Pulmonary functions and sleep-related breathing disorders in lipid storage disease.

PURPOSE: Pulmonary function abnormalities and sleep-related breathing disorders (SRBD) are frequent in subjects with several neuromuscular diseases but there is no data about lipid storage diseases (LSD). Therefore, we aimed to evaluate pulmonary functions and SRBD in adults with LSD. METHODS: Pulmonary functions (forced expiratory volume (FEV1), forced vital capacity (FVC), supine FVC, upright-supine FVC% change, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), peak cough flow (PCF)), arterial blood gases, and polysomnographic data of all subjects were evaluated. RESULTS: Twenty-five subjects with LSD were evaluated [17 males, 8 females; age 34.9 ± 15 years; BMI 26.5 ± 3.4 kg/m2]. MIP was - 72.2 ± 32.7 cmH2O (< - 80 cmH2O in 13 subjects), MEP was 80.9 ± 39.1 cmH2O (< 80 cmH2O in 9 subjects, < 40 cmH2O in 6 subjects), and PCF was 441.3 ± 190.9 L/min (< 360 L/min in 11 subjects). FVC was 87.8% ± 25.7 and 6 subjects had FVC < 80%. Seven subjects had diaphragm dysfunction (four upright-supine FVC% ≥ 15, three dyspnea in supine position with paradoxical abdominal respiration). Five subjects had hypoxemia (PaO2 < 80 mmHg) and 8 subjects had hypercapnia (PaCO2 > 45 mmHg). REM sleep had decreased in all subjects (10.2% ± 6.1). Obstructive sleep apnea (OSA) was found in 80% of the subjects (n = 20; 9 mild, 9 moderate, 2 severe). For subjects with OSA, apnea-hypopnea index (AHI) was 20.8 ± 15.9/h, oxygen desaturation index (ODI) was 11.9 ± 15.4/h, AHIREM was 30.6 ± 19.7/h, AHINREM was 19.7 ± 16.6/h, ODIREM was 27.2 ± 26.1/h, and ODINREM was 11.4 ± 15/h. Five subjects (20%) diagnosed as REM-related OSA. Nocturnal mean SpO2 was 94.9% ± 1.7, lowest SpO2 was 73.3% ± 13.9, and time spent with SpO2 < 90% was 2.4% ± 7.2. CONCLUSION: In subjects with LSD, pulmonary function impairment, daytime hypercapnia and hypoxemia, and OSA, especially REM-related OSA, are frequent. Therefore, pulmonary functions and polysomnography should be performed routinely.

Prompt Response to Prednisone Predicts Benign Course in MuSK-MG.

BACKGROUND: The difficult course of patients with myasthenia gravis (MG) with anti-muscle-specific tyrosine kinase antibodies (MuSK) has been emphasized. However, no clear information is available on patients who have a benign course. METHODS: This study was aimed at comparing patients with favorable (minimal manifestations [MM] or better) and unfavorable outcomes to determine whether excellent response to corticosteroid (CS) treatment within 3 months (good response-3 months) has any predictive effect on the prognosis. RESULTS: Forty-six percent of 46 patients had a favorable outcome at year 3 and 54% at final follow-up. The major finding of this study was its high predictive value with good response-3 months. Those with good response-3 months had significantly more favorable outcome as compared to those without at year 3. The positive predictive value of good response-3 months was high (89% at year 3 and 84% at final follow-up). The negative predictive value diminished from 85% at year 3 to 67% at final follow-up due to increasing number of patients improving in the long run. Overall, 33% of the patients had a benign course with good response-3 months and no major exacerbations until the end of follow-up. CONCLUSIONS: Excellent response to CSs within 3 months appears to predict a favorable outcome in MuSK-MG.

Muscle magnetic resonance imaging in spinal muscular atrophy type 3: Selective and progressive involvement.

INTRODUCTION: In this study we sought to identify magnetic resonance imaging (MRI) signs of selective muscle involvement and disease progression in patients with spinal muscular atrophy type 3b (SMA3b). METHODS: Twenty-five patients with genetically confirmed SMA3b underwent MRI on a 1.5-Tesla MR scanner. RESULTS: MRI showed significantly more severe involvement of the iliopsoas than of the gluteus maximus muscles, and more severe involvement of the triceps brachii than of the biceps brachii muscles. The quadriceps femoris muscles were severely involved. The deltoid, adductor longus, portions of the hamstrings, gracilis, sartorius, and rectus abdominis muscles were well preserved. We found a significant positive correlation between MRI changes and disease duration for gluteus maximus and triceps brachii. Follow-up MRIs of 4 patients showed disease progression. CONCLUSIONS: This study confirms the pattern of selective muscle involvement suggested by previous studies and further refines muscle MRI changes in SMA3b. Progressive muscle involvement is implicated. Muscle Nerve 55: 651-656, 2017.

