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Background and purpose: Very‐long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD) is a hereditary disorder of mitochondrial long‐chain fatty acid oxidation that has variable presentations, including exercise intolerance, cardiomyopathy and liver disease. The aim of this study was to describe the clinical and genetic manifestations of six patients with adult‐onset VLCADD. Methods: In this study, the clinical, pathological and genetic findings of six adult patients (four from Iran and two from Serbia) with VLCADD and their response to treatment are described. Results: The median (range) age of patients at first visit was 31 (27–38) years, and the median (range) age of onset was 26.5 (19–33) years. Parental consanguinity was present for four patients. Four patients had a history of rhabdomyolysis, and the recorded CK level ranged between 67 and 90 000 IU/l. Three patients had a history of exertional myalgia, and one patient had a non‐fluctuating weakness. Through next‐generation sequencing analysis, we identified six cases with variants in the ACADVL gene and a confirmed diagnosis of VLCADD. Of the total six variants identified, five were missense, and one was a novel frameshift mutation identified in two unrelated individuals. Two variants were novel, and three were previously reported. We treated the patients with a combination of L‐carnitine, Coenzyme Q10 and riboflavin. Three patients responded favorably to the treatment. Conclusion: Adult‐onset VLCADD is a rare entity with various presentations. Patients may respond favorably to a cocktail of L‐carnitine, Coenzyme Q10, and riboflavin. [ABSTRACT FROM AUTHOR]

Introduction Generic patient reported outcome measures have had varied success in tracking QoL in myotonic dystrophy type 1 ( DM1). Aim To analyze changes of Individualized Neuromuscular Quality of Life questionnaire ( INQoL) scores in clinic patients with DM1 over a 6-year period. Method Patients completed the INQoL at baseline and after a 6-year period through their attendance in a neurology outpatient clinic. Severity of muscular involvement in DM1 was analyzed using the Muscular Impairment Rating Scale ( MIRS). Results Ninety-nine DM1 patients completed a baseline visit. Sixty-seven of these patients were retested at an interval time. The overall INQoL score improved in our sample of patients ( P<.05) as did the following subscales: myotonia ( P<.05), pain ( P<.05), activities ( P<.01), social relationships ( P<.01), and body image ( P<.05). No changes were observed for the independence and emotions scales. There were no differences in mean change of INQoL scores between patients with worsened MIRS and those with no change in MIRS scale after follow-up ( P>.05). Conclusion Individualized Neuromuscular Quality of Life questionnaire scores improved in our cohort of DM1 patients during a 6-year period. INQoL score did not correlate with progression of muscle weakness. This must be better understood before the selection of the instrument for use in trials to measure therapeutic benefit in DM1 patients. [ABSTRACT FROM AUTHOR]

Background and purpose The aim was to determine the electrophysiological profile of our cohort of low density lipoprotein receptor related protein 4 ( LRP4) positive myasthenia gravis ( MG) patients. Methods A repetitive nerve stimulation ( RNS) test and jitter analysis using a concentric needle electrode were performed in 17 LRP4 positive MG patients. The results were compared to 31 muscle-specific tyrosine kinase (Mu SK) positive and 28 acetylcholine receptor ( AChR) positive MG patients. Results The RNS test was negative in almost all patients belonging to the LRP4/seronegative and LRP4/Mu SK groups. It was positive most frequently in the AChR MG patients, especially those without anti- LRP4 antibodies. The presence of anti- LRP4 antibodies was connected to lower decrement values, whilst the independent presence of anti- AChR or anti-Mu SK antibodies was connected to higher decrement values. Lowest jitter was recorded in patients with LRP4/seronegative MG. The highest percentage of pathological jitter analysis test results was present in Mu SK and AChR MG patients. The isolate presence of anti- LRP4 antibodies did not influence the mean consecutive difference values, whilst mean consecutive difference values were higher in the presence of anti- AChR or anti-Mu SK antibodies. Conclusions Low density lipoprotein receptor related protein 4 positive patients make a distinct MG subgroup with rarely detected pathological electrophysiological test results. The lack of influence of anti- LRP4 antibodies on the different electrophysiological parameters brings into question the pathogenic role of anti- LRP4 antibodies in MG. [ABSTRACT FROM AUTHOR]

