RESUMO
INTRODUCTION: In this study we aimed to determine the contribution of the E2 (reference electrode) to the compound muscle action potential (CMAP) amplitude during fibular motor recording to the tibialis anterior (TA) when E2 is placed over routine referential vs. alternative sites. METHODS: The CMAP was obtained from 10 healthy subjects, using the active electrode (E1) over sites routinely used as E2 for the TA, whereas the E2 was over the contralateral knee. The same procedure was performed with the E1 over alternative E2 sites. RESULTS: Significant electrical signal was captured over routine E2 placement sites. Among the tested alternative E2 sites, the ipsilateral patella (especially its medial aspect) was the most electrically silent. DISCUSSION: Using alternative E2 sites with near isoelectric recordings can optimize near-field potential measurement in the fibular motor recording to the TA and represents a more accurate way of measuring nerve and muscle function. Muscle Nerve 59:249-253, 2019.
Assuntos
Potenciais de Ação/fisiologia , Músculo Esquelético/fisiologia , Condução Nervosa/fisiologia , Nervo Fibular/fisiologia , Adulto , Idoso , Estimulação Elétrica , Eletrodos , Eletromiografia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Our objective was to determine the utility of motor unit number index (MUNIX) and neurophysiological index (NI) as surrogate biomarkers of disease progression in limbs without clinical signs of lower motor neuron (LMN) involvement from patients with slowly progressive amyotrophic lateral sclerosis (ALS). METHODS: Patients with slowly progressive ALS and at least 1 clinically unaffected limb were prospectively enrolled. Clinical signs of LMN loss and results from hand-held dynamometer (HHD), revised ALS Functional Rating Scale (ALSFRS-R), mean-MUNIX (from 3 different muscles), and NI were longitudinally recorded. RESULTS: Eighteen patients with 43 presymptomatic muscles were evaluated. Twenty-seven muscles remained clinically unaffected during study, with stable ALSFRS-R subscores and HHD measures. However, a significant decline in mean-MUNIX and NI was detected. DISCUSSION: Mean-MUNIX and NI were more sensitive than clinical measures at detecting LMN loss in presymptomatic limbs from patients with slowly progressive ALS. Therefore, these electrophysiological biomarkers should be included in early study phases as meaningful outcome measures. Muscle Nerve 58: 204-212, 2018.
Assuntos
Esclerose Lateral Amiotrófica/patologia , Neurônios Motores/patologia , Fibras Musculares Esqueléticas/patologia , Potenciais de Ação , Idoso , Biomarcadores , Contagem de Células , Progressão da Doença , Eletrodiagnóstico , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Dinamômetro de Força Muscular , Estudos Prospectivos , Resultado do TratamentoRESUMO
Solid organ transplantation is a significant development in the treatment of chronic kidney, liver, heart and lung diseases. This therapeutic approach has increased patient survival and improved quality of life. New surgical techniques and immunosuppressive drugs have been developed to achieve better outcomes. However, the variety of neurological complications following solid organ transplantation is broad and carries prognostic significance. Patients may have involvement of the central or peripheral nervous system due to multiple causes that can vary depending on time of onset after the surgical procedure, the transplanted organ, and the intensity and type of immunosuppressive therapy. Neurological manifestations following solid organ transplantation pose a diagnostic challenge to medical specialists despite extensive investigation. This review aimed to provide a practical approach to help neurologists and clinicians assess and manage solid organ transplant patients presenting with acute or chronic neurological manifestations.
Assuntos
Doenças do Sistema Nervoso/etiologia , Transplante de Órgãos/efeitos adversos , HumanosRESUMO
ABSTRACT Solid organ transplantation is a significant development in the treatment of chronic kidney, liver, heart and lung diseases. This therapeutic approach has increased patient survival and improved quality of life. New surgical techniques and immunosuppressive drugs have been developed to achieve better outcomes. However, the variety of neurological complications following solid organ transplantation is broad and carries prognostic significance. Patients may have involvement of the central or peripheral nervous system due to multiple causes that can vary depending on time of onset after the surgical procedure, the transplanted organ, and the intensity and type of immunosuppressive therapy. Neurological manifestations following solid organ transplantation pose a diagnostic challenge to medical specialists despite extensive investigation. This review aimed to provide a practical approach to help neurologists and clinicians assess and manage solid organ transplant patients presenting with acute or chronic neurological manifestations.
