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Introduction/Aims: Somatosensory evoked potentials (SSEPs) are described as a supportive tool to diagnose chronic inflammatory demyelinating polyradiculoneuropathy (CIDP); however, there is a lack of studies determining the effectiveness of SSEPs in monitoring the clinical course of individuals with this condition. The aims of this study are to evaluate the utility of SSEPs in monitoring patients with CIDP and to assess their association with clinical outcomes following immunomodulatory therapy. Methods: This was a single‐center retrospective observational study that included patients who met European Federation of Neurological Societies and Peripheral Nerve Society criteria for CIDP between 2018 and 2023. SSEPs were performed at diagnosis and during follow‐up after the start of immunomodulatory treatment. Fisher's exact test was employed to assess the association between clinical improvement and SSEP improvement. Results: Eighteen patients were included in the study. Ten patients had a typical CIDP pattern and 11 were male. In 17, SSEPs were abnormal prior to the start of immunomodulatory treatment. In patients who showed clinical improvement with immunomodulatory therapy, we observed that 15/17 had partial or complete improvement in SSEPs. Patients who showed no clinical improvement with first‐line treatment exhibited worsening SSEPs. There was a significant association between clinical and SSEPs improvement (p = 0.009). Discussion: We observed a positive association between improvement in SSEPs and clinical improvement in patients with CIDP. Our data suggest that SSEPs may be useful for monitoring the clinical course of patients with CIDP, but additional, larger studies are needed. [ABSTRACT FROM AUTHOR]

Novel surgical treatments for painful neuromas are increasingly used, but determining which provides the greatest benefit has been difficult due to the inconsistent use of outcome measures. We mapped the current literature of outcome measures used to evaluate peripheral nerve surgery for the management of symptomatic neuromas in patients who underwent an adult‐acquired upper extremity amputation (UEA). Medline, Embase, Cochrane, and CINAHL were searched for primary research written in the English language from inception to February 2023. The search yielded 1137 articles, of which 35 were included for final analysis. Studies varied in their assessment of pain, health‐related quality of life (HRQOL), neurotrophic measures, psychological and sensorimotor function, highlighting a consensus on crucial domains but also revealing significant heterogeneity in the use and application of outcome measures among primary studies. Our findings highlight the need to establish common standards that reflect the best evidence and unique needs of the UEA population. This includes developing a core outcome set, utilizing multi‐center trials, and maintaining flexibility to adapt to ongoing advancements in patient‐reported outcome measures (PROMs) research. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disorder with complex biology and significant clinical heterogeneity. Many preclinical and early phase ALS clinical trials have yielded promising results that could not be replicated in larger phase 3 confirmatory trials. One reason for the lack of reproducibility may be ALS biological and clinical heterogeneity. Therefore, in this review, we explore sources of ALS heterogeneity that may reduce statistical power to evaluate efficacy in ALS trials. We also review efforts to manage clinical heterogeneity, including use of validated disease outcome measures, predictive biomarkers of disease progression, and individual clinical risk stratification. We propose that personalized prognostic models with use of predictive biomarkers may identify patients with ALS for whom a specific therapeutic strategy may be expected to be more successful. Finally, the rapid application of emerging clinical and biomarker strategies may reduce heterogeneity, increase trial efficiency, and, in turn, accelerate ALS drug development.

INTRODUCTION:There are no validated, practical, and quantitative measures of disease severity in Lambert-Eaton myasthenia (LEM). METHODS:Data from the Effectiveness of 3,4-Diaminopyridine in Lambert-Eaton Myasthenic Syndrome (DAPPER) trial were analyzed to assess triple timed up-and-go (3TUG) reproducibility and relationships between 3TUG times and other measures of LEM severity. RESULTS:The coverage probability technique showed ≥0.90 probability for an acceptable 3TUG difference of ≤0.2, indicating that it is reproducible in LEM patients. The correlation between 3TUG times and lower extremity function scores was significant in subjects who continued and in those who were withdrawn from 3,4-diaminopyridine free base. Worsening patient-reported Weakness Self-Assessment Scale and Investigator Assessment of Treatment Effect scores corresponded with prolongation of 3TUG times. DISCUSSION:The 3TUG is reproducible, demonstrates construct validity for assessment of lower extremity function in LEM patients, and correlates with changes in patient and physician assessments. These findings, along with prior reliability studies, indicate 3TUG is a valid measure of disease severity in LEM.

Introduction/aims: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune‐mediated peripheral nerve disorder with variable prognosis and long‐term dependence on immunotherapy. Frequent assessment of grip strength can be a useful tool to identify intravenous immunoglobulin (IVIG) treatment‐related fluctuations (TRFs) and optimize IVIG treatment in real‐time, but the long‐term implications of TRFs are unknown. We aimed to explore the impact that real‐time TRFs had on long‐term CIDP prognosis, strength impairment, and disability. Methods: This retrospective observational cohort study analyzed standard of care clinical and treatment outcomes in patients who participated in a published prospective study of intra‐IVIG‐cycle grip strength quantification. Patients were analyzed based upon the presence or absence of TRFs, as determined in the initial prospective study. Results: Data were available for 23 CIDP patients with a mean follow‐up period of 44.7 mo. There were no differences in baseline or follow‐up strength, disability, or IVIG usage in patients with a low number of fluctuations compared to those with a high number of fluctuations. In both groups, drug‐free remission was achieved in about one‐third of patients. Discussion: TRFs are important to identify in order to optimize treatment in real time, but poorly predict long‐term disease activity status. The presence of minor TRFs are unlikely to result in substantial accumulation of disability over time. Periodic IVIG optimization trials using objective outcomes are encouraged in all CIDP patients receiving chronic IVIG treatment as a means to identify the lowest effective IVIG dose and frequency. [ABSTRACT FROM AUTHOR]

