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Defects in TRIM32 were reported in limb-girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathies (STM) and in Bardet-Biedl syndrome. Few cases have been described to date in LGMD2H/STM, but this gene is not systematically analysed because of the absence of specific signs and difficulties in protein analysis. By using high-throughput variants screening techniques, we identified variants in TRIM32 in two patients presenting nonspecific LGMD. We report the first case of total inactivation by homozygous deletion of the entire TRIM32 gene. Of interest, the deletion removes part of the ASTN2 gene, a large gene in which TRIM32 is nested. Despite the total TRIM32 gene inactivation, the patient does not present a more severe phenotype. However, he developed a mild progressive cognitive impairment that may be related to the loss of function of ASTN2 because association between ASTN2 heterozygous deletions and neurobehavioral disorders was previously reported. Regarding genomic characteristics at breakpoint of the deleted regions of TRIM32, we found a high density of repeated elements, suggesting a possible hotspot. These observations illustrate the importance of high-throughput technologies for identifying molecular defects in LGMD, confirm that total loss of function of TRIM32 is not associated with a specific phenotype and that TRIM32/ASTN2 inactivation could be associated with cognitive impairment.

Background: The Human T-cell Leukemia Virus type 1 (HTLV-1) is the causative agent of several inflammatory diseases, including HTLV-1-associated inflammatory myopathies (HAIM). Little is known about the virological and immunological characteristics of this viral disease., Objectives: To characterize the histological and virological features of HAIM patients, in order to better understand the pathogenetic mechanisms and unravel new biological markers of this disease., Study Design: We conducted a retrospective study on 13 patients with HAIM, based on blood and muscle samples. We included blood samples from HTLV-1-infected individuals without myopathy as controls. Muscle biopsies were used for a broad immunohistological evaluation of tissue damage and inflammation, as well as identification of infected cells through in situ hybridization. DNA extracted from patients' PBMC was used to identify the virus genotype by sequencing and to assess the proviral load by quantitative PCR. Anti-viral antibodies in plasma samples were titrated by indirect immunofluorescence., Results: Patients originate from HTLV-1 endemic areas, the West Indies and West Africa. Histological alterations and inflammation in patients muscles were mostly moderate, with classical features of idiopathic myositis and rare HTLV-1-infected infiltrating cells. In all patients, HTLV-1 belonged to the A subtype, transcontinental subgroup. Anti-HTLV-1 antibodies titers were high, but the proviral load was not elevated compared to asymptomatic HTLV-1 carriers., Conclusion: We show here that muscle inflammation is moderate in HAIM, and accompanied by a low HTLV-1 proviral load, suggesting that the pathogenetic events do not exactly mirror those of other HTLV-1-associated inflammatory diseases., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Very Long-Chain Acyl-CoA dehydrogenase (VLCAD) deficiency is an inborn error of mitochondrial long-chain fatty acid oxidation (FAO) most often occurring in childhood with cardiac or liver involvement, but rhabdomyolysis attacks have also been reported in adults. We report in this study the clinical, biochemical and molecular studies in 13 adult patients from 10 different families with VLCAD deficiency. The enzyme defect was demonstrated in cultured skin fibroblasts or lymphocytes. All patients exhibited exercise intolerance and recurrent rhabdomyolysis episodes, which were generally triggered by strenuous exercise, fasting, cold or fever (mean age at onset: 10 years). Inaugural life-threatening general manifestations also occurred before the age of 3 years in four patients. Increased levels of long-chain acylcarnitines with tetradecenoylcarnitine (C14:1) as the most prominent species were observed in all patients. Muscle biopsies showed a mild lipidosis in four patients. For all patients but two, molecular analysis showed homozygous (4 patients) or compound heterozygous genotype (7 patients). For the two remaining patients, only one mutation in a heterozygous state was detected. This study confirms that VLCAD deficiency, although being less frequent than CPT II deficiency, should be systematically considered in the differential diagnosis of exercise-induced rhabdomyolysis. Measurement of fasting blood acylcarnitines by tandem mass spectrometry allows accurate biochemical diagnosis and should therefore be performed in all patients presenting with unexplained muscle exercise intolerance or rhabdomyolysis.

Introduction: Limb girdle muscular dystrophy type 1b (LGMD1B), due to LMNA gene mutations, is a relatively rare form of LGMD characterized by proximal muscle involvement associated with heart involvement comprising atrio-ventricular conduction blocks and dilated cardiomyopathy. Its clinical and genetic diagnosis is crucial for cardiac management and genetic counselling. Seven LMNA mutations have been previously reported to be responsible for LGMD1B., Patients and Methods: We describe the neurological and cardiologic features of 14 patients belonging to 8 families in whom we identified 6 different LMNA mutations, 4 of them having never been reported. Results. Eleven patients had an LGMD1B phenotype with scapulohumeral and pelvic-femoral involvement. Thirteen patients had cardiac disease associating conduction defects (12 patients) or arrhythmias (9 patients). Seven patients needed cardiac device (pacemaker or implantable cardiac defibrillator) and two had heart transplantation., Conclusion: This study allowed us to specify the clinical characteristics of this entity and to outline the first phenotype/genotype relations resulting from these observations.

Dilated cardiomyopathy (DCM) of genetic origin represents about 25% of all so-called primary DCM. Cases due to mutation of the gene which codes the lamins A and C (LMNA) carry a poor prognosis with a high risk of sudden death. The finding of primary DCM in a young person associated with conduction defects or arrhythmias should lead to investigation for mutation of the gene of lamins A and C, even in the absence of a suggestive family history. The authors report 5 cases of DCM, with and without associated skeletal muscular disease, due to laminopathies.