Genotypic and phenotypic presentation of transthyretin-related familial amyloid polyneuropathy (TTR-FAP) in Turkey.

Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is an autosomal dominant disorder caused by mutations of the transthyretin (TTR) gene. The mutant amyloidogenic transthyretin protein causes the systemic accumulation of amyloid fibrils that result in organ dysfunction. TTR-associated FAP is a progressive and fatal disease, if left untreated, and should be considered in the differential diagnosis of any person presenting with a progressive polyneuropathy, particularly with accompanying autonomic involvement. The clinical, electrophysiological, histopathological, and genetic characteristics of 17 patients from Turkey (5 female, 13 male) from nine families with polyneuropathy and mutations in TTR were evaluated. Sequence analysis of the TTR gene revealed five mutations (Val30Met, Glu89Gln, Gly53Glu, Glu54Gly and Gly47Glu). Mean age at disease onset was 40.4 ± 13.9 years (range 21-66 years). The most commonly reported initial complaint was paresthesia in the feet (asymmetric in three patients). Three patients (2 male) with the Glu89Gln mutation presented with carpal tunnel syndrome. Two patients with the Gly53Glu mutation showed episodes of dysarthria and hemiparesis, consistent with this genotype. Seven patients died during the period of follow-up as a result of systemic involvement. Our study suggests that a cohort of patients from Turkey with TTR-FAP exhibits clinical and genetic heterogeneity.

Nerve conduction studies in Charcot-Marie-Tooth disease in a cohort from Turkey.

INTRODUCTION: In the demyelinating form of Charcot-Marie-Tooth disease, median motor conduction velocity (MCV) was noted to be around 20 m/s in peripheral myelin protein 22 (PMP22) duplications, in contrast to higher MCVs in connexin 32 gene (Cx32) mutations and lower MCVs in the demyelinating form of myelin protein zero gene (MPZ) mutations. METHODS: Nerve conduction studies were performed in 64 families with both common and rare mutations. RESULTS: Mean MCV of the median nerve was 20 ± 5 m/s in PMP22 duplications, 34 ± 6 m/s in Cx32 mutations, 20 ± 9 m/s in KIAA1985 (SH3TC2) mutations, and 11 ± 8 m/s in MPZ mutations. Conduction was generally uniform; however, conduction blocks were present in 1 patient each with the MPZ mutation and PMP22 duplication, both with unusual phenotypes. CONCLUSION: Our results confirm those of the other investigators. Electrophysiological results of the rare KIAA1985 (SH3TC2) mutation reveal that their MCVs span a broad range and that conduction is uniform.

Evaluation of biventricular functions with tissue Doppler imaging in patients with myotonic dystrophy.

BACKGROUND: Myotonic dystrophy (MD) is characterized by myotonia with dystrophic involvement of the muscles. Cardiac involvement is usually not evident in the early stages of MD. HYPOTHESIS: We investigated biventricular functions by tissue Doppler imaging (TDI) in MD patients with no overt cardiac involvement to explore the value of TDI in the early detection of myocardial dysfunction. METHODS: A total of 21 MD patients (15 male, age: 32.2 +/- 12.3 yrs) and 21 healthy controls (13 male, age: 32.2 +/- 7.8 yrs) were included. In addition to conventional echocardiography, pulsed Doppler and TDI were performed including measurement of myocardial performance index (MPI); peak systolic (Sm) and early (Em) and atrial (Am) diastolic myocardial velocities at the basal mitral and tricuspid annulus. RESULTS: All patients and controls had normal ejection fraction. Transmitral E peak velocity was significantly lower while both deceleration time of E velocity and isovolumic relaxation time were significantly longer in MD patients (P = 0.007, P = 0.001, and P < 0.001, respectively). Sm, Em and Am peak velocities were significantly lower in MD patients in all segments except for Em of the mitral anterior annulus and Am of the tricuspid lateral annulus. Both left and right ventricular MPI were significantly higher in MD patients (P < 0.001 and P = 0.013, respectively). CONCLUSION: There are changes in myocardial systolic and diastolic functions in MD patients although they have no overt heart failure. Myocardial tissue velocities and MPI are useful in identifying subclinical biventricular involvement in these patients.

