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Brody disease is a rare myopathy characterized by exercise-induced muscle stiffness caused by mutations in the ATP2A1 gene. In the largest cohort of Brody patients to date, Molenaar et al. clarify the phenotype and diagnostic possibilities to help improve understanding and recognition of this distinct myopathy., Brody disease is an autosomal recessive myopathy characterized by exercise-induced muscle stiffness due to mutations in the ATP2A1 gene. Almost 50 years after the initial case presentation, only 18 patients have been reported and many questions regarding the clinical phenotype and results of ancillary investigations remain unanswered, likely leading to incomplete recognition and consequently under-diagnosis. Additionally, little is known about the natural history of the disorder, genotype-phenotype correlations, and the effects of symptomatic treatment. We studied the largest cohort of Brody disease patients to date (n = 40), consisting of 22 new patients (19 novel mutations) and all 18 previously published patients. This observational study shows that the main feature of Brody disease is an exercise-induced muscle stiffness of the limbs, and often of the eyelids. Onset begins in childhood and there was no or only mild progression of symptoms over time. Four patients had episodes resembling malignant hyperthermia. The key finding at physical examination was delayed relaxation after repetitive contractions. Additionally, no atrophy was seen, muscle strength was generally preserved, and some patients had a remarkable athletic build. Symptomatic treatment was mostly ineffective or produced unacceptable side effects. EMG showed silent contractures in approximately half of the patients and no myotonia. Creatine kinase was normal or mildly elevated, and muscle biopsy showed mild myopathic changes with selective type II atrophy. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) activity was reduced and western blot analysis showed decreased or absent SERCA1 protein. Based on this cohort, we conclude that Brody disease should be considered in cases of exercise-induced muscle stiffness. When physical examination shows delayed relaxation, and there are no myotonic discharges at electromyography, we recommend direct sequencing of the ATP2A1 gene or next generation sequencing with a myopathy panel. Aside from clinical features, SERCA activity measurement and SERCA1 western blot can assist in proving the pathogenicity of novel ATP2A1 mutations. Finally, patients with Brody disease may be at risk for malignant hyperthermia-like episodes, and therefore appropriate perioperative measures are recommended. This study will help improve understanding and recognition of Brody disease as a distinct myopathy in the broader field of calcium-related myopathies.

Background Several viruses have been described as causes of acquired inflammatory myopathies; however, the mechanisms by which they cause muscle disease are still unclear. The aim of this study was to describe the laboratory features of benign acute myositis in a small case series. Methods A detailed pathological and serological analysis was performed in five African migrants who developed an acute viral myositis complicated by rhabdomyolysis. Results Muscle biopsies clearly documented an inflammatory myopathy with histological features similar to polymyositis including CD8+ T cells surrounding and invading nonnecrotic muscle fibers, CD68+ macrophages and major histocompatibility complex class I antigen upregulation. In addition, positivity for myositis-specific antibodies (MSA), in particular anti-aminoacyl tRNA synthetases, was found in the serum of two patients. Conclusions Our study demonstrated that T-cell mediated injury occurs in muscle of patients with acute viral myositis, and that MSA may be present in the serum of these patients.

Introduction/aims Stromal Interaction Molecule 1 (STIM1) is a reticular Ca2+ sensor composed of a luminal and a cytosolic domain. Autosomal dominant mutations in STIM1 cause tubular aggregate myopathy and Stormorken syndrome or its variant York platelet syndrome. We aimed to expand the features related to new variants in STIM1. Methods We performed a cross-sectional study of individuals harboring monoallelic STIM1 variants recruited in five tertiary centers involved in a study of inherited myopathies analyzed with a multigene-targeted panel. Results We identified seven individuals (age range: 26-57 years) harboring variants in STIM1, including five novel changes: three located in the EF-hand domain, one in the sterile α motif (SAM) domain and one in the cytoplasmatic region of the protein. Functional evaluation of the pathogenic variants using a heterologous expression system and measuring store-operated calcium entry demonstrated their causative role and suggested a link of new variants with the clinical phenotype. Muscle contractures, found in three individuals, showed variability in body distribution and in the number of joints involved. Three patients showed cardiac and respiratory involvement. Short stature, hyposplenism, sensorineural hearing loss, hypothyroidism and Gilbert syndrome were variably observed among the patients. Laboratory tests revealed hyperCKemia in six patients, thrombocytopenia in two and hypocalcemia in a single patient. Muscle biopsy showed the presence of tubular aggregates in three patients, type I fiber atrophy in one patient, and non-specific myopathic changes in two. Discussion Our clinical, histological and molecular data expand the genetic and clinical spectrum of STIM1-related diseases. This article is protected by copyright. All rights reserved.

