Showing papers in "Muscle & Nerve in 2010"
TL;DR: A modified 6MWT is feasible and safe, documents disease‐related limitations on ambulation, is reproducible, and offers a new outcome measure for DMD natural history and therapeutic trials.
Abstract: Walking abnormalities are prominent in Duchenne muscular dystrophy (DMD). We modified the 6-minute walk test (6MWT) for use as an outcome measure in patients with DMD and evaluated its performance in 21 ambulatory boys with DMD and 34 healthy boys, ages 4 to 12 years. Boys with DMD were tested twice, approximately 1 week apart; controls were tested once. The groups had similar age, height, and weight. All tests were completed. Boys who fell recovered rapidly from falls without injury. Mean +/- SD [range] 6-minute walk distance (6MWD) was lower in boys with DMD than in controls (366 +/- 83 [125-481] m vs. 621 +/- 68 [479-754] m; P < 0.0001; unpaired t-test). Test-retest correlation for boys with DMD was high (r = 0.91). Stride length (R(2) = 0.89; P < 0.0001) was the major determinant of 6MWD for both boys with DMD and controls. A modified 6MWT is feasible and safe, documents disease-related limitations on ambulation, is reproducible, and offers a new outcome measure for DMD natural history and therapeutic trials.
339 citations
TL;DR: Both muscle thickness and echo intensity showed gender differences and a muscle‐specific non‐linear correlation with age, which demonstrate the effect of age on muscle characteristics and provide normative values that can be used in clinical practice.
Abstract: Ultrasonography can detect structural muscle changes caused by neuromuscular disease. Quantitative analysis is the preferred method to determine if ultrasound findings are within normal limits, but normative data are incomplete. The purpose of this study was to provide normative muscle ultrasonography data for muscle thickness and echo intensity for five different muscle groups in adults. Bilateral scans of the sternocleidomastoid, biceps brachii/brachialis, forearm flexor group, quadriceps femoris, and tibialis anterior were made in 95 volunteers, aged 17-90 years. Both muscle thickness and echo intensity showed gender differences and a muscle-specific non-linear correlation with age. The muscles of the upper extremities showed right-left differences. These data demonstrate the effect of age on muscle characteristics and provide normative values that can be used in clinical practice.
326 citations
TL;DR: 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.
Abstract: 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.
287 citations
TL;DR: The first preliminary data that detected the distribution of local muscle stiffness within and between resting and contracting muscles at different muscle lengths with stand‐alone ultrasound shear wave imaging are reported.
Abstract: A stand-alone ultrasound shear wave imaging technology has been developed to quantify and visualize Young's modulus distribution by remotely applying ultrasound radiation force and tracking the resulting microvibrations in soft tissues with ultrafast ultrasound imaging. We report the first preliminary data that detected the distribution of local muscle stiffness within and between resting and contracting muscles at different muscle lengths with this technology. This technique may assist clinicians in characterizing muscle injuries or neuromuscular disorders.
206 citations
TL;DR: Whether physicians can validly and reproducibly diagnose diabetic sensorimotor polyneuropathy (DSPN) is tested and individual physicians' clinical dx was excessively variable and frequently inaccurate.
Abstract: The purpose was to test whether physicians can validly and reproducibly diagnose diabetic sensorimotor poly- neuropathy (DSPN). Twelve physicians assessed 24 patients with diabetes mellitus (DM) on consecutive days (576 examina- tions) with physical features and voice disguised. Results were compared to gold standard 75% group diagnosis (dx) and a nerve conduction score (R5 NC nds). Masking of patients was achieved. Reproducibility measured by the kappa coefficient and compared to R5 NC nd varied considerably among physi- cians: median and ranges: signs 0.8 (0.32-1.0); symptoms 0.79 (0.36-1.0), and diagnoses 0.47 (0.33-0.84), both low and high scores indicating poor performance. There was substantial agreement between 75% group dx and confirmed NC abnor- mality (abn). As compared to R5 NC, individual physicians' clini- cal dx was excessively variable and frequently inaccurate. Study physician dx from signs and symptoms were excessively variable, often overestimating DSPN. Specific approaches to improving clinical proficiency should be tested. Muscle Nerve 42: 157-164, 2010
187 citations
TL;DR: MUNIX would be useful to study MU loss in degenerative diseases of motor neurons, indicating MU loss compensated by reinnervation in ALS patients with minimal change in CMAP amplitude.
