Anatomic variation of the innervation of the flexor digitorum profundus muscle and its clinical implications

In anterior interosseous nerve syndrome and ulnar neuropathy, paralysis or weakness of the flexor digitorum profundus (FDP) muscles has been shown to vary according to the degree of involvement of the median and ulnar nerves, respectively. We traced these nerves in 50 cadaveric specimens in which each FDP was completely separated. The specimens were classified into six anatomic and another six presumptive electromyography (EMG) types according to the innervation patterns of the entire and the proximal one‐third of the FDP muscles, respectively. The diverse anatomic and presumptive EMG types in this study suggest that the FDP muscles of the 2nd to the 5th digits should be examined by functional tests and EMG in lesions of the median or ulnar nerve. Muscle Nerve, 2009     

Contrasting echogenicity in flexor digitorum profundus–flexor carpi ulnaris: A diagnostic ultrasound pattern in sporadic inclusion body myositis

Introduction: In this study we aimed to clarify whether muscle ultrasound (US) of the forearm can be used to differentiate between patients with sporadic inclusion body myositis (s‐IBM) and those with s‐IBM–mimicking diseases. Methods: We compared the echo intensity (EI) of the flexor digitorum profundus (FDP) muscle and the flexor carpi ulnaris (FCU) muscles in patients with s‐IBM (n = 6), polymyositis/dermatomyositis (PM/DM; n = 6), and amyotrophic lateral sclerosis (ALS; n = 6). Results: We identified EI abnormalities in 100% of patients with s‐IBM, 33% of those with PM/DM, and 33% of those with ALS. An “FDP–FCU echogenicity contrast,” a US pattern involving a higher EI in the FDP than in the FCU, was observed in all patients with s‐IBM, but in none of those with PM/DM or ALS. Conclusions: FDP–FCU echogenicity contrast in muscle US is a sensitive diagnostic indicator of s‐IBM. Muscle Nerve 49 : 745–748, 2014     

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.     

TREX1 mutations are not associated with sporadic inclusion body myositis

Background: Sporadic inclusion body myositis (sIBM) is the most frequent acquired myopathy above the age of fifty. The exact mechanism causing this disease is not known, but immune‐mediated features are prominent and are probably to play a role in its pathogenesis. TREX1 gene mutations are associated with a large range of autoimmune diseases, such as systemic lupus erythematosus. We investigated whether mutations in the TREX1 gene were associated with sIBM. Methods: Fifty‐four patients with sIBM were tested for TREX1 mutations by direct sequencing. Results: All 54 patients tested negative for pathogenic mutations in the TREX1 gene. One presumed non‐pathogenic polymorphism was found in 42 out of 54 patients. Conclusion: TREX1 mutations do not play a role in the pathogenesis of sIBM.     

包涵体肌炎的临床与病理特点(附2例报告)

目的 探讨包涵体肌炎的临床与病理特点。方法 对2例包涵体肌炎患者的临床表现、肌肉组织化学、酶组织化学和超微结构等资料进行分析。结果 本组2例患者分别于41岁及54岁发病,均以双下肢无力起病,远端重于近端,并逐渐向上肢发展;血清肌酶轻～中度升高;肌电图示肌源性损害;肌肉活检光镜下主要表现为肌纤维内出现镶边空泡,少数变性坏死纤维,伴炎性细胞浸润。电镜观察证实肌浆内有大量涡轮状髓样小体及管状细丝包涵体。结论 包涵体肌炎临床表现缺乏特异性,肌肉病理学检查是诊断包涵体肌炎的重要手段。     

Physical function and muscle strength in sporadic inclusion body myositis

Introduction: In this study, self‐reported physical function, functional capacity, and isolated muscle function were investigated in sporadic inclusion body myositis (sIBM) patients. Methods: The 36‐item Short Form (SF‐36) Health Survey and 2‐min walk test (2MWT), timed up & go test (TUG), and 30‐s chair stand performance were evaluated. In addition, patients were tested for knee extensor muscle strength (isokinetic dynamometer) and leg extension power (Nottingham power rig). Results: TUG performance was the strongest predictor of self‐reported physical function (r ² = 0.56, P < 0.05). Knee extension strength and between‐limb strength asymmetry were the strongest multi‐regression indicators of TUG performance (r ² = 0.51, P < 0.05). Strength asymmetry showed the strongest single‐factor (negative) association with 2MWT performance (r ² = 0.49, P < 0.05). Discussion: TUG assessment appears to sensitively predict self‐perceived physical function in sIBM patients. Notably, between‐limb asymmetry in lower limb muscle strength had a substantial negative impact on motor tasks involving gait function. Muscle Nerve 56 : E50–E58, 2017     

Electrophysiological spectrum of inclusion body myositis

We present electrodiagnostic data on 30 patients with inclusion body myositis (IBM) in order to better delineate its electrophysiological features. Comprehensive electromyography (EMG) and nerve conduction studies (NCS) were performed in all cases. Twelve patients had single fiber electromyography (SFEMG). EMG showed abundant short-small motor unit potentials (MUP) with fibrillations and positive sharp waves in 56.6% of patients, and a mixed pattern of large and small MUP in 36.7%. In 6.7%, only "neurogenic" features were seen. NCS were slow in 33.3%. SFEMG revealed a mildly abnormal jitter and a slightly increased fiber density. IBM demonstrates a heterogeneous EMG profile. A pattern of large and small MUP is highly suggestive of IBM but is seen in only about one third of cases.     