Muscular dystrophies in dogs and cats represent a heterogeneous group of inherited, sometimes congenital, but infrequently diagnosed, progressive neuromuscular disorders. A correct identification and characterization of canine and feline muscular dystrophies could increase diagnostic and treatment strategies for veterinary neurologists and could identify useful animal models for the study of human dystrophies. However, in dogs and cats, diagnosis of muscular dystrophies is challenging due to a nonspecific clinical phenotype and pathological lesions, thus is most likely underestimated. We performed immunofluorescence and Western blot techniques using a wide panel of antibodies against proteins involved in human dystrophies (dystrophin mid-rod and carboxyterminal domain, α, β, γ, and δ-sarcoglycan, α-dystroglycan, caveolin-3, emerin, merosin, dysferlin, calpain-3, spectrin epitopes), on 9 canine and 3 feline muscle biopsies characterized by myopathic changes. Dystrophin deficiency was detected in 3 dogs and 2 novel canine muscular dystrophies have been identified, characterized by deficiency of caveolin-3 and calpain-3, respectively. In 2 cats, deficiency of β-SG and carboxyterminal domain of dystrophin in all muscle fibers has been detected. Performing immunofluorescence and Western blot analyses with a wider panel of antibodies allowed a correct identification of muscular dystrophies in dogs and cats and provides a direction for subsequent targeted genetic testing.

Background Camptocormia is a disabling complication of Parkinson's disease (PD), but its pathophysiology is poorly elucidated. Depending on the fulcrum of forward trunk flexion, two subtypes have been defined, upper (UCC) and lower camptocormia, the former being much more frequent. The aim of the study was to explore possible pathophysiological mechanisms of PD-related UCC. Methods Ten PD patients with UCC (UCC-PD) and ten PD patients without camptocormia (NoUCC-PD) underwent simultaneous electromyography (EMG) of thoracic paraspinal (TPS), obliquus externus abdominis (OEA), rectus abdominis (RA), and iliopsoas (IP) muscles during relaxed standing (both groups) and trunk realignment (UCC-PD group). Quantitative EMG and magnetic resonance imaging (MRI) of TPS muscles were also performed. Results UCC-PD patients showed hyperactivity of TPS and OEA muscles in quiet stance. During voluntary trunk extension, hyperactivity of OEA muscles persisted, thus revealing a co-contraction of flexor and extensor trunk muscles. Motor unit potentials (MUP) of TPS muscles showed shorter duration (p = 0.005) and lower amplitude (p = 0.004) in UCC-PD than in NoUCC-PD patients. MRI did not detect significant between-group differences in the cross-sectional area and fat fraction of TPS muscles, although the latter was higher in the UCC-PD than in the NoUCC-PD group at all thoracic levels. Conclusion Our findings suggest that hyperactivity of OEA might sustain UCC in PD. Concurrent mild myopathic changes in TPS muscles in PD with UCC may be secondary to muscle disuse but nevertheless may contribute to abnormal trunk posture.

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Background: Chronic graft versus host disease (cGVHD) occurs in 20-30% of paediatric patients receiving haemopoietic stem cell transplantation (HSCT). Neuromuscular disorders such as polymyositis are considered a rare and distinctive but non-diagnostic manifestation of cGVHD and, in absence of other characteristic signs and symptoms, biopsy is highly recommended to exclude other causes. Case report: We report a case of a 17-months-old child affected by hemophagocytic lymphohistiocytosis who underwent a matched unrelated donor haematopoietic stem cell transplantation (HSCT). She developed a severe cGVHD-related polymyositis that was successfully treated with high-dose steroid therapy, rituximab and sirolimus. Conclusions: This is the first case of cGVHD-related-polymyositis described in a pediatric patient which was successfully treated with rituximab.