Abstract: The motor unit number index (MUNIX) is a method for assessment of number and size (MUSIX) of motor units (MUs) using the compound muscle action potential (CMAP) and surface electromyographic interference pattern (SIP). This method was used to study the hypothenar muscle in 34 healthy subjects to define normal range, and to study reproducibility. Four healthy subjects and 13 patients with amyotrophic lateral sclerosis (ALS) were studied serially over a 1-year period. In healthy subjects, MUNIX showed good reproducibility. In serial studies, healthy subjects showed no change in the CMAP amplitude and MUNIX. ALS patients with minimal change in CMAP amplitude had a significant drop in MUNIX and increase in MUSIX, indicating MU loss compensated by reinnervation. When the CMAP changed significantly (>30%) in 1 year, the CMAP and MUNIX decreased in parallel. MUNIX would be useful to study MU loss in degenerative diseases of motor neurons. Muscle Nerve 42: 798-807, 2010.
159 citations
TL;DR: Changes in 6MWD depended on stride length and age; improvements usually occurred by 7–8 years of age; older DBMD subjects worsened, whereas older healthy subjects were stable.
Abstract: In this study we used the 6-minute walk distance (6MWD) to characterize ambulation over time in Duchenne/Becker muscular dystrophy (DBMD). The 6MWD was assessed in 18 boys with DBMD and 22 healthy boys, ages 4-12 years, over mean [range] intervals of 58 [39-87] and 69 [52-113] weeks, respectively. Height and weight increased similarly in both groups. At 52 weeks, 6MWD decreased in 12 of 18 (67%) DBMD subjects (overall mean [range]: 357 [125-481] to 300 [0-510] meters; Δ -57 meters, -15.9%), but increased in 14 of 22 (64%) healthy subjects (overall mean [range]: 623 [479-754] to 636 [547-717] meters; Δ +13 meters, +2.1%). Two DBMD subjects lost ambulation. Changes in 6MWD depended on stride length and age; improvements usually occurred by 7-8 years of age; older DBMD subjects worsened, whereas older healthy subjects were stable. The 6MWD changes at 1 year confirm the validity of this endpoint and emphasize that preserving ambulation must remain a major goal of DBMD therapy.
158 citations
TL;DR: This survey reinforces several cardinal features of MuSK‐Ab‐positive MG, including prominent bulbar involvement and anticholinesterase nonresponsiveness, and long‐term outcome is favorable in about 60% of cases.
Abstract: We performed a retrospective chart review on 53 muscle-specific kinase antibody (MuSK-Ab)-positive myasthenia gravis (MG) patients at nine university-based centers in the U.S. Of these, 66% were Caucasian, 85% were women, and age of onset was 9-79 years. Twenty-seven patients were nonresponsive to anticholinesterase therapy. Myasthenia Gravis Foundation of America improvement status was achieved in 53% patients on corticosteroids, 51% with plasma exchange, and in 20% on intravenous immunoglobulin (IVIG). Thymectomy was beneficial in 7/18 patients at 3 years. Long-term (> or =3 years) outcome was very favorable in 58% of patients who achieved remission and/or minimal manifestation status. Overall, 73% improved. There was one MG-related death. This survey reinforces several cardinal features of MuSK-Ab-positive MG, including prominent bulbar involvement and anticholinesterase nonresponsiveness. Facial or tongue atrophy was rare. Most patients respond favorably to immunotherapy. The best clinical response was to corticosteroids and plasma exchange, and the poorest response was to IVIG. Long-term outcome is favorable in about 60% of cases.
156 citations
TL;DR: The case of a 56‐year‐old woman with metal neuropathy, who had metallosis after hip arthroplasty with a cobalt–chromium alloy prosthesis, and sural nerve biopsy indicated axonopathy is reported.