RESUMO O transplante de órgãos sólidos é um importante avanço no tratamento de doenças crônicas renal, hepática e cardíaca. Esta terapia tem aumentado a sobrevida e melhorado a qualidade de vida dos pacientes. Novas técnicas cirúrgicas e imunossupressores tem sido desenvolvidos para alcançar melhores desfechos. Entretanto, a variedade de complicações neurológicas que acompanham o transplante de órgãos sólidos é ampla, e carrega significado prognóstico. Pacientes podem ter acometimento do sistema nervoso central ou periférico devido a múltiplas causas que podem variar conforme o tempo após a realização da cirurgia, órgão transplantado e grau e tipo de terapia de imunossupressão. Manifestações neurológicas após o transplante de órgãos sólidos representam um desafio diagnóstico para médicos especialistas apesar de extensa investigação. O objetivo desta revisão é oferecer uma abordagem prática para ajudar neurologistas e clínicos a avaliar e manejar pacientes com transplante de órgãos sólidos que se apresentem com manifestações neurológicas agudas ou crônicas.
Assuntos
Humanos , Transplante de Órgãos/efeitos adversos , Doenças do Sistema Nervoso/etiologiaRESUMO
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant degenerative disease. Pathological studies have demonstrated not only cerebellar and brainstem atrophy, but substantia nigra, motoneurons, basal ganglia, thalamus, and peripheral nerves involvement. These findings may explain non-motor and extra-cerebellar features in SCA2. We accessed the non-motor symptoms and extra-cerebellar signs in SCA2 patients in order to provide a better understanding on pathophysiological mechanisms and natural history of brain degeneration in the disease. Thirty-three SCA2 patients were evaluated and compared with 26 healthy subjects. We investigated the following variables: sleep disorders, cognitive deficit, olfactory impairment, urinary dysfunction, psychiatric symptoms, cramps, pain, movement disorders, and weight loss. SCA2 had a high frequency of REM sleep behavior disorder (48.48 %, N = 16) as well as excessive daytime sleepiness (42.42 %, N = 14). Chorea was present in 15.15 % (N = 5), dystonia in 27.27 % (N = 9), and parkinsonism in 27.27 % (N = 9). Slow saccadic pursuit was present in 87.87 % (N = 29) and ophtalmoparesis in 78.78 % (N = 26) of patients. Regarding sleep disorders, 18.18 % (N = 6) of patients had restless leg syndrome. Dysphagia was present in 39.39 % (N = 13), weight loss 24.24 % (N = 8), and urinary dysfunction 27.27 % (N = 9). Cramps was present in only 6 % of patients (N = 2). This study highlighted the high frequency of non-motor symptoms and extra-cerebellar signs in SCA2. Our findings demonstrate the widespread of nervous system involvement in SCA2 patients and contribute to better understand the natural history of brain degeneration in this genetic condition.
Assuntos
Ataxias Espinocerebelares/fisiopatologia , Adulto , Feminino , Humanos , Entrevistas como Assunto , Masculino , Entrevista Psiquiátrica Padronizada , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Ataxias Espinocerebelares/complicações , Ataxias Espinocerebelares/psicologiaRESUMO
BACKGROUND: VCP (valosin-containing protein gene) variants have been associated with peripheral and central neurodegenerative processes, including inclusion body myopathy (IBM), Paget disease of bone (PDB), frontotemporal dementia (FTD), and familial amyotrophic lateral sclerosis (ALS) type 14. The combination of IBM, PDB (IBMPFD1) can presented in one individual. However, the association of IBMPFD1 and ALS in the same family is rare. METHODS: We reported three individuals from a Brazilian kindred with intrafamilial phenotype variability. Whole exome sequencing (WES) of the proband was performed and revealed a novel VCP variant. VCP Sanger sequencing was performed in the proband and his family members to confirm WES finding and segregation. We performed a systematic review of the literature regarding the genotypic-phenotypic VCP correlations. RESULTS: Each individual presented with either myopathy with rimmed vacuoles, ALS, or FTD. There was no PDB. WES of the proband identified the heterozygous variant c.271A>T (p.Asn91Tyr) in the exon 3 of VCP. Sanger sequencing confirmed the segregation of this variant in an autosomal-dominant pattern. CONCLUSION: This study expands the genotypic spectrum of the missense mutations of the VCP gene with a novel p.Asn91Tyr variant found in a Brazilian family presenting with the unusual intrafamiliar association of myopathy with rimmed vacuoles, ALS and FTD.
