Electromyographs of the flexor digitorum profundus muscle are useful for the diagnosis of inclusion body myositis

Introduction: The frequent observation of high‐amplitude and long‐duration motor unit potentials (MUPs) in inclusion body myositis (IBM) is problematic, because it may lead to a misdiagnosis of amyotrophic lateral sclerosis (ALS). Objective: To document the diagnostic utility of EMG from the flexor digitorum profundus (FDP) muscle for IBM. Methods: Quantitative analyses of MUP parameters were performed in the FDP and biceps brachii (BB) muscles from 7 biopsy‐confirmed IBM patients. Results: In the FDP muscle, all MUP parameters were significantly decreased in IBM patients, which indicated the predominance of low‐amplitude and short‐duration MUPs in this muscle. In the BB muscle, most parameters were increased, suggesting the frequent contamination of high‐amplitude and long‐duration MUPs. Conclusions: Low‐amplitude MUPs in the FDP muscle indicate the presence of an advanced myopathy in this muscle that was extremely weak for all subjects. Examining the FDP muscle would reduce the chance of misdiagnosing IBM as ALS. Muscle Nerve 46: 181–186, 2012     

Dose response with onabotulinumtoxinA for post‐stroke spasticity: A pooled data analysis

Clinical trials demonstrate that onabotulinumtoxinA reduces upper limb post‐stroke spasticity, with therapeutic response influenced by injected dose. Individual studies provide limited insight regarding muscle group‐specific dose–response relationships. Our objective was to characterize dose–response relationships between onabotulinumtoxinA and muscle tone in specific upper limb muscles. Individual patient data from seven multicenter, randomized, double‐blind, placebo‐controlled trials were pooled. Of 544 post‐stroke patients enrolled, 362 received onabotulinumtoxinA and 182 received placebo, injected into the flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), flexor digitorum profundus (FDP), and/or biceps brachii (BB). Ashworth Scale score change at week 6 (AshworthCBL) was the primary outcome measure for muscle tone. For a broader analysis of response, AshworthCBL/onabotulinumtoxinA dosage relationships were characterized using three techniques: (1) AshworthCBL plotted as a function of onabotulinumtoxinA dose in Units (U) [dose–response curve]; (2) mean AshworthCBL per onabotulinumtoxinA dose depicting the responses seen with specific dose injection clusters/groups for each specific muscle group; and (3) onabotulinumtoxinA dose estimated to produce a mean 1‐point decrease in AshworthCBL as an indicator of clinically meaningful benefit of treatment. Increasing onabotulinumtoxinA doses produced greater AshworthCBLs (muscle tone improvements). The maximal week 6 response (E_max) model indicated a saturating dose–response relationship, with mean E_max AshworthCBL values of ‐1.48, ‐1.48, ‐0.63, ‐0.77, and ‐0.61 in the FCR, FCU, FDS, FDP, and BB, respectively. OnabotulinumtoxinA doses estimated to produce a mean 1‐point decrease in AshworthCBL were: 22.5U, 18.4U, 66.3U, 42.5U in the FCR, FCU, FDS, and FDP, respectively, and not determinable in the BB. These analyses demonstrate a saturating effect of greater muscle tone improvements with increasing onabotulinumtoxinA doses in post‐stroke spasticity patients. These findings suggest potentially effective onabotulinumtoxinA doses in selected muscle groups in this study population. © 2010 Movement Disorder Society.     

Entrapment neuropathy of the ulnar nerve at its point of exit from the flexor carpi ulnaris muscle

The ulnar nerve normally enters the flexor carpi ulnaris (FCU) proximally and anteriorly between the humeral and ulnar heads of the muscle. After an intramuscular course of several centimeters, the nerve exits the FCU distally to lie in a tissue plane between the FCU and the flexor digitorum profundus (FDP). A patient with ulnar neuropathy studied by intraoperative electroneurography demonstrated major focal conduction block at the point where the nerve exited the FCU. A fivefold increase in amplitude and reversal of a dispersed, irregular compound muscle action potential to a more normal configuration occurred with stimulation just distal to the point of exit. There was no evidence by inspection, probing, or electroneurography of compression in the retrocondylar groove or at the cubital tunnel. In a series of 100 cadaver dissections, the intermuscular septum between FCU and FDP was thick and tough in several specimens. This septum may represent a site of ulnar nerve entrapment.     

