Thigh magnetic resonance imaging for the evaluation of disease activity in patients with idiopathic inflammatory myopathies followed in a single center

Introduction: In patients with idiopathic inflammatory myopathies (IIM), magnetic resonance imaging (MRI) has been proposed as a useful tool for diagnosis and follow‐up. It may identify muscle inflammation (edema) and fatty infiltration for evaluation of disease activity and damage. Little information is available on the role of MRI in assessment of large cohorts of adult patients with IIM. Methods: Fifty‐one patients underwent MRI of the thigh muscles, laboratory tests, and clinical evaluation, including Physician Global Assessment (PGA) of myositis activity and the Manual Muscle Test 8 (MMT8). Results: Muscle edema correlated significantly with creatine kinase values (P = 0.017) and PGA (P < 0.001). A significant correlation between edema and MMT8 values (P = 0.025) was observed when patients with muscle fatty infiltration were excluded. With respect to clinical diagnosis, the sensitivity of MRI was 92.3%, and specificity was 83.3%. Conclusions: MRI appears to provide additional information that complements clinical and biochemical examinations. Muscle Nerve 54 : 666–672, 2016     

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     

Clinical and imaging hallmarks of the MYH7‐related myopathy with severe axial involvement

Introduction: MYH7 gene mutations are related to a heterogeneous group of skeletal and cardiac myopathies. Methods: We evaluated clinical and muscle MRI changes in patients with mutations in the rod domain of MYH7, including 1 with mosaicism and 3 with novel missense mutations. Results: Patients presented in childhood with a distal and axial phenotype. Biopsy findings were variable. Half of the cases displaying some type of core pathology, including minicores and eccentric cores. Most patients demonstrated internal bands of infiltration (“inverted‐collagen‐VI sign”) in multiple muscles, particularly the soleus, and prominent atrophy and fatty infiltration of the tongue and the paraspinal, gluteus minimus, sartorius, gracilis, tibialis anterior, and extensor digitorum longus muscles. Discussion: Muscle imaging findings in patients with axial involvement provide significant clues permitting the distinction between MYH7‐related myopathies and other axial myopathies such as those related to SEPN1 and LMNA genes. Muscle Nerve 58 : 224–234, 2018     

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     

Vasculitic neuropathy: Comparison of clinical predictors with histopathological outcome

Introduction:To improve diagnostic accuracy, in this study we compared prebiopsy clinical parameters with subsequent pathological confirmation of peripheral nerve vasculitis. Methods: Clinical, laboratory, and neurophysiological parameters were analyzed for consecutive patients referred for nerve biopsy with suspected vasculitis. Patients were assigned pathological categories of definite, probable, possible, or absent vasculitis using validated guidelines. Patients with definite or probable vasculitis were considered to have pathologically confirmed vasculitis. Results: From a cohort of 78 patients, biopsy confirmed vasculitis in 29.5%. Parameters that best differentiated between pathologically confirmed and pathologically unlikely vasculitis were stepwise clinical progression (34.8% vs. 5.6%), the presence of serum anti-myeloperoxidase antibody (28.6% vs. 2.2%) and rheumatoid factor seropositivity (38.1% vs. 10.7%). Pathologically absent vasculitis was frequent in patients with normal (100%) or primarily demyelinating (87.5%) nerve conduction studies. Discussion: Factoring the negative predictors of pathologically confirmed vasculitis into decision-making can reduce the frequency of diagnostically unhelpful nerve biopsies. Muscle Nerve 59:643–649, 2019     

Longitudinal 2‐point dixon muscle magnetic resonance imaging in becker muscular dystrophy

Introduction: Quantitative MRI techniques detect disease progression in myopathies more sensitively than muscle function measures or conventional MRI. To date, only conventional MRI data using visual rating scales are available for measurement of disease progression in Becker muscular dystrophy (BMD). Methods: In 3 patients with BMD (mean age 36.8 years), the mean fat fraction (MFF) of the thigh muscles was assessed by MRI at baseline and at 1‐year follow‐up using a 2‐point Dixon approach (2PD). The motor function measurement scale (MFM) was used for clinical assessment. Results: The mean MFF of all muscles at baseline was 61.6% (SD 7.6). It increased by 3.7% to 65.3% (SD 4.7) at follow‐up. The severity of muscle involvement varied between various muscle groups. Conclusions: As in other myopathies, 2PD can quantify fatty muscle degeneration in BMD and can detect disease progression in a small sample size and at relatively short imaging intervals. Muscle Nerve 51 : 918–921, 2015     

Neurophysiological techniques to detect early small‐fiber dysfunction in transthyretin amyloid polyneuropathy

