Shahar, Shelly

Abstract Background and purpose Elevation of serum creatine kinase (CK) or hyperCKemia is considered a biological marker of myopathies. However, selective elevation of serum aldolase with normal CK has been reported in a few myopathies, including dermatomyositis, immune‐mediated myopathy with perimysial pathology and fasciitis with associated myopathy. The aim was to investigate the disease spectrum of myopathies with isolated aldolase elevation. Methods Medical records were reviewed to identify patients >18 years old seen between December 1994 and June 2020 who had pathologically proven myopathies with elevated aldolase and normal CK level. Patients with alternative causes of aldolase elevation were excluded. Results Thirty‐four patients with various types of myopathies were identified. Myopathies were treatable in 27 patients. The three most common etiologies were dermatomyositis ( n = 8), overlap myositis ( n = 4) and nonspecific myopathy ( n = 4). Perimysial pathology comprising inflammation, fragmentation, vasculitis, calcified perimysial vessels or extracellular amyloid deposition was found in 17/34 patients (50%). Eight dermatomyositis patients with selective elevated aldolase were compared to 24 sex‐ and age‐matched patients with dermatomyositis and hyperCKemia. Dermatomyositis patients with normal CK significantly ( p < 0.05) had less frequent cutaneous involvement (50.0% vs. 100.0%) and fibrillation potentials (50.0% vs. 90.5%) but higher median erythrocyte sedimentation rate (33.5 vs. 13.5 mm/h) and more common perifascicular mitochondrial pathology (37.5% vs. 4.2%). Conclusion Isolated aldolase elevation can be found in a greater variety of myopathies than initially thought and most were treatable. Dermatomyositis is the most common myopathy with selective elevation of aldolase in our cohort, which features some unique characteristics compared to dermatomyositis with hyperCKemia.

AbstractIntroduction/AimsAmyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disorder of motor neurons in which the cause is mostly unknown. Early identification of genetic ALS cases, of which C9ORF72 (C9ALS) is the most frequent, can have important implications for evaluation, prognosis, and therapeutics. Here, we aimed to characterize the clinical and electrophysiological hallmarks of C9ALS and investigate differences from C9ORF72 negative ALS (non‐C9ALS).MethodsWe retrospectively reviewed clinical and electrodiagnostic (EDX) data for all genetically confirmed C9ALS cases seen between 1/1/2012 and 10/1/2020 who met Gold Coast criteria and compared them 1:1 with non‐C9ALS patients within the same time frame.ResultsA total of 99 C9ALS and 99 non‐C9ALS cases were identified. Compared to non‐C9ALS, C9ALS demonstrated higher prevalence in women, lesser racial variability, stronger family history of ALS, and higher frequency of upper motor neuron signs. EDX testing of C9ALS showed higher median sensory nerve and lower fibular compound muscle action potential amplitudes.DiscussionAlthough the differences between C9ALS and non‐C9ALS reached statistical significance in certain nerve conduction parameters, they were not sufficient to discriminate between groups on a case‐by‐case basis. Genetic testing is required to identify C9ALS patients.

AbstractObjectivesTo investigate immune-mediated necrotizing myopathy (IMNM) association with cancer and its clinical implications.MethodsIMNM cases were identified 1 January 2000 to 31 December 2020 matching sex and age controls (4:1).ResultsA total of 152 patients with IMNM were identified and among serologically tested, 60% (83/140) were HMGCR-IgG+, 14% (20/140) were SRP-IgG+ and 26% (37/140) were seronegative. Cancer rates were not significantly different between serological subgroups; 18.1% (15/83) HMGCR-IgG+, 25% (5/20) SRP-IgG+ and 30% (11/37) seronegative (P = 0.34). Cancer screening was performed within 12 months from IMNM diagnosis in 88% (134/152) (whole-body CT plus FDG-PET CT in 53, CT alone in 72 and FDG-PET alone in 9). FDG-PET/CT was positive in 73% (25/34) of cancers. Increasing age was the only risk associated with cancer (P = 0.02). The odds of developing cancer at ±3 or ±5 years from IMNM diagnosis was not higher than controls (OR = 0.49; CI: 0.325–0.76). Lifetime IMNM diagnosis of cancer was less compared with controls (OR = 0.5 CI: 0.33–0.78, P = 0.002). Most patients responded to treatment (137/147, P &lt; 0.001). Death and treatment response did not significantly differ between cancer [23% (8/34); 88% (29/33)] and non-cancer patients [19% (23/118); 92% (108/118)]. In total, 13% (20/152) of patients died during follow-up compared with 14% (41/290) of medicine and 16% (46/290) of neurology controls (P = 0.8). Seropositives had greater life expectancy than seronegatives (P = 0.01).ConclusionsGreater cancer risk is not observed in IMNM vs controls. Cancer screening in IMNM should be individualized based on age-personal and family history, including consideration of FDG-PET/CT. Immune-treatment response did not differ with cancer.