Measurement of platelet‐derived microparticle levels using an enzyme‐linked immunosorbent assay in polymyositis and dermatomyositis patients

Platelet‐derived microparticle (PDMP) levels were measured using an enzyme‐linked immunosorbent assay (ELISA) to elucidate the role of platelet activation in patients with polymyositis or dermatomyositis (PM/DM). PDMP levels in active PM/DM patients (median 13.3 U/ml, interquartile range 9.9–20.7 U/ml, n = 16) and those in patients undergoing treatment (12.1 U/ml, 7.4–16.7 U/ml, n = 12) were significantly higher than in controls (6.5 U/ml, 5.0–8.4 U/ml, n = 26, vs. active, P = 0.0001; vs. treatment, P = 0.004). In a paired sampling study, PDMP decreased significantly after glucocorticoid treatment (P = 0.04). PDMP in the active PM/DM patients correlated significantly with serum C‐reactive protein levels (r_s = 0.67, P = 0.01). These results suggest that platelets may play an important role in the inflammatory process, and that PDMP level could be a useful marker of inflammatory activity in PM/DM patients. Muscle Nerve 39: 586–590, 2009     

ALS disease onset may occur later in patients with pre‐morbid diabetes mellitus

Background Several metabolic derangements associated with diabetes mellitus type 2 (DM) have been associated with a better outcome in amyotrophic lateral sclerosis (ALS), including hyperlipidemia and obesity. Here, we tested the hypothesis that DM would have a positive effect on the motor and cognitive findings of ALS. Methods: We compared data from ALS patients with pre‐morbid DM (ALS‐DM; n = 175) versus without DM (ALS; n = 2196) with regard to the age of onset, rate of motor progression, survival, and neuropsychological test performance. Results: The age of onset was later for women, Caucasians and patients with bulbar‐onset ALS. However, we also found that after adjusting for gender, ethnicity and site of onset, DM was associated with a 4‐year later onset of ALS (ALS = 56.3, ALS‐DM = 60.3, P < 0.05). Conclusion: Diabetes mellitus type 2 may delay the onset of motor symptoms in ALS. These findings support other studies suggesting a relationship between the pathophysiology of ALS and metabolic derangements. Further investigations are needed to ascertain whether manipulating metabolic parameters would improve outcomes in ALS.     

Muscle echogenicity ratio can indicate severity of carpal tunnel syndrome

Introduction: The purpose of this study was to investigate the usefulness of the echogenicity (EI) ratio of the thenar to hypothenar muscle measured using ultrasonography in assessing the severity of carpal tunnel syndrome (CTS). Methods: Fifty‐nine hands of 30 patients electrodiagnostically confirmed as having CTS were classified into 3 subgroups (mild, moderate, and severe). The EI of the thenar and hypothenar muscles was measured with ultrasonography, and the EI ratio was calculated in the patients and 13 normal participants (26 hands). Results: The average EI ratio was higher in the CTS group than in the control group. We also found a positive correlation between the severity of CTS and a high EI ratio measured with ultrasonography. Discussion: The EI ratio of the thenar to hypothenar muscle is a useful parameter that can indicate the severity of CTS. Muscle Nerve 58 : 304–306, 2018     

Optineurin is potentially associated with TDP‐43 and involved in the pathogenesis of inclusion body myositis

