Evaluation of muscle strength and motor abilities in children with type II and III spinal muscle atrophy treated with valproic acid

<p>Abstract</p> <p>Background</p> <p>Spinal muscular atrophy (SMA) is an autosomal recessive disorder that affects the motoneurons of the spinal anterior horn, resulting in hypotonia and muscle weakness. The disease is caused by deletion or mutation in the telomeric copy of <it>SMN </it>gene (<it>SMN1</it>) and clinical severity is in part determined by the copy number of the centromeric copy of the <it>SMN </it>gene (<it>SMN2</it>). The <it>SMN2 </it>mRNA lacks exon 7, resulting in a production of lower amounts of the full-length SMN protein. Knowledge of the molecular mechanism of diseases has led to the discovery of drugs capable of increasing SMN protein level through activation of <it>SMN2 </it>gene. One of these drugs is the valproic acid (VPA), a histone deacetylase inhibitor.</p> <p>Methods</p> <p>Twenty-two patients with type II and III SMA, aged between 2 and 18 years, were treated with VPA and were evaluated five times during a one-year period using the Manual Muscle Test (Medical Research Council scale-MRC), the Hammersmith Functional Motor Scale (HFMS), and the Barthel Index.</p> <p>Results</p> <p>After 12 months of therapy, the patients did not gain muscle strength. The group of children with SMA type II presented a significant gain in HFMS scores during the treatment. This improvement was not observed in the group of type III patients. The analysis of the HFMS scores during the treatment period in the groups of patients younger and older than 6 years of age did not show any significant result. There was an improvement of the daily activities at the end of the VPA treatment period.</p> <p>Conclusion</p> <p>Treatment of SMA patients with VPA may be a potential alternative to alleviate the progression of the disease.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01033331">NCT01033331</a></p

UN MODELO EN RATA FRL DETERIORO COGNITIVO EN LA ENFERMEDAD DE PARKINSON

Aunque el mal de Parkinson (DP) es considerado clásicamente como undesorden del sistema motor, pueden observarse ligeros deterioros cognitivosaun en las fases iniciales del DP. En este artículo revisamos estudios conductualesy neuroquímicos sobre alteraciones cognitivas observadas en ratastratadas con infusiones intranigrales de la neurotoxina MPTP. El papel críticode la liberación de dopamina en el estriado dorsal y su modulación por losreceptores de adenosina también es revisada como una estrategia potencialpara tratar los deterioros cognitivos en pacientes con desorden de Parkinson(PD) que no mejoran con la terapia de levo dopa. Resultados: La mayoríade de los daños presentados en ratas con infusiones intranigrales de MPTPson similares a los observados en las primeras fases de PD, una pérdidamoderada de neuronas nigrales dopaminérgicas (40-70%) que causa défi -cits sensoriales y motores y poco deterioro motor. Estos animales tambiénmodelan los défi cits de memoria de trabajo y aprendizaje de hábitos, con lamemoria de largo plazo espacial (episódica) mayormente preservada comose observa en los pacientes sin DP. La infusión intranigral de MPTP en ratasa llevado al desarrollo de modelos útiles, ya que no presentan un deterioromotor excesivo que podría de otra manera comprometer la interpretación dede la ejecución de los animales en tareas cognitivas

Medida de função motora, corticoterapia e pacientes com distrofia muscular de Duchenne

Objective: To assess the evolution of motor function in patients with Duchenne muscular dystrophy (DMD) treated with steroids (prednisolone or deflazacort) through the Motor Function Measure (MFM), which evaluates three dimensions of motor performance (D1, D2, D3). Methods: Thirty-three patients with DMD (22 ambulant, 6 non-ambulant and 5 who lost the capacity to walk during the period of the study) were assessed using the MFM scale six times over a period of 18 months. Results: All the motor functions remained stable for 14 months in all patients, except D1 for those who lost their walking ability. In ambulant patients, D2 (axial and proximal motor capacities) motor functions improved during six months; an improvement in D3 (distal motor capacity) was noted during the total follow-up. D1 (standing posture and transfers) and total score were useful to predict the loss of the ability to walk. Conclusions: The use of the MFM in DMD patients confirms the benefits of the steroid treatment for slowing the progression of the disease.OBJETIVO: Avaliar a evolução da função motora de pacientes com distrofia muscular de Duchenne (DMD) em corticoterapia (predinisolona e deflazacort), por meio da escala Medida da Função Motora (MFM), que avalia três dimensões de funções motoras (D1, D2, D3). \ud MÉTODOS: Trinta e três pacientes com DMD (22 deambulantes, seis cadeirantes e cinco que perderam a capacidade de andar ao longo do estudo) foram avaliados pela escala MFM em seis momentos durante 18 meses. \ud RESULTADOS: Todas as funções motoras mantiveram-se estáveis durante 14 meses, exceto D1 para os pacientes que perderam a marcha. Nos pacientes deambulantes, a D2 (função motora axial e proximal) apresentou melhora durante seis meses. Melhora em D3 (função motora distal) também foi observada durante o seguimento. A D1 (postura em pé e transferências) e o escore total foram importantes para predizer a perda de marcha. \ud CONCLUSÕES: O uso da MFM nos pacientes com DMD confirma os benefícios do tratamento com corticoides na diminuição da velocidade de progressão da doença

Lung function monitoring in patients with duchenne muscular dystrophy on steroid therapy

Background\ud Duchenne muscular dystrophy (DMD) is a sex-linked inherited muscle disease characterized by a progressive loss in muscle strength and respiratory muscle involvement. After 12 years of age, lung function declines at a rate of 6 % to 10.7 % per year in patients with DMD. Steroid therapy has been proposed to delay the loss of motor function and also the respiratory involvement.\ud \ud Method\ud In 21 patients with DMD aged between seven and 16 years, the forced vital capacity (FVC) and the forced expiratory volume in one second (FEV1) were evaluated at three different times during a period of two years.\ud \ud Results\ud We observed in this period of evaluation the maintenance of the FVC and the FEV1 in this group of patients independently of chronological age, age at onset of steroid therapy, and walking capacity.\ud \ud Conclusion\ud The steroid therapy has the potential to stabilize or delay the loss of lung function in DMD patients even if they are non-ambulant or older than 10 years, and in those in whom the medication was started after 7 years of age.DLM was supported by CAPES (Coordenação de Aperfeiçoamento Pessoal de Ensino Superior)

Salicylsalicylic acid causes less gastroduodenal mucosal damage than enteric-coated aspirin

The gastroduodenal mucosal damage caused by aspirin and nonsteroidal antiinflammatory drugs is a common clinical problem. We compared two medications designed to diminish mucosal damage: enteric-coated aspirin and salicylsalicylic acid (salsalate). Ten healthy volunteers were randomized to receive either 1.5 g salsalate twice a day or 650 mg enteric-coated aspirin four times a day for six days and were then crossed over to the other drug after a one-week medication-free period. Endoscopic inspection of gastroduodenal mucosa was performed at entry and again after six days of drug therapy for each medicine. Mean serum salicylate concentrations taken before the morning drug dose were 11.2 mg/dl for enteric-coated aspirin and 18.1 mg/dl for salsalate. Only one of 10 subjects receiving salsalate developed mild (grade 1) mucosal damage while six of 10 receiving enteric-coated aspirin developed moderate to severe damage (grade 2–3) (P= 0.01 ). Symptoms were mild in both groups. We conclude that salsalate causes less gastroduodenal mucosal damage than enteric-coated aspirin .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44409/1/10620_2005_Article_BF01536056.pd