Abstract: Although metal intoxication after arthroplasty causes various symptoms, polyneuropathy has never been the focus of clinical investigation. We report the case of a 56-year-old woman with metal neuropathy. She had metallosis after hip arthroplasty with a cobalt-chromium alloy prosthesis. She developed progressive sensory disturbance, hearing loss, and hypothyroidism. Sural nerve biopsy indicated axonopathy. After exchange arthroplasty, blood levels of cobalt and chromium decreased, and her symptoms improved. Cobalt or chromium can cause axonopathy.
136 citations
TL;DR: The results strongly suggest that leucine supplementation attenuates muscle wasting induced by immobilization via minimizing gene expression of E3 ligases, which consequently could downregulate UPS‐driven protein degradation.
Abstract: The aim of this study was to assess the effect of leucine supplementation on elements of the ubiquitin-proteasome system (UPS) in rat skeletal muscle during immobilization. This effect was evaluated by submitting the animals to a leucine supplementation protocol during hindlimb immobilization, after which different parameters were determined, including: muscle mass; cross-sectional area (CSA); gene expression of E3 ligases/deubiquitinating enzymes; content of ubiquitinated proteins; and rate of protein synthesis. Our results show that leucine supplementation attenuates soleus muscle mass loss driven by immobilization. In addition, the marked decrease in the CSA in soleus muscle type I fibers, but not type II fibers, induced by immobilization was minimized by leucine feeding. Interestingly, leucine supplementation severely minimized the early transient increase in E3 ligase [muscle ring finger 1 (MuRF1) and muscle atrophy F-box (MAFbx)/atrogin-1] gene expression observed during immobilization. The reduced peak of E3 ligase gene expression was paralleled by a decreased content of ubiquitinated proteins during leucine feeding. The protein synthesis rate decreased by immobilization and was not affected by leucine supplementation. Our results strongly suggest that leucine supplementation attenuates muscle wasting induced by immobilization via minimizing gene expression of E3 ligases, which consequently could downregulate UPS-driven protein degradation. It is notable that leucine supplementation does not restore decreased protein synthesis driven by immobilization.
128 citations
TL;DR: The possibility that the incidence of DSP may be reduced with avoidance of stavudine‐containing regimens in older subjects, especially with a history of prior TB infection is raised.
Abstract: The purpose was to estimate the frequency, characteristics, and risk factors of HIV-associated distal sensory polyneuropathy (DSP) among South Africans who attend an urban community-based clinic. In a cross-sectional study, neuropathy status was determined in 598 HIV-infected adults using validated tools (Brief Peripheral Neuropathy Screen and a modified version of the Total Neuropathy Score) to categorize subjects as DSP versus no DSP. Symptomatic DSP (SDSP) required the presence of at least two neuropathic signs together with symptoms. Clinical, anthropometric, and laboratory evaluations were prospectively performed. CD4 counts, antiretroviral therapy (ART), and questionnaires regarding previous tuberculosis (TB) and alcohol exposure were collected retrospectively. Approximately half (49%) of the study population were diagnosed with DSP, and 30% of the study population were diagnosed with SDSP. In multivariate analyses the odds ratio (OR) (95% confidence interval) of DSP were independently associated with ART use (OR 1.7, 1.0–2.9), age (per 10 year increment) (OR 1.7, 1.4–2.2), and prior TB (OR 2.0, 1.3–3.0). Pain or paresthesias were reported as moderately severe by 70% of those with SDSP. Stavudine use was significantly associated with DSP. DSP is a clinically significant problem in urban HIV-infected Africans. Our findings raise the possibility that the incidence of DSP may be reduced with avoidance of stavudine-containing regimens in older subjects, especially with a history of prior TB infection. Muscle Nerve, 2010
TL;DR: A positive correlation was found in young and elderly adults between the coefficient of variation (CV) of center of pressure during quiet standing and the CV of force during plantar flexion only at contraction intensities of ≤5% maximum voluntary contraction that corresponded to muscle activity during quietStanding.
