Perivascular and endomysial macrophages expressing VEGF and CXCL12 promote angiogenesis in anti-HMGCR immune-mediated necrotizing myopathy.

Objectives: To study the phenotype of macrophage infiltrates and their role in angiogenesis in different idiopathic inflammatory myopathies (IIMs).

Methods: The density and distribution of the subpopulations of macrophages subsets (M1, inducible nitric oxide+, CD11c+; M2, arginase-1+), endomysial capillaries (CD31+, FLK1+), degenerating (C5b-9+) and regenerating (NCAM+) myofibres were investigated by immunohistochemistry in human muscle samples of diagnostic biopsies from a large cohort of untreated patients (n: 81) suffering from anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR)+ immune mediated necrotizing myopathy (IMNM), anti-signal recognition particle (anti-SRP)+ IMNM, seronegative IMNM, DM, PM, PM with mitochondrial pathology, sporadic IBM, scleromyositis, and anti-synthetase syndrome. The samples were compared with mitochondrial myopathy and control muscle samples.

Autophagy markers LC3 and p62 accumulate in immune-mediated necrotizing myopathy.

Introduction: The molecular mechanism of immune-mediated necrotizing myopathy (IMNM) remains unknown. Autophagy impairment, described in autoimmune diseases, is a key process in myofiber protein degradation flux and muscle integrity and has not been studied in IMNM.

Methods: Muscle biopsies from patients with IMNM (n = 40), dermatomyositis (DM; 24), polymyositis (PM; 8), polymyositis with mitochondrial pathology (4), sporadic inclusion body myositis (8), and controls (6) were compared by immunohistochemistry.

Mitochondrial genome aberrations in skeletal muscle of patients with motor neuron disease.

Our objective was to assess the role of defects of mitochondrial function as contributing factors in the pathogenesis and/or progression of amyotrophic lateral sclerosis (ALS); mitochondrial genome structural alterations were investigated. DNA lesions, point alterations and gross rearrangements were screened by specific applications of real-time PCR including an optimized rapid gene-specific method for the accurate quantification of mitochondrial DNA (mtDNA) lesions as well as sequencing on skeletal muscle biopsies of three patients presenting with motor neuron disease. We found a higher frequency of mtDNA lesions, including multiple deletions, particularly in the only SOD1 mutated patient as well as in a patient negative for mutations in SOD1 but presenting a severe form of the disease.

Clinical features and new molecular findings in muscle phosphofructokinase deficiency (GSD type VII).

Muscle phosphofructokinase (PFKM) deficiency, a rare disorder of glycogen metabolism also known as glycogen storage disease type VII (GSDVII), is characterized by exercise intolerance, myalgias, cramps and episodic myoglobinuria associated with compensated hemolytic anaemia and hyperuricemia. We studied five patients with PFKM deficiency coming from different Italian regions. All probands showed exercise intolerance, hyperCKemia, cramps and myoglobinuria.

Autoimmune autonomic ganglionopathy: a possible postganglionic neuropathy.

Objective: To evaluate postganglionic autonomic and somatic nerve fiber involvement in a patient with chronic autoimmune autonomic ganglionopathy.

Design: Case report.

Setting: Department of Neurological Sciences, University Federico II of Naples.

A new locus on 3p23-p25 for an autosomal-dominant limb-girdle muscular dystrophy, LGMD1H.

Limb-girdle muscular dystrophies (LGMDs) are a genetically heterogeneous group of neuromuscular disorders with a selective or predominant involvement of shoulder and pelvic girdles. We clinically examined 19 members in a four-generation Italian family with autosomal-dominant LGMD. A total of 11 subjects were affected.

Molecular analysis in a family presenting with a mild form of late-onset autosomal dominant chronic progressive external ophthalmoplegia.

Nuclear genes affecting mitochondrial genome stability were screened in an Italian family presenting with autosomal dominant progressive external ophthalmoplegia (adPEO) associated with multiple mitochondrial DNA (mtDNA) deletions. We report on a heterozygous c.907C>T (p.

Motoneuron disease after electric injury: a case report.

Several cases of motor neuron disease (MND) after electric injury have been reported in the last number of years, but the relationship between electric injury and MND remains controversial. Herein we report the case of a 60-year-old man who developed a MND following an electrical trauma. In the case presented here, the onset of disease at the site of lightning strike and the short interval of time between the electrical injury and the clinical onset of MND raise the possibility of considering electrical shock as a trigger factor for MND.

Predictors of long survival in amyotrophic lateral sclerosis: a population-based study.

Background: Although amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder, some ALS cases can survive beyond 10 years. However, the predictors of long survival in ALS patients remain uncertain.

Objective: To define clinical predictors of long survival in a cohort of ALS incident cases.

ALS multidisciplinary clinic and survival. Results from a population-based study in Southern Italy.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motorneurons, for which there is no effective cure. Because of the multifactorial nature of impairment and disablity in ALS, multidisciplinary clinics (MDC) have been recently introduced in the management of ALS patients; their effects on survival remain, however, largely debated.

Objective: To compare survival of ALS patients who received their care at MDC with that of patients followed by general neurology clinics.

A case of vacuolar myopathy during the course of chronic hepatitis C.

Several cases of inflammatory myopathy have been reported during the chronic course of hepatitis C (HC) in recent years. It has been suggested that this muscular inflammatory involvement in HC is related to an immune-mediated mechanism caused by the hepatitis C virus (HCV), as HCV RNA has been detected in the muscle of patients with concomitant inflammatory myopathy and chronic HC. Herein, we report on a patient with a history of chronic HC, who developed a slowly progressive proximal muscle weakness; muscle biospy revealed a vacuolar myopathy.

Predictors of delay in the diagnosis and clinical trial entry of amyotrophic lateral sclerosis patients: a population-based study.

Background: The El Escorial and the revised Airlie House diagnostic criteria for amyotrophic lateral sclerosis (ALS) were introduced to select patients for clinical trials. Heterogeneity of clinical presentation at onset and delay in diagnosis may decrease the likelihood for trial entry.

Objective: Identify risk factors for delay in the diagnosis and trial exclusion.

Unusual clinical presentation of a patient carrying a novel single 1.8 kb deletion of mitochondrial DNA.

Kearns-Sayre syndrome (KSS) is a mitochondrial encephalomyopathy characterized by progressive external ophthalmoplegia (PEO), pigmentary retinopathy and onset before the age of 20 years. Cerebellar ataxia, as well as short stature and increased protein content in the cerebrospinal fluid, are frequent additional symptoms. A single large mitochondrial (mt) DNA deletion of 4,977 bp is the most common molecular defect in KSS.