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The clinical relevance and extent of cognitive impairment in adult myotonic dystrophy type 1 (DM1) and 2 (DM2) is still unclear. The aim of this study was to determine whether previously reported cognitive abnormalities progress over time and if this occurs in DM2 as it does in DM1. Fifty-six patients with DM1 and 29 patients with DM2 were subjected to muscle strength assessment, and to a complete battery of neuropsychological tests. Repeated assessment was performed in 20 DM1 and 13 DM2 over time (DM1 mean follow-up: 7.3±2.7 years; DM2 mean follow- up: 9.5±2.4 years). Muscle strength and test scores for frontal lobe functions worsened significantly over time ( p<0.01), in both DM1 and DM2. DM2 is a progressive muscle disorder, although less severe than DM1. In both DM1 and DM2 frontal cognitive impairment (attentional) worsens over time but does not extend to additional areas of cognition. [ABSTRACT FROM AUTHOR]

Abstract: We studied respiratory function and Chest Wall kinematics in a large population of adult patients affected by slow course muscular dystrophies such as Limb-Girdle Muscular Dystrophy (LGMD, n=38), Becker Muscular Dystrophy (BMD, n=20) and Facio-Scapulo Humeral Dystrophy (FSHD, n=30), through standard spirometry and through the Optoelectronic Plethysmography, to measure the thoraco-abdominal motion during Quiet Breathing and Slow Vital Capacity maneuvers. Within the restrictive pulmonary syndrome characterizing LGMD and FSHD, several different thoraco-abdominal patterns compared to those of healthy subjects were present in the more advanced stages of the disease. These differences were present in the seated position, during the execution of a maximal maneuver such as Slow Vital Capacity. A global respiratory (both inspiratory and expiratory) muscle involvement was more pronounced in the LGMD and FSHD than in the BMD patients, and a significant reduction of abdominal contribution in wheelchair bound patients was observed. In conclusion, OEP technique is able to reveal mild initial modifications in the respiratory muscles in FSHD and LGMD patients, which could be helpful for functional and new therapeutic strategy evaluation. [Copyright &y& Elsevier]

Background and purpose: A quality of life (QoL) questionnaire for neuromuscular diseases was recently constructed and validated in the United Kingdom in a sample of adult patients with a variety of muscle disorders. Preliminary results suggested it could be a more relevant and practical measure of QoL in muscle diseases than generic health measures of QoL. The purpose of our work was: (i) To validate INQoL in Italy on a larger sample of adult patients with muscle diseases (ii) to compare INQoL to SF-36. Methods: We have translated into Italian and applied language adaptations to the original UK INQoL version. We studied 1092 patients with different muscle disorders and performed (i) test–retest reliability ( n = 80); (ii) psychometric ( n = 345), known-group ( n = 1092), external criterion ( n = 70), and concurrent validity with SF-36 ( n = 183). Results: We have translated and formally validated the Italian version of INQoL confirming and extending results obtained in the United Kingdom. In addition to good results in terms of reliability, known-group and criterion validity, a comparison with the SF-36 scales showed a stronger association between INQoL total index and SF-36 physical ( r = −0.72) than mental ( r = −0.38) summary health indexes. When considering comparable domains of INQoL and SF-36 with respect to an objective measure of muscle strength assessment (MMRC), regression analysis showed a stronger correlation using INQoL rather than SF-36 scores. Conclusions: INQoL is recommended to assess QoL in muscle diseases because of its ability to capture physical limitations that are specifically relevant to the muscle condition. [ABSTRACT FROM AUTHOR]

Allogeneic cord blood transplantation (CBT), especially from unrelated donors, is being increasingly used for treating paediatric patients with both malignant and non-malignant disorders. Recent clinical and experimental evidence suggests that human cord blood mononuclear cells (CBMC) may acquire in utero a state of tolerance towards non-inherited maternal antigens (NIMA). In order to better define this phenomenon, we measured, by means of a limiting dilution assay (LDA), the frequency of NIMA-specific CTL precursors (CTLp) in cord blood samples obtained from 13 healthy neonates. The immunophenotype of the effector cells recovered from LDA was also analysed. Data concerning both CTLp frequency and phenotype of effector cells were compared with those obtained stimulating CBMC with cells of paternal origin (NIPA) and adult PBMC with allogeneic targets. Results showed that cytotoxic cells directed towards cells of maternal origin could be detected in all cord blood samples tested. Phenotype analysis demonstrated that NIPA elicit the expansion of CD3+/CD8bright T cells, a phenotype associated with alloreactive CTL. By contrast, NIMA preferentially stimulated the expansion of CD3-/CD8dim+ cells, a phenotype associated with NK cells, which are known to be able, in certain clinical conditions, to kill allogeneic haematopoietic cells without causing GVHD. Thus, our results indicate that, when evaluated in a limiting dilution condition, NIMA-reactive cord blood cells are detectable and a preferential expansion of NK cells is observed. [ABSTRACT FROM AUTHOR]