Assuntos
Adenosina Trifosfatases/genética , Esclerose Lateral Amiotrófica/genética , Proteínas de Ciclo Celular/genética , Saúde da Família , Demência Frontotemporal/genética , Doenças Musculares/genética , Mutação/genética , Fenótipo , Adulto , Idoso , Análise Mutacional de DNA , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Proteína com ValosinaRESUMO
Peripheral neuropathy is frequent in spinocerebellar ataxia type 2 (SCA2), but the pattern and characteristics of nerve involvement are still an unsettled issue. This study aimed to evaluate the prevalence, extent, and distribution of nerve involvement in SCA2 patients through neurophysiological studies. Thirty-one SCA2 patients and 20 control subjects were enrolled in this study. All subjects were prospectively evaluated through electromyography, including nerve conduction, needle electromyography in proximal and distal muscles of the upper and lower limbs, and sural radial amplitude ratio (SRAR). We aimed to differentiate distal axonopathy from diffuse nerve commitment, characterizing neuronopathy. Nerve involvement was observed in 83.6 % (26 individuals) of SCA2 patients. Among these, 19 had diffuse sensory abnormalities on nerve conduction predominantly on the upper limbs, with diffuse chronic denervation on needle electromyography and elevated SRAR values. Four individuals had only diffuse sensory involvement, and 2 had only motor involvement on needle evaluation and normal nerve conduction. These were interpreted as neuronopathy due to the diffuse distribution of the involvement. One individual had distal sensory axonopathy, with lower limb predominance. In this study, we found neuronopathy as the main pattern of nerve involvement in SCA2 patients and that motor involvement is a frequent feature. This information brings new insights into the understanding of the pathophysiology of nerve involvement in SCA2 and sets some key points about the phenotype, which is relevant to guide the genetic/molecular diagnosis.
Assuntos
Nervos Periféricos/fisiopatologia , Ataxias Espinocerebelares/fisiopatologia , Adulto , Eletromiografia , Feminino , Humanos , Extremidade Inferior/fisiopatologia , Masculino , Músculo Esquelético/fisiopatologia , Condução Nervosa , Neurofisiologia , Fenótipo , Estudos Prospectivos , Transtornos de Sensação/etiologia , Transtornos de Sensação/fisiopatologia , Ataxias Espinocerebelares/complicações , Extremidade Superior/fisiopatologiaRESUMO
Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia characterized by a combination of neurological involvement, cardiomyopathy, and skeletal and glucose metabolism disturbances. FRDA is caused by mutations in FXN gene that results in reduction of mRNA and protein levels of frataxin. Previous microarray and real-time quantitative PCR (qPCR) studies showed that the downregulation of FXN is associated with a complex gene expression profile. However, these studies showed a wide variability in the subset of genes with altered expression among tissues and models. Genes differentially expressed in peripheral blood cells (PBC) could potentially help in the understanding of FRDA pathophysiology and also function as reliable disease biomarkers obtained from an easily accessible tissue, which could have implications in clinical practice. This study aimed to validate by qPCR the expression of 26 genes, revealed as differentially expressed by other studies, using peripheral blood cells (PBC) of 11 FRDA patients compared to 11 healthy controls. We found a robust downregulation of FXN, but no statistically significant differences were found between FRDA and controls for the remaining genes. Except for FXN, our study did not find a differential gene expression profile in PBC of FRDA patients and a reliable gene expression profile biomarker in a clinical relevant and noninvasive tissue remains unclear.
Assuntos
Ataxia de Friedreich/sangue , Adolescente , Adulto , Biomarcadores/sangue , Feminino , Ataxia de Friedreich/genética , Expressão Gênica , Humanos , Proteínas de Ligação ao Ferro/sangue , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Mensageiro/sangue , Adulto Jovem , FrataxinaRESUMO
Alteplase (recombinant tissue plasminogen activator [rt-PA]) label approval by the Food and Drug Administration remarks the contraindication of its use with known intracranial neoplasm because of potential bleeding complications. Despite this concern, the real risk of intracerebral bleeding in patients with intracranial neoplasms treated with rt-PA is unknown, and there are few reports of thrombolysis in patients with brain tumors. We report a case of a 78-year-old man who was seen in our emergency department within 2 hours from sudden onset of aphasia, right-sided hemiplegia, hypoesthesia, and homonymous hemianopsia. The National Institutes of Health Stroke Scale (NIHSS) score at admission was 20. Intra-arterial thrombolysis was performed with administration of .3 mg/kg of alteplase combined with mechanical thrombectomy. At discharge, his NIHSS score was 1, and after 90 days, his modified Rankin score was 1. To our knowledge, this is the first report of intra-arterial thrombolysis in a patient with acute ischemic stroke with an intracranial tumor.