S. Yamashita, E. Kimura, N. Tawara, H. Sakaguchi, T. Nakama, Y. Maeda, T. Hirano, M. Uchino and Y. Ando (2013) Neuropathology and Applied Neurobiology 39, 406–416 Optineurin is potentially associated with TDP‐43 and involved in the pathogenesis of inclusion body myositis Aims: Increasing evidences suggest a similarity in the pathophysiological mechanisms of neuronal cell death in amyotrophic lateral sclerosis (ALS) and myofibre degeneration in sporadic inclusion body myositis (sIBM). The aim of this study is to elucidate the involvement of ALS‐causing proteins in the pathophysiological mechanisms in sIBM. Methods: Skeletal muscle biopsy specimens of five patients with sIBM, two with oculopharyngeal muscular dystrophy (OPMD), three with polymyositis (PM), three with dermatomyositis (DM), three with neurogenic muscular atrophy, and three healthy control subjects were examined. We analysed the expression and localization of familial ALS‐causing proteins, including transactive response DNA binding protein‐43 (TDP‐43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), Cu/Zn superoxide dismutase (SOD1) and optineurin (OPTN) by immunohistochemistry. Results: TDP‐43, OPTN and, to a lesser extent, FUS/TLS were more frequently accumulated in the cytoplasm in patients with sIBM and OPMD than in patients with PM, DM, neurogenic muscular atrophy, or healthy control subjects. SOD1 was accumulated in a small percentage of myofibres in patients with sIBM and OPMD, and to a very small extent in patients with PM and DM. Confocal microscopy imaging showed that TDP‐43 proteins more often colocalized with OPTN than with FUS/TLS, p62 and phosphorylated Tau. Conclusions: These findings suggest that OPTN in cooperation with TDP‐43 might be involved in the pathophysiological mechanisms of skeletal muscular degeneration in myopathy with rimmed vacuoles. Further investigation into these mechanisms is therefore warranted.     

Assessing the accuracy of neuromuscular ultrasound for inclusion body myositis

Introduction: Inclusion body myositis (IBM) can have clinical and electrodiagnostic features similar to other neuromuscular diseases, making it a diagnostic challenge. This prospective study was designed to determine the accuracy of forearm ultrasound for IBM. Methods: Sixty adults were recruited (15 with IBM, 15 with amyotrophic lateral sclerosis [ALS], 15 with other myopathies, and 15 healthy controls), and each underwent ultrasound of the bilateral forearms (imaging the flexor digitorum profundus and flexor carpi ulnaris muscles). Three clinicians with varying ultrasound expertise assigned a diagnosis of IBM, ALS, other myopathy, or control, based on images alone. Results: Intrarater reliability was moderately strong. Interrater reliability varied based on clinician experience. Sensitivity was 73.33% and 66.67% for the expert raters. Specificity was strong for all 3 clinicians (93.33%, 84.44%, and 91.11%). Discussion: Neuromuscular ultrasound of the forearm is reliable and accurate for the diagnosis of IBM, although sensitivity was higher among experienced clinicians. Muscle Nerve 59:478–481, 2019     

Skeletal muscle oxidative capacity in amyotrophic lateral sclerosis

Introduction: Mitochondrial dysfunction in the motor neuron has been suspected in amyotrophic lateral sclerosis (ALS). If mitochondrial abnormalities are also found in skeletal muscle, assessing skeletal muscle could serve as an important biomarker of disease progression. Methods: Using ³¹P magnetic resonance (³¹P‐MRS) and near infrared (NIRS) spectroscopy, we compared the absolute values and reproducibility of skeletal muscle oxidative capacity in people with ALS (n = 6) and healthy adults (young, n = 7 and age‐matched, n = 4). Results: ALS patients had slower time constants for phosphocreatine (PCr) and muscle oxygen consumption (mVO₂) compared with young, but not age‐matched controls. The coefficient of variation for the time constant was 10% (SD = 2.8%) and 17% (SD = 6.2%) for PCr and mVO₂, respectively. Conclusions: People with ALS had, on average, a small but not statistically significant, impairment in skeletal muscle mitochondrial function measured by both ³¹P‐MRS and NIRS. Both methods demonstrated good reproducibility. Muscle Nerve 50 : 767–774, 2014     

