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INTRODUCTION/AIMS: Critical illness myopathy (CIM) and critical illness polyneuropathy (CIP) are common disorders associated with substantial morbidity. Electrodiagnostic studies (EDx) are effective in diagnosing CIM/CIP and identifying mimicking conditions. We surveyed intensive care unit (ICU) providers to better understand their approach to ICU-acquired weakness (ICU-AW) and the perceived utility of EDx. METHODS: This was a single health system, Web-based survey of ICU providers. RESULTS: Survey responses were received from 52 providers with a response rate of 22.1%. Most providers were somewhat familiar with CIM/CIP and median perceived prevalence was 30-49%. The majority (92.3%) of providers had no standard evaluation approach for ICU-AW. Electrodiagnostic testing was commonly considered, but many providers obtained it infrequently in presumed CIM/CIP cases. Electrodiagnostic studies were used to rule out other causes of weakness or to confirm the diagnosis of CIM/CIP. Many providers ordered EDx within 1 wk of identifying weakness. Finally, EDx were overshadowed by personal experience as the most helpful management tool for ICU-AW. DISCUSSION: Overall, ICU providers perceive that CIM/CIP are commonly encountered, but they may not have a standard approach to evaluation. Clinical experience increased familiarity of ICU-AW and is central to management. EDx results are usually thought to be helpful, albeit not often ordered, and more study is needed to determine when implementation is of most assistance. Increasing education and developing institutional standards may lead to increased awareness and improved evaluation of CIM/CIP, but more study is needed to determine if algorithmic approaches would change patient outcomes.
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Doenças Musculares , Polineuropatias , Estado Terminal , Humanos , Unidades de Terapia Intensiva , Doenças Musculares/complicações , Polineuropatias/complicaçõesRESUMO
BACKGROUND/OBJECTIVE: Immune-mediated necrotizing myopathy (IMNM) is a subtype of myositis that is associated with a refractory phenotype and poorer prognosis. The aim of the study was to provide single large center experience of outcomes of intravenous immunoglobulin (IVIg) for patients with IMNM using longitudinally collected data. METHODS: This case series longitudinally evaluated 4 of the 6 myositis core set measures at baseline and at 3 and 6 months after IVIg on 20 adult IMNM patients from 2014 to 2019 at the University of Pittsburgh. We assessed patients for improvement in core set measures, prednisone dose, adverse effects, and by the "limited" ACR/EULAR 2016 myositis response criteria. The mean differences in CK and manual muscle testing (MMT-8) were compared using a paired t test. A clinically significant response was defined as a >10% absolute improvement in the MMT-8 and a >50% absolute reduction in serum CK at 6 months of IVIg. RESULTS: Intravenous immunoglobulin treatment was associated with marked improvement in IMNM patients, with 85% of patient meeting clinically significant response. The median (interquartile range) relative percent improvement in CK level was 96% (85%-98%) and in MMT was 29% (14%-36%) at 6 months.There was a significant reduction in the mean (SD) dose of prednisone at 6 months and had minimal adverse effects. In addition, with IVIg, most (13/14) patients had at least minimal improvement as per ACR/EULAR 2016 myositis response criteria. CONCLUSIONS: Based on objective, meaningful improvement in MMT-8 and CK as well as marked reduction in prednisone doses with acceptable tolerability, early implementation of IVIg should be considered in adult IMNM.
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Doenças Autoimunes , Doenças Musculares , Miosite , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Miosite/diagnóstico , Miosite/tratamento farmacológicoRESUMO
Patients with pulmonary emphysema often develop locomotor muscle dysfunction, which is independently associated with disability and higher mortality in that population. Muscle dysfunction entails reduced force generation capacity, which partially depends on fibers' oxidative potential, yet very little mechanistic research has focused on muscle respiration in pulmonary emphysema. Using a recently established animal model of pulmonary emphysema-driven skeletal muscle dysfunction, we found downregulation of SDHC (succinate dehydrogenase subunit C) in association with lower oxygen consumption and fatigue tolerance in locomotor muscles. Reduced SDH activity has been previously observed in muscles from patients with pulmonary emphysema, and we found that SDHC is required to support respiration in cultured muscle cells. Moreover, in vivo gain of SDH function in emphysema animals' muscles resulted in better oxygen consumption rate and fatigue tolerance. These changes correlated with a larger number of relatively more oxidative type 2-A and 2X fibers and a reduced amount of 2B fibers. Our data suggest that SDHC is a key regulator of respiration and fatigability in pulmonary emphysema-driven skeletal muscles, which could be impactful in developing strategies aimed at attenuating this comorbidity.