Assuntos
Fibrinolíticos/administração & dosagem , Infarto da Artéria Cerebral Média/tratamento farmacológico , Neoplasias Meníngeas/complicações , Meningioma/complicações , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Angiografia Cerebral/métodos , Avaliação da Deficiência , Humanos , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/diagnóstico , Masculino , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Índice de Gravidade de Doença , Trombectomia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Cerebral infarcts can be overlooked or grossly underestimated in the second and third week after an ischemic stroke. We report a patient who presented with a vanishing stroke on a follow-up brain computed tomography scan, a condition known as the "fogging effect" phenomenon.
Assuntos
Isquemia Encefálica/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Erros de Diagnóstico , Feminino , Humanos , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Fatores de TempoRESUMO
Nitric oxide (NO) acts in both pathological and biological processes. We investigated the role of NO in the regulation of cigarette smoke-induced oxidative stress in rat alveolar macrophages (RAM). RAM collected from Wistar rats were cultured in 5% concentration cigarette smoke extract (CSE) for 1h. RAM exposed to CSE were then co-incubated with L-NAME (LN), L-arginine (LA), N-acetylcysteine (NAC) and both LN and NAC. RAM cultured only with medium was considered as control group. Biochemical analysis were performed to measure cellular metabolism (MTT), nitrite levels, superoxide dismutase (SOD) and glutathione peroxidase activities, reduced glutathione (GSH) and oxidized (GSSG), malondialdehyde and myeloperoxidase activity. During exposure to CSE, increased NO levels were not only associated with an increase of cell activation, but also affected MTT levels in RAM. CSE exposure resulted in significant redox imbalance in RAM. NAC administration affected SOD antioxidant profile regardless NO levels; however nitrite values were associated with GSH/GSSG ratio. In addition, lipid peroxidation appeared to be nitric-oxide dependent. Furthermore, the use of NAC significantly reduced the expression of NFkB normally observed in RAM exposed to CSE. The present results show that NO appeared to be involved in RAM activation, oxidative status maintenance and lipid peroxidation process during exposure to CSE.
Assuntos
Misturas Complexas/toxicidade , Macrófagos Alveolares/efeitos dos fármacos , Nicotiana , Fumaça , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Glutationa/metabolismo , Dissulfeto de Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Macrófagos Alveolares/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , Nitritos/metabolismo , Oxirredução , Peroxidase/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
Neurosarcoidosis (NS) more commonly occurs in the setting of systemic disease. The diagnosis is based on a clinical history suggestive of NS, presence of noncaseating granulomas, and supportive evidence of sarcoid pathology, laboratory, and imaging studies. NS could involve any part of the nervous system and often demands high doses of steroids for symptom control. It presents low response to isolated steroids administration and frequently requires immunosuppressive agents. In NS, lymphocytes are polarized toward an excessive Th1 response, leading to overproduction of TNF-alpha and INF-gama, as well as lL-2 and IL-15. Infliximab, a chimeric monoclonal antibody that neutralizes the biological activity of TNF-alpha, is a new option in the NS treatment. We revised pathophysiology, clinical manifestations, diagnostic work up, and treatment of NS as guidance for the general neurologist.
Assuntos
Encefalopatias/diagnóstico , Encefalopatias/tratamento farmacológico , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/tratamento farmacológico , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Neurosarcoidosis (NS) more commonly occurs in the setting of systemic disease. The diagnosis is based on a clinical history suggestive of NS, presence of noncaseating granulomas, and supportive evidence of sarcoid pathology, laboratory, and imaging studies. NS could involve any part of the nervous system and often demands high doses of steroids for symptom control. It presents low response to isolated steroids administration and frequently requires immunosuppressive agents. In NS, lymphocytes are polarized toward an excessive Th1 response, leading to overproduction of TNF-alpha and INF-gama, as well as lL-2 and IL-15. Infliximab, a chimeric monoclonal antibody that neutralizes the biological activity of TNF-alpha, is a new option in the NS treatment. We revised pathophysiology, clinical manifestations, diagnostic work up, and treatment of NS as guidance for the general neurologist.