Medication of inclusion body myositis: a systematic review

To investigate the existing evidence on the effectiveness of approaches to treating inclusion body myositis and to assess the methodological quality of this evidence. The Cochrane Controlled Trials Register (CENTRAL), Medline, Embase, Cinahl, Physiotherapy Evidence (Pedro), McMaster and Web of Science databases were searched. The references of identified articles and reviews were also checked for relevancy. The methodological quality was assessed according to the Cochrane Collaboration's domain‐based evaluation framework. Of the 331 identified records, 10 were considered relevant for a qualitative analysis. The risk of bias was considered being low for six studies and high for four. Eight studies were randomized controlled trials, and two were controlled clinical trials. In the samples, male gender predominated, and the mean age of the participants varied from 51 to 72 years. The duration of intervention varied from 3 to 17 months. One small trial on the effect of oxandrolone reported a significant positive result. The other trials observed no improvement or insignificant improvement among the participants treated with intravenous immunoglobulin, methotrexate, etanercept or interferon. Thus far, there is no evidence indicating that any specific treatment is the effective in treating inclusion body myositis.     

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     

Sarcoplasmic redistribution of nuclear TDP‐43 in inclusion body myositis

The nucleic acid binding protein TDP‐43 was recently identified in normal myonuclei and in the sarcoplasm of inclusion body myositis (IBM) muscle. Here we found TDP‐43 sarcoplasmic immunoreactivity in 23% of IBM myofibers, while other reported IBM biomarkers were less frequent, with rimmed vacuoles in 2.8%, fluorescent Congo red material in 0.57%, SMI‐31 immunoreactivity in 0.83%, and focal R1282 beta‐amyloid immunoreactivity in 0.00% of myofibers. The presence of as little as >1% of myofibers with nonnuclear sarcoplasmic TDP‐43 was highly sensitive (91%) and specific (100%) to IBM among 50 inflammatory myopathy patient samples, although some patients with hereditary inclusion body myopathies and myofibrillar myopathy also had sarcoplasmic TDP‐43. TDP‐43 mutations were sought, and none were identified. TDP‐43 could be one of many nucleic acid binding proteins that are abnormally present in IBM sarcoplasm. They could potentially interfere with the normal function of extranuclear RNAs that maintain myofiber protein production. Muscle Nerve 40: 19–31, 2009     

Demographic and clinical features of inclusion body myositis in north America

Introduction: Few studies of the demographics, natural history, and clinical management of inclusion body myositis (IBM) have been performed in a large patient population. To more accurately define these characteristics, we developed and distributed a questionnaire to patients with IBM. Methods: A cross‐sectional, self‐reporting survey was conducted. Results: The mean age of the 916 participants was 70.4 years, the male‐to‐female ratio was 2:1, and the majority reported difficulty with ambulation and activities of daily living. The earliest symptoms included impaired use and weakness of arms and legs. The mean time from first symptoms to diagnosis was 4.7 years. Half reported that IBM was their initial diagnosis. A composite functional index negatively associated with age and disease duration, and positively associated with participation in exercise. Conclusions: These data are valuable for informing patients how IBM manifestations are expected to impair daily living and indicate that self‐reporting could be used to establish outcome measures in clinical trials. Muscle Nerve 52: 527–533, 2015     

Tau aggregates are abnormally phosphorylated in inclusion body myositis and have an immunoelectrophoretic profile distinct from other tauopathies

Sporadic inclusion body myositis (s-IBM) is the most frequent progressive acquired inflammatory myopathy in people older than 50 years. Abnormal aggregates of 'Alzheimer's proteins', including tau proteins, have been previously demonstrated in s-IBM. In the present study, we have investigated by immunohistochemistry and immunoblotting analysis the presence of tau proteins in muscle biopsy samples from patients with s-IBM and other myopathies with rimmed vacuoles, using newly developed antibodies raised against tau protein epitopes found in Alzheimer's disease brain. Tau immunoreactivity was shown in rimmed vacuoles or inclusions, preferentially with antibodies directed against phosphorylated carboxy-terminal epitopes of tau proteins. Cytoplasmic reactivity was also demonstrated in atrophic, nonvacuolated fibres, as well as in non-necrotic fibres invaded by inflammatory cells. Abnormally phosphorylated tau aggregates were also found in other compartments of the muscle fibre in s-IBM and other myopathies. Tau immunoblotting showed an electrophorectic profile of a doublet within the range of 60–62 kDa isovariants, which was different from tauopathies of the central nervous system. Finally, the unique pattern of immunoreactivity of s-IBM samples towards anti-tau antibodies is a new clue to a possible distinct subclass of peripheral tauopathy, different from the tauopathies of the central nervous system.     