Within the last 5 years, the US Food and Drug Administration (FDA) has approved complement and neonatal Fc receptor (FcRN) inhibitors for treatment of generalized myasthenia gravis, and several other therapies are in late‐stage clinical trials or under regulatory review. However, questions about which patients are most likely to benefit from which therapies, and the relative effectiveness of these very expensive drugs, has resulted in uncertainty around the place that they should occupy in the existing therapeutic armamentarium. MGNet (a Rare Diseases Clinical Research Consortium funded by the National Institute of Neurological Diseases and Stroke) held two meetings during the 14th International Conference of the Myasthenia Gravis Foundation of America to discuss the most critical needs for clinical trial readiness and biomarker development in the context of therapy development for myasthenia gravis. Herein we provide a summary of these discussions, but not a consensus opinion, and offer a series of recommendations to guide focused research in the most critical areas. We welcome ongoing discussion through comments on this work. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Treatment response and its timing are variable in chronic inflammatory demyelinating polyneuropathy (CIDP). In this study we assessed the variability using multiple outcome measures. Methods: We performed a post hoc analysis of the PRISM trial, a 24‐week prospective, multicenter, single‐arm, open‐label, phase III study of a 10% intravenous immunoglobulin preparation for CIDP. We ascertained timing of response with primary/secondary outcome measures. Results: At 6 weeks after treatment initiation, 13 of 40 subjects (32.5%) were defined as responders on the primary outcome measure, the adjusted Inflammatory Neuropathy Cause And Treatment (INCAT) scale. This increased to 20 of 41 (48.8%) at 12 weeks and to 32 of 42 (76.2%) at 24 weeks. Use of minimal important difference (MID)‐determined amelioration of the inflammatory Rasch‐built Overall Disability Scale (I‐RODS), or of the Medical Research Council sum score (MRCSS), or of dominant hand‐grip strength, in addition to the adjusted INCAT, indicated a sensitivity of 41.7% in identifying adjusted INCAT nonresponders at week 12 who subsequently responded at week 24. Specificity was 60% vs INCAT nonresponders at week 24. Consideration of amelioration of any amplitude on any secondary outcome measure indicated a 75% sensitivity, but only 30% specificity vs adjusted INCAT nonresponders at week 24. Discussion: Immunoglobulin treatment continuation may be justified for up to 24 weeks in CIDP. Additional outcome measures may help in the early treatment stages to predict delayed response on the adjusted INCAT. However, their use is limited by high false‐positive rates. More robust, reliable, and relevant outcome measures are needed to detect early improvement in immunoglobulin‐treated CIDP. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Remote study visits (RSVs) are emerging as important tools for clinical research. We tested the feasibility of using RSVs to evaluate patients with myotonic dystrophy type 1 (DM1), including remote quantitative assessment of muscle function, and we assessed correlations of remote assessments with patient‐reported function. Methods: Twenty three subjects with DM1 were consented remotely. Toolkits containing a tablet computer, grip dynamometer, and spirometer were shipped to participants. The tablets were loaded with software for video‐conferencing and questionnaires about functional impairment, patient experience with technology, and willingness to participate in future remote studies. Grip strength, forced vital capacity, peak cough flow, timed‐up‐and‐go (TUG), and grip myotonia (hand opening time) were determined during RSVs. We assessed correlations of remote assessments with patient‐reported outcomes of muscle function and with CTG repeat size. Results: All 23 subjects completed RSVs. 95% of participants were able to complete all components of the remote study. All toolkit components were returned upon completion. Grip strength and TUG demonstrated moderate to strong correlations with self‐reported inventories of upper and lower extremity impairment, respectively (ρ = 0.7 and ρ = −0.52). A total of 91% of subjects expressed interest in participating in future RSVs. Discussion: Results of this study support the feasibility of using portable devices and video‐conferencing for remote collection of patient‐reported outcomes and quantitative assessment of muscle function in DM1. See Editorial on pages 233‐235 in this issue [ABSTRACT FROM AUTHOR]