Introduction: Transthyretin familial amyloid polyneuropathy (TTR‐FAP) is characterized by early selective involvement of small nerve fibers. Initial clinical diagnosis is complicated by psychosocial factors. We evaluated diagnostic accuracy of sural sensory nerve action potentials, plantar sympathetic skin response (SSR), and cortical laser‐evoked potentials (LEP) to dorsal foot stimulation in the early diagnosis of TTR‐FAP.Methods: Sixty‐three subjects with TTR‐FAP (Val30Met) mutation were split into 2 groups (asymptomatic carriers and early‐symptomatic patients) and compared with 33 healthy controls. Results: The diagnostic accuracy of plantar SSR amplitude and LEP N2 latency was similar; all had very high specificity (94 to 97%) but low sensitivity (22 to 32%) in distinguishing controls from carriers and early‐symptomatic patients. No control had abnormal results on both tests. Conclusions: Plantar SSR and LEPs have similar diagnostic performance in detecting small‐fiber dysfunction in early TTR‐FAP; we propose that both tests should be used to investigate this population. Muscle Nerve 49 : 181–186, 2014     

Cytoplasmic 5′‐nucleotidase autoantibodies in inclusion body myositis: Isotypes and diagnostic utility

Introduction: Recent studies have identified circulating immunoglobulin (Ig) G autoantibodies against cytoplasmic 5′‐nucleotidase 1A (cN1A; NT5C1A) in patients with inclusion body myositis (IBM), whose detection provides for an IBM blood diagnostic test. Whether or not anti‐cN1A autoantibody isotypes other than IgG are present in IBM has not previously been reported. Methods: Plasma and serum samples from 205 patients (50 with and155 without IBM) were studied for the presence of IgM and IgA, in addition to IgG, anti‐cN1A autoantibodies using immunoblots and enzyme‐linked immunoassays (ELISAs). Results: IgM, IgA, and IgG anti‐cN1A autoantibodies were detected by ELISA with similar sensitivities (49–53%) and specificities (94–96%), but with differing patterns of autoantibody isotype presence. Combination assays of all 3 autoantibody levels improved diagnostic sensitivity to 76%. Conclusions: In addition to previously recognized IgG anti‐cN1A autoantibodies, IBM patients have circulating IgM and IgA anti‐cN1A autoantibodies. Differing patterns of these isotypes may be present and useful for diagnosis. Muscle Nerve 50 : 488–492, 2014     

Neuroimaging of classic neuralgic amyotrophy

Introduction: Neuralgic amyotrophy (NA) often imposes diagnostic problems. Recently, MRI and high‐resolution ultrasound (HRUS) have proven useful in diagnosing peripheral nerve disorders. Methods: We performed a chart and imaging review of patients who were examined using neuroimaging and who were referred because of clinically diagnosed NA between March 1, 2014 and May 1, 2015. Results: Six patients were included. All underwent HRUS, and 5 underwent MRI. Time from onset to evaluation ranged from 2 weeks to 6 months. HRUS showed segmental swelling of all clinically affected nerves/trunks. Atrophy of muscles was detected in those assessed >1 month after onset. MRI showed T2‐weighted hyperintensity in all clinically affected nerves, except for the long thoracic nerve, and denervation edema of muscles. Conclusions: HRUS and MRI are valuable diagnostic tools in NA. This could change the diagnostic approach from one now focused on excluding other disorders to confirming NA through imaging markers. Muscle Nerve 54 : 1079–1085, 2016     

Muscle magnetic resonance imaging and histopathology in ACTA1‐related congenital nemaline myopathy

Introduction: Muscle biopsy is usually diagnostic in nemaline myopathy (NM), but some patients may show nonspecific findings, leading to pitfalls in diagnosis. Muscle MRI is a helpful complementary tool. Methods: We assessed the clinical, histopathological, MRI, and molecular findings in a 19‐year‐old patient with NM in whom 2 muscle biopsies with ultrastructural examination showed no nemaline bodies. We analyzed the degree and pattern of muscle MRI involvement of the entire body, including the tongue and pectoral muscles. Results: Muscle MRI abnormalities in sartorius, adductor magnus, and anterior compartment muscles of the leg suggested NM. A previously unreported fatty infiltration of the tongue was found. A third biopsy after the muscle MRI showed scant nemaline bodies. A novel heterozygous de novo ACTA1 c.611C>T/p.Thr204Ile mutation was detected. Conclusions: We highlight the contribution of muscle imaging in addressing the genetic diagnosis of ACTA1‐related NM. Muscle Nerve 50: 1011–1016, 2014     

