Neuromuscular tetanic hyperexcitability syndrome associated to a heterozygous Kv1.1 N255D mutation with normal serum magnesium levels.

Mutations of the main voltage-gated K channel members Kv1.1 are linked to several clinical conditions, such as periodic ataxia type 1, myokymia and seizure disorders. Due to their role in active magnesium reabsorption through the renal distal convoluted tubule segment, mutations in the KCNA1 gene encoding for Kv1.1 has been associated with hypomagnesemia with myokymia and tetanic crises. Here we describe a case of a young female patient who came to our attention for a history of muscular spasms, tetanic episodes and muscle weakness, initially misdiagnosed for fibromyalgia. After a genetic screening she was found to be carrier of the c.736A > G (p.Asn255Asp) mutation in KCNA1, previously described in a family with autosomal dominant hypomagnesemia with muscular spasms, myokymia and tetanic episodes. However, our patient has always presented normal serum and urinary magnesium values, whereas she was affected by hypocalcemia. Calcium supplementation gave only partial clinical benefit, with an improvement on tetanic episodes yet without a clinical remission of her spasms, whereas magnesium supplementation worsened her muscular symptomatology.

Psychosocial impact of sport activity in neuromuscular disorders.

Previous studies demonstrated the benefits of motor exercise and physical activity in neuromuscular disorders. However, very few papers assessed the effects of sport practise. The aim of this multicentre study was to assess the impact of sport activity on self-esteem and emotional regulation in a cohort of athletes with neuromuscular disorders. The 38 patients with Duchenne, Becker or other types of muscular dystrophy or spinal muscular atrophy practising sport (aged 13-49 years) and 39 age-, gender-, disability- and disease-matched patients not practising sport were enrolled. Testing procedures to assess self-esteem, anxiety and depression disorder, personality trait and quality of life (QoL) were used. Patients practising sport had a significantly higher self-esteem, lower level of depression, greater social own identity and adherence and QoL. Frequency of sport activity may represent a complementary therapy in neuromuscular disorders to improve mental and social well-being.

Integrated care of muscular dystrophies in Italy. Part 2. Psychological treatments, social and welfare support, and financial costs.

This paper describes the psycho-social treatments received by 502 patients with MDs and their relatives, and the costs for care sustained by the families in the previous six month period. Data were collected by the MD-Care Schedule (MD-CS) and the Family Problems Questionnaire (FPQ). Psycho-educational interventions were provided to 72 patients (14.3%), and social/welfare support to 331 patients (65.9%). Social/welfare support was higher in patients with DMD or LGMD, in those showing more severe disability, and in patients who were in contact with centres located in Northern Italy. Psycho-educational interventions were received by 156 (31%) relatives, and social/welfare support by 55 (10.9%) and mainly provided by Family/Patients Associations (83.6%). Relatives with higher educational levels, who spent more daily hours in the assistance of patients with DMD, and in contact with centres in Central Italy more frequently benefited from psycho-educational interventions. In the previous year, costs for care were sustained by 314 (63.9%) relatives. Financial difficulties related to patient's condition, were higher in families of patients who needed more intensive rehabilitation and daily hours of caregiving, and in families who lived further away from the reference's centre. These results showed that psycho-social aspects of MDs care are only partially met in Italy, and that ad hoc supportive interventions for these patients and their families should be potentiated.

Integrated care of muscular dystrophies in Italy. Part 1. Pharmacological treatment and rehabilitative interventions.

This paper describes the pharmacological therapies and rehabilitative interventions received by 502 patients with Muscular Dystrophies, evaluated in relation to patient's socio-demographic and clinical variables, and geographical areas. Data were collected by the MD-Socio-Demographic and Clinical Schedule (MD-SC-CS) and by the Family Problems Questionnaire (FPQ). The most part of the enrolled patients were in drug treatment. The number of the medications increased in relation to patient's age, disability degree and duration of illness and was higher among patients with Duchenne Muscular Dystrophy (DMD) compared with Becker (BMD) or Limb-Girdle Muscular Dystrophies (LGMD). Steroids (deflazacort or prednisone) were the drug most frequently used, followed by cardiologic and bone metabolism drugs. In general, patients using steroids were younger and had a shorter duration of illness; patients using cardiac drugs and dietary supplements were older and had a longer duration of illness. Rehabilitative interventions were provided to about 70% (351/502) of patients, mainly DMD. Of these, physiotherapy was the more frequent treatment (96.6%) and was prevalently performed in rehabilitative centres (about 70% of patients) and at home in only 30%. Hydrokinetic-therapy was practiced by 6.8% of patients. Respiratory rehabilitation was provided to 47.0% of patients (165/351) and assisted mechanical ventilaventilation to 13.1% (46). The amount of rehabilitative interventions increased in relation to the patient's age, level of disability and duration of illness. Compared to Central and Northern Italy, in Southern Italy there was a higher attention to cardiological impairment as shown by a higher number of patients receiving heart drugs. No statistically significant differences concerning the possibility to have access to rehabilitative interventions were noted among the three geographical areas. However, patient living in Southern Italy tend to receive rehabilitation more often at home.

Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion.

BACKGROUND AND AIM: Breast cancer remains a leading cause of mortality among women. In metastasis, cascade migration of cancer cells and invasion of extracellular matrix (ECM) represent critical steps. Urokinase-type plasminogen activator (uPA), as well as metalloproteinases MMP-2 and MMP-9, strongly contribute to ECM remodelling, thus becoming associated with tumour migration and invasion. In addition, the high expression of cytoskeletal (CSK) proteins, as fascin, has been correlated with clinically aggressive metastatic tumours, and CSK proteins are thought to affect the migration of cancer cells. Consumption of fruits and vegetables, characterized by high procyanidin content, has been associated to a reduced mortality for breast cancer. Therefore, we investigated the biological effect of grape seed extract (GSE) on the highly metastatic MDA-MB231 breast cancer cell line, focusing on studying GSE ability in inhibiting two main metastatic processes, i.e., cell migration and invasion. METHODS: After MDA-MB231 breast cancer cells stimulated with GSE migration and invasion were evaluated by means of trans-well assays and uPA as well as MMPs activity was detected by gelatin zymography. Fascin, ß-catenin and nuclear factor-κB (NF-κB) expression were determined using western blot technique. ß-Catenin localization was observed by confocal microscopy. RESULTS: We observed that high concentrations of GSE inhibited cell proliferation and apoptosis. Conversely, low GSE concentration decreased cell migration and invasion, likely by hampering ß-catenin expression and localization, fascin and NF-κB expression, as well as by decreasing the activity of uPA, MMP-2 and MMP-9. CONCLUSIONS: These results make GSE a powerful candidate for developing preventive agents against cancer metastasis.