Abstract: To investigate the functional significance of force fluctuations during voluntary contraction with a select muscle group, we examined the association between force fluctuations during voluntary contraction with plantar flexor muscles and postural sway during quiet standing in 20 young and 20 elderly adults. Young and elderly subjects maintained a quiet standing position on a force platform. They also performed a force-matching task with unilateral isometric plantar flexion. A positive correlation was found in young and elderly adults between the coefficient of variation (CV) of center of pressure during quiet standing and the CV of force during plantar flexion only at contraction intensities of < or =5% maximum voluntary contraction that corresponded to muscle activity during quiet standing. The electromyogram power in the medial gastrocnemius was greater in the elderly than in young adults by approximately 10 Hz during quiet standing and at low contraction intensities during plantar flexion. Fluctuations in motor output during low-intensity plantar flexion were associated with postural sway during quiet standing in both young and elderly adults.
TL;DR: CRP levels were increased in the CSF of ALS patients, and cystatin C level correlated with survival in patients with limb‐onset disease, and the biomarker panel predicted ALS with an overall accuracy of 82%.
Abstract: Recent studies using mass spectrometry have discovered candidate biomarkers for amyotrophic lateral sclerosis (ALS) However, those studies utilized small numbers of ALS and control subjects Additional studies using larger subject cohorts are required to verify these candidate biomarkers Cerebrospinal fluid (CSF) samples from 100 patients with ALS, 100 disease control, and 41 healthy control subjects were examined by mass spectrometry Sixty-one mass spectral peaks exhibited altered levels between ALS and controls Mass peaks for cystatin C and transthyretin were reduced in ALS, whereas mass peaks for posttranslational modified transthyretin and C-reactive protein (CRP) were increased CRP levels were 584 +/- 101 ng/ml for controls and 1124 +/- 152 ng/ml for ALS subjects, as determined by enzyme-linked immunoassay This study verified prior mass spectrometry results for cystatin C and transthyretin in ALS CRP levels were increased in the CSF of ALS patients, and cystatin C level correlated with survival in patients with limb-onset disease Our biomarker panel predicted ALS with an overall accuracy of 82%
TL;DR: Sixty days of moderate‐ to high‐dose CoQ10 treatment had minor effects on cycle exercise aerobic capacity and post‐exercise lactate but did not affect other clinically relevant variables such as strength or resting lactate.
Abstract: Case reports and open-label studies suggest that coenzyme Q(10) (CoQ(10)) treatment may have beneficial effects in mitochondrial disease patients; however, controlled trials are warranted to clinically prove its effectiveness. Thirty patients with mitochondrial cytopathy received 1200 mg/day CoQ(10) for 60 days in a randomized, double-blind, cross-over trial. Blood lactate, urinary markers of oxidative stress, body composition, activities of daily living, quality of life, forearm handgrip strength and oxygen desaturation, cycle exercise cardiorespiratory variables, and brain metabolites were measured. CoQ(10) treatment attenuated the rise in lactate after cycle ergometry, increased (∽1.93 ml) VO(2)/kg lean mass after 5 minutes of cycling (P < 0.005), and decreased gray matter choline-containing compounds (P < 0.05). Sixty days of moderate- to high-dose CoQ(10) treatment had minor effects on cycle exercise aerobic capacity and post-exercise lactate but did not affect other clinically relevant variables such as strength or resting lactate.
TL;DR: It is demonstrated that the phenotype with FUS mutations extends beyond classical ALS cases, and there are specific clinicogenetic correlations and the first detailed neuropathological description is provided.