Background - Myotonic dystrophy type 1 ( DM1) is the most common muscular dystrophy in adults. There is a complete lack of studies that assessed quality of life (QoL) trajectory during time in DM1 cohorts. Aim - To analyze changes of QoL in patients with DM1 during a 5-year follow-up period and to assess responsiveness of the SF-36 questionnaire. Patients and Method - At the baseline, this study comprised 84 DM1 patients, of whom 62 were retested after the mean period of 64.2 ± 3.9 months. Severity of muscular weakness was assessed using the Muscular Impairment Rating Scale ( MIRS). Patients completed Serbian version of the SF-36 questionnaire as a measure of health-related QoL. Results - After 5 years, MIRS score of our DM1 patients showed significant progression of 0.5 grade ( P < 0.01). All mental subdomains, role physical, and total SF-36 scores significantly improved after 5 years ( P < 0.01). Unexpectedly, worsening of muscular weakness from mild to severe was in association with improvement of QoL. Conclusion - QoL improved in our cohort of DM1 patients during a 5-year period despite the progression of the disease. SF-36 should be used with caution as a patient-reported outcome measure in DM1 clinical trials. [ABSTRACT FROM AUTHOR]

Background and purpose Myasthenia gravis ( MG) is an autoimmune disease but certain genetic factors predispose its development. Since susceptibility to different forms of MG is linked to a number of allelic variants, the aim of this study was to explore the human leukocyte antigen ( HLA) profile of our patients with muscle-specific tyrosine kinase (Mu SK) MG. Methods Human leukocyte antigen ( HLA) typing was performed in our cohort of 31 Mu SK MG patients available for the study. The allele groups of DRB1* and DQB1* loci were typed with sequence-specific oligonucleotide probes and high resolution typing for DQB1* was performed using sequence-specific primers. HLA frequencies were compared with unrelated healthy bone marrow donors. Results Significant association of Mu SK MG with alleles DRB1*14 [odds ratio ( OR) 3.8], DRB1*16 ( OR 3.3) ( P < 0.01) and DQB1*05 ( OR 2.2) ( P < 0.05) was found. In our patients the most frequent DQB1* allele was DQB1*05:02. An absolute absence of DRB1*13 in our cohort of Mu SK MG patients was also found, whilst this allele was present in 25% (495/1992) of control subjects ( OR 0) ( P < 0.01). The HLA DRB1*16− DQB1*05 ( OR 2.9) haplotype was found to be associated with Mu SK MG ( P < 0.05). Conclusions The strong association of Mu SK MG with DQB1*05 alleles observed in patient series from other countries was confirmed. The novel finding in our cohort of Mu SK MG patients was the absolute absence of DRB1*13 allele, which might have a protective role in the development of Mu SK MG, at least in our population. [ABSTRACT FROM AUTHOR]

Objectives To analyze frequency and type of personality pattern in patients with myotonic dystrophy type 1 ( DM1), to correlate these findings with clinical data, and to assess its possible influence on quality of life ( Qo L). Materials and Methods This cross-sectional study comprised 62 patients with DM1. Following measures were used: Muscular Impairment Rating Scale, Raven's Standard Progressive Matrices ( RSPM), Millon Multiaxial Clinical Inventory I ( MMCI), SF-36, and Individualized Neuromuscular Quality of Life ( INQoL) questionnaires. Results The presence of at least one pathological personality trait with score above 85 on MMCI was found in 47 (75.8%) patients. After clinical interview, 36 (58.1%) subjects had significant personality impairment. The most common personality trait in our cohort of patients was dependent found in 51.6% of patients, followed by paranoid (38.7%). Higher score on dependent personality scale correlated with lower education (rho = −0.251, P = 0.049). Dependent personality scores significantly differed between patients with physical and intellectual work (93.1 ± 8.9 vs 66.9 ± 31.7, P = 0.011). Paranoid score was higher in patients with lower education (rho = −0.293, P = 0.021), lower score on RSPM test (rho = −0.398, P = 0.004) and larger number of CTG repeats (rho = 0.254, P = 0.046). Presence of dependent personality was not in association with Qo L scores ( P > 0.05). On the other hand, patients with paranoid personality trait had worse Qo L than those without it ( P < 0.05). Conclusion Almost 60% of our patients with DM1 had clinically significant personality impairment, with dependent and paranoid personality patterns being the most common. Paranoid personality may decrease QoL in these patients, which gives us new opportunities for symptomatic therapy in DM1. [ABSTRACT FROM AUTHOR]

