Dysferlinopathy course and sportive activity: clues for possible treatment.

LGMD2B is a frequent proximo-distal myopathy with rapid evolution after age 20. Exacerbating factors may be physical exercise and inflammation. There is very little information about the effect of sportive activity in LGMD2B, since eccentric exercise frequently results in muscle damage. LGMD2B has often an onset with myalgia and MRI imaging (STIR-sequences) shows myoedema. In a prolonged observational study of a series of 18 MM/LGMD2B patients we have studied the pattern of clinical and radiological evolution. The disease has an abrupt onset in the second decade and most patients perform sports before definite disease onset. On the basis of Gardner-Medwin and Walton scale, grade 4 is reached two years faster in patients who performed sports (over 1000 hours). Other considerations regarding pathogenetic mechanism and response to treatment show a poor response to immunosuppressive treatment of muscle inflammation. Preventing a strenuous physical activity should be recommended in patients with high CK and diagnosed or suspected to have dysferlin deficiency.

Cognitive profile and MRI findings in limb-girdle muscular dystrophy 2I.

Limb-girdle muscular dystrophy 2I (LGMD2I) is a neuromuscular disorder with a heterogeneous phenotype. It is caused by mutations in the Fukutin Related Protein (FKRP) gene, which is ubiquitously expressed in human tissues. FKRP functions in CNS are largely unknown. To investigate possible cognitive impairment in LGMD2I and to describe brain MRI features. Ten LGMD2I patients (four males and six females, mean age 44 years, age range 19-69 years) were assessed with an extensive neuropsychological battery, psychopathological tests and neuromuscular specific quality-of-life questionnaire. Adults were compared with ten matched healthy controls. All patients underwent complete neurological examination, and nine underwent brain MRI scanning. Patients showed a fairly specific cognitive profile with mild impairment in executive functions and visuo-spatial planning without substantial impairment in global and logic IQ. MRI findings were heterogeneous: four patients showed non-specific white matter abnormalities; two patients showed moderate ventriculomegaly; three patients showed mild enlargement of subarachnoid spaces, without a specific pattern. Cerebellar atrophy was marked in one patient. Abnormal glycosylation of α-dystroglycan in LGMD2I may interfere with brain development and cognitive performances involving the frontal and posterior parietal regions, but does not result in specific brain MRI abnormalities.

The clinical course of calpainopathy (LGMD2A) and dysferlinopathy (LGMD2B).

OBJECTIVE: Autosomal recessive limb girdle muscular dystrophies (LGMD type 2) are a clinically and genetically heterogeneous group of disorders, characterized by progressive involvement and wasting of limb girdle muscles. In order to describe the peculiar clinical features of LGMD2A (calpainopathy) and LGMD2B (dysferlinopathy), the most frequent forms of LGMD in European countries, we analysed and compared the phenotype and the clinical course in two relatively large groups of these patients. METHODS: We selected 22 patients with a molecular diagnosis of LGMD2A and 21 patients with LGMD2B and reported their clinical data collected from both clinical history and during periodical neuromuscular examinations: age and distribution of muscle involvement at onset, clinical functional score by the use of ten-point modified scale of Gardner-Medwin and Walton at onset and at last clinical examination, and the rate of disease progression. RESULTS: LGMD2A group included patients with different ages at onset (early-onset or late-onset), different phenotypes (upper girdle in Erb LGMD or lower girdle in Leyden-Moebius LGMD) and different disease progressions (rapid or slow course). LGMD2B patients differed for pattern of muscle involvement at onset (distal in Miyoshi dystrophy or proximal in Leyden-Moebius LGMD) but they had a rather homogeneous age at onset (in the second/third decade) and rate of disease progression. DISCUSSION: Our data show that besides the clinical differences within each group of patients, the two forms of LGMD present distinctive clinical features. The various phenotypes and courses can be attributed to specific pathogenetic mechanisms and might suggest differential therapeutic strategies.