Heterogeneous characteristics of MRI changes of thigh muscles in patients with dysferlinopathy

Introduction: The aim of this study was to evaluate the pattern of thigh muscle MRI changes in a large cohort of patients with dysferlinopathy. Methods: MRI of the thigh was performed in 60 patients. We correlated the scale of muscle involvement on MRI with the modified Gardner‐Medwin and Walton (GM‐W) scale and disease duration. We also analyzed the relationship between muscle changes and genetic mutations. Results: Fatty infiltration and edema were observed in 95.50% and 86.67% of patients, respectively. The hamstring muscles had the highest frequency and mean score of fatty infiltration, although a posterior‐dominant pattern was found in only 56%. Edema most commonly and severely affected the quadriceps and adductor magnus muscles. Fatty infiltration score correlated positively with disease duration and GM‐W scale. Conclusions: The pattern of fatty infiltration was heterogeneous in dysferlinopathy patients. Muscle edema was common. Fatty infiltration can be used to assess disease progression. Muscle Nerve 54 : 1072–1079, 2016     

Electrical impedance myography in the diagnosis of radiculopathy

Introduction: We sought to determine whether electrical impedance myography (EIM) could serve as a diagnostic procedure for evaluation of radiculopathy. Methods: Twenty‐seven patients with clinically and radiologically diagnosed cervical or lumbosacral radiculopathy who met a “gold standard” definition underwent EIM and standard needle electromyography (EMG) of multiple upper or lower extremity muscles. Results: EIM reactance values revealed consistent reductions in the radiculopathy‐affected myotomal muscles as compared with those on the unaffected side; the degree of asymmetry was associated strongly with the degree of EMG abnormality (P < 0.001). EIM had a sensitivity of 64.5% and a specificity of 77.0%; in comparison, EMG had a sensitivity of 79.7% but a specificity of 69.7%. Conclusions: These findings support the potential for EIM to serve as a new non‐invasive tool to assist in diagnosis of radiculopathy; however, further refinement of the technique is needed for this specific application. Muscle Nerve 48:800–805, 2013     

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     

Camptocormia as presenting manifestation of a spectrum of myopathic disorders

Introduction: Camptocormia is the involuntary flexion of the thoracolumbar spine leading to an abnormal posture. Methods: We retrospectively identified patients with myopathy who manifested with camptocormia and were seen in our neuromuscular clinic. The diagnosis of myopathy was based on myopathic electromyographic changes, often accompanied by 1 or more of the following: elevated creatine kinase (CK); myopathic histopathological findings; and genetic confirmation. Results: Fifty‐two patients were identified; 35 had symptoms limited to camptocormia, but were found to have additional weakness of facial (8 patients), neck (11 patients), and limb muscles (17 patients). CK values were normal or mildly to moderately elevated. MRI/CT of the spine showed paraspinal muscle atrophy and fat replacement. Facioscapulohumeral muscular dystrophy and sporadic inclusion body myositis were the most commonly identified myopathies in this cohort. Conclusions: Despite the difficulty in characterizing the myopathy in patients with camptocormia, a definitive diagnosis was possible in 54% of cases. The pattern of associated extra‐axial weakness may provide clues to the diagnosis. Muscle Nerve 52 : 1008–1012, 2015     

Combining MRI and muscle biopsy improves diagnostic accuracy in subacute‐onset idiopathic inflammatory myopathy

Introduction: In 10–20% of patients with subacute‐onset idiopathic inflammatory myopathy (IIM), muscle biopsy is normal or shows nonspecific findings. MRI can be used as a triage test before muscle biopsy and as an add‐on test if the biopsy is nondiagnostic. Methods: MRI scans of skeletal muscles and muscle biopsies were evaluated prospectively in 48 patients suspected to have IIM. The interpretations of MRI and muscle biopsy were compared with the definite diagnosis (based on European Neuromuscular Centre criteria and response to corticosteroids). Results: The false negative rate (FNR) of all muscle biopsies was 0.23. Biopsies of a muscle showing hyperintensity on MRI (as triage test) had an FNR of 0.19. The result of MRI as an add‐on test in patients with a nondiagnostic muscle biopsy decreased the FNR from 0.23 to 0.06. Conclusions: We recommend both MRI and muscle biopsy in patients suspected of having IIM. Muscle Nerve 51 : 253–258, 2015     