Multiple acyl-CoA dehydrogenase deficiency, or glutaric aciduria type II, is an autosomal recessive disorder of fatty acid oxidation due to defects in electron transfer flavoprotein (ETF) encoded by ETFA and ETFB, or in electron transfer flavoprotein dehydrogenase (ETFDH) encoded by the ETFDH gene. The disease may present as a severe neonatal onset form and a mild late-onset form which is heterogeneous for the age at onset and clinical presentation. We describe two patients in their seventies, referred for a nonspecific myopathy, which resulted to manifest carriers of ETFDH gene mutation. Treatment with riboflavin and L-carnitine improved the clinical picture and the biochemical profile. This condition should be included in the differential diagnosis of myopathies even at an old age.

Simple Summary Multiple myeloma (MM) is a still uncurable tumor of mainly elderly patients originating from the terminally differentiated B cells. Introduction to the treatment of MM patients of a new class of drugs called proteasome inhibitors (bortezomib followed by carfilzomib and ixazomib) significantly improved disease control. Proteasome inhibitors interfere with the major mechanism of protein degradation in a cell leading to the severe imbalance in the protein turnover that is deadly to MM cells. Currently, these drugs are the mainstream of MM therapy but are also associated with an increased rate of the injuries to multiple organs and tissues. In this review, we summarize the current knowledge on the molecular mechanisms of the first-in-class proteasome inhibitor bortezomib-induced disturbances in the function of peripheral nerves and cardiac and skeletal muscle. Abstract The overall approach to the treatment of multiple myeloma (MM) has undergone several changes during the past decade. and proteasome inhibitors (PIs) including bortezomib, carfilzomib, and ixazomib have considerably improved the outcomes in affected patients. The first-in-class selective PI bortezomib has been initially approved for the refractory forms of the disease but has now become, in combination with other drugs, the backbone of the frontline therapy for newly diagnosed MM patients, as well as in the maintenance therapy and relapsed/refractory setting. Despite being among the most widely used and highly effective agents for MM, bortezomib can induce adverse events that potentially lead to early discontinuation of the therapy with negative effects on the quality of life and outcome of the patients. Although peripheral neuropathy and myelosuppression have been recognized as the most relevant bortezomib-related adverse effects, cardiac and skeletal muscle toxicities are relatively common in MM treated patients, but they have received much less attention. Here we review the neuromuscular and cardiovascular side effects of bortezomib. focusing on the molecular mechanisms underlying its toxicity. We also discuss our preliminary data on the effects of bortezomib on skeletal muscle tissue in mice receiving the drug.

Emery Dreifuss muscular dystrophy (EDMD) is an inherited myopathy characterized by early contractures, slow progressive muscle weakness and cardiac involvement. To date at least seven genes have been associated to EDMD with different inheritance patterns, being emerin gene responsible for the X-linked form of the disease. We report a 40-year-old man who was referred for severe gait difficulty. At age 6 years the patient presented with a waddling gate, lumbar lordosis and heel contractures. Both electrophysiology and muscle biopsy were consistent with a neurogenic disorder and he received a diagnosis of spinal muscular atrophy type 3. At the age of 30 the patient developed heart involvement with junctional escape rhythm and, eight years later, had a spontaneous chordae tendinae rupture. A new clinical examination showed severe muscular weakness and atrophy in scapulohumeroperoneal pattern with significant involvement of the lower facial and intrinsic hand muscles and on a second muscle biopsy emerin was absent by immunohistochemistry and by immunoblot analysis. Sequence analysis of EMD gene revealed the presence of a novel mutation represented by an out-of-frame deletion spanning from the beginning of exon 1 to the half of intron 2 (p.Asp6Glyfs*27). Our study expands the clinical and molecular spectrum of X-linked EDMD.