AbstractIntroduction/AimsImmune‐mediated necrotizing myopathy (IMNM) is considered a rare subtype of the immune‐mediated myopathies, but its incidence and prevalence are unknown. In this study we aimed to determine the incidence and prevalence of IMNM among adults in Olmsted County, Minnesota.MethodsWe identified adult patients with IMNM, as defined by the 2016 European Neuromuscular Centre diagnostic criteria, among residents of Olmsted County, Minnesota over a 20‐year period.ResultsSeven patients fulfilled the inclusion criteria. Six patients were tested for IMNM antibodies: four were anti–3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) positive, one was anti–signal recognition particle positive, and one was seronegative. The incidence of IMNM during 2010‐2019 was 8.3 per million person‐years. The prevalence of IMNM in 2010 was 1.85 per 100 000 people at least 50 years of age. Median age at symptom onset was 64 (range, 52‐86) years and median time from symptom onset to diagnosis was 3 (range, <1 to 156) months. Statin use among anti‐HMGCR IMNM patients, but not the entire IMNM cohort, was higher than in controls (P = .024). Two IMNM patients developed cancers. The incidence of malignancy in IMNM was not higher than that of the general population. Treatment outcome was favorable in all patients except for one patient with delayed treatment and another with insufficient therapy. Among three deceased patients, one died of cancer and another died of IMNM‐related cardiorespiratory complications.DiscussionIMNM is a rare disease. Its prevalence is one tenth that of inclusion‐body myositis in Olmsted County, Minnesota. IMNM patients in our cohort were not at higher risk for developing cancer.

AbstractIntroduction/AimsRecently, our group found an association between diabetes mellitus (DM) and lumbosacral radiculoplexus neuropathy (LRPN) in Olmsted County, Minnesota; we found a higher risk (odds ratio [OR], 7.91) for developing LRPN in diabetic compared with nondiabetic patients. However, the influence of other comorbidities and anthropomorphic variables was not studied.MethodsDemographic and clinical data from 59 LRPN patients and 177 age/sex‐matched controls were extracted using the Rochester LRPN epidemiological study. Differences between groups were compared by chi‐square/Fisher exact test or Wilcoxon rank‐sum test. Uni‐ and multivariate logistic regression analysis were performed.ResultsFactors predictive of LRPN on univariate analysis were DM (OR, 7.91; 95% confidence interval [CI], 4.11‐15.21), dementia (OR, 6.36; 95% CI, 1.13‐35.67), stroke (OR, 3.81; 95% CI, 1.32‐11.01), dyslipidemia (OR, 2.844; 95% CI, 1.53‐5.27), comorbid autoimmune disorders (OR, 2.72; 95% CI, 1.07‐6.93), hypertension (OR, 2.25; 95% CI, 1.2‐4.13), obesity (OR, 2.05; 95% CI, 1.11–3.8), body mass index (BMI) (OR, 1.1; 95% CI, 1.04‐1.15), and weight (OR, 1.02; 95% CI, 1.009‐1.037). On multivariate logistic regression analysis only DM (OR, 8.03; 95% CI, 3.86‐16.7), comorbid autoimmune disorders (OR, 4.58; 95% CI, 1.45‐14.7), stroke (OR, 4.13; 95% CI, 1.2‐14.25), and BMI (OR, 1.07; 95% CI, 1.01‐1.13) were risk factors for LRPN.DiscussionDM is the strongest risk factor for the development of LRPN, followed by comorbid autoimmune disorders, stroke, and higher BMI. Altered metabolism and immune dysfunction seem to be the most influential factors in the development of LRPN.

Abstract Objective To evaluate survival and associated comorbidities in inclusion body myositis (IBM) in a population-based, case-control study. Methods We utilized the expanded Rochester Epidemiology Project medical records-linkage system, including 27 counties in Minnesota and Wisconsin, to identify patients with IBM, other inflammatory myopathies (IIM), and age/sex-matched population-controls. We compared the frequency of various comorbidities and survival among groups. Results We identified 50 IBM patients, 65 IIM controls and 294 population controls. Dysphagia was most common in IBM (64%) patients. The frequency of neurodegenerative disorders (dementia/parkinsonism) and solid cancers was not different between groups. Rheumatoid arthritis was the most common rheumatic disease in all groups. A total of 36% of IBM patients had a peripheral neuropathy, 6% had Sjögren’s syndrome and 10% had a haematologic malignancy. T-cell large granular lymphocytic leukaemia was only observed in the IBM group. None of the IBM patients had hepatitis B or C, or HIV. IBM patients were 2.7 times more likely to have peripheral neuropathy, 6.2 times more likely to have Sjögren’s syndrome and 3.9 times more likely to have a haematologic malignancy than population controls. IBM was associated with increased mortality, with a 10-year survival of 36% from index, compared with 67% in IIM and 59% in population controls. Respiratory failure or pneumonia (44%) was the most common cause of death. Conclusions IBM is associated with lower survival, and higher frequency of peripheral neuropathy, Sjögren’s syndrome and haematologic malignancies than the general population. Close monitoring of IBM-related complications is warranted.