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A 40-year-old man presented with slowly progressive weakness and eyelid droopiness. His symptoms began in his early 30s as increased fatigue with exertion. In his mid 30s, he developed droopy eyelids without double vision. About 3 years before presentation, he started having progressive difficulty swallowing, initially with solid food but later with both solid and liquid consistencies. He also reported the food getting stuck in his throat. He had been treated for aspiration pneumonia once. A year later, he noticed slowly progressive limb weakness affecting his hands and proximal lower limbs, described as difficulty holding a tablet at church, frequently dropping objects from his hands, and difficulty with standing up from a seated position. More recently, he started experiencing dyspnea on exertion and mild orthopnea. He occasionally experienced blurry vision without diplopia, mild head drop, and hoarseness of voice, mainly towards the end of the day or when he was tired. He was diagnosed with seronegative myasthenia gravis at a local facility, with negative acetylcholine receptor, muscle-specific kinase, and low-density lipoprotein receptor-related protein 4 antibodies. His medical and social history were otherwise unremarkable. The patient's father was French Canadian. The patient also had Native American and African American ancestry. There was no family history of myopathy or any neuromuscular disorder. Neurologic examination was significant for moderate bilateral ptosis, bilateral ophthalmoparesis with limited upward gaze and to a lesser extent horizontal gaze (both eye abduction and adduction), mild weakness of both upper and lower facial muscles, moderate weakness of the proximal lower extremities most prominent at the hip abductors (Medical Research Council [MRC] grade 3 to 4-/5), and mild (MRC grade 4) weakness of finger extensors and intrinsic hand muscles. He had no demonstrable fatigable weakness on examination in any of the affected muscles. He had a mildly waddling gait and absent ankle jerks bilaterally. Sensory and coordination evaluations were unremarkable.

Variable differences of nerve conduction amplitudes vs velocities and distal latencies (DLs) of healthy subjects assessed in ethnic cohorts. Introduction/aims The variables affecting reference compound muscle (CMAP) and sensory nerve action potential (SNAP) amplitudes as compared to ones affecting conduction velocities and DLs have not been adequately evaluated in previous studies. In this report, this subject is studied in healthy subject cohorts mainly of Northern European extraction, Northern Plains Indians, and Latinos. Methods Nineteen variables and 18 attributes of nerve conductions (NCs) were assessed using highly standard testing conditions and techniques. Classification and Regression Tree analyses were used to assess variable differences among amplitudes, conduction velocities, and DLs. Results The most important variable affecting CMAP and SNAP amplitudes was age. For conduction velocities (CVs) and DLs, the variables were height, ethnic cohort, and age. Discussion The variables affecting attributes of NCs were similar for the three ethnic cohorts evaluated. The differences of variables affecting amplitudes compared to CVs and DLs need to be taken into account in interpretation of NC results and in setting reference limits for use in medical practice, epidemiology surveys, and therapeutic trials. Scores of CMAP and SNAP amplitudes are suitable measures of sensorimotor polyneuropathy severity, whereas conduction velocities and DLs reflect physiologic/pathologic abnormality of nerve fibers.

Granulomatous myopathies are etiologically heterogeneous myopathies, pathologically characterized by the presence of intramuscular granulomas. Treatment outcomes are variable. We aimed to identify prognostic factors of treatment outcomes in myopathies featuring non-caseating granulomas. Sixteen patients were identified (9 sarcoid myopathy, 6 inclusion body myositis, and 1 granulomatous myopathy of indeterminate cause) over a 21-year period. The median age at diagnosis was 67 years in sarcoid myopathy group, and 64 years in inclusion body myositis group. Three inclusion body myositis patients were initially diagnosed with sarcoid myopathy based on the presence of systemic features of sarcoidosis and findings on muscle biopsies, but subsequent biopsies performed because of treatment refractoriness, showed all canonical pathologic features of inclusion body myositis. We identified sarcoplasmic congophilic inclusions in 6 sarcoid myopathy patients without associated rimmed vacuoles or typical weakness pattern of inclusion body myositis. Four inclusion body myositis and 4 of 5 sarcoid myopathy patients with congophilic inclusions were refractory to immunotherapy. Our study portrays the overlapping clinical and pathological features of sarcoid myopathy and inclusion body myositis. The presence of sarcoplasmic congophilic inclusions in sarcoid myopathy may predict an unfavorable outcome of immunosuppressive therapy, but a larger prospective study is required to further validate this observation.