Inclusion‐body myositis presenting with facial diplegia

Introduction: The hallmark clinical presentation of inclusion‐body myositis (IBM) is slowly progressive weakness that characteristically affects the quadriceps and finger and wrist finger flexor muscles. Facial weakness can also occur, but it is typically mild and not a prominent finding. Methods: We describe the clinical features, laboratory investigations, and muscle biopsy findings in a 58‐year old man who presented with a 6‐year history of marked progressive symmetrical facial weakness. Examination also showed shoulder abduction and hip extensor weakness. Results: The patient's serum creatine kinase level was 655 U/L, and electromyography showed fibrillation potentials and myopathic motor unit potentials. A biopsy specimen of the left biceps muscle was pathognomonic for IBM. Conclusions: This patient did not have a typical presentation for IBM but rather fulfilled the pathological criteria for IBM. To our knowledge, facial diplegia has not been reported previously as a presenting manifestation of IBM. Muscle Nerve 49 : 287–289, 2014     

Quantitative muscle ultrasonography in the follow‐up of juvenile dermatomyositis

Introduction: We explored the use of quantitative muscle ultrasonography (QMUS) for follow‐up of juvenile dermatomyositis (JDM). Methods: Seven JDM patients were evaluated at diagnosis and 1, 3, 6, 12, and 24 months using the Childhood Myositis Assessment Scale (CMAS) and QMUS. Muscle thickness (MT) and quantitative muscle echo intensity (EI) were assessed with QMUS in 4 muscles. Results: Six patients experienced a monocyclic course. At diagnosis EI was slightly increased, and MT was relatively normal. After start of treatment MT first decreased and EI increased, with normalization of EI within 6–12 months (n = 4). One patient had higher EIs at diagnosis and slower normalization, indicating fibrosis, despite early normalization of CMAS. One patient experienced a chronic course, with high EIs and atrophy during follow‐up. Conclusions: QMUS can provide additional information for follow‐up of JDM regarding disease severity and residual muscle damage, particularly after normalization of CMAS. Muscle Nerve 52: 540–546, 2015     

In vivo assessment of muscle membrane properties in myotonic dystrophy

Introduction: Myotonia in myotonic dystrophy types 1 (DM1) and 2 (DM2) is generally attributed to reduced chloride‐channel conductance. We used muscle velocity recovery cycles (MVRCs) to investigate muscle membrane properties in DM1 and DM2, using comparisons with myotonia congenita (MC). Methods: MVRCs and responses to repetitive stimulation were compared between patients with DM1 (n = 18), DM2 (n = 5), MC (n = 18), and normal controls (n = 20). Results: Both DM1 and DM2 showed enhanced late supernormality after multiple conditioning stimuli, indicating delayed repolarization as in MC. Contrary to MC, however, DM1 showed reduced early supernormality after multiple conditioning stimuli, and weak DM1 patients also showed abnormally slow latency recovery after repetitive stimulation. Conclusions: These findings support the presence of impaired chloride conductance in both DM1 and DM2. The early supernormality changes indicate that sodium currents were reduced in DM1, whereas the weakness‐associated slow recovery after repetitive stimulation may provide an indication of reduced Na⁺/K⁺‐ATPase activation. Muscle Nerve 54 : 249–257, 2016     

Correlation of single‐breath count test and neck flexor muscle strength with spirometry in myasthenia gravis