A neurosarcoidose (NS) ocorre frequentemente no contexto de doença sistêmica. O diagnóstico é baseado na história clínica sugestiva de NS, presença de granulomas não-caseosos e achados anatomopatológicos, laboratoriais e radiológicos de sarcoidose. A NS causa manifestações neurológicas variadas, que apresentam, em geral, baixa resposta ao corticoide isoladamente e, portanto, necessitam uso de imunossupressores. Na NS, os linfócitos estão polarizados para resposta Th1 excessiva, levando à produção aumentada de TNF-alfa e IFN-gama, assim como IL-2 e IL-15. Infliximabe, um anticorpo monoclonal quimérico que neutraliza a atividade biológica do TNF-alfa, é uma nova opção no tratamento da NS. Revisou-se a fisiopatologia, as manifestações clínicas, o diagnóstico e o tratamento da NS para orientar neurologistas gerais.
Assuntos
Humanos , Encefalopatias/diagnóstico , Encefalopatias/tratamento farmacológico , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/tratamento farmacológico , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Diagnóstico Diferencial , Imageamento por Ressonância MagnéticaRESUMO
Multiple system atrophy (MSA) is characterized by a variable combination of cerebellar ataxia, parkinsonism and pyramidal signs associated with autonomic failure. Classically, cognitive impairment was not considered a clinical feature of MSA and dementia was pointed out as an exclusion diagnostic criteria. Based on comprehensive neuropsychological assessment, cognitive impairment was found to be a frequent feature in MSA, and clinically-defined dementia is now reported in 14-16% of cases. This article reviews the current data on cognitive impairment in MSA along with its neuropsychological profile and pathophysiology.
A Atrofia de Múltiplos Sistemas (AMS) é caracterizada por uma combinação variável de ataxia cerebelar, parkinsonismo e sinais piramidais, associados à disfunção autonômica. Classicamente, o comprometimento cognitivo não é considerado como manifestação clínica da AMS e a demência é apontada como um critério de exclusão para o diagnóstico. Baseado na avaliação neuropsicológica ampla, o comprometimento neuropsicológico revelou-se frequente na AMS e a presença de demência é atualmente descrita em 14-16% dos casos. Este artigo revisa os dados atuais sobre o comprometimento cognitivo na AMS, seu perfil neuropsicológico e fisiopatologia.
Assuntos
Humanos , Atrofia de Múltiplos Sistemas , Transtornos Parkinsonianos , Demência , Disfunção Cognitiva , Testes NeuropsicológicosRESUMO
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder characterized by late-infantile onset spastic ataxia and other neurological features. ARSACS has a high prevalence in northeastern Quebec, Canada. Several ARSACS cases have been reported outside Canada in recent decades. This is the first report of typical clinical and neuroimaging features in a Brazilian family with probable diagnosis of ARSACS.
Assuntos
Espasticidade Muscular/diagnóstico , Ataxias Espinocerebelares/congênito , Adulto , Amitriptilina/análogos & derivados , Amitriptilina/uso terapêutico , Baclofeno/uso terapêutico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Relaxantes Musculares Centrais/uso terapêutico , Espasticidade Muscular/tratamento farmacológico , Linhagem , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/tratamento farmacológicoRESUMO
We report a case of a non-Hodgkin's lymphoma in a young woman presenting with an abdominal mass and an unusual instance of cranial nerve palsies mimicking Gradenigo's syndrome. This condition is characterized by a triad of otorrhea, facial pain and diplopia, related to otitis media in the pre-antibiotic era. Incomplete and atypical clinical features of Gradenigo's syndrome have been described and noninfectious causes may mimic this condition. Careful clinical history and physical examination, including neuroimaging, are necessary to make a differential diagnosis.
RESUMO
Multiple system atrophy (MSA) is characterized by a variable combination of cerebellar ataxia, parkinsonism and pyramidal signs associated with autonomic failure. Classically, cognitive impairment was not considered a clinical feature of MSA and dementia was pointed out as an exclusion diagnostic criteria. Based on comprehensive neuropsychological assessment, cognitive impairment was found to be a frequent feature in MSA, and clinically-defined dementia is now reported in 14-16% of cases. This article reviews the current data on cognitive impairment in MSA along with its neuropsychological profile and pathophysiology.
A Atrofia de Múltiplos Sistemas (AMS) é caracterizada por uma combinação variável de ataxia cerebelar, parkinsonismo e sinais piramidais, associados à disfunção autonômica. Classicamente, o comprometimento cognitivo não é considerado como manifestação clínica da AMS e a demência é apontada como um critério de exclusão para o diagnóstico. Baseado na avaliação neuropsicológica ampla, o comprometimento neuropsicológico revelou-se frequente na AMS e a presença de demência é atualmente descrita em 14-16% dos casos. Este artigo revisa os dados atuais sobre o comprometimento cognitivo na AMS, seu perfil neuropsicológico e fisiopatologia.