M-line is the narrow transverse band located in the center of the sarcomeric A-band that is mainly responsible for the stabilization of myosin thick filaments. A 27-year-old male patient with a positive medical history for ankylosing spondylitis presented with one month of proximal upper limb muscle weakness associated with pain on both acromioclavicular joints. A biopsy of deltoid muscle documented the disappearance of M-line, the misalignment of myofilaments, and the loss of the distinction between the A and I bands. Complete resolution of muscle weakness occurred after one year of treatment with antiTNFα agent Etanercept. Because of the acute onset of symptoms and the recovery after immunosuppressive treatment we hypothesized that an immune-mediated mechanism was responsible for the muscle disorder. The serum IgG-mediated autoreactivity to skeletal muscle antigens resolved by bidimensional electrophoresis was assessed in the described patient and compared with that of control subjects. The comparative analysis of the immunoreactive spots revealed that ATP synthase subunit α is specifically recognized by patient's serum, suggesting that the protein might represent a putative antigenic target in the disease. This study reports an acute reversible myopathy pathologically characterized by M-line involvement and associated with serological antibodies to the subunit α of ATP synthase.

Brody disease (BD, OMIM #601003) is an inherited skeletal muscle disease clinically characterized by exercise-induced impairment of muscle relaxation and stiffness due to the delay in the Ca2+ re-uptake in the sarcoplasmic reticulum (SR)[1, 2]. The delayed muscle relaxation mainly affects legs, harms, hands and eyelids and usually improves after a few minutes rest [1-3]. Patients frequently report myalgia, painless or mildly painful cramps whereas recurrent rhabdomyolysis have been described in a few cases [2, 3]. A reduction in sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) activity characterizes the skeletal muscle of these patients [2-5]. This article is protected by copyright. All rights reserved.

Multiple myeloma (MM) accounts for ∼13% of all hematologic malignancies. Bortezomib treatment is effective in MM, but can be complicated with neurological side effects. We describe a patient with symptomatic MM who had a reversible metabolic myopathy associated with bortezomib administration and pathologically characterized by excessive storage of lipid droplets together with mitochondrial abnormalities. In a single-center prospective study, 14 out of 24 patients with symptomatic MM were treated with bortezomib and, among these, 7 developed muscular signs and/or symptoms. The myopathy was characterized by a proximal muscle weakness involving lower limbs and was an early complication. Complete resolution of muscle weakness occurred after treatment discontinuation. Conversely, none of the patients who received a treatment without bortezomib developed muscular symptoms. Experimental studies demonstrate that in primary human myoblasts bortezomib at low concentrations leads to excessive storage of lipid droplets together with structural mitochondrial abnormalities, recapitulating the pathologic findings observed in patient's muscle. Our data suggest that patients treated with bortezomib should be monitored for muscular signs and/or symptoms and muscle weakness should alert the clinician to the possibility of myopathy. Bortezomib-induced metabolic myopathy is a potentially reversible entity with important implications for management and treatment of patients with MM.

A 59-year-old male patient complained, from age 36, of insidious appearance in several weeks of a circumscribed painful mass, single or multiple, under the skin with hard consistency on palpation. At first, these masses were localised on sural aspect of the legs, thereafter on arms, thighs and, occasionally, on trunk and face. They had a diameter ranging from 3 cm to 5 cm and the overlying skin tissue was normal. Pain might increase with movement causing functional limitation of the corresponding limb. In the first years, they spontaneously remitted within 2–3 months, successively in 6–7 months. Onset of these lesions was never preceded or accompanied by systemic symptoms such as fever, weakness and fatigue. A muscle biopsy was taken …