Abstract: Mutations in the fused in sarcoma (FUS) gene have recently been found to cause familial amyotrophic lateral sclerosis (FALS). We screened FUS in a cohort of 200 ALS patients [32 FALS and 168 sporadic ALS (SALS)]. In one FALS proband, we identified a mutation (p.R521C) that was also present in her affected daughter. Their clinical phenotype was remarkably similar and atypical of classic ALS, with symmetric proximal pelvic and pectoral weakness. Distal weakness and upper motor neuron features only developed late. Neuropathological examination demonstrated FUS-immunoreactive neuronal and glial inclusions in the spinal cord and many extramotor regions, but no TDP-43 pathology. We also identified a novel mutation (p.G187S) in one SALS patient. Overall, FUS mutations accounted for 3% of our non-SOD1, non-TARDBP FALS cases and 0.6% of SALS. This study demonstrates that the phenotype with FUS mutations extends beyond classical ALS cases. Our findings suggest there are specific clinicogenetic correlations and provide the first detailed neuropathological description.
TL;DR: H2O2 may be an important initiator of these signaling pathways that lead to muscle atrophy in skeletal muscle during disuse atrophy.
Abstract: We examined reactive oxygen species as upstream activators of nuclear factor kappaB; (NF-kappaB) and forkhead box O (Foxo) in skeletal muscle during disuse atrophy. Catalase, an enzyme that degrades H2O2, was overexpressed in soleus muscles via plasmid injection prior to 7 days of hindlimb immobilization. The increased catalase activity abolished immobilization-induced transactivation of both NF-kappaB and Foxo and attenuated the loss of muscle mass. Thus, H2O2 may be an important initiator of these signaling pathways that lead to muscle atrophy.
TL;DR: Results show that aged regenerating nerve is sensitive to IGF‐1 treatment, and significantly improved axon number, diameter, and density.
Abstract: Age is an important predictor of neuromuscular recovery after peripheral nerve injury. Insulin-like growth factor 1 (IGF-1) is a potent neurotrophic factor that is known to decline with increasing age. The purpose of this study was to determine if locally delivered IGF-1 would improve nerve regeneration and neuromuscular recovery in aged animals. Young and aged rats underwent nerve transection and repair with either saline or IGF-1 continuously delivered to the site of the nerve repair. After 3 months, nerve regeneration and neuromuscular junction morphology were assessed. In both young and aged animals, IGF-1 significantly improved axon number, diameter, and density. IGF-1 also significantly increased myelination and Schwann cell activity and preserved the morphology of the postsynaptic neuromuscular junction (NMJ). These results show that aged regenerating nerve is sensitive to IGF-1 treatment.
TL;DR: A simple, reliable, easily used tool to define the clinical expression of FSHD is developed and longitudinal studies will assess its sensitivity and utility in measuring changes for widespread use.
Abstract: To define numerically the clinical severity of facioscapulohumeral muscular dystrophy (FSHD), we developed a protocol that quantifies muscle weakness by combining the functional evaluation of six muscle groups affected in this disease. To validate reproducibility of the protocol, 69 patients were recruited. Each patient was evaluated by at least five neurologists, and an FSHD severity score was given by each examiner. The degree of agreement among clinicians' evaluations was measured by kappa-statistics. Nineteen subjects received a score between 0 and 1, 9 had a score between 2 and 4, 20 received a score between 5 and 10, and 8 had a score between 11 and 15. Of the 13 subjects with D4Z4 alleles within the normal range (ranging from 10 to 150 repeats), 12 obtained a score of 0 and only 1 had a score of 1. Kappa-statistics showed a very high concordance for all muscle groups. We developed a simple, reliable, easily used tool to define the clinical expression of FSHD. Longitudinal studies will assess its sensitivity and utility in measuring changes for widespread use.
TL;DR: Relative drop from baseline paralleled the clinical course and was greater than the drop of other markers of disease progression, and MUNIX measurements in multiple muscles are suitable for serial neurophysiologic investigations in ALS.
Abstract: Motor unit number estimation techniques in amyotrophic lateral sclerosis (ALS) patients are technically challenging and time-consuming. The Motor Unit Number Index (MUNIX) is a novel technique based on surface-EMG recordings and requires only 3-5 minutes per muscle. The objective was to explore the feasibility of longitudinal MUNIX measurements in ALS patients. In seven patients enrolled in a clinical trial, eight muscles were studied every 2 months for up to 15 months in addition to the revised ALS-functional rating scale, slow vital capacity, and compound muscle action potentials. The method was well tolerated and easy to perform. Initial MUNIX measures were significantly reduced compared to controls (487 +/- 194 vs. 1459 +/- 113; P < 0.001). Relative drop from baseline paralleled the clinical course and was greater than the drop of other markers of disease progression. MUNIX measurements in multiple muscles are suitable for serial neurophysiologic investigations in ALS. Further longitudinal data are needed for reliability validation.
