Stiffness as a presenting symptom of an odd clinical condition caused by multiple sclerosis and myotonia congenita

A 24-year-old woman complained of a 4-year history of muscle cramps, stiffness of the right lower limb and walking difficulties. After clinical and laboratory investigations, a diagnosis of multiple sclerosis was made. However, her family history revealed that her father and an older sister had lifelong symptoms of impaired muscle relaxation following contraction, improving with physical exercise. Molecular genetic studies in both sisters confirmed the diagnosis of myotonia congenita, due to a c.568GG>TC (Gly190Ser) pathogenic mutation in CLCN1 gene. Occurrence of two different neurological conditions in the same patient, both manifesting with stiffness, is quite unusual and suggests the opportunity of an accurate differential diagnosis.     

Defining the Epsilon‐Sarcoglycan (SGCE) Gene Phenotypic Signature in Myoclonus‐Dystonia: A Reappraisal of Genetic Testing Criteria

Mutations or exon deletions of the epsilon‐sarcoglycan (SGCE) gene cause myoclonus‐dystonia (M‐D), but a subset of M‐D patients are mutation‐negative and the sensitivity and specificity of current genetic testing criteria are unknown. We screened 46 newly enrolled M‐D patients for SGCE mutations and deletions; moreover, 24 subjects previously testing negative for SGCE mutations underwent gene dosage analysis. In our combined cohorts, we calculated sensitivity, specificity, positive and negative predictive values, and area under the curve of 2 published sets of M‐D diagnostic criteria. A stepwise logistic regression was used to assess which patients' characteristics best discriminated mutation carriers and to calculate a new mutation predictive score (“new score”), which we validated in previously published cohorts. Nine of 46 (19.5%) patients of the new cohort carried SCGE mutations, including 5 novel point mutations and 1 whole‐gene deletion; in the old cohort, 1 patient with a complex phenotype carried a 5.9‐Mb deletion encompassing SGCE. Current diagnostic criteria had a poor ability to discriminate SGCE‐positive from SGCE‐negative patients in our cohort; conversely, age of onset, especially if associated with psychiatric features (as included in the new score), showed the best discriminatory power to individuate SGCE mutation carriers, both in our cohort and in the validation cohort. Our results suggest that young age at onset of motor symptoms, especially in association with psychiatric disturbance, are strongly predictive for SGCE positivity. We suggest performing gene dosage analysis by multiple ligation‐dependent probe amplification (MLPA) to individuate large SGCE deletions that can be responsible for complex phenotypes. © 2013 Movement Disorder Society     

Adult-onset mitochondrial movement disorders: a national picture from the Italian Network

Journal of Neurology - Both prevalence and clinical features of the various movement disorders in adults with primary mitochondrial diseases are unknown. Based on the database of the...     

Adverse genetic prognostic profiles define a poor outcome for cystectomy in bladder cancer

Fluorescence in situ hybridization analysis was performed to evaluate P16 (9p21), P53 (17p13.1), RB1 (13q14), HER2 (17q11.2) genes and chromosomes 3, 7, 9 and 17 in 62 bladder cancer cystectomies. We found chromosome aneusomy ranged between 74.2% and 91.9%. The highest percentage of homozygous deletion was found in the P16 gene (48.4%), while the highest percentage of heterozygous deletion was in the RB1 gene (51.6%). Chromosome 17 aneusomy significantly increased in tumors with higher stage, and RB heterozygous deletion showed a higher percentage of tumors with positive lymph node. Multiple correspondence analysis (MCA) showed four different biological tumor profiles, but only one could be associated with survival, defining the most unfavorable biological profile, characterized by P53 and P16 as homozygous and heterozygous and RB as homozygous deletion. Overall survival was significantly shorter in patients with at least two positive variables out of the five detected by MCA using the Kaplan-Meier's method. The biological stratification of advanced bladder cancer patients is of particular clinical interest, because the assessment of genetic factors predictive of tumor aggressiveness may influence postoperative therapeutic strategies.     

Nicotine withdrawal increases body weight, neuropeptide Y and Agouti-related protein expression in the hypothalamus and decreases uncoupling protein-3 expression in the brown adipose tissue in high-fat fed mice

Nicotine is known to decrease body weight in normal rodents and human smokers, whereas nicotine withdrawal or smoking cessation can increase body weight. We have found that mice fed a high fat diet do not show the anorectic effect of chronic nicotine treatment, but do increase their body weight following nicotine withdrawal. Nicotine withdrawal is accompanied by increased expression of the orexigenic peptides neuropeptide Y and Agouti-related protein in the hypothalamus, and decreased expression of the metabolic protein uncoupling protein-3 in brown adipose tissue. These data suggest that diet can influence the ability of nicotine to modulate body weight regulation and demonstrate that chronic nicotine exposure results in adaptive changes in central and peripheral molecules which regulate feeding behavior and energy metabolism.     

Correlations between incisor and condylar movements during lateral excursion in children with primary dentition

The purpose of this study was to look for associations between lower incisor movement and working and balancing condylar movement during lateral excursion in children with primary dentition and adults with permanent dentition. Mandibular movement was recorded using a TRI-MET (an optoelectronic analysis system with six degrees-of-freedom) at a sampling frequency of 100 Hz. The movement data was transferred to a graphics workstation for analysis. Subjects were categorized by age into two groups. The primary dentition group consisted of 19 children (mean age: 5 years and 5 months, s.d.: 8.7 months), and the permanent dentition group consisted of 22 women (mean age: 20 years and 5 months, s.d.: 26.3 months). The occlusion and TMJ in both groups were normal, with no history of orthodontic treatment. Three orthogonal excursive ranges and the 3D linear distance of the incisal and balancing and working condylar points, along with inter- and intra-individual correlations between the incisor and the balancing and working condyles during lateral excursion, were estimated by using multilevel statistical models. Lateral excursion in children with primary dentition was characterized by smaller incisor excursive ranges and 3D linear distance than in adults, and stronger inter- and intra-individual correlations between incisor and balancing condylar movements than in adults. In both children and adults the lateral excursion of the incisor was a good indicator of the extent of balancing condylar movement, but not working condylar movement.