Brody disease is a rare inherited myopathy due to reduced sarcoplasmic reticulum Ca(2+) ATPase (SERCA)1 activity caused by mutations in ATP2A1, which causes delayed muscle relaxation and silent cramps. So far the disease has mostly been diagnosed by measurement of SERCA1 activity. Since mutation analysis became more widely available, it has appeared that not all patients with reduced SERCA1 activity indeed have ATP2A1 mutations, and a distinction between Brody disease (with ATP2A1 mutations) and Brody syndrome (without ATP2A1 mutations) was proposed. We aim to compare the clinical features of patients with Brody disease and those with Brody syndrome and detect clinical features which help to distinguish between the two. In addition, we describe the Brody syndrome phenotype in more detail. We therefore performed a literature review on clinical features of both Brody disease and Brody syndrome and a cross-sectional clinical study consisting of questionnaires, physical examination, and a review of medical files in 17 Brody syndrome patients in our centre. The results showed that Brody disease presents with an onset in the 1st decade, a generalized pattern of muscle stiffness, delayed muscle relaxation after repetitive contraction on physical examination, and autosomal recessive inheritance. Patients with Brody syndrome more often report myalgia and experience a considerable impact on daily life. Future research should focus on the possible mechanisms of reduction of SERCA activity in Brody syndrome and other genetic causes, and on evaluation of treatment options.

BACKGROUND Epoxyeicosatrienoic acids (EETs) derived from cytochrome P450 (CYP)-dependent metabolism of arachidonic acid are increased in the plasma of women with preeclampsia as compared with normal pregnancy and are significantly higher in fetal than in maternal plasma and erythrocytes. We hypothesized that differences in EET synthesis or metabolism in the feto-placental unit contributed to the observed differences in circulating EETs. METHOD To evaluate EETs, formation as well as the expression of relevant CYP isoforms and the metabolizing enzyme, soluble epoxide hydrolase (sEH), biopsies of placenta were collected from 19 normal pregnancy and 10 preeclampsia at the time of cesarean section delivery. EETs were extracted from tissue homogenates and analyzed by liquid chromatography coupled with tandem mass spectrometry. RESULTS Both cis-EETs and trans-EETs were detected in the placenta. Concentration of total EETs was higher in the placenta from preeclampsia compared with normal pregnancy (2.37 ± 1.42 ng/mg vs. 1.20 ± 0.72 ng/mg, mean ± SD, P

MDs (mitochondrial diseases) are a clinically heterogeneous group of disorders characterized by impairment of the respiratory chain function with altered oxidative phosphorylation. We tested the hypothesis that the function of vascular endothelium is affected by increased oxidative stress in MDs. A total of 12 patients with MDs and pair-matched controls were studied. Endothelial function was assessed by measuring FMD (flow-mediated vasodilation) of brachial and common femoral arteries. The test was repeated after vitamin C (500 mg, twice a day) and E (400 mg, once a day) supplementation for 30 days and 90 days after vitamin withdrawal. FMD was reduced in patients compared with controls [AUC/τ (time-averaged area under the curve) for the brachial artery, 1.05±0.24 compared with 4.19±0.59% respectively, P

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We tested the hypothesis that maternal peripheral blood leukocytes contribute to elevated levels of soluble TNF receptors (sTNFR) in preeclampsia (PE) with concomitant intrauterine growth restriction (IUGR). TNFR1 and TNFR2 were evaluated in a cross-sectional study comparing preeclamptic (n = 15) with or without IUGR versus normotensive pregnant women (PREG, n = 30), and non-pregnant controls (Con; n = 20). Plasma levels of sTNFR1 were higher in PE (1675.0 ± 227.1 pg/mL) compared with PREG (1035.0 ± 101.1 pg/mL) and Con (589.3 ± 82.67 pg/mL), with the highest values observed in PE with IUGR (2624.0 ± 421.4 pg/mL; n = 6). Plasma sTNFR2 was higher during pregnancy (PE: 1836.0 ± 198.7 pg/mL; PREG: 1697.0 ± 95.0 pg/mL) compared with Con (598.3 ± 82.7 pg/mL). Urinary levels of sTNFR1 and sTNFR2 were higher in PE and PREG compared with the Con group. Abundance of TNFR1 mRNA in peripheral blood leukocytes was strongly correlated with plasma levels of sTNFR1 in PE. However, TNFR2 mRNA accumulation in leukocytes did not correlate with sTNFR2 plasma levels. The level of sTNFR1 in plasma was correlated with body weight of the newborn (r = -0.56). The data suggest that maternal leukocytes contribute to sTNFR1 levels in plasma in association with decreasing newborn weight and PE with concomitant IUGR.