TL;DR: The largest CSA measurement is the most valuable ultrasonographic measurement both for diagnosis and determining the severity of UNE.
Abstract: The aim of this study was to determine the diagnostic value of ultrasonographic measurements in ulnar neuropathy at the elbow (UNE) and to assess the relationship between the measurements and the electrophysiological severity. The largest anteroposterior diameter (LAPD) and cross-sectional area (CSA) measurements of the ulnar nerve were noted at multiple levels along the arm, and the distal-to-proximal ratios were calculated. Almost all of the measurements and swelling ratios between patients and controls showed statistically significant differences. The largest CSA, distal/largest CSA ratio, CSA at the epicondyle, and proximal LAPD had larger areas under the curve than other measurements. The sensitivity and specificity in diagnosing UNE were 95% and 71% for the largest CSA, 83% and 85% for the distal/largest CSA ratio, 83% and 81% for the CSA at the epicondyle, and 93% and 43% for the proximal LAPD, respectively. There was a statistically significant correlation between the electrophysiological severity scale score (ESSS) and the largest CSA, the CSA at the epicondyle and 2 cm proximal to the epicondyle, and the LAPD at the level of the epicondyle (P < 0.05). None of the swelling ratios showed a significant correlation with the ESSS. The largest CSA measurement is the most valuable ultrasonographic measurement both for diagnosis and determining the severity of UNE.
TL;DR: The results suggest that HPR is the favored protocol for training, and LPR is better suited for prolonged stimulation.
Abstract: We present a low-frequency stimulation method via multi-pad electrodes for delaying muscle fatigue. We compared two protocols for muscle activation of the quadriceps in paraplegics. One protocol involved a large cathode at 30 HZ (HPR, high pulse-rate), and the other involved four smaller cathodes at 16 HZ (LPR, low pulse-rate). The treatment included 30-min daily sessions for 20 days. One leg was treated with the HPR protocol and the other with the LPR protocol. Knee-joint torque was measured before and after therapy to assess the time interval before the knee-joint torque decreased to 70% of the initial value. The HPR therapy provided greater increases in muscle endurance and force in prolonged training. Yet the LPR stimulation produced less muscle fatigue compared to the HPR stimulation. The results suggest that HPR is the favored protocol for training, and LPR is better suited for prolonged stimulation.
TL;DR: It is believed that severe survival motor neuron (SMN) deficiency may present as vasculopathy in patients with severe SMA type I who had only one SMN2 copy and developed ulcerations and necroses of the fingers and toes.
Abstract: Infantile spinal muscular atrophy (SMA) caused by homozygous SMN1 gene deletions/mutations is characterized by neuronal loss and axonopathy of motor neurons. We report two unrelated patients with severe SMA type I who had only one SMN2 copy and developed ulcerations and necroses of the fingers and toes. Sural nerve biopsy was normal in patient 1, whose affected skin displayed necroses and thrombotic occlusions of small vessels. Corresponding to a mouse model and other patients with similar findings, we believe that severe survival motor neuron (SMN) deficiency may present as vasculopathy.
TL;DR: It is suggested that patients presenting acutely with a demyelinating polyneuropathy and the aforementioned clinical features should be closely monitored as they may be more likely to have CIDP at follow‐up.