Introduction/Aims: Magnetic resonance imaging (MRI) of peripheral nerves can provide image‐based anatomical information and quantitative measurement. The aim of this pilot study was to investigate the feasibility of high‐resolution anatomical and quantitative MRI assessment of sciatic nerve fascicles in patients with Charcot–Marie–Tooth (CMT) 1A using 7T field strength. Methods: Six patients with CMT1A underwent imaging on a high‐gradient 7T MRI scanner using a 28‐channel knee coil. Two high‐resolution axial images were simultaneously acquired using a quantitative double‐echo in steady‐state (DESS) sequence. By comparing the two DESS echoes, T2 and apparent diffusion coefficient (ADC) maps were calculated. The cross‐sectional areas and mean T2 and ADC were measured in individual fascicles of the tibial and fibular (peroneal) portions of the sciatic nerve at its bifurcation and 10 mm distally. Disease severity was measured using Charcot–Marie–Tooth Examination Score (CMTES) version 2 and compared to imaging findings. Results: We demonstrated the feasibility of 7T MRI of the proximal sciatic nerve in patients with CMT1A. Using the higher field, it was possible to measure individual bundles in the tibial and fibular divisions of the sciatic nerve. There was no apparent correlation between diffusion measures and disease severity in this small cohort. Discussion: This pilot study indicated that high‐resolution MRI that allows for combined anatomical and quantitative imaging in one scan is feasible at 7T field strengths and can be used to investigate the microstructure of individual nerve fascicles. [ABSTRACT FROM AUTHOR]

Introduction: The Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM) have been widely used in natural history studies and clinical trials. Our aim was to establish how the scales relate to each other at different age points in spinal muscular atrophy (SMA) type 2 and 3, and to describe their coherence over 12 mo. Methods: The study was performed by cross‐sectional and longitudinal reanalysis of previously published natural history data. The longitudinal analysis of the 12‐mo changes also included the analysis of concordance between scales with changes grouped as stable (±2 points), improved (>+2) or declined (>−2). Results: Three hundred sixty‐four patients were included in the cross‐sectional analysis, showing different trends in score and point of slope change for the two scales. For type 2, the point of slope change was 4.1 y for the HFMSE and 5.8 for the RULM, while for type 3, it was 6 y for the HFMSE and 7.3 for the RULM. One‐hundred‐twenty‐one patients had at least two assessments at 12 mo. Full concordance was found in 57.3% of the assessments, and in 40.4% one scale remained stable and the other changed. Each scale appeared to be more sensitive to specific age or functional subgroups. Discussion: The two scales, when used in combination, may increase the sensitivity to detect clinically meaningful changes in motor function in patients with SMA types 2 and 3. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Telemedicine may be particularly well‐suited for myasthenia gravis (MG) due to the disorder's need for specialized care, its hallmark fluctuating muscle weakness, and the potential for increased risk of virus exposure among patients with MG during the coronavirus disease 2019 (COVID‐19) pandemic during in‐person clinical visits. A disease‐specific telemedicine physical examination to reflect myasthenic weakness does not currently exist. Methods: This paper outlines step‐by‐step guidance on the fundamentals of a telemedicine assessment for MG. The Myasthenia Gravis Core Exam (MG‐CE) is introduced as a MG‐specific, telemedicine, physical examination, which contains eight components (ptosis, diplopia, facial strength, bulbar strength, dysarthria, single breath count, arm strength, and sit to stand) and takes approximately 10 minutes to complete. Results: Pre‐visit preparation, remote ascertainment of patient‐reported outcome scales and visit documentation are also addressed. Discussion: Additional knowledge gaps in telemedicine specific to MG care are identified for future investigation. See Editorial on pages 241–242 in this issue. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Clinical trials addressing treatments for Duchenne muscular dystrophy (DMD) require reliable and valid measurement of muscle contractile function across all disease severity levels. In this work we aimed to evaluate a protocol combining voluntary and evoked contractions to measure strength and excitability of wrist extensor muscles for safety, feasibility, reliability, and discriminant validity between males with DMD and controls. Methods: Wrist extensor muscle strength and excitability were assessed in males with DMD (N = 10; mean ± standard deviation: 15.4 ± 5.9 years of age), using the Brooke Upper Extremity Rating Scale (scored 1‐6), and age‐matched healthy male controls (N = 15; 15.5 ± 5.0 years of age). Torque and electromyographic (EMG) measurements were analyzed under maximum voluntary and stimulated conditions at two visits. Results: A protocol of multiple maximal voluntary contractions (MVCs) and evoked twitch contractions was feasible and safe, with 96% of the participants completing the protocol and having a less than 7% strength decrement on either measure for both DMD patients and controls (P ≥.074). Reliability was excellent for voluntary and evoked measurements of torque and EMG (intraclass correlation coefficient [ICC] over 0.90 and over 0.85 within and between visits, respectively). Torque, EMG, and timing of twitch‐onset measurements discriminated between DMD and controls (P <.001). Twitch contraction time did not differ significantly between groups (P =.10). Discussion: Findings from this study show that the protocol is a safe, feasible, reliable, and a valid method to measure strength and excitability of wrist extensors in males with DMD. [ABSTRACT FROM AUTHOR]