Recently, guidelines have been outlined for management of immune-related adverse events occurring with immune checkpoint inhibitors in cancer, irrespective of affected organ systems. Increasingly, these complications have been recognized as including diverse neuromuscular presentations, such as demyelinating and axonal length–dependent peripheral neuropathies, vasculitic neuropathy, myasthenia gravis, and myopathy. We present 2 cases of brachial plexopathy developing on anti–programmed cell death-1 checkpoint inhibitor therapies (pembrolizumab, nivolumab). Both cases had stereotypic lower-trunk brachial plexus–predominant onsets, and other clinical features distinguishing them from Parsonage-Turner syndrome (ie, idiopathic plexitis). Each case responded to withholding of anti–programmed cell death-1 therapy, along with initiation of high-dose methylprednisiolone therapy. However, both patients worsened when being weaned from corticosteroids. Discussed are the complexities in the decision to add a second-line immunosuppressant drug, such as infliximab, when dealing with neuritis attacks, for which improvement may be prolonged, given the inherent slow recovery seen with axonal injury. Integrated care with oncology and neurology is emphasized as best practice for affected patients.

Introduction Although peripheral neuropathy and cardiomyopathy are well-recognized manifestations of transthyretin (ATTR) amyloidosis, myopathy has been rarely reported. Methods In this study we reviewed our muscle biopsy database (January 1998 to June 2018) to identify patients with ATTR amyloid myopathy confirmed by molecular or proteomic analysis. Clinical and laboratory findings were reviewed. Results We identified eight ATTR amyloid myopathy patients (5 hereditary ATTR [ATTRv] and 3 wild-type ATTR [ATTRwt]). Myopathy was the initial manifestation in all ATTRwt patients and followed peripheral neuropathy (4 patients) or cardiomyopathy (1 patient) in ATTRv patients. One ATTRv patient developed myopathy after liver transplant. Peripheral neuropathy and cardiac amyloidosis occurred in seven and six patients, respectively. Muscle biopsy showed interstitial amyloid deposition in all patients, rare necrotic/regenerating fibers in six, and vacuoles in four. Discussion Myopathy can be the initial manifestation of ATTRwt amyloidosis and can precede the peripheral neuropathy or occur after liver transplant in ATTRv amyloidosis.

We read with great interest the recent article by Dr. Dieudonne et al.1 The authors reported the high prevalence of sporadic inclusion body myositis (SIBM) in patients with granulomatous myositis, and a significant proportion of these SIBM patients also had systemic features suggestive of sarcoidosis. Their observation is similar to what we previously reported.2 In addition, we found that the majority of treatment-refractory granulomatous myositis patients had sarcoplasmic congophilic deposits, including those who did not fulfill the ENMC diagnostic criteria of SIBM. Although this was not statistically significant, the presence of congophilic aggregates—regardless of the diagnosis of SIBM—could be an indicator of treatment refractoriness. Dr. Dieudonne et al. analyzed the protein accumulation using TDP43 or p62 immunoreactivity, but we are not certain whether congo red stain was performed. We would appreciate if they can share their experience with congo red stain in their cohort because this is more widely available stain in routine clinical practice when compared with TDP43 and p62 immunostains. Last but not least, given the similar results of 2 relatively large cohorts of granulomatous myositis,1,2 an epidemiologic study looking into the incidence of SIBM in sarcoidosis could be of clinical interest.

Dropped head syndrome can be the presenting feature of a wide spectrum of neurological conditions. In this study, we aimed to define the clinical characteristics and treatment outcomes of 107 patients, where head drop was the presenting or predominant clinical feature of a myopathy. Median age at presentation was 68 years (range 42–88). A specific diagnosis was reached in 53% of patients: Inflammatory myopathy (n = 16), myopathy with rimmed vacuoles (n = 10), radiation-induced myopathy (n = 8), sporadic late-onset nemaline myopathy (n = 7), myofibrillar myopathy (n = 4), facioscapulohumeral dystrophy (n = 3), inclusion body myositis (n = 2), mitochondrial myopathy (n = 2), scleroderma-associated myopathy (n = 2), and single cases of necrotizing autoimmune myopathy, drug-induced myopathy, and B-cell chronic lymphocytic leukemia-myopathy. Splenius capitis had the highest diagnostic yield for a muscle biopsy (67%). When tested, 31/35 (89%) of patients had abnormal pulmonary function tests, 15/30 (50%) abnormal swallow evaluation, 24/65 (37%) abnormal electrocardiogram and 5/38 (13%) abnormal transthoracic echocardiogram. 23/43 (53%) treated patients responded to treatment. Patient-reported limb weakness and neck flexion weakness on physical examination were associated with good response to treatment. A wide spectrum of acquired and hereditary myopathies can present with head drop, some of which are potentially treatable. Establishing a diagnosis is crucial for timely treatment administration, screening for swallowing and cardiorespiratory involvement, and counseling regarding prognosis.