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Fadiga/enzimologia , Proteínas de Membrana/metabolismo , Músculo Esquelético/enzimologia , Consumo de Oxigênio , Enfisema Pulmonar/enzimologia , Animais , Modelos Animais de Doenças , Fadiga/genética , Fadiga/patologia , Fadiga/fisiopatologia , Proteínas de Membrana/genética , Camundongos , Camundongos Transgênicos , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Enfisema Pulmonar/genética , Enfisema Pulmonar/patologia , Enfisema Pulmonar/fisiopatologiaRESUMO
BACKGROUND: To collect preliminary data on the effects of mexiletine on cortical and axonal hyperexcitability in sporadic amyotrophic lateral sclerosis (ALS) in a phase 2 double-blind randomized controlled trial. METHODS: Twenty ALS subjects were randomized to placebo and mexiletine 300 or 600 mg daily for 4 wk and assessed by transcranial magnetic stimulation and axonal excitability studies. The primary endpoint was change in resting motor threshold (RMT). RESULTS: RMT was unchanged with 4 wk of mexiletine (combined active therapies) as compared to placebo, which showed a significant increase (P = .039). Reductions of motor evoked potential (MEP) amplitude (P = .013) and accommodation half-time (P = .002), secondary outcome measures of cortical and axonal excitability, respectively, were also evident at 4 wk on mexiletine. CONCLUSIONS: The relative stabilization of RMT in the treated subjects was unexpected and could be attributed to unaccounted sources of error or chance. However, a possible alternative cause is neuromodulation preventing an increase. The change in MEP amplitude and accommodation half-time supports the reduction of cortical and axonal hyperexcitability with mexiletine.
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Esclerose Lateral Amiotrófica/tratamento farmacológico , Axônios , Excitabilidade Cortical , Mexiletina/uso terapêutico , Bloqueadores do Canal de Sódio Disparado por Voltagem/uso terapêutico , Adulto , Idoso , Esclerose Lateral Amiotrófica/fisiopatologia , Método Duplo-Cego , Eletrodiagnóstico , Eletromiografia , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Nervo Mediano/fisiopatologia , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Dados Preliminares , Estimulação Magnética TranscranianaRESUMO
Diffusion MRI tractography has been used to map the axonal structure of the human brain, but its ability to detect neuronal injury is yet to be explored. Here we report differential tractography, a new type of tractography that utilizes repeat MRI scans and a novel tracking strategy to map the exact segment of fiber pathways with a neuronal injury. We examined differential tractography on multiple sclerosis, Huntington's disease, amyotrophic lateral sclerosis, and epileptic patients. The results showed that the affected pathways shown by differential tractography matched well with the unique clinical symptoms of the patients, and the false discovery rate of the findings could be estimated using a sham setting to provide a reliability measurement. This novel approach enables a quantitative and objective method to monitor neuronal injury in individuals, allowing for diagnostic and prognostic evaluation of brain diseases.
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Esclerose Lateral Amiotrófica/diagnóstico por imagem , Imagem de Tensor de Difusão/normas , Epilepsia/diagnóstico por imagem , Doença de Huntington/diagnóstico por imagem , Esclerose Múltipla/diagnóstico por imagem , Neurônios/patologia , Adulto , Esclerose Lateral Amiotrófica/fisiopatologia , Biomarcadores , Epilepsia/fisiopatologia , Feminino , Humanos , Doença de Huntington/fisiopatologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Adulto JovemRESUMO
INTRODUCTION: Since the late 1980s, critical illness myopathy (CIM) and critical illness polyneuropathy (CIP) have been increasingly recognized in the intensive care unit (ICU). We explored whether these causes of ICU weakness were now more likely to lead to electrodiagnostic studies (EDX) at our institution than they were 19-20 years earlier. METHODS: We reviewed 100 consecutive ICU patients who underwent EDX from 2009 to 2015 and compared them to a previously reported study population from 1990-1995. RESULTS: Thirty-seven (39%) had CIM, CIP, or both versus 55% in the previous study (P = 0.04). Thirty-four (36%) were diagnosed with "traditional" pre-ICU causes of weakness, such as motor neuron disease or Guillain-Barre syndrome, versus 29% in the earlier study (P = 0.3). DISCUSSION: CIM and CIP continue to be common disorders that lead to ICU EDX, but their proportion declined compared with 19-20 years earlier, possibly due to the perceived role and selective use of EDX in the ICU. Muscle Nerve 57: 772-776, 2018.