Safety and efficacy of strength training in patients with sporadic inclusion body myositis

We studied the effects of a 12-week progressive resistance strength training program in weakened muscles of 5 patients with sporadic inclusion body myositis (IBM). Strength was evaluated with Medical Research Council (MRC) scale ratings and quantitative isometric and dynamic tests. Changes in serum creatine kinase (CK), lymphocyte subpopulations, muscle size (determined by magnetic resonance imaging), and histology in repeated muscle biopsies were examined before and after training. After 12 weeks, the values of repetition maximum improved in the least weakened muscles, 25–120% from baseline. This dynamic effect was not captured by MRC or isometric muscle strength measurements. Serum CK, B cells, T-cell subsets, and NK cells remained unchanged. Repeat muscle biopsies did not reveal changes in the number and degree of degenerating fibers or inflammation. The size of the trained muscles did not change. We conclude that a supervised progressive resistance training program in IBM patients can lead to gains in dynamic strength of the least weak muscles without causing muscle fatigue and muscle injury or serological, histological, and immunological abnormalities. Even though the functional significance of these gains is unclear, this treatment modality is a safe and perhaps overlooked means of rehabilitation of IBM patients. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 1242–1248, 1997     

Expression of Bcl-2 in inclusion body myositis

OBJECTIVES: On the background of the possible role of the anti-apoptotic protein Bcl-2 to inhibit apoptosis induced by the Fas/Fas ligand system in inflammatory myopathies we investigated the expression of Bcl-2 in inclusion body myositis (IBM). MATERIAL AND METHODS: We examined muscle tissue from seven IBM patients and controls by immunocytochemistry using antibodies against Bcl-2, Fas (a member of the tumor necrosis factor receptor family) and the regeneration marker, neural cell adhesion molecule (N-CAM). We also investigated the occurrence of DNA fragmentation by the terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL)-method. RESULTS: Both Bcl-2 and Fas were up-regulated in muscle fibers in IBM and disease controls. Bcl-2 was expressed by regenerating muscle fibers while Fas was expressed by non-regenerating muscle fibers associated with inflammatory cell infiltrates. Bcl-2 and Fas were also expressed by inflammatory cells. There were scattered TUNEL positive nuclei and most of these appeared to be inflammatory cells. CONCLUSION: The low occurrence of apoptotic myonuclei is not related to Bcl-2 expression, which is confined to regenerating muscle cells in IBM and other myopathies.     

Patterns of muscle involvement in inclusion body myositis: clinical and magnetic resonance imaging study.

The differential patterns of muscle involvement in the upper and lower limbs in sporadic inclusion body myositis (sIBM) were examined in 18 patients using both quantitative and manual muscle testing as well as magnetic resonance imaging (MRI) in 9 patients. Weakness of the quadriceps femoris and the forearm flexors was present in most patients, but there was considerable variability in the patterns and severity of muscle involvement. MRI disclosed preferential patterns of muscle involvement within functional groups such as the quadriceps femoris, in which there was severe involvement of the vasti with relative sparing of the rectus femoris, and the triceps surae, in which selective involvement of the medial gastrocnemius was common. Involvement of flexor digitorum profundus on MRI was found in only one third of patients. The results emphasize the variability in the clinical phenotype and differential susceptibility of muscles to the disease process in sIBM.     

Sleep disordered breathing and subclinical impairment of respiratory function are common in sporadic inclusion body myositis

Relatively little is known about frequency and extent of respiratory problems in sporadic inclusion body myositis (IBM). To address this issue a study of peripheral muscle and respiratory function and related symptoms was performed in a cohort with biopsy-proven IBM. Dyspnoea, daytime sleepiness, dysphagia, spirometry, respiratory muscle strength, arterial blood gas tensions and ventilation during sleep were assessed. Sixteen patients were studied (10 males; age 68.1 ± 9.9 years; disease duration 11.9 ± 5.0 years; body mass index 28.5 ± 4.0 kg/m²). Four reported excessive daytime sleepiness; 8 had at least mild dysphagia; forced vital capacity was <80% predicted normal in 7; sniff nasal inspiratory pressure was reduced in 3; daytime hypoxemia was present in 9 and hypercapnia in one. Sleep study was performed in 15 and revealed sleep disordered breathing (apnoea–hypopnoea index 23.4 ± 12.8 (range 7–50.3) events/h) in all. There were no consistent relationships between respiratory function impairment, occurrence of sleep disordered breathing, and severity of peripheral muscle weakness. Thus, asymptomatic impairment of respiratory function was common and sleep disordered breathing observed in all patients tested, irrespective of daytime respiratory function. This suggests respiratory function testing, including sleep study, should be performed routinely in IBM, irrespective of peripheral muscle function or other disease severity parameters.