The gold standard to characterize idiopathic inflammatory myopathies is the morphological, immunohistochemical and immunopathological analysis of muscle biopsy. Mononuclear cell infiltrates and muscle fiber necrosis are commonly shared histopathological features. Inflammatory cells that surround, invade and destroy healthy muscle fibers expressing MHC class I antigen are the typical pathological finding of polymyositis. Perifascicular atrophy and microangiopathy strongly support a diagnosis of dermatomyositis. Randomly distributed necrotic muscle fibers without mononuclear cell infiltrates represent the histopathological hallmark of immune-mediated necrotizing myopathy; meanwhile, endomysial inflammation and muscle fiber degeneration are the two main pathological features in sporadic inclusion body myositis. A correct differential diagnosis requires immunopathological analysis of the muscle biopsy and has important clinical implications for therapeutic approach. In particular, unnecessary, potentially harmful, immune-suppressive therapy should be avoided alike in dystrophic myopathies with secondary inflammation.

Tacrolimus, also known as FK506, is an immunosuppressive agent widely used for the prevention of acute allograft rejection in organ transplantation and for the treatment of immunological diseases. This study reports two male patients who underwent solid organ transplantation (liver and kidney). After transplant, the patients received continuous immunosuppressive therapy with oral tacrolimus and later presented clinical manifestations and laboratory signs of myopathy. Muscle biopsies of both patients clearly documented an inflammatory myopathy with the histological features of polymyositis including CD8 + T cells which invaded healthy muscle fibers and expressed granzyme B and perforin, many CD68 + macrophages and MHC class I antigen upregulation on the surface of most fibers. Because of the temporal association while receiving tacrolimus and since other possible causes for myopathy were excluded, the most likely cause of polymyositis in our patients was tacrolimus toxicity. We suggest that patients on tacrolimus should be carefully monitored for serum CK levels and clinical signs of muscle disease.

CNS complications of varicella-zoster virus (VZV) occur mainly in immunocompromised or elderly patients and include meningitis, myelitis, acute encephalitis, vasculopathy, and, rarely, cerebellitis.1–8

The pathophysiology of postural abnormalities in patients with Parkinson’s disease is poorly understood. In the present study, 13 patients with Pisa syndrome (PS) underwent EMG study of paraspinal lumbar (L2–L4) and thoracic (T8–T10) muscles, and of non-paraspinal muscles. Patients also underwent a whole spine X-ray and an MRI assessment of paraspinal muscles (L1–S1). The EMG evaluation disclosed two main patterns: patients with pattern I (n = 6, hyperactivity of lumbar paraspinals ipsilateral to the trunk leaning side) or pattern II (n = 7: hyperactivity of lumbar paraspinals contralateral to the trunk leaning side. In pattern I, half the patients also had ipsilateral hyperactivity of the thoracic paraspinals, the other half had contralateral thoracic hyperactivity; in pattern II, thoracic paraspinal hyperactivity was contralateral in all patients (like the lumbar paraspinal hyperactivity). Non-paraspinal muscles were hyperactive ipsilaterally in four of six patients with pattern I and in all patients with pattern II. The MRI showed mild muscular atrophy with fatty degeneration in patients with pattern I, whereas in pattern II patients this was greater and prevalent on paraspinal lumbar muscles ipsilateral to the leaning side. The present data support the hypothesis that two main patterns of muscular activation are associated with PS. In both patterns, hyperactivity of contralateral paraspinal muscles is probably compensatory for the trunk leaning.

INTRODUCTION Calpain 3 deficiency causes limb girdle muscular dystrophy type 2A, which is one of the most common forms of limb girdle muscular dystrophy. Nevertheless, calpainopathy is not always associated with mutations in the specific gene and secondary reduction in protein expression has been described. CASE REPORT We report a case of a 43-year-old man who complained of thigh muscle stiffness and had muscle hypertrophy of both vastus medialis with prolonged myotonic contraction by percussion. A muscle biopsy showed dystrophic features and calpain 3 deficiency was shown by immunoblot analysis although mutations in the specific gene were not found. Known cases of secondary calpain 3 protein deficiency were ruled out and mutations in MD1 and MD2 genes were excluded. CONCLUSIONS This patient represents the first case of calpain 3 deficiency with selective pseudohypertrophy of vastus medialis muscles.