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Eletrodiagnóstico/métodos , Unidades de Terapia Intensiva , Doenças Musculares/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
Diffusion MRI enabled in vivo microstructural imaging of the fiber tracts in the brain resulting in its application in a wide range of settings, including in neurological and neurosurgical disorders. Conventional approaches such as diffusion tensor imaging (DTI) have been shown to have limited applications due to the crossing fiber problem and the susceptibility of their quantitative indices to partial volume effects. To overcome these limitations, the recent focus has shifted to the advanced acquisition methods and their related analytical approaches. Advanced white matter imaging techniques provide superior qualitative data in terms of demonstration of multiple crossing fibers in their spatial orientation in a three dimensional manner in the brain. In this review paper, we discuss the advancements in diffusion MRI and introduce their roles. Using examples, we demonstrate the role of advanced diffusion MRI-based fiber tracking in neuroanatomical studies. Results from its preliminary application in the evaluation of intracranial space occupying lesions, including with respect to future directions for prognostication, are also presented. Building upon the previous DTI studies assessing white matter disease in Huntington's disease and Amyotrophic lateral sclerosis; we also discuss approaches which have led to encouraging preliminary results towards developing an imaging biomarker for these conditions.
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We developed a novel calcium (Ca(2+)) channel agonist that is selective for N- and P/Q-type Ca(2+) channels, which are the Ca(2+) channels that regulate transmitter release at most synapses. We have shown that this new molecule (GV-58) slows the deactivation of channels, resulting in a large increase in presynaptic Ca(2+) entry during activity. GV-58 was developed as a modification of (R)-roscovitine, which was previously shown to be a Ca(2+) channel agonist, in addition to its known cyclin-dependent kinase activity. In comparison with the parent molecule, (R)-roscovitine, GV-58 has a â¼20-fold less potent cyclin-dependent kinase antagonist effect, a â¼3- to 4-fold more potent Ca(2+) channel agonist effect, and â¼4-fold higher efficacy as a Ca(2+) channel agonist. We have further evaluated GV-58 in a passive transfer mouse model of Lambert-Eaton myasthenic syndrome and have shown that weakened Lambert-Eaton myasthenic syndrome-model neuromuscular synapses are significantly strengthened following exposure to GV-58. This new Ca(2+) channel agonist has potential as a lead compound in the development of new therapeutic approaches to a variety of disorders that result in neuromuscular weakness.
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Agonistas dos Canais de Cálcio/uso terapêutico , Síndrome Miastênica de Lambert-Eaton/tratamento farmacológico , Purinas/uso terapêutico , Tiofenos/uso terapêutico , Potenciais de Ação/efeitos dos fármacos , Adulto , Idoso , Animais , Linhagem Celular , Quinases Ciclina-Dependentes/antagonistas & inibidores , Interpretação Estatística de Dados , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Humanos , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Junção Neuromuscular/efeitos dos fármacos , Neurotransmissores/metabolismo , Técnicas de Patch-Clamp , Fosfotransferases/metabolismo , RoscovitinaRESUMO
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder in which a significant fraction of the presynaptic P/Q-type Ca(2+) channels critical to the triggering of neurotransmitter release at the neuromuscular junction (NMJ) are thought to be removed. There is no cure for LEMS, and the current most commonly used symptomatic treatment option is a potassium channel blocker [3,4-diaminopyridine (3,4-DAP)] that does not completely reverse symptoms and can have dose-limiting side-effects. We previously reported the development of a novel Ca(2+) channel agonist, GV-58, as a possible alternative treatment strategy for LEMS. In this study, we tested the hypothesis that the combination of GV-58 and 3,4-DAP will elicit a supra-additive increase in neurotransmitter release at LEMS model NMJs. First, we tested GV-58 in a cell survival assay to assess potential effects on cyclin-dependent kinases (Cdks) and showed that GV-58 did not affect cell survival at the relevant concentrations for Ca(2+) channel effects. Then, we examined the voltage dependence of GV-58 effects on Ca(2+) channels using patch clamp techniques; this showed the effects of GV-58 to be dependent upon Ca(2+) channel opening. Based on this mechanism, we predicted an interaction between 3,4-DAP and GV-58. We tested this hypothesis using a mouse passive transfer model of LEMS. Using intracellular electrophysiological ex vivo recordings, we demonstrated that a combined application of 3,4-DAP plus GV-58 had a supra-additive effect that completely reversed the deficit in neurotransmitter release magnitude at LEMS model NMJs. This reversal contrasts with the less significant improvement observed with either compound alone. Our data indicate that a combination of 3,4-DAP and GV-58 represents a promising treatment option for LEMS and potentially for other disorders of the NMJ.