Abstract: Up to 16% of chronic inflammatory demyelinating polyneuropathy (CIDP) patients may present acutely We performed a retrospective chart review on 30 acute inflammatory demyelinating polyneuropathy (AIDP) and 15 acute-onset CIDP (A-CIDP) patients looking for any clinical or electrophysiological parameters that might differentiate AIDP from acutely presenting CIDP A-CIDP patients were significantly more likely to have prominent sensory signs They were significantly less likely to have autonomic nervous system involvement, facial weakness, a preceding infectious illness, or need for mechanical ventilation With regard to electrophysiological features, neither sural-sparing pattern, sensory ratio >1, nor the presence of A-waves was different between the two groups This study suggests that patients presenting acutely with a demyelinating polyneuropathy and the aforementioned clinical features should be closely monitored as they may be more likely to have CIDP at follow-up
TL;DR: Patients with refractory MG appeared to respond to rituximab in this small, retrospective study, and this result suggests that a larger, prospective trial is indicated.
Abstract: Myasthenia gravis (MG) is an immune-mediated disorder with a variable response to treatment. In this study, patients with refractory MG who were treated with rituximab were identified. A review of patients referred to the Yale Neuromuscular Clinic was performed. Patients with refractory MG who were treated with rituximab were reviewed for response to treatment. Patients who had muscle-specific kinase (MuSK(+)) or acetylcholine receptor (AChR(+)) antibodies were included. Six patients were identified who met the criteria described. All patients tolerated rituximab without side effects and had a reduced need for immunosuppressants and/or improvement in clinical function. Patients with refractory MG appeared to respond to rituximab in this small, retrospective study. This result suggests that a larger, prospective trial is indicated.
TL;DR: This retrospective analysis provides class IV evidence that MMF begins to improve AChR‐positive MG after 6 months, both with prednisone and as monotherapy.
Abstract: Two recent randomized, controlled trials failed to demonstrate a benefit of mycophenolate mofetil (MMF) over prednisone in the treatment of myasthenia gravis (MG). We reviewed our experience with MMF in MG to determine whether these trials may have been unsuccessful because of their short duration and the unpredicted benefit of prednisone. We reviewed outcomes and prednisone dosage for all our acetylcholine-receptor (AChR)-antibody positive MG patients treated with MMF alone or with prednisone for at least 3 months. The percentage of patients with a desirable outcome (MG-specific Manual Muscle Test score 24 months had a desirable outcome. Prednisone dose decreased after 12 months; after 25 months, 54.5% of patients took no prednisone and 75% took <7.5 mg/day. This retrospective analysis provides class IV evidence that MMF begins to improve AChR-positive MG after 6 months, both with prednisone and as monotherapy.
TL;DR: The biomarker profile suggests iron homeostasis is disrupted in ALS patients, and changes in ferritin and transferrin appear to be indicators of ongoing inflammatory processes.
Abstract: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with complicated pathogenesis with variable presentation and disease progression. There is a critical need for a panel of biomarkers to provide clinicians and researchers with additional information. In this study, multiplex immunoassays were used to screen a number of cytokines, growth factors, and iron-related proteins. ALS patients had significantly higher plasma levels of L-ferritin and lower concentrations of transferrin when compared to healthy controls and together classified a test group of subjects with 82% accuracy. Duration of ALS symptoms correlated positively with levels of monocyte chemoattractant protein 1 (MCP-1) and negatively with levels of granulocyte-macrophage colony stimulating factor (GM-CSF). The biomarker profile suggests iron homeostasis is disrupted in ALS patients, and changes in ferritin and transferrin (Tf) appear to be indicators of ongoing inflammatory processes. The data demonstrate a plasma biomarker profile in ALS patients that may differ from published reports of cerebrospinal fluid biomarkers.
TL;DR: Maximum ulnar CMAP amplitude and area is a feasible, valid, and reliable outcome measure for use in pediatric multicenter clinical trials in SMA and has potential value as a relevant surrogate for disease status.