We report a case of cerebral deep venous thrombosis that manifested clinically by a pseudobulbar syndrome with major trismus, abnormal movements and static cerebellar syndrome. To our knowledge, only three other cases of deep cerebral venous thrombosis associated with cerebellar or pseudobulbar syndrome have been published since 1985. The relatively good prognosis in our patient could be explained by the partially intact internal cerebral veins as well as use of early anticoagulant therapy. There was a spontaneous hyperdensity of the falx cerebri and the tentorium cerebelli on the brain CT scan, an aspect highly contributive to diagnosis. This hyperdensity of the falx cerebri was found in 19 out of 22 cases of deep venous thrombosis detailed in the literature.

Optic neuritis frequently occurs in multiple sclerosis (MS), and shares several similarities with the optic neuritis of Leber's hereditary optic neuropathy (LHON), which is mainly due to maternally transmitted mitochondrial DNA (mtDNA) mutations. Our report shows for the first time that a mitochondrial DNA background could influence the clinical expression of MS. One European mtDNA haplogroup was found only in MS patients with optic neuritis but not in MS patients without visual symptoms. Therefore, we hypothesize that mtDNA haplogroup J might constitute a risk factor for optic neuritis occurrence when it is coincidentally associated with MS, but not be a risk factor for developing MS per se as suggested previously.

Three cases of extracranial vertebral artery dissections with upper limb peripheral motor deficit (C5-C6) are reported. Six similar cases were also found in the literature. Central neurological symptoms occurred in five of these nine cases, suggesting the diagnosis of dissection. The peripheral motor or sensorial deficit was strictly isolated in the four other cases, simulating radicular neuralgia due to discopathy or foraminal compression. In case of dissections, a precise analysis of pain is helpful to guide diagnosis; sharp, unbearable, continuous and extended neck pain without nocturnal paroxysms and posterior neck stiffness is typical. Analgesics or anti-inflammatory drugs are ineffective. Peripheral motor deficit is more common than sensory deficit. Recovery was complete in this series. In most cases, the radiculopathy appears to be due to cervical root compression in its extraforaminal course due to the dissection hematoma and rarely to radicular ischemia.

Background: Hypokaliemic periodic paralysis is an uncommon complication of hyperthyroidism occurring sporadically almost exclusively in young Asian men. The clinical presentation is the same as in familial hypokaliemic periodic paralysis. Treatment consists of conventional management for thyrotoxicosis., Case Report: A Laotian man aged 42 years had suffered episodes of pain and fatigue in the lower limbs lasting 2 to 7 days over the last few months. The patient was hospitalized with severe limb pain. Clinical examination found severe motor deficit involving all four limbs. Laboratory findings induced hypokaliemia (1.8 mmol/l) and hyperthyroidism (free thyroxin 36 pmol/l, TSH < 0.005 mlU/l). Thyroid echography revealed multinodular goitre with two heterogeneous nodules. Strong uptake was seen on the scintigram. The motor deficit regressed within 8 hours and the kaliemia was restored with 1.50 g KCl. The patient was discharged with carbimazole (30 mg/d). Three months later he was euthyroid and symptom free. Total thyroidectomy was performed and L-thyroxin prescribed. The patient remains symptom-free at the last follow-up, 5 months after thyroidectomy., Discussion: The pathogenesis of hypokaliemic periodic paralysis involves the ATPase-dependent sodium-potassium pump whose activity is stimulated by thyroid hormones. The reasons for the ethnic and male predominance are poorly elucidated.

It has been suggested that inflammation may be a possible cause of Alzheimer's disease (AD). Increased anti-NGF autoantibody levels and increased NGF frequency in serum have previously been associated with inflammatory responses. In this study no changes in anti-NGF autoantibody titers or in NGF frequency were detected in sera of AD patients, suggesting that they are not involved in the neuroimmunological mechanisms underlying AD. There were neither age-associated changes in NGF frequency in sera of four groups of normal subjects between 18-91 years of age. In contrast, anti-NGF autoantibodies were significantly increased in sera of the 31-45 yr age group.

Two cases of spinal muscular atrophy, localized on the lower limbs and strictly unilateral, in two half brothers, are reported. Such a distribution of clinical changes and such a hereditary transmission appear to be unusual in hereditary motor-neuronopathies. A recessive heterotopic transmission may be suspected. To our knowledge, it has been reported in Kennedy's disease only.

A 47-year-old woman developed a progressive sensory deficit of the upper limbs. She lost perception of joint position, vibratory sense, skin-writing and stereognosis. Repeated tests by several examiners, up to 10 years after the onset, demonstrated normal pain and temperature sensation. The right hypoglossal nerve was involved at a late stage of the disease. CT and MRI showed an intramedullary cavity from C1 to T7. Somato-sensory evoked potentials from stimulation of the median nerves confirmed the bilateral impairment of the lemniscal pathways.

Two new cases of X-chromosome linked bulbospinal muscular atrophy associated with gynecomastia (described by Kennedy in 1968) are reported. In one patient, an electrophysiological study and a muscle nerve biopsy were performed. Motor nerve conduction studies were normal but sensory action potentials were small or unrecordable in the absence of clinical sensory loss. Superficial peroneal nerve biopsy showed axonal lesions. These findings suggest that this disease is not purely due to degeneration of spinal motor neurons and is also associated with an axonopathy.

A case of facial palsy first unilateral then bilateral, due to Lyme disease, is reported. This disease, transmitted by ticks, is caused by a spirochete (Borrelia burgdorferi) known as the etiologic agent since 1982.