Background and purpose The aim of the present study was to analyze cerebrospinal fluid ( CSF) levels of total tau ( T-tau), phosphorylated tau ( P-tau) and the 42-amino-acid form of β-amyloid ( Aβ42) in patients with myotonic dystrophy type 1 ( DM1), and their possible correlations with cognitive and behavioral manifestations in these patients. Methods Lumbar puncture was performed in 74 patients with DM1 [27 with the childhood/juvenile form (j DM1) and 47 with the adult form (a DM1) of the disease] and 26 control subjects who were subjected to orthopedic surgery. Sandwich ELISA was used for measuring the levels of T-tau, P-tau and Aβ42. Results The CSF level of Aβ42 was at its lowest in patients with j DM1 and at its highest in controls ( P < 0.05). A tendency of T-tau and P-tau to increase was greater in aDM1 patients than in jDM1 patients and controls ( P > 0.05). In both j DM1 and a DM1 patients, significant correlations were found between Aβ42 and T-tau (rho = 0.81 and rho = 0.67, respectively, P < 0.01), as well as between Aβ42 and P-tau (rho = 0.87 and rho = 0.67, respectively, P < 0.01). The Aβ42/P-tau ratio decreased with age in a DM1 patients (rho = −0.30, P < 0.05). Only the level of Aβ42 in the CSF of j DM1 patients was correlated with the size of the CTG expansion (rho = −0.53, P < 0.05). Only a few correlations were observed between levels of biomarkers and neuropsychological testing. Conclusion The CSF level of Aβ42 was decreased in patients with j DM1, whilst the Aβ42/ P-tau ratio was decreased in a DM1 patients. Positive correlations between Aβ42, T-tau and P-tau were observed in both forms of disease. Further studies with larger cohorts of DM1 patients are necessary. [ABSTRACT FROM AUTHOR]

Rakocevic Stojanovic V, Peric S, Lavrnic D, Popovic S, Ille T, Stevic Z, Basta I, Apostolski S. Leptin and the metabolic syndrome in patients with myotonic dystrophy type 1. Acta Neurol Scand: 2010: 121: 94–98. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – To evaluate serum leptin concentration and its relation to metabolic syndrome (MSy) in non-diabetic patients with myotonic dystrophy type 1 (DM1). Materials and methods – This study included 34 DM1 patients, and the same number of healthy subjects matched for age, sex and body mass index (BMI). Results – DM1 patients had increased BMI and insulin resistance, and increased leptin and insulin concentrations, but the other features of MSy such as diabetes, glucose intolerance and hypertension were not detected in DM1 patients. Serum leptin levels were higher in patients with DM1 than in healthy controls (8.5 ± 6.6 ng/ml vs 3.6 ± 2.9 ng/ml in men, and 13.9 ± 10.0 ng/ml vs 10.9 ± 6.9 ng/ml in women, respectively). In DM1 patients, leptin levels correlated with BMI, fasting insulin and insulin resistance (HOMA) ( P < 0.01). Conclusions – The leptin overproduction correlated with insulin resistance in DM1 patients but the significance of this finding remains unclear. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to determine survival and mortality in patients with myotonic dystrophy type 1 (DM1) in the Belgrade population within the period from 1983 to 2002. Data of a number of diagnosed DM1 patients with their demographic, clinical and genetic characteristics were gathered from hospital records in all neurologic institutions in Belgrade for the period 1983–2002. Death certificates were reviewed to determine the cause of death. Survival analysis by life table method and Cox proportional hazard model was performed. Within the observed period, in the population of Belgrade, 15 fatal outcomes among 101 patients with DM1 were registered. Average DM1 mortality rate was 0.5/1 000 000 (95% CI 0.3–0.8), and standardized mortality ratio (SMR) was 5.3. A significant inverse correlation was found between age at onset of DM1 and CTG repeats ( P = 0.023). The cumulative probability of 15-year survival for DM1 patients in Belgrade was 49 ± 5% (48 ± 2% for males and 50 ± 7% for females). Younger age at onset was a significant unfavorable prognostic factor (hazard ratio = 4.2; P = 0.012). [ABSTRACT FROM AUTHOR]

Lavrnic D, Vujic A, Rakocevic-Stojanovic V, Stevic Z, Basta I, Pavlovic S, Trikic R, Apostolski S. Cyclosporine in the treatment of myasthenia gravis.Acta Neurol Scand 2005 DOI: 10.1111/j.1600-0404.2005.00378.x© Blackwell Munksgaard 2005.Cyclosporine A (CsA) treatment was evaluated in 52 patients with severe generalized myasthenia gravis (MG) whose illness was not controlled by anticholinesterase drugs, thymectomy, corticosteroids, and azathioprine. The efficacy of CsA treatment was expressed by mean disability score quotient (MDSQ), which was obtained by comparing mean disability score (MDS) at the beginning of the treatment with the MDS at the end of the follow-up period. For the entire group of patients MDSQ was 53.3%, indicating moderate improvement. Analyzing individual cases, eight patients (15%) did not improve, 17 (33%) showed moderate improvement, 20 (38%) showed remarkable improvement, and seven patients (14%) achieved complete remission. The most common side effects were rise of serum creatinine (seven), hypertension (two), gingival hyperplasia (two), hypertrichosis (six), myalgia (10), and‘flu-like’ symptoms (10 patients). The results of this study suggest that CsA is efficacious and safe treatment in severe and resistant forms of MG. [ABSTRACT FROM AUTHOR]