Introduction: Although formal spirometry is the gold standard for monitoring respiratory function in patients with myasthenia gravis (MG), such testing is often delayed or unavailable. There is a need for a simple bedside test that can accurately measure respiratory function. Methods: We conducted a prospective, cross‐sectional, single‐blind study in adults with acetylcholine receptor antibody positive MG. Participants performed the single breath count test (SBCT) and underwent manual muscle strength testing, and a respiratory therapist performed spirometry blinded to SBCT and strength results. Results : Thirty‐one patients, aged 57 ± 19 years participated. SBCT showed significant correlations with forced vital capacity (FVC), negative inspiratory force, and neck flexor strength (P < 0.01). FVC showed significant correlation with neck flexor strength (P = 0.02) but no correlation with shoulder abductor strength. Conclusions: These data suggest that the SBCT and neck flexor strength testing are valuable tools for bedside assessment of respiratory function in MG patients. Muscle Nerve 53 : 134–136, 2016     

Reliability of panoramic ultrasound imaging to simultaneously examine muscle size and quality of the medial gastrocnemius

Introduction: In this study we examined the test–retest reliability of panoramic brightness‐mode ultrasound (US) imaging to simultaneously measure both muscle size and quality from a single US image. Methods: Sixteen healthy, recreationally active men (age = 20.9 ± 2.5 years) volunteered for this investigation. Test–retest reliability was evaluated using intraclass correlation coefficients (ICCs) and the standard error of measurement as a percentage of the mean (SEM%). Muscle size [cross‐sectional area (CSA)], and muscle quality [echo intensity (EI)] of the medial gastrocnemius were examined on 2 separate days. Results: These measures demonstrated acceptable reliability between assessment days with ICCs and SEM% of 0.914 and 0.720 and 5.830 and 3.680 for CSA and EI, respectively. Conclusions: These results suggest that panoramic US imaging may be a reliable technique for simultaneous assessment of both muscle size and quality from a single US scan. Muscle Nerve 49 : 736–740, 2014     

Sarcolemmal excitability in the myotonic dystrophies

Introduction: Chloride conductance disturbances contribute to sarcolemmal dysfunction in myotonic dystrophy type 1 (DM1) and type 2 (DM2). Studies using muscle velocity recovery cycles (MVRCs) suggest Na⁺/K⁺‐adenosine triphosphatase activation becomes defective in advanced DM1. We used MVRCs to investigate muscle excitability in DM1 and DM2. Methods: MVRCs were measured for patients with mild (n = 8) and advanced (n = 11) DM1, DM2 (n = 4), and normal controls (n = 30). Results: Residual supernormality after multiple conditioning stimuli was increased in DM2 and advanced DM1. Advanced DM1 was distinguished by increases in muscle relative refractory period (MRRP) and reduced early supernormality as well as peak amplitude decrements for the first and last responses in train during repetitive stimulation. Discussion: Prolongation of the MRRP indicates that depolarization of the resting muscle membrane potential occurs in advanced DM1, with possible implications for future therapeutic approaches. Muscle Nerve 57 : 595–602, 2018     

Impact of expiratory strength training in amyotrophic lateral sclerosis

Introduction: We evaluated the feasibility and impact of expiratory muscle strength training (EMST) on respiratory and bulbar function in persons with amyotrophic lateral sclerosis (ALS). Methods: Twenty‐five ALS patients participated in this delayed intervention open‐label clinical trial. Following a lead‐in period, patients completed a 5‐week EMST protocol. Outcome measures included: maximum expiratory pressure (MEP); physiologic measures of swallow and cough; and penetration–aspiration scale (PAS) scores. Results: Of participants who entered the active phase of the study (n = 15), EMST was well tolerated and led to significant increases in MEPs and maximum hyoid displacement during swallowing post‐EMST (P < 0.05). No significant differences were observed for PAS scores or cough spirometry measures. Conclusions: EMST was feasible and well tolerated in this small cohort of ALS patients and led to improvements in expiratory force‐generating pressures and swallow kinematics. Further investigation is warranted to confirm these preliminary findings. Muscle Nerve 54 : 48–53, 2016     