We have been monitoring the respiratory function in 95 DMD patients (aged between 6 and 24 years) who were evaluated once or twice a year in relation to age and clinical conditions, making a total of 429 evaluations. During every evaluation, forced vital capacity, nocturnal oxygen saturation and the abdominal percentage contribution to tidal volume (an index of the action of the diaphragm) were respectively measured with spirometry, pulse oximetry and opto-electronic plethysmography. 46 patients underwent therapy with steroid while the remaining 49 never assumed steroid. No differences ( p = 0.122) were found in forced vital capacity, nocturnal saturation and the action of the diaphragm between the 231 evaluations of the steroid group and the 198 evaluations of the sham group. Steroid therapy seems not to have any effects on the respiratory function decline in DMD patients. [ABSTRACT FROM AUTHOR]

Non progressive cognitive impairment and increased rates psychosocial disorders, ADHD and Autism are reported in DMD patients. Through structured and validated questionnaire (Wechsler scales or Griffiths developmental scale, CBCL, Youth Self Report, Strengths and Difficulties Questionnaire, ADOS and DAWBA) we explored the possible role of cognitive impairment on the neuropsychiatric comorbidity in 32 boys with DMD (4–18 years). Our preliminary analysis shows a mean Full Intelligence Quotient of the whole group of 83.90 ± 16.68, lower in the patients with deletions in the distal portion of the gene (78.28 ± 16.72) than in the ones with proximal deletions (88.52 ± 15.62), with a very high frequency of Autism (about 20%) particularly in children with lower IQ level, and a high frequency of internalizing problems at CBCL, in boys with FIQ within the normal range, suggesting a role of cognitive capabilities in DMD children psychopathology. [ABSTRACT FROM AUTHOR]

Limb girdle muscular dystrophies (LGMD) are genetic heterogeneous disorders characterized by slow but progressive muscular impairment. Despite the recent identification of new genes, about 30% of these LGMDs remain without molecular diagnosis. However clinical-genetic correlations are fundamental for genetic counselling, definition of natural history and insight into pathogenesis. We collected detailed clinical, biochemical, histological and molecular data of 467 Italian LGMD patients, belonging to 8 neuromuscular Italian centres. Detailed data about neuromuscular, cardiological, respiratory involvement as far as molecular analysis and muscle biopsy were collected. Molecular analysis identified mutations in LGMD causative genes in 312 patients; 109 patients (23.1%) are still without a molecular diagnosis and 46 subjects (9.8%) carried heterozygous mutations in genes responsible for autosomal recessive forms. The relative frequency was as follows: 5.8% LGMD1B, 11.2% LGMD1C, 24.3% LGMD2A, 25.6% LGMD2B, 9.6% LGMD2I, 9.9% LGMD2D, 6.4% LGMD2E, 4.2% LGMD2C, 1.9% LGMD2L, 0.3% LGMD2F. Interestingly 1 LGMD patient (0.3%) carried mutations in ISPD and one patient in LAMA2 gene. Onset spans from the first decade to adulthood; LGMD2E being the most precocious (6.2 ± 5.3 years) and LGMD2L the latest (36.6 ± 7.1 years). Creatine-kinase values were generally increased, especially in sarcoglycanopathies, LGMD2B, LGMD1C. Cardiomyopathy was more frequent in LGMD1B (100%), LGMD2E (47%) and LGMD2I (50%) and restrictive pulmonary involvement in LGMD2I (53%) and LGMD2E (47%). About 30% of patients were wheelchair bound. The study of undiagnosed patients will potentially lead to identification of new LGMD causative genes. Overall this study defined the relative frequency of Italian LGMD and improved the knowledge about clinical, morphological and molecular spectrum as far as their natural history as far as the parameters that can better define the clinical evolution of these forms. [ABSTRACT FROM AUTHOR]