Introduction/aim: The use of outcome measures is recommended for chronic inflammatory demyelinating polyneuropathy (CIDP). Implications of minimal important differences (MID) to ascertain responder status are unknown. The reliability of patient-reported treatment-response in relation to clinically relevant change is also unknown.Methods: We retrospectively studied 72 subjects with "definite" or "probable" CIDP evaluated at pre-specified time-intervals pre- and post-treatment. We derived MID and the minimum detectable change with 95% confidence intervals (MDC95 ) for four scales. Scale sensitivities were determined with applicable MID-defined cutoffs (aMIDc), to detect subjects with self-identifying treatment response through a single question.Results: The use of MID was not valid for the Medical Research Council Sum Score, as MDC95  > MID. The aMIDc for the Overall Neuropathy Limitation Score (ONLS) was 1 (sensitivity: 84.7%). The aMIDc for the centile Inflammatory Rasch-built Overall Disability Scale (cI-RODS) was 8 (sensitivity: 62.3%). The aMIDc for grip strength was 4 kg (sensitivity: 79.1%). MID-defined amelioration of any one scale among ONLS, cI-RODS, or grip strength, significantly improved sensitivity to detect treatment-responders compared with the ONLS alone (McNemar test: P = .008, odds ratio: 3.36 [95% confidence interval: 1.44-7.86]). Patient-reported improvement was highly reliable in relation to MID-defined amelioration on any one scale.Discussion: In subjects with CIDP, MID-defined amelioration of any one of three commonly used outcome measures offers optimum relevance and sensitivity to detect self-identifying treatment-responders. Patient reliability to single-question ascertainment of response is high in relation to MID-defined clinical relevance. These findings support use of multiple outcome measures in CIDP monitoring and justify enhanced patient involvement in the process. [ABSTRACT FROM AUTHOR]

Introduction: Pediatric myasthenia encompasses juvenile myasthenia gravis (JMG) and congenital myasthenic syndrome (CMS), which are chronic disorders with fluctuating symptoms amenable to medical therapy. Disease activity and treatment response may be difficult to assess, but, unlike adults, outcome measures have not been developed in children. Methods: The study was performed in children (0‐18 years of age) at the neuromuscular center of a pediatric hospital over a 3‐year period. Patients were recruited prospectively as part of their routine clinical care. Demographic data, diagnosis (JMG/CMS), and the following scales were recorded at each visit: Myasthenia Gravis Foundation of America (MGFA) class, Myasthenia Gravis Composite (MGC), and Pediatric Myasthenia–Quality of Life 15 (PM‐QOL15). Results: Thirty‐three patients (24 JMG, 9 CMS) were included in the study, 22 had two or more visits. We established known‐groups validity of the MGC and PM‐QOL15 scores as compared with the MGFA class. To establish concurrent validity, we constructed a receiver‐operating characteristic curve and calculated threshold values of MGC and PM‐QOL15 with optimal sensitivity and specificity for identifying a patient with more severe (MGFA III or higher) disease. Finally, we demonstrated the concordance between the MGC and PM‐QOL15 by their statistically significant positive Pearson and Spearman correlations. Discussion: Our study suggests that MGC and PM‐QOL15 are important disease outcome measures in pediatric myasthenia that are easy to administer and provide reliable assessment of disease activity in the clinic setting. Further studies are needed to validate their use for pediatric clinical research trials. [ABSTRACT FROM AUTHOR]

Background: The Boston Carpal Tunnel Questionnaire (BCTQ) is a patient-reported outcome measure (PROM) used to measure symptom severity and function in carpal tunnel syndrome (CTS). Despite its wide use, investigation of its measurement properties using modern psychometric methodologies is limited.Methods: Completed BCTQ data collected routinely in the Canterbury carpal tunnel clinic was used to investigate the structural validity and measurement properties of the BCTQ through application of a Rasch model analytic approach.Results: A total of 600 patients with electrodiagnostically confirmed CTS in their right hand were randomly selected from the database and analyzed. Mean age was 48.8 y, and 73% were women. Initial analysis showed that the 19 items could not be reliably added up to form a single linear construct. All subsequent analyses were done by subscale only. The Symptom Severity Subscale (SSS) displayed a large amount of local dependence. This could be accommodated through the creation of four clinically derived testlets, allowing for the ordinal SSS raw score to be transformed to a linear measure. The Functional Status Subscale (FSS) displayed a number of issues regarding its psychometric integrity. These include scale and item fit, targeting, differential item functioning, and dimensionality.Conclusions: This study shows that a single total score generated across all BCTQ items is not psychometrically valid, and that the SSS and FSS subscales should be treated separately. We propose a modified scoring system for the SSS, resulting in a linear measure that can be used in the analysis of future and existing datasets. [ABSTRACT FROM AUTHOR]

Background: We studied the performance of a 15‐item, health‐related quality‐of‐life polyneuropathy scale in a longitudinal study of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: Sixty‐one patients with CIDP completed the Chronic Acquired Polyneuropathy Patient‐Reported Index (CAPPRI) scale and Patient Impression of Change (PIC) at baseline and follow‐up visits. Clinicians completed Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores at baseline and follow‐up visits. Conventional and modern psychometric analyses were performed on the completed forms. Results: CAPPRI was psychometrically stable between visits without significant difference in response pattern between visits 1 and 2 (paired t‐test P =.72). There was strong correlation between changes in INCAT and changes in CAPPRI scores between two visits (rho = 0.6, P <.001). In addition, we showed robust CAPPRI effect sizes between PIC categories. Conclusions: We demonstrated psychometric stability and construct longitudinal validity of CAPPRI. [ABSTRACT FROM AUTHOR]