Diagnostic accuracy of concentric needle jitter in myasthenia: Prospective study

Introduction: The aim of this study was to estimate jitter parameters in the orbicularis oculi muscle using a concentric needle electrode (CNE) in patients with myasthenia gravis (MG) and to determine its diagnostic accuracy for jitter analysis (CNEMG‐jitter). Methods: CNEMG‐jitter was performed in 20 healthy subjects and 33 MG patients using the voluntary contraction technique. Receiver operating characteristic (ROC) curves were constructed to determine cut‐off points with the best sensitivity/specificity combination for jitter analysis. Results: CNEMG‐jitter yielded high positivity rates for ocular MG (92.3%) and generalized MG (100%). The ROC curve cut‐off point that provided the highest sensitivity without false positives was 24.7 μs for mean jitter and 33.1 μs for the 18th highest value. Sensitivity was 93.9% for both parameters. Diagnostic accuracy of CNEMG‐jitter was > 96%. Conclusions: CNEMG‐jitter yielded high sensitivity and specificity rates. Our reference values were lower than previously published values, possibly due to less technical variation between the different recordings. Muscle Nerve 55 : 190–194, 2017     

The role of cranial and thoracic electromyography within diagnostic criteria for amyotrophic lateral sclerosis

Introduction: The contribution of cranial and thoracic region electromyography (EMG) to diagnostic criteria for amyotrophic lateral sclerosis (ALS) has not been evaluated. Methods: Clinical and EMG data from each craniospinal region were retrospectively assessed in 470 patients; 214 had ALS. Changes to diagnostic classification in Awaji‐Shima and revised El Escorial criteria after withdrawal of cranial/thoracic EMG data were ascertained. Results: Sensitivity for lower motor neuron involvement in ALS was highest in the cervical/lumbar regions; specificity was highest in cranial/thoracic regions. Cranial EMG contributed to definite/probable Awaji‐Shima categorization in 1.4% of patients. Thoracic EMG made no contribution. For revised El Escorial criteria, cranial and thoracic data reclassified 1% and 5% of patients, respectively. Conclusion: Cranial EMG data make small contributions to both criteria, whereas thoracic data contribute only to the revised El Escorial criteria. However, cranial and thoracic region abnormalities are specific in ALS. Consideration should be given to allowing greater diagnostic contribution from thoracic EMG. Muscle Nerve 54 : 378–385, 2016     

Rigid spine syndrome associated with sensory‐motor axonal neuropathy resembling Charcot–Marie‐Tooth disease is characteristic of Bcl‐2‐associated athanogene‐3 gene mutations even without cardiac involvement

Introduction: Bcl‐2‐associated athanogene‐3 (BAG3) mutations have been described in rare cases of rapidly progressive myofibrillar myopathies. Symptoms begin in the first decade with axial involvement and contractures and are associated with cardiac and respiratory impairment in the second decade. Axonal neuropathy has been documented but usually not as a key clinical feature. Methods: We report a 24‐year‐old woman with severe rigid spine syndrome and sensory‐motor neuropathy resembling Charcot–Marie–Tooth disease (CMT). Results: Muscle MRI showed severe fat infiltration without any specific pattern. Deltoid muscle biopsy showed neurogenic changes and discrete myofibrillar abnormalities. Electrocardiogram and transthoracic echocardiography results were normal. Genetic analysis of a panel of 45 CMT genes showed no mutation. BAG3 gene screening identified the previously reported c.626C>T, pPro209Leu, mutation. Discussion: This case indicates that rigid spine syndrome and sensory‐motor axonal neuropathy are key clinical features of BAG3 mutations that should be considered even without cardiac involvement. Muscle Nerve, 57 : 330–334, 2018     

Sural sparing pattern discriminates Guillain–Barré syndrome from its mimics

Introduction: Electrodiagnostic features of demyelination are essential for establishing the diagnosis in demyelinating subtypes of Guillain‐Barré syndrome (GBS), but they may also occur in disorders that mimic GBS clinically. Information about their frequency in GBS mimics is sparse. Methods: Evaluation of electrodiagnostic features from 38 patients with suspected GBS in whom the diagnosis was later refuted (GBS mimics). Their diagnostic accuracy was analyzed by comparison with nerve conduction studies (NCS) from 73 confirmed GBS patients. Results: Disorders that mimicked GBS clinically at the time of hospital admission included other inflammatory, metabolic, toxic, or infectious neuropathies and spinal cord disorders. The sural sparing pattern was the most specific electrodiagnostic feature for demyelinating GBS. Conclusions: Common electrodiagnostic abnormalities in early demyelinating GBS do not usually exclude other rare differential diagnoses. An exception to this is the sural sparing pattern described here, which strongly supports the diagnosis of demyelinating GBS. Muscle Nerve 50 : 780–784, 2014