Mitochondrial pathology in muscle of a patient with a novel parkin mutation.

Mutations of the parkin gene on chromosome 6 cause early-onset parkinsonism. Myopathy has not been reported to be a feature of this condition. Here we report the muscle biopsy findings of a 53-year-old man with a novel parkin gene mutation (IVS-9-1 deletion). His symptoms were characterized by typical early-onset, dopa-responsive, and slowly progressive parkinsonism. Parkin gene analysis revealed a homozygous IVS-9-1 deletion in the proband and his sibling. The unusual feature was hypertrophy of bilateral thigh muscles in the proband. Muscle biopsy from the biceps brachii muscle showed abundant cytochrome oxidase (COX) (-) fibers. This is the first report on the coexistence of a myopathy with COX deficiency with parkin disease and may shed light on the function of parkin in muscle.

Early outcomes of video-assisted thoracoscopic resection of thymus in 181 patients with myasthenia gravis: who are the candidates for the next morning discharge?

The aims of this study are to present the results of videothoracoscopic thymectomy in patients with myasthenia gravis (MG) and to predict the factors affecting the next morning discharge (NMD). This is a retrospective analysis of the prospectively recorded data of 181 consecutive myasthenic patients who underwent videothoracoscopic thymectomy from June 2002 to September 2009. Sixty-one patients (33.7%) were discharged on the next morning. Univariate and multivariate analyses were evaluated to determine the predictors for NMD. Mean calculated variables were: age (29.8 years), duration of symptoms (22.5 months), duration of surgery (51.3 min), postoperative stay (2.1) days, and visual analogue scale (2.1). No mortality occurred. Four patients were required to stay in intensive care unit (ICU) with a mean of 18.6 h. With logistic regression analysis, duration of operation (DoO) was calculated to be the only predictive factor for NMD (P=0.006). Video-assisted thoracoscopic thymectomy (VAT thymectomy) is a safe surgery procedure with a smooth postoperative period for MG. Although a detailed analysis was performed, only DoO was found to be a predictive factor for NMD in MG patients.

Scapulothoracic arthrodesis in facioscapulohumeral dystrophy with multifilament cable.

UNLABELLED: Patients with facioscapulohumeral dystrophy (FSHD) are affected mostly by impaired shoulder function. Scapulothoracic arthrodesis was introduced to improve shoulder function. We evaluated the outcomes of scapulothoracic arthrodesis using multifilament cables, performed on 13 patients with FSHD (18 shoulders). There were eight males and five females (mean age, 29 years; range, 20-50 years). Outcome criteria were active shoulder forward flexion and abduction, the Disabilities of the Arm, Shoulder, and Hand (DASH) score, respiratory function tests, and a new shoulder function score. Patients were followed for a minimum of 24 months (average, 35.5 months; range, 24-87 months). Solid fusion was obtained in all shoulders (two after revision); active abduction range increased from 47.2 degrees +/- 11.6 degrees to 102.2 degrees +/- 10.0 degrees (mean +/- standard deviation) and anterior flexion range from 55.6 degrees +/- 16.1 degrees to 126.1 degrees +/- 20.9 degrees . The DASH score decreased from 33.6 +/- 8.9 points preoperatively to 11.6 +/- 8.0 points postoperatively. Shoulder function score increased from 15.9 +/- 2.4 points to 22.2 +/- 1.3 points. Scapulothoracic arthrodesis provides satisfactory function in patients with FSHD. Our data suggest use of multifilament cables for fixation is a reasonable option with an acceptable complication rate. LEVEL OF EVIDENCE: Level IV, case series. See the Guidelines for Authors for a complete description of levels of evidence.

Natural history of SMA IIIb: muscle strength decreases in a predictable sequence and magnitude.