Introduction: Monitoring grip strength at home may detect improvement between intravenous immunoglobulin (IVIg) treatments in patients with chronic inflammatory neuropathies (CINs).Methods: Fifteen patients recorded grip strength each day, from one IVIg treatment until the next. We analyzed grip strength changes comparing thresholds of 8 kPa and 14 kPa. "Random" fluctuations of grip strength were distinguished from treatment response by smoothing the data.Results: "Random" fluctuations of at least 8 kPa occurred in 27% of patients. Smoothed daily grip strength increased by at least 8 kPa above baseline in 11 (73%) patients. Grip strength increased by at least 8 kPa for 3 consecutive days in 9 (60%) patients, and 5-day block mean increased by at least 8 kPa in 10 (67%) patients.Discussion: Home monitoring of grip strength confirmed treatment response in most patients with CINs on IVIg. To detect improvement in an individual patient, we suggest a threshold of at least 8 kPa on 3 consecutive days or on 5-day block mean. [ABSTRACT FROM AUTHOR]

Introduction: Electrical impedance myography (EIM) has been proposed as a noninvasive biomarker of muscle composition in facioscapulohumeral muscular dystrophy (FSHD). Here we determine the associations of EIM variables with muscle structure measured by MRI.Methods: We evaluated 20 patients with FSHD at two centers, comparing EIM measurements (resistance, reactance, and phase at 50, 100, and 211 kHZ) recorded from bilateral vastus lateralis, tibialis anterior, and medial gastrocnemius muscles to MRI skin and subcutaneous fat thickness, MRI T1-based muscle severity score (T1 muscle score), and MRI quantitative intramuscular Dixon fat fraction (FF).Results: While reactance and phase both correlated with FF and T1 muscle score, 50 kHz reactance was most sensitive to muscle structure alterations measured by both T1 score (ρ = -0.71, P < .001) and FF (ρ = -0.74, P < .001).Discussion: This study establishes the correlation of EIM with structural MRI features in FSHD and supports further evaluation of EIM as a potential biomarker in FSHD clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: The comparative value and suitability of outcome measures are uncertain in chronic inflammatory demyelinating polyneuropathy (CIDP).Methods: We studied 35 patients with CIDP using the Overall Neuropathy Limitation Scale (ONLS), the inflammatory Rasch-built Overall Disability Scale (I-RODS), and the Medical Research Council Sum Score (MRCSS).Results: Significant associations were determined between initial deficit and ONLS score (P = .002) and MRCSS improvement (P = .001) but not I-RODS score. A strong inverse correlation was observed between disease duration and I-RODS score(P = .002) but not ONLS/MRCSS improvement. A strong association was observed between age ≤ 40 years and I-RODS score (P = .001) but not ONLS/MRCSS improvement. When minimum important differences were used, ONLS and I-RODS sensitivities were comparable (P = .19).Discussion: Overall Neuropathy Limitation Scale and I-RODS are equally sensitive in identifying change. Ease of administration, better ability to detect improvement in severe disease, and greater amplitude responses throughout the disease and in older patients favor the ONLS. The I-RODS appears more useful in early disease/younger patients. [ABSTRACT FROM AUTHOR]

Background: Nephropathic cystinosis is a lysosomal storage disorder. Patient survival years after renal transplantation has revealed systemic complications including distal myopathy and dysphagia.Methods: We evaluated 20 adult patients with nephropathic cystinosis using patient-reported and clinical outcome measures. Standard motor measures, video fluoroscopy swallow studies, and tests of respiratory function were performed. We also used Rasch analysis of an initial survey to design a 16-item survey focused on upper and lower extremity function, which was completed by 31 additional patients.Results: Distal myopathy and dysphagia were common in patients with nephropathic cystinosis. Muscle weakness ranges from mild involvement of intrinsic hand muscles to prominent distal greater than proximal weakness and contractures.Conclusions: In addition to further characterization of underlying dysphagia and muscle weakness, we propose a new psychometrically devised, disease specific, functional outcome measures for distal myopathy in patients with nephropathic cystinosis. [ABSTRACT FROM AUTHOR]

See article on pages 37–42 in this issue. [ABSTRACT FROM AUTHOR]

Introduction: We determined whether instrumenting timed functional tasks with wireless inertial motion sensors were responsive to facioscapulohumeral muscular dystrophy (FSHD) progression and movement pattern changes.Methods: Ten individuals who were clinically affected with genetically confirmed FSHD, mean age 54 years (range 42-65), performed an instrumented timed up and go (iTUG) trial at each visit, wearing six wireless inertial sensors. We determined the estimated average monthly slope of progression and 12-month change for temporal and spatial motion variables using a linear mixed effects model.Results: For an average of 20.6 months (range 6.1-34.5), the iTUG duration stayed constant, whereas stride length, stride velocity, and trunk sagittal range of motion changed, indicating poorer performance. Arm swing changed in a compensatory direction toward the normative mean.Discussion: This study provides preliminary evidence that iTUG motion variables could be sensitive to progression in FSHD, but this requires validation in a larger study. [ABSTRACT FROM AUTHOR]