Effect of strength training on regional hypertrophy of the elbow flexor muscles

Introduction: Muscle hypertrophy is the main structural adaptation to strength training. We investigated the chronic effects of strength training on muscle hypertrophy in different regions of the elbow flexor muscles. Methods: Eleven untrained men (21.8 ± 1.62 years) underwent magnetic resonance imaging to determine the proximal, medial, distal, and mean cross‐sectional areas (CSA) of the elbow flexors. The volunteers completed 12 weeks of strength training. The training protocol consisted of 4 sets of 8–10 maximum repetitions of unilateral elbow flexion. The interval between sets was 120 s. The training frequency was 3 sessions per week. Results: The magnetic resonance images verified the presence of significant and similar hypertrophy in the distal, medial, and proximal portions of the elbow flexor muscles. Conclusions: Muscle hypertrophy may be assessed using only the medial CSA. We should not expect different degrees of hypertrophy among the regions of the elbow flexor muscles. Muscle Nerve 54 : 750–755, 2016     

Further observations on forearm flexor weakness in inclusion body myositis

In order to further characterize and provide a possible mechanism for the asymmetrical involvement of forearm muscles in inclusion body myositis (IBM), we measured isometric hand and pinch grip strength, and forearm muscle girth on 15 IBM patients. Forearm muscle strength and girth were significantly greater on the dominant versus nondominant side: mean grip strength, 173.9 vs. 98.8 N; mean pinch strength, 47.6 vs. 29.7 N; and mean forearm girth, 22.5 vs. 19.9 cm. This observation may suggest a role for exercise in delaying the disease progression in IBM. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:659–661, 1998.     

Quantitative neuromuscular ultrasound in intensive care unit–acquired weakness: A systematic review

Intensive care unit–acquired weakness (ICU‐AW) causes significant morbidity and impairment in critically ill patients. Recent advances in neuromuscular ultrasound (NMUS) allow evaluation of neuromuscular pathology early in critical illness. Here we review application of ultrasound in ICU‐AW. MEDLINE‐indexed articles were searched for terms relevant to ultrasound and critical illness. Two reviewers evaluated the resulting abstracts (n = 218) and completed full‐text review (n = 13). Twelve studies and 1 case report were included. Ten studies evaluated muscle thickness or cross‐sectional area (CSA): 8 reported a decrease, and 2 reported no change. Two studies reported preservation of muscle thickness in response to neuromuscular electrical stimulation, and 1 found no preservation. One study found decreases in gray‐scale standard deviation, but no change in echogenicity. One study described increases in echogenicity and fasciculations. Ultrasound reliability in ICU‐AW is not fully established. Further investigation is needed to identify ultrasound measures that reliably predict clinical, electrodiagnostic, and pathologic findings of ICU‐AW. Muscle Nerve 52 : 701–708, 2015     

Pre‐morbid type 2 diabetes mellitus is not a prognostic factor in amyotrophic lateral sclerosis

Introduction: The aim of this study was to determine whether a history of pre‐morbid type 2 diabetes mellitus (DM2) is a prognostic factor in amyotrophic lateral sclerosis (ALS). Methods: The relationship between DM2 and survival was analyzed in a study population consisting of 1,322 participants from 6 clinical trials. Results: Survival did not differ by diabetes status (log‐rank test, P = 0.98), but did differ by body mass index (BMI) (log‐rank test, P = 0.008). In multivariate analysis, there was no significant association between diabetes and survival (P = 0.18), but the risk of reaching a survival endpoint decreased by 4% for each unit increase in baseline BMI (HR 0.96, 95% CI 0.94–0.99, P = 0.001). DM2 was less prevalent among ALS clinical trial participants than predicted. Conclusions: A history of pre‐morbid DM2 is not an independent prognostic factor in ALS clinical trial databases. The low DM2 prevalence rate should be examined in a large, prospective study to determine whether DM2 affects ALS risk. Muscle Nerve 52:339–343, 2015