Abstract: Reliable outcome measures that reflect the underlying disease process and correlate with motor function in children with SMA are needed for clinical trials. Maximum ulnar compound muscle action potential (CMAP) data were collected at two visits over a 4-6-week period in children with SMA types II and III, 2-17 years of age, at four academic centers. Primary functional outcome measures included the Modified Hammer- smith Functional Motor Scale (MHFMS) and MHFMS-Extend. CMAP negative peak amplitude and area showed excellent dis- crimination between the ambulatory and non-ambulatory SMA cohorts (ROC ¼ 0.88). CMAP had excellent test-retest reliabil- ity (ICC ¼ 0.96-0.97, n ¼ 64) and moderate to strong correla- tion with the MHFMS and MHFMS-Extend (r ¼ 0.61-0.73, n ¼ 68, P < 0.001). Maximum ulnar CMAP amplitude and area is a feasible, valid, and reliable outcome measure for use in pediat- ric multicenter clinical trials in SMA. CMAP correlates well with motor function and has potential value as a relevant surrogate for disease status. Muscle Nerve 42: 703-708, 2010
TL;DR: It is found that the subcellular labeling of dysferlin colocalizes with the developing T‐tubule system, and Dysferlin‐deficient skeletal muscle is characterized by abnormally configured T-tubules.
Abstract: Mutations in the dysferlin gene cause limb-girdle muscular dystrophy type 2B, Miyoshi myopathy, and distal anterior compartment myopathy. Dysferlin mainly localizes to the sarcolemma in mature skeletal muscle where it is implicated in membrane fusion and repair. In different forms of muscular dystrophy, a predominantly cytoplasmic localization of dysferlin can be observed in regenerating myofibers, but the subcellular compartment responsible for this labeling pattern is not yet known. We have previously demonstrated an association of dysferlin with the developing T-tubule system in vitro. To investigate the role of dysferlin in adult skeletal muscle regeneration, we studied dysferlin localization at high resolution in a rat model of regeneration and found that the subcellular labeling of dysferlin colocalizes with the developing T-tubule system. Furthermore, ultrastructural analysis of dysferlin-deficient muscle revealed primary T-tubule anomalies similar to those seen in caveolin-3-deficient muscle. These findings indicate that dysferlin is necessary for correct T-tubule formation, and dysferlin-deficient skeletal muscle is characterized by abnormally configured T-tubules.
TL;DR: Electrical impedance myography is a non‐invasive, painless technique for the evaluation of neuromuscular disease, and here it is confirmed that EIM can accurately categorize patients with SMA.
Abstract: Electrical impedance myography (EIM) is a non-invasive, painless technique for the evaluation of neuromuscular disease, and here we evaluate its potential application in spinal muscular atrophy (SMA). Twenty-one SMA patients and 18 healthy children underwent EIM of biceps brachii and tibialis anterior using a commercially available impedance device. Hand-held dynamometry and ultrasound assessment of subcutaneous fat thickness were also performed. All EIM parameters differed significantly between both SMA patients and normal subjects and between type 2 and type 3 SMA patients. In addition, EIM had an accuracy level as high as 93% for correctly categorizing patients as type 2 or type 3. Multiple regression analyses confirmed a strong association between EIM and dynamometry. These results confirm that EIM can accurately categorize patients with SMA. Because EIM requires no patient effort and is rapid to apply, it may serve a useful role in future SMA clinical trials.
TL;DR: It is suggested that variations in the reported incidence of PRCTS largely depend on the methods used to detect this syndrome, and that symptoms persist in a substantial number of patients 1 or more years after delivery.
Abstract: The reported incidence of pregnancy-related carpal tunnel syndrome (PRCTS) ranges from 08% to 70%, and little is known of its natural history We systematically reviewed the reported incidence of PRCTS and evaluated its natural history We identified 214 studies that fulfilled our selection criteria Six publications fulfilled the inclusion criteria Five fulfilled the incidence criteria, 3 fulfilled the natural history criteria, and 2 of the 6 publications satisfied both The reported incidence of neurophysiologically confirmed PRCTS ranged from 7% to 43%, whereas the incidence of clinically diagnosed PRCTS ranged from 31% to 62% Symptoms persisted in more than 50% of the patients after 1 year and in about 30% after 3 years Our review suggests that variations in the reported incidence of PRCTS largely depend on the methods used to detect this syndrome Our data also suggest that symptoms persist in a substantial number of patients 1 or more years after delivery