Sporadic inclusion-body myositis (IBM) is the most common, progressive muscle disease of older individuals. We investigated the presence of BACE1 and BACE2-two beta secretases that cleave amyloid-beta-precursor protein-in muscle-biopsy samples from patients with IBM and from controls. On immunofluorescence, BACE1 and BACE2 co-localised with amyloid beta in IBM vacuolated muscle fibres, but were not found in controls. Immunoblotting showed increased BACE2 but not BACE1 in patients with IBM compared with controls. Our study suggests that both of these proteases might participate in processing of amyloid-beta-precursor protein in IBM muscle fibres.

Objective: To evaluate the muscle biopsy findings from 240 patients who had isolated muscle pain. Methods: Histopathology, immunohistochemistry for dystrophin, dystrophin-related proteins, major histocompatibility complex type I, and biochemical analysis of glycolytic and mitochondrial respiratory chain enzymes were performed on muscle biopsies. An attempt was made to correlate pathologic data and clinical findings (sex, age, quality and distribution of symptoms, serum CK levels, and EMG recording). Results: We have described five groups of patients based on muscle biopsy findings: 51.6% had heterogeneous myopathic abnormalities; only 19% of them had a specific myopathic picture, i.e., central nuclei myopathy, central core disease, myopathy with tubular aggregates or with trabecular fibers or abnormalities of fiber typing; 20% had signs of respiratory chain dysfunction but only one patient had a probable mitochondrial disease; 7% had a neurogenic pattern; 2.4% had a metabolic myopathy (phosphorylase or phosphofructokinase deficiency); and 19% had normal muscle biopsy. No clear-cut correlation between muscle biopsy and clinical data was observed except for those patients with a metabolic myopathy. Conclusions: The probability that a patient complaining only of muscle pain and with a normal neurologic examination has a definite muscle pathology is 2%. Only patients with sole exercise-related muscle pain and sCK seven times higher than the normal value are strongly suspected of having a metabolic myopathy. A rigorous selection of patients is needed before performing a muscle biopsy.

Acquired isolated unilateral or bilateral blepharoptosis has many aetiologies. When the pupils are normal, a myasthenic syndrome or myopathy has to be ruled out. If the tests for myasthenia gravis are negative, the next step is to perform a muscle biopsy to establish a diagnosis. Muscle examination may show a mitochondrial disorder, non-specific abnormalities or be quite normal. We identified three patients, who had previously undergone various investigations, including a muscle biopsy, whose lid ptosis disappeared using eye drops containing naphazoline nitrate, a sympathomimetic drug, thus suggesting partial Horner's syndrome. We emphasise the usefulness of this simple and cheap test before performing more traumatic and expensive investigations.

Extraocular muscle involvement, although frequently described in neuromuscular diseases, is not usually reported in muscular dystrophies, except for oculopharyngeal muscular dystrophy.1 Limb girdle muscular dystrophy 1C (LGMD1C) is caused by mutations in the caveolin-3 gene (CAV3) that codes for the muscle isoform of caveolin, which is the main component of caveolae sarcoplasmic microdomains involved in signal transduction mechanisms.2 Mutations in CAV3 cause at least three other muscle phenotypes: distal myopathy, isolated hyperCKaemia and rippling muscle disease (RMD), an autosomal dominant disorder characterised by mechanically triggered contractions of skeletal muscle.2 The clinical features of the LGMD phenotype include calf hypertrophy and mild to moderate proximal muscle weakness but not external ophthalmoparesis (EO). We report on a patient with EO and a CAV3 linked LGMD phenotype without clinical or electric features of rippling phenomenon. A 37-year-old man, healthy until age 25 years, came to our attention for progressive limb weakness causing difficulty in climbing stairs and running. Family members (parents, two maternal aunts, maternal uncle, paternal uncle and six first cousins) were reported to be healthy but refused to be examined. Neurological examination showed extraocular muscle paresis with vertical and lateral gaze limitation, bilateral exophthalmos and partial blepharoptosis, more evident …