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4-Aminopiridina/análogos & derivados , Agonistas dos Canais de Cálcio/farmacologia , Síndrome Miastênica de Lambert-Eaton/metabolismo , Junção Neuromuscular/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/farmacologia , Purinas/farmacologia , Potenciais Sinápticos , Tiofenos/farmacologia , 4-Aminopiridina/farmacologia , Amifampridina , Animais , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Humanos , Síndrome Miastênica de Lambert-Eaton/fisiopatologia , Camundongos , Junção Neuromuscular/fisiopatologia , Purinas/uso terapêutico , Tiofenos/uso terapêuticoRESUMO
BACKGROUND/AIMS: Environmental and occupational exposures are implicated as risk factors for amyotrophic lateral sclerosis (ALS), the etiology of which is largely unknown, although no causal relationships have been established. OBJECTIVE: The aim of the study was to evaluate the associations of personal risk factors and self-reported environmental and occupational exposures with risk of ALS. METHODS: The cases involved ALS patients (n = 66) identified from major neurological centers in Pittsburgh and Philadelphia, Pa., USA, from 2008 to 2010. The age-, race- and sex-matched controls included outpatient hospital and population-based controls (n = 66). A detailed questionnaire obtaining data on occupation, vocational and avocational exposure as well as personal lifestyle factors was administered. RESULTS: Occupational exposure to metals (odds ratio, OR = 3.65; 95% CI: 1.15, 11.60) and pesticides (OR = 6.50; 95% CI: 1.78, 23.77) was related to increased risk of ALS after controlling for smoking and education. No associations were found for occupational exposure to organic or aromatic solvents. CONCLUSION: Workers exposed to metals and pesticides may be at greater risk of ALS. Future research should involve more accurate exposure assessment through the use of job exposure matrices, confirmation of occupation and biomarkers.
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Esclerose Lateral Amiotrófica/etiologia , Exposição Ocupacional/efeitos adversos , Adolescente , Adulto , Idoso , Esclerose Lateral Amiotrófica/epidemiologia , Estudos de Casos e Controles , Exposição Ambiental , Feminino , Humanos , Inseticidas/efeitos adversos , Masculino , Metais/efeitos adversos , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
ABSTRACT: This update begins with a section on inflammatory myopathies covering inclusion body myositis in younger patients, the possibility of a pathogenic role for anti-cN1A antibodies, and a negative trial of arimoclomol in inclusion body myositis. The potential study of Janus kinase inhibitors in dermatomyositis is discussed as well as the possible role of targeted therapy for immune checkpoint inhibitor neuromuscular complications. Next, studies of disease-modifying or potential disease-modifying therapies for inherited myopathies are addressed including the encouraging follow-up study of gene replacement therapy for Duchenne muscular dystrophy (DMD), a negative trial of tamoxifen in DMD, and the complex topic of gene therapy for X-linked myotubular myopathy. A newly identified condition of muscular dystrophy from 3-hydroxy-3-methylglutaryl-CoA reductase mutations is addressed along with possible therapy. Other papers regarding GNE myopathy and long-term outcome of enzyme replacement therapy in infantile onset Pompe disease round out that section. Updates on the expanding spectra of anoctamin-5 myopathies, caveolinopathies, and congenital and mylagic myopathies from CACNA1S mutations follow as well as extensive discussion of Valosin containing protein proteinopathies, comprehensive management of Becker muscular dystrophy, and gastrointestinal complications in adult DMD.