Recent years have seen steady progress in the identification of genetic muscle diseases as well as efforts to develop treatment for these diseases. Consequently, sensitive and objective new methods are required to identify and monitor muscle pathology. Magnetic resonance imaging offers multiple potential biomarkers of disease severity in the muscular dystrophies. This Review uses a pathology-based approach to examine the ways in which MRI and spectroscopy have been used to study muscular dystrophies. Methods that have been used to quantitate intramuscular fat, edema, fiber orientation, metabolism, fibrosis, and vascular perfusion are examined, and this Review describes how MRI can help diagnose these conditions and improve upon existing muscle biomarkers by detecting small increments of disease-related change. Important challenges in the implementation of imaging biomarkers, such as standardization of protocols and validating imaging measurements with respect to clinical outcomes, are also described. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to assess 12 month changes in upper limb function in patients affected by spinal muscular atrophy type 2 and 3.Methods: Longitudinal 12 month data was collected in 114 patients, 60 type 2 and 54 type 3, using the Revised Upper Limb Module.Results: The 12 month changes ranged between -7 and 9 (mean: -0.41; SD: 2.93). The mean changes were not significantly different between the three spinal muscular atrophy groups (-0.45 in type 2, -0.23 in non-ambulant type 3 and -0.34 in ambulant type 3, p = 0.96) and the relationship between 12 month change and age classes was not significantly different among the three types of SMA patients.Discussion: Our results confirm that the Module explores a wide range of functional abilities and can be used in ambulant and non-ambulant patients of different ages in conjunction with other functional scales. Muscle Nerve 59:426-430, 2019. [ABSTRACT FROM AUTHOR]

Introduction: Tests of ambulatory function are common clinical trial endpoints in Duchenne muscular dystrophy (DMD). Using these tests, the ImagingDMD study has generated a large data set that can describe the contemporary natural history of DMD in 5-12.9-year-olds.Methods: Ninety-two corticosteroid-treated boys with DMD and 45 controls participated in this longitudinal study. Participants performed the 6-minute walk test (6MWT) and timed function tests (TFT: 10-m walk/run, climbing 4 stairs, supine to stand).Results: Boys with DMD had impaired functional performance even at 5-6.9 years old. Boys older than 7 had significant declines in function over 1 year for 10-m walk/run and 6MWT. Eighty percent of participants could perform all functional tests at 9 years old. TFTs appear to be slightly more responsive and predictive of disease progression than the 6MWT in 7-12.9 year olds.Discussion: This study provides insight into the contemporary natural history of key functional endpoints in DMD. Muscle Nerve 58: 631-638, 2018. [ABSTRACT FROM AUTHOR]

Introduction: We developed an evaluator-administered functional facioscapulohumeral muscular dystrophy composite outcome measure (FSHD-COM) comprising patient-identified areas of functional burden for future clinical trials.Methods: We performed a prospective observational study of 41 patients with FSHD at 2 sites. The FSHD-COM includes functional assessment of the legs, shoulders and arms, trunk, hands, and balance/mobility. We determined the test-retest reliability and convergent validity compared to established FSHD disease metrics.Results: The FSHD-COM demonstrated excellent test-retest reliability (intraclass correlation coefficient [ICC] 0.96; subscale ICC range, 0.90-0.94). Cross-sectional associations between the FSHD-COM and disease duration, clinical severity, and strength were moderate to strong (Pearson correlation coefficient range |0.51-0.92|).Discussion: The FSHD-COM is a disease-relevant, functional composite outcome measure suitable for future FSHD clinical trials that shows excellent test-retest reliability and cross-sectional associations to disease measures. Future directions include determining multisite reliability, sensitivity to change, and the minimal clinically important change in the FSHD-COM. Muscle Nerve, 2018. [ABSTRACT FROM AUTHOR]

Introduction: We report the reliability of a new measure, the triple-timed up-and-go (3TUG) test, for assessing clinical function in patients with Lambert-Eaton myasthenia (LEM).Methods: Intrarater reproducibility and interrater agreement of the 3TUG test were assessed in 25 control participants, 24 patients with non-LEM neuromuscular disease, and 12 patients with LEM. The coverage probability (CP) method was the primary measure of reproducibility and agreement. The a priori acceptable range was < 20% difference in 3TUG test times and a CP ≥0.90 confirmed agreement.Results: CP values > 0.90 for intrarater and interrater tests confirmed acceptable reproducibility and agreement for all groups.Discussion: The 3TUG test is a quick, noninvasive, and reproducible measure that is easy to perform, measures clinically important weakness in LEM patients, and requires little training. Additional evaluation in a larger number of LEM patients is in progress to validate the 3TUG test as a clinical measure in LEM. Muscle Nerve 57: 136-139, 2017. [ABSTRACT FROM AUTHOR]

Introduction: Gait impairment is a common presenting symptom in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). However, gait parameters have not previously been evaluated in detail as potential independent outcome measures.Methods: We prospectively measured changes in spatiotemporal gait parameters of 20 patients with CIDP at baseline and following treatment with intravenous immunoglobulin (IVIG), using GAITRite® a computerized walkway system with embedded sensors.Results: Overall, study patients showed significant improvements in gait velocity, cadence, stride length, double support time, stance phase, and swing phase following IVIG treatment. Mean changes in velocity, stance phase, and swing phase, exhibited the greatest statistical significance among the subgroup that exhibited clinically meaningful improvement in Inflammatory Neuropathy Cause and Treatment disability score, Medical Research Council sum score, and grip strength.Conclusions: Assessment of gait parameters, in particular velocity, step phase and swing phase, is a potentially sensitive outcome measure for evaluating treatment response in CIDP. Muscle Nerve 56: 732-736, 2017. [ABSTRACT FROM AUTHOR]

