non-responders (NR) (n = 54) based on clinical response to treatment. The groups were compared using analysis of variance, contingency tables and Kruskal-Wallis analyses.ResultsCIDP+DM subjects had more severe neuropathy based on higher lower limb vibration potential thresholds (VPT)(p = 0.004), higher Toronto Clinical Neuropathy Score (TCNS) (p = 0.0009), more proximal weakness (p = 0.03), more gait abnormality (p = 0.03) and more abnormal NCS. CIDP+DM subjects had more abnormal sural NCS with lower sural sensory nerve action potential amplitudes (2.4±3.0 µV, 6.6±6.0 µV, pDiscussionThe clinical phenotype and electrophysiological profile of CIDP patients differs according to the presence or absence of diabetes. Despite CIDP+DM patients having more severe clinical and electrophysiological neuropathy, they are less likely to receive disease-modifying/specific therapy, yet have similar response rates to treatment as those without diabetes. Specifically, the duration of neuropathy - not diabetes status - was associated with treatment response.

In generalized MG (GMG), 90% of patients have circulating acetylcholine receptor antibodies (AChRAb) and 80% have abnormal thymic pathology, either lymphoid follicular hyperplasia (LFH) or thymoma.1,2⇓ Whereas thymectomy for patients with thymoma is indicated, the need for surgery in the presence of atrophic thymus or LFH is hotly debated and will be the object of a therapeutic trial. We report that a proportion of patients with atrophic thymus secrete AChRAb in culture and thus might benefit from removal of the immunologically active gland. ### Patients. All patients with GMG underwent transsternal thymectomy after a series of plasmapheresis at University of British Columbia–affiliated hospitals from April 1990 to April 1999. This article reports on the 16 patients who had a pathologic diagnosis of atrophic thymus. Diagnosis was made after review of an average of 6.9 ± 3.4 slides by a single pathologist unaware of the …

We report two patients with myasthenia gravis (MG) who underwent thymectomy but developed thymic carcinoma years after the initial surgery. In one patient, the initial thymic pathology was normal, whereas the other had an encapsulated benign thymoma that was found only on pathological assessment. These cases demonstrate that MG may occur as part of a "new" paraneoplastic syndrome even after thymectomy. The late appearance of metastatic thymoma raises questions about monitoring for these patients.

Objective: The aim of this study was to evaluate the accuracy of different methods for evaluation of small fiber neuropathy (SFN) using intra epidermal nerve fiber density (IENFD) as the reference standard. Background IENFD is the current standard for evaluation of SFN but limited by invasiveness, expense and availability. Heat-induced neurogenic vasodilation by Laser Doppler Imaging (LDI), cold detection thresholds (CDT) and heat perception (HP) are noninvasive nerve function alternatives whose accuracy relative to morphological IENFD is unknown. Design/Methods: We performed a retrospective chart review of 75 patients suspected of having SFN at the Toronto General Hospital, University Health Network from 2008-2011. A detailed history and clinical examination, laboratory studies, nerve conduction studies (NCS), CDT, HP, LDI and IENFD were performed in all patients. We quantitatively compared the results of clinical evaluation including pain on the visual analogue scale (VAS), LDI, CDT and HP relative to IENFD for the diagnosis of SFN. Results: The mean IENFD was 7.52 +/- 4.12 with a median value of 7.59 and interquartile range of 4.64-10.91 (25% to 75%). 34.7% had abnormal IENFD and 65.3% had normal IENFD according to published criteria (normal defined as > 5.4 fibers/mm). Low-magnitude correlation was observed between IENFD and CDT (R2 =0.0812, p Conclusions: None of the objective measures reflected IENFD with very good diagnostic validity, but of these small fiber non-invasive methods, CDT had the highest level of accuracy, while we could not demonstrate acceptable performance of LDI. Alternate non-invasive methods for the determination of small fiber function or morphology are urgently needed. Disclosure: Dr. Ebadi has nothing to disclose. Dr. Perkins has nothing to disclose. Dr. Katzberg has received personal compensation for activities with Genzyme as a speaker and participant on an advisory board. Dr. Katzberg has received research support from Griffolds Biotherapeutics. Dr. Bril has received personal compensation for activities with Talecris Biotherapeutics as a consultant. Dr. Bril has received research support from Talecris Biotherapeutics.

Objective: To study if one or more FcR polymorphisms are correlated with response to IVIG treatment in Myasthenia Gravis (MG). Background Intravenous immunoglobulin (IVIG) is an effective treatment of moderate to severe MG, but only about 60% of patients respond to treatment, and there are no clear predictors of response. Fc receptors play an important role in the mechanism of action of IVIG, so genetic variation of these might predict response to treatment. Design/Methods: 71 patients who participated in previous studies of IVIG efficacy, and new patients treated with IVIG for worsening MG were included. Patients were considered responders if the quantitative myasthenia gravis score (QMGS) improved by > 3.5 units 14 days after treatment. Polymorphisms within the FCγR2A, FCγR2B, FCγR3A and FCγR3B (NA1/NA2) genes were genotyped and the rates of treatment response were analyzed by each genotype. Results: The mean age was 56 years and 59% of patients were female. The mean QMGS at baseline was 13.4 ± 4.5. The FCγR2B-232I/I genotype was significantly more common in responders (94%) compared to non-responders (77%) (p=0.04). None of the other polymorphisms were associated with response. Patients with the FCγR2B 232I/I genotype had a higher QMGS at baseline (14 ± 5) compared to heterozygotes (10 ±2, p=0.025) and higher baseline QMGS was associated with response to treatment (responders: 15 ± 5; non-responders 12 ±4, p=0.01). Multivariate logistic regression analysis showed that only the baseline QMGS independently predicted response to IVIG (p=0.036). Conclusions: We found that the FCγR2B I/I genotype is associated with greater disease severity in MG and this, in turn, predicts a better response to IVIG. Although confirmation of this finding in larger population samples is required, the finding that the wild type inhibitory FcγR predisposes to more severe disease suggests that the FCγR2B does not act by directly inhibiting the pathogenic antibodies in MG. Supported by: An unrestricted educational grant from Talecris Biotherapeutics for clinician-initiated research. Disclosure: Dr. Barnett Tapia has nothing to disclose. Dr. Grinberg has nothing to disclose. Dr. Ghani has nothing to disclose. Dr. Rogaeva has nothing to disclose. Dr. St George-Hyslop has received personal compensation for activities with Finnegan LLC. Dr. Katzberg has received personal compensation for activities with Genzyme as a speaker and participant on an advisory board. Dr. Katzberg has received research support from Griffolds Biotherapeutics. Dr. Bril has received personal compensation for activities with Talecris Biotherapeutics as a consultant. Dr. Bril has received research support from Talecris Biotherapeutics.

Recently an article provided patient perspectives on therapies and perceived effectiveness in preventing muscle cramps. However, there are few studies evaluating physicians’ point of view in the management of this common symptom. In our study, we studied physician practice patterns in the treatment of muscle cramps by surveying a group of neurologists in Canada. We demonstrated that most physicians use a combination of pharmacological and non-pharmacological methods in treating muscle cramps. The most commonly used medications are baclofen, quinine and gabapentin, of which baclofen and quinine were reported to be the most tolerated.