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Doenças Musculares , Humanos , Doenças Musculares/diagnóstico , Doenças Musculares/genética , Doenças Musculares/terapiaRESUMO
Transthyretin amyloidosis (ATTR) is a condition defined by accumulation of insoluble transthyretin amyloid deposits in multiple organs, especially in the peripheral nerve and heart muscle. ATTR may result from transthyretin mutations (variant ATTR or ATTRv) or may occur with normal transthyretin genotype (wild type ATTR or ATTRwt). ATTRwt was previously known as "senile amyloidosis" and causes cardiomyopathy which may lead to heart failure with a preserved ejection fraction, affecting predominantly elderly men. The exact prevalence of ATTRwt in the general population remains unclear, but its occurrence may be underestimated in women. It was observed that a proportion of ATTRwt cardiomyopathy patients may develop slowly progressing neuropathy that is milder and indolent in comparison with typical progressive neuropathy associated with ATTRv. Furthermore, the causality of neuropathy is often uncertain in patients with ATTRwt. Neuropathy symptoms, including distal sensory loss, unsteadiness and (neuropathic) pain are common in elderly patients with multiple potential causes, and as ATTRwt patients are typically older, relatively high prevalence of peripheral neuropathy is expected with frequent comorbidities. Relatively high prevalence of ATTRwt in elderly population contrasts few documented cases of neuropathy caused by ATTRwt, and there is uncertainty whether ATTRwt neuropathy is an infrequent occurrence or a significant manifestation of multisystemic ATTRwt. We review neurologic and musculoskeletal manifestations of ATTRwt and present clinical features of a single center cohort of ATTRwt patients with suspected peripheral neuropathy.
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ABSTRACT: X-linked myopathy with excessive autophagy is a rare disorder caused by a mutation in the vacuolar ATPase assembly factor gene which causes slowly progressive early onset proximal weakness and loss of ambulation by the age of 50-70 years. Electrodiagnostic (EDx) testing usually shows widespread complex repetitive and myotonic discharges, even in muscles unaffected clinically. We report a 65-year-old man who presented with progressive proximal weakness since his teenage years. Extensive workup over 30 years revealed inconclusive EDx and muscle histopathology findings. The diagnosis was finally made with genetic testing. Subsequent neuromuscular ultrasound was more informative of disease severity than repeat EDx and directed a muscle biopsy that showed an autophagic vacuolar myopathy and the novel identification of vacuoles in capillary endothelial cells. Although genetic testing is required for confirmation, in milder cases of X-linked myopathy with excessive autophagy, neuromuscular ultrasound may aid in diagnosis even when EDx findings are inconclusive.
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Doenças Genéticas Ligadas ao Cromossomo X , Músculo Esquelético , Doenças Musculares , Ultrassonografia , Humanos , Masculino , Idoso , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico por imagem , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Musculares/genética , Doenças Musculares/diagnóstico por imagem , Doenças Musculares/diagnóstico , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Eletrodiagnóstico , Autofagia/genética , Testes GenéticosRESUMO
OBJECTIVE: Neurotoxic chemicals are suggested in the etiology of amyotrophic lateral sclerosis (ALS). We examined the association of environmental and occupational risk factors including persistent organochlorine pesticides (OCPs) and ALS risk among cases from the Centers for Disease Control and Prevention National ALS Registry and age, sex, and county-matched controls. METHODS: Participants completed a risk factor survey and provided a blood sample for OCP measurement. ALS cases were confirmed through the Registry. Conditional logistic regression assessed associations between ALS and risk factors including OCP levels. RESULTS: 243 matched case-control pairs (61.7% male, mean [SD] age = 62.9 [10.1]) were included. Fifteen of the 29 OCPs examined had sufficient detectable levels for analysis. Modest correlations of self-reported years of exposure to residential pesticide mixtures and OCP serum levels were found (p<.001). Moreover, occupational exposure to lead including soldering and welding with lead/metal dust and use of lead paint/gasoline were significantly related to ALS risk (OR = 1.77, 95% CI: 1.11-2.83). Avocational gardening was a significant risk factor for ALS (OR = 1.57, 95% CI: 1.04-2.37). ALS risk increased for each 10 ng/g of α-Endosulfan (OR = 1.42, 95% CI: 1.14-1.77) and oxychlordane (OR = 1.24, 95% CI: 1.01-1.53). Heptachlor (detectable vs. nondetectable) was also associated with ALS risk (OR = 3.57, 95% CI: 1.50-8.52). CONCLUSION: This national case-control study revealed both survey and serum levels of OCPs as risk factors for ALS. Despite the United States banning many OCPs in the 1970s and 1980s, their use abroad and long half-lives continue to exert possible neurotoxic health effects.