Introduction: Lower limb strength has never been characterized separately for late-onset and adult myotonic dystrophy type 1 (DM1) phenotypes.Methods: The purpose of this study was to: (1) describe and compare lower limb strength between the 2 DM1 phenotypes; and (2) compare the impairment profiles obtained from 2 assessment methods [manual (MMT) and quantitative (QMT) muscle testing] among 107 patients.Results: Both MMT and QMT showed more pronounced weakness in the adult phenotype. In the late-onset phenotype, although MMT showed normal strength, QMT revealed a loss of 11.7%-20.4%. Participants with grade 1 or 2 on the Muscle Impairment Rating Scale had weakness detected using QMT, which suggests earlier muscle impairment than MMT alone would suggest.Conclusions: To avoid muscle wasting, physical activity recommendations should be made for the late-onset phenotype and in the early stages of the disease for the adult phenotype. MMT is not recommended for use in clinical trials. Muscle Nerve 56: 57-63, 2017. [ABSTRACT FROM AUTHOR]

Introduction: There is a growing need for a robust clinical measure to assess upper limb motor function in spinal muscular atrophy (SMA), as the available scales lack sensitivity at the extremes of the clinical spectrum. We report the development of the Revised Upper Limb Module (RULM), an assessment specifically designed for upper limb function in SMA patients.Methods: An international panel with specific neuromuscular expertise performed a thorough review of scales currently available to assess upper limb function in SMA. This review facilitated a revision of the existing upper limb function scales to make a more robust clinical scale.Results: Multiple revisions of the scale included statistical analysis and captured clinically relevant changes to fulfill requirements by regulators and advocacy groups.Conclusions: The resulting RULM scale shows good reliability and validity, making it a suitable tool to assess upper extremity function in the SMA population for multi-center clinical research. Muscle Nerve 55: 869-874, 2017. [ABSTRACT FROM AUTHOR]

Introduction: In preparation for future clinical trials, we determined the reliability, relationship to measures of disease severity, and consistency across sites of the 6 Minute Walk Test (6MWT) in patients with facioscapulohumeral muscular dystrophy (FSHD).Methods: Genetically defined and clinically affected FSHD participants at 2 sites performed the 6MWT, the Timed Up and Go, and the 30 foot Go/Timed 10 meter test as measures of mobility using standard procedures.Results: Eight-six participants representing the full range of severity performed the 6MWT. The mean 6MWT distance was 404.3 meters (SD 123.9), with no difference between sites. The 6MWT was reliable (n = 25; intraclass correlation coefficient = 0.99) and demonstrated moderate to strong correlations with lower extremity strength, functional outcomes, and FSHD Clinical Score.Conclusions: The 6MWT is reliable and is associated with other measures of FSHD disease severity. Future directions include assessing its sensitivity to disease progression. Muscle Nerve 55: 333-337, 2017. [ABSTRACT FROM AUTHOR]

Introduction: No treatments for axonal peripheral neuropathy are approved by the United States Food and Drug Administration (FDA). Although patient- and clinician-reported outcomes are central to evaluating neuropathy symptoms, they can be difficult to assess accurately. The inability to identify efficacious treatments for peripheral neuropathies could be due to invalid or inadequate outcome measures.Methods: This systematic review examined the content validity of symptom-based measures of diabetic peripheral neuropathy, HIV neuropathy, and chemotherapy-induced peripheral neuropathy.Results: Use of all FDA-recommended methods to establish content validity was only reported for 2 of 18 measures. Multiple sensory and motor symptoms were included in measures for all 3 conditions; these included numbness, tingling, pain, allodynia, difficulty walking, and cramping. Autonomic symptoms were less frequently included.Conclusions: Given significant overlap in symptoms between neuropathy etiologies, a measure with content validity for multiple neuropathies with supplemental disease-specific modules could be of great value in the development of disease-modifying treatments for peripheral neuropathies. Muscle Nerve 55: 366-372, 2017. [ABSTRACT FROM AUTHOR]