OBJECTIVE: To assess the natural progression of muscle weakness in spinal muscular atrophy (SMA) IIIb. METHODS: Ten patients with SMA IIIb were followed for at least 10 years. Age at disease onset varied between 9 and 18 years. Patients were initially seen 2 to 10 years after disease onset. They were evaluated at approximately 2, 5, 10, 15, and 20 years of disease duration depending on the timing of their initial visit after onset. Medical Research Council (MRC) scale was used with particular attention to proximal muscles. RESULTS: The MRC grade declined with years in all of the muscles. The decline was usually not more than by one MRC grade for each 5-year period. There were 5-10 year periods when some muscles appeared to remain stationary. The succession of weakness was first triceps, then biceps and deltoid for upper extremity muscles and first thigh adductors, then iliopsoas, then quadriceps femoris, then hamstrings, thigh abductors, and gluteus maximus for lower extremity muscles. There was a remarkable uniformity between patients in the MRC grade for each muscle at each stage: in the first 5 years of the disease, triceps, iliopsoas, thigh adductors, and quadriceps femoris were the muscles which had noticeable weakness. CONCLUSIONS: These findings show that strength in spinal muscular atrophy IIIb decreases over time, explaining the progressive functional loss. The sequence of weakness in the lower extremities suggests that the disease starts segmentally involving the upper lumbar segments of the medulla spinalis initially. The slowness of the deterioration may have implications for clinical trials.

Thymoma appearing 10 years after an extended thymectomy for myasthenia gravis.

Occurrence of thymoma after an extended thymectomy through a full median sternotomy for nonthymomatous thymectomy has been very rarely reported. A 60-year-old male patient who had myasthenia gravis (MG) for 11 years had an extended thymectomy operation with a pathology of thymic hyperplasia and developed a mass in the aortopulmonary window. We resected the mass via anterior left thoracotomy by dividing the ductus arteriosus and mobilizing the aorta. Cord vocal augmentation procedure was done due to the resection of the left recurrent laryngeal nerve.

Videothoracoscopic thymectomy for nonthymomatous myasthenia gravis: results of 90 patients.

BACKGROUND: Videothoracoscopic thymectomy is an alternative surgical procedure for patients with nonthymomatous myasthenia gravis. The aim of this study is to present our experience and to analyze the factors contributing to the operative morbidity. METHODS: Ninety myasthenia gravis patients were operated through right-sided videothoracoscopy from June 2002 to September 2006. Prospective data recording was performed. Surgeon-related conversion to open surgery, length of the operation, chest tube duration time, duration of hospital stay, amount of drainage, pain score, and complications were evaluated. Factors contributing to longer operation time and longer postoperative stay were studied. RESULTS: The mean length of chest tube duration and postoperative hospital stay was 26.7 +/- 18.6 hours and 2.2 days +/- 1.1 days respectively. Visual analogue scale (VAS) values for pain evaluation were 2.0 +/- 1.4. Surgeon-related open conversion occured in two patients (2.2%). Body mass index (BMI) was the sole significant factor for longer operation time. (23.04 +/- 2.93 versus 25.61 +/- 2.70 (p = 0.001). The amount of pyridostigmine was the only significant factor for longer hospital stay (213.3 +/- 101.5 mg versus 270. 0 +/- 122.6 mg (p = 0.044). CONCLUSIONS: This study demonstrates the right-sided videothoracoscopy is a safe procedure. The only contributing factors were: BMI >25.61 for longer operation time, and pyridostigmine level >270 mg for duration of postoperative stay.

Polymorphisms of interferon-gamma, interleukin-10, and interleukin-12 genes in myasthenia gravis.

To assess the involvement of polymorphisms in genetic susceptibility to myasthenia gravis (MG), this study analyzed four polymorphisms of interferon (IFN)-gamma, interleukin (IL)-10, and IL-12 genes in 115 patients and 204 healthy controls (HC). IFNG +874T carriers were less frequent in MG, in patients with anti-acetylcholine receptor (AChR) (63%) and anti-titin (56.2%) antibodies compared with HC (p = 0.01 for all, OR: 0.5, 0.5, and 0.4, respectively). The presence of thymoma was also associated with lower frequency of IFNG +874T allele (p = 0.018, OR = 0.34). At IL10, -2763A allele was found to be slightly more frequent in MG and in patients with anti-AChR than in HC group (p = 0.05, OR = 1.7, p = 0.036, OR = 1.83). However, these associations did not remain significant after correction for multiple comparisons. IL12B allele distribution was not different among groups. These data suggest that some cytokine gene polymorphisms may contribute to susceptibility to or antibody production in MG. These findings need to be replicated in further studies.

Camptocormia in a patient with Parkinson disease and a myopathy with nemaline rods.