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Esclerose Lateral Amiotrófica , Exposição Ambiental , Sistema de Registros , Humanos , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/sangue , Esclerose Lateral Amiotrófica/induzido quimicamente , Masculino , Feminino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Idoso , Fatores de Risco , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/estatística & dados numéricos , Praguicidas/sangue , Praguicidas/efeitos adversos , Estados Unidos/epidemiologiaRESUMO
Reduced skeletal muscle mass and oxidative capacity coexist in patients with pulmonary emphysema and are independently associated with higher mortality. If reduced cellular respiration contributes to muscle atrophy in that setting remains unknown. Using a mouse with genetically induced pulmonary emphysema that recapitulates muscle dysfunction, we found that reduced activity of succinate dehydrogenase (SDH) is a hallmark of its myopathic changes. We generated an inducible, muscle-specific SDH knockout mouse that demonstrates lower mitochondrial oxygen consumption, myofiber contractility, and exercise endurance. Respirometry analyses show that in vitro complex I respiration is unaffected by loss of SDH subunit C in muscle mitochondria, which is consistent with the pulmonary emphysema animal data. SDH knockout initially causes succinate accumulation associated with a down-regulated transcriptome but modest proteome effects. Muscle mass, myofiber type composition, and overall body mass constituents remain unaltered in the transgenic mice. Thus, while SDH regulates myofiber respiration in experimental pulmonary emphysema, it does not control muscle mass or other body constituents.
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Respiração Celular , Camundongos Knockout , Contração Muscular , Músculo Esquelético , Enfisema Pulmonar , Succinato Desidrogenase , Animais , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/genética , Enfisema Pulmonar/patologia , Enfisema Pulmonar/etiologia , Succinato Desidrogenase/metabolismo , Succinato Desidrogenase/genética , Camundongos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Complexo II de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/genética , Modelos Animais de Doenças , Camundongos Transgênicos , Mitocôndrias Musculares/metabolismo , Mitocôndrias Musculares/patologia , Consumo de OxigênioRESUMO
INTRODUCTION: Neuromuscular disorders, predominantly critical illness myopathy (CIM) and critical illness polyneuropathy (CIP) occur in approximately one-third of patients in intensive care units. The aim of this study was to review the important role of electrophysiology in this setting. RESULTS: In CIM, sarcolemmal inexcitability causes low amplitude compound muscle action potentials (CMAPs) that may have prolonged durations. Needle electrode examination usually reveals early recruitment of short duration motor unit potentials, often with fibrillation potentials. In CIP, the findings are usually those of a generalized axonal sensorimotor polyneuropathy. Direct muscle stimulation aids in differentiating CIP and CIM and in identifying mixed disorders along with other electrodiagnostic and histopathologic studies. Identifying evolving reductions in fibular CMAP amplitudes in intensive care unit (ICU) patients predicts development of neuromuscular weakness. CONCLUSIONS: Knowledge of the various neuromuscular disorders in critically ill patients, their risk factors, and associated electrodiagnostic findings can lead to development of a rational approach to diagnosis of the cause of neuromuscular weakness in ICU patients.
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Estado Terminal , Doenças Neuromusculares/fisiopatologia , Animais , Cuidados Críticos , Modelos Animais de Doenças , Estimulação Elétrica , Eletrodiagnóstico , Fenômenos Eletrofisiológicos , Humanos , Debilidade Muscular/etiologia , Debilidade Muscular/fisiopatologia , Doenças Musculares/etiologia , Doenças Musculares/fisiopatologia , Bloqueio Neuromuscular , Doenças Neuromusculares/complicações , Doenças Neuromusculares/epidemiologia , Doenças Neuromusculares/prevenção & controle , Polineuropatias/etiologia , Polineuropatias/fisiopatologia , Resultado do TratamentoRESUMO
ABSTRACT: This update begins with the results of a positive trial of intravenous immunoglobulin in dermatomyositis and a study of molecular and morphologic patterns in inclusion body myositis that may explain treatment refractoriness. Single center reports of muscular sarcoidosis and immune-mediated necrotizing myopathy follow. There is also a report of caveolae-associated protein 4 antibodies as a potential biomarker and cause of immune rippling muscle disease. The remainder covers updates on muscular dystrophies as well as congenital and inherited metabolic myopathies with an emphasis on genetic testing. Rare dystrophies, including one involving ANXA11 mutations and a series on oculopharyngodistal myopathy, are discussed.