Introduction: There is a diversity of rating scales that assess function in muscle disease. Definitive knowledge of the content covered by these scales would help in making choices. Methods: We searched for activity rating scales used for muscle disease and assessed their content by linking scale items to the International Classification of Functioning, Disability and Health (ICF) and the muscle regions they cover. Results: Of the 119 scales found, 19 muscle disease-specific and 9 generic scales were prioritized for analysis. These 28 scales contained 457 items, from which 1145 concepts were identified and 160 were unique. Of these concepts, 97.8% could be linked to the ICF, most to the activities and participation domain (68.7%), followed by environmental factors (22.5%) and body functions (6.6%). Global muscle function was assessed most frequently, followed by lower and upper extremity function. Conclusions: This content comparison should allow for a better-informed choice of activity rating scales for muscle disease. Muscle Nerve 50: 14-23, 2014 [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: In an accompanying study we reported on the content of several activity rating scales that have been used for muscle disease. To further aid in achieving consensus we conducted a systematic review to assess the quality of the 19 activity rating scales designed specifically for muscle disease. Methods: We analyzed the measurement properties and the feasibility of the 19 instruments. Several databases were searched for studies relating to the quality of the instruments under review. Two independent reviewers selected studies and assessed instrument quality using pre-agreed criteria based on published frameworks. Results: We found that none of the 19 instruments have sufficiently comprehensive reporting of measurement or feasibility performance as would be required by regulatory authorities. Conclusions: Further work is required urgently to address these deficiencies of reporting or acquiring additional data. Until then, there will remain a major barrier for translational research to overcome. Muscle Nerve 50: 24-33, 2014 [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: The objective of this study is to determine if change in acetylcholine receptor antibody (AChR-ab) levels reflects change in clinical severity in patients with myasthenia gravis (MG). Methods: We reviewed results from a prospective trial in MG and from all 85 patients in an MG Clinic who had AChR-ab determinations performed at least twice by the same commercial laboratory. Results: Change in AChR-ab levels correlated only weakly with change in clinical severity. AChR-ab levels fell in 92% of patients who improved and in 63% who did not. A fall in AChR-ab level had a positive predictive value for clinical improvement of 83% and a negative predictive value of only 59%. Conclusions: AChR-ab levels fell in almost all patients who improved, but also in most patients who did not. Thus, we do not recommend commercially available AChR-ab levels as a biomarker of improvement in MG. However, antibody levels might be useful as a marker for inadequate immunotherapy. Muscle Nerve 49:483-486, 2014 [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: Trial design for SMA depends on meaningful rating scales to assess outcomes. In this study Rasch methodology was applied to 9 motor scales in spinal muscular atrophy (SMA). Methods: Data from all 3 SMA types were provided by research groups for 9 commonly used scales. Rasch methodology assessed the ordering of response option thresholds, tests of fit, spread of item locations, residual correlations, and person separation index. Results: Each scale had good reliability. However, several issues impacting scale validity were identified, including the extent that items defined clinically meaningful constructs and how well each scale measured performance across the SMA spectrum. Conclusions: The sensitivity and potential utility of each SMA scale as outcome measures for trials could be improved by establishing clear definitions of what is measured, reconsidering items that misfit and items whose response categories have reversed thresholds, and adding new items at the extremes of scale ranges. Muscle Nerve 49:422-430, 2014 [ABSTRACT FROM AUTHOR]

Introduction: Fatigue and excessive daytime sleepiness are frequent complaints in myotonic dystrophy type 1 (DM1) that often overlap. We aimed to construct a combined fatigue and daytime sleepiness rating scale for DM1 using the Rasch measurement model. Methods: Questionnaires, including the Epworth Sleepiness Scale, Fatigue Severity Scale, and Daytime Sleepiness Scale, were completed by 354 patients. Data were subjected to Rasch analyses and tested for required measurement issues such as appropriate response categories, absence of item bias, local independence, and unidimensionality. Results: The initial 22 items did not meet Rasch model expectations. After rescoring and removing misfitting items, the final 12-item scale showed good model fit and unidimensionality. High internal consistency (person separation index = 0.80) and validity were demonstrated. Conclusions: The Rasch-built Fatigue and Daytime Sleepiness Scale, developed specifically for DM1 patients, provides interval measures on a single continuum. Its use is suggested for future clinical trials and therapeutic follow-up. Muscle Nerve, 2013 [ABSTRACT FROM AUTHOR]

The recommendations for clinical research standards published in 2000 by a task force of the Medical Scientific Advisory Board (MSAB) of the Myasthenia Gravis Foundation of America (MGFA) were largely successful in introducing greater uniformity in the recording and reporting of MG clinical trials. Recognizing that changes in clinical trial design and implementation may increase the likelihood that new therapies are developed for MG, the MGFA MSAB Task Force here presents updated recommendations for the design and implementation of clinical trials in MG, including (a) the use of a quantitative measure, such as the MG-Composite, that is weighted for clinical significance and incorporates patient reported outcomes; (b) consideration of nontrial strategies; and (c) development of biomarkers that support mechanistic studies of pharmacotherapies. The hope is that these updated task force recommendations will expedite the development and acceptance of more effective and less noxious therapies for MG. Muscle Nerve 45: 909-917, 2012 [ABSTRACT FROM AUTHOR]

Introduction: The clinical course of late-onset Pompe disease is heterogeneous, and new clinical outcome measures are needed to evaluate enzyme replacement therapy (ERT). Methods: We correlated the 6-Minute Walk Test (6MWT), Walton and Gardner-Medwin (WGM) score, and GSGC (Gait, Stairs, Gower, Chair) scores in 40 patients. Results: At baseline, the GSGC score correlated with both WGM ( P < 0.001, n = 33) and 6MWT ( P < 0.001, n = 26). After 1 year of ERT, we observed a significant change in gait, stairs and chair performance on the GSGC scale. The 6MWT significantly increased from 319 to 371 meters in 32 patients, and the WGM score was reduced. Conclusions: GSGC is a group of functional tests that requires only a few minutes to perform, therefore, this score might be a good indicator to be used in future studies. Muscle Nerve 45: 831-834, 2012 [ABSTRACT FROM AUTHOR]