Camptocormia, also referred to as bent spine, is a gait disorder characterized by hyperflexion of the thoracolumbar spine that develops in recumbent position while walking and that disappears in supine position. Myopathy is one of the frequent causes of camptocormia. A 77-yr-old male patient who was followed up with the diagnosis of rheumatoid arthritis for 2 yrs was admitted with progressive gait deterioration. Hyperflexion of trunk, disappearing in supine position, was detected and diagnosed as camptocormia. He also exhibited the signs of parkinsonism. A paraspinal muscle biopsy showed myopathy with rods in many muscle fibers. Camptocormia in this patient may be attributable to the myopathic weakness of thoracolumbar paraspinal muscles. The normal biceps brachii muscle biopsy refers to the isolated affection of paraspinal muscles in this patient. A camptocormia (bent spine) case of myopathy with nemaline rods associated with Parkinson disease is presented.

Incidental raised transaminases: a clue to muscle disease.

Twenty-one patients with incidental hypertransaminasaemia who were eventually diagnosed as muscular dystrophy are described. There were two females and 19 males aged between 2 and 11 years [mean (SD) 6.7 (3.4) y]. Serum alanine and aspartate transaminase levels were between 73 and 595 IU/L (30-35) and 68 and 550 IU/L (30-35), respectively. Muscle disease was suspected when creatine phosphokinase levels were elevated and confirmed in each patient by muscle biopsy. The time interval between incidental hypertransaminasemia and the diagnosis of muscle disease was between 3 and 12 months. Eleven patients were diagnosed as Becker's muscle dystrophy, eight as Duchenne muscle dystrophy and two had sarcoglycanopathy. Long-term elevation of transaminase levels might be a sign of occult muscle disease. Invasive tests such as liver biopsy should not be performed in patients with unexplained hypertransaminasaemia without first determining creatinine phosphokinase levels.

Decrement pattern in Lambert-Eaton myasthenic syndrome is different from myasthenia gravis.

The decrement pattern at low rates of repetitive nerve stimulation in myasthenia gravis (MG) is characterized by a decrease of compound muscle action potential size within the first 4-5 responses. With subsequent stimuli, compound muscle action potential size either increases or does not change. Following an observation that the pattern of decrement might be different in patients with Lambert-Eaton myasthenic syndrome (LEMS), we retrospectively studied traces from eight LEMS patients and 14 patients with seropositive generalized MG, calculating decrement percent from first to fourth and from first to ninth compound muscle action potential. In the LEMS patients, compound muscle action potential amplitude decreased progressively from first to ninth stimulus at 2, 3 or 5Hz in all traces but one. In contrast, MG patients demonstrated the expected improvement after the initial decrement in all traces except one. In the evaluation of patients suspected of having myasthenia gravis, the finding of progressive decrement pattern at low rates of repetitive nerve stimulation may alert the electromyographer to the possibility of Lambert-Eaton syndrome and prompt the performance of further electrodiagnostic tests.

HLA-DQ polymorphism in Turkish patients with myasthenia gravis.

Genetic susceptibility to myasthenia gravis (MG) is reported frequently and varies depending on the clinical presentation of the patients. HLA-DQ genotyping was performed in 132 patients using polymerase chain reaction and sequence-specific oligonucleotide hybridizations in the Turkish population for the first time in this study. Antibody positivities against acetylcholine receptor and titin were 81 and 27%, respectively. Sixty-five percent of the patients had disease onset before 40 years of age (EOMG). Overall distribution of DQA1*0103 (odds ratio (OR): 0.5) and DQB1*0502 (OR: 1.9) alleles was different in patients and an ethnically matched healthy control group. Among the subgroups, DQB1*02 was significantly more frequent in EOMG (OR: 1.8), in women with MG (OR: 2.4), and in women with EOMG (OR: 2.8), whereas DQA1*0102 and DQB1*502 (OR: 2.3 for both) were increased and DQA1*0103 (OR: 0.04) was decreased in men with MG. Seropositivity was associated with both DQA1*03 (OR: 12.1) and DQB1*0302 (OR: 14.2) in the patient group. DQA1*02 (OR: 4.9) was associated with the presence of anti-titin antibodies, whereas DQA1*0101 (OR: 3.7) and *0102 (OR: 2.9) were more frequent in patients without this antibody. The presence of thymoma in MG was positively associated with DQB1*0301 (OR: 2.8), and DQB1*02 (OR: 0.3) was significantly less frequent in this group. The HLA-DQ associations in subgroups of MG suggest that the heterogeneity of the disease may be influenced by different genes or even by different alleles. DQ alleles have proved to be relatively informative polymorphisms in studying MG.