RESUMO
BACKGROUND: The disease course of polyneuropathy associated with immunoglobulin M monoclonal gammopathy (IgM MGUSP) can be highly variable. In order to identify factors that influence long-term disease outcome, a prospective cohort study was performed of 140 patients with IgM MGUSP over a period of 23 years. METHODS: All patients with IgM MGUSP who were diagnosed in our tertiary referral center for polyneuropathy were eligible. All patients underwent nerve conduction studies and were tested for anti-MAG antibodies. The modified Rankin Scale, graded muscle strength, quantified sensory function, and laboratory testing were performed at 0, 1, 2, and 5 years and at last visit. The primary outcome measure was the risk of developing a modified Rankin Scale score of > or = 3 points. RESULTS: A total of 140 patients with IgM MGUSP fulfilled inclusion criteria (101 [72%] demyelinating, 39 [28%] axonal, 63 [44%] MAG positive). The median age at onset was 59 years (interquartile range 52-67), median disease duration at baseline was 3.2 years (interquartile range 1.9-6). Anti-MAG antibodies were associated with a lower risk of Rankin Scale score > or = 3. Demyelination and a higher age at onset were associated with a higher risk for Rankin Scale score > or = 3. Based on these 3 factors, a Web-based prognostic model was developed that directly allows clinicians to estimate the probability of developing disability (http://www.umcutrecht.nl/subsite/Prognosis-MGUS-Neuropathy). CONCLUSION: Higher age at onset and demyelination increase the risk, whereas anti-MAG antibodies decrease the risk, of developing Rankin Scale score > or = 3 in polyneuropathy associated with immunoglobulin M monoclonal gammopathy (IgM MGUSP). Our Web-based prognostic model allows determination of prognosis in IgM MGUSP.
Assuntos
Imunoglobulina M/imunologia , Gamopatia Monoclonal de Significância Indeterminada/complicações , Polineuropatias/diagnóstico , Polineuropatias/etiologia , Idoso , Medula Óssea/patologia , Estudos de Coortes , Doenças Desmielinizantes/complicações , Avaliação da Deficiência , Progressão da Doença , Eletromiografia , Feminino , Glicoproteínas/sangue , Glicoproteínas/urina , Humanos , Imunoterapia/métodos , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/terapia , Força Muscular , Condução Nervosa/fisiologia , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
BACKGROUND: In the Netherlands, the proportion of patients with amyotrophic lateral sclerosis (ALS) who choose the option of euthanasia or physician-assisted suicide (PAS) is relatively high (20%). The objective of this study was to determine which factors influence end-of-life practices in ALS and whether rates are changing over time. METHODS: In a cohort survey, 204 physicians and 198 informal caregivers (response rates 75% and 80%) of patients with ALS who died between 2000 and 2005 filled out questionnaires of the end-of-life circumstances of the patient. Results were compared with those of a similar study performed during the period 1994-1998. RESULTS: In 2000-2005, 16.8% of the patients decided on euthanasia or PAS compared to 20.2% in 1994-1998. Thirty-one (14.8%) patients died during continuous deep sedation (CDS) in 2000-2005. Euthanasia or PAS, but not CDS, were significantly associated with religion not being important to the patient, being more educated, and dying at home. Euthanasia or PAS were not associated with quality of care items or symptoms of depression. Loss of function was similar in both groups. Informal caregivers of patients who died after euthanasia or PAS more frequently reported fear of choking (p = 0.003), no chance of improvement (p = 0.001), loss of dignity (p = 0.02), being dependent on others (p = 0.002), and fatigue (p = 0.018) as reasons for shortening life. Hopelessness was associated with euthanasia or PAS, as with CDS. CONCLUSION: The frequency of euthanasia or physician-assisted suicide (PAS) in amyotrophic lateral sclerosis (ALS) appeared stable over time and 1 in 7 patients died during CDS. CDS is relatively common in ALS, but appears to have other determinants than euthanasia or PAS. Subjective factors may be important in explaining euthanasia or PAS in ALS.
Assuntos
Esclerose Lateral Amiotrófica/mortalidade , Esclerose Lateral Amiotrófica/enfermagem , Atitude Frente a Morte , Eutanásia Ativa Voluntária/estatística & dados numéricos , Suicídio Assistido/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude do Pessoal de Saúde , Cuidadores/estatística & dados numéricos , Cuidadores/tendências , Estudos de Coortes , Tomada de Decisões , Depressão/epidemiologia , Eutanásia Ativa Voluntária/tendências , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Consentimento Livre e Esclarecido/psicologia , Consentimento Livre e Esclarecido/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Cuidados Paliativos , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/tendências , Qualidade de Vida/psicologia , Religião , Direito a Morrer , Índice de Gravidade de Doença , Estresse Psicológico , Suicídio Assistido/tendências , Inquéritos e Questionários , Assistência Terminal , Adulto JovemRESUMO
BACKGROUND: Polyneuropathy with IgM monoclonal gammopathy can be a disabling disorder necessitating treatment. METHODS: In a prospective open label trial, 17 patients with disabling IgM MGUS polyneuropathy were treated with rituximab, a chimeric anti-CD-20 monoclonal antibody. RESULTS: Rituximab induced an improvement of >or=1 point on the Overall Disability Sum Score in 2/17 patients, an improvement of >or=5% of the distal MRC sum score in 4/17 and the sensory sum score in 9/17 patients. Bone marrow investigations showed CD 20 B cell depletion in all patients. There were no serious adverse events. Compared with treatment with intermittent cyclophosphamide with prednisone or treatment with fludarabine, it shows a comparable response percentages but fewer side effects. The presence of anti-MAG and a disease duration shorter than 10 years may predict treatment response. CONCLUSION: Rituximab is a candidate for treatment of IgM MGUS polyneuropathy and should be further investigated in a double-blind randomised trial.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunoglobulina M/imunologia , Fatores Imunológicos/uso terapêutico , Paraproteinemias/tratamento farmacológico , Paraproteinemias/imunologia , Idade de Início , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Murinos , Antígenos CD20/metabolismo , Linfócitos B/imunologia , Células da Medula Óssea/fisiologia , Ciclofosfamida/uso terapêutico , Avaliação da Deficiência , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Imunossupressores/uso terapêutico , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Condução Nervosa/fisiologia , Prednisona/uso terapêutico , Estudos Prospectivos , Rituximab , Sensação/fisiologia , Resultado do Tratamento , Vidarabina/análogos & derivados , Vidarabina/uso terapêuticoRESUMO
OBJECTIVE: To investigate the association between cigarette smoking, level of education, occupation, and the occurrence of sporadic amyotrophic lateral sclerosis (ALS). METHODS: A total of 364 patients and 392 controls completed a questionnaire covering smoking habits, level of education, and occupational history. Main occupations were coded according to the International Standard Classification of Occupations and compared between patients and controls. RESULTS: The univariate analysis showed an increased risk of developing ALS among current cigarette smokers (OR = 1.7; 95% CI = 1.1 to 2.6; p = 0.01), those with a low level of education (elementary school) (OR = 2.2; 95% CI = 1.2 to 3.8; p < 0.01), and among women whose main occupation was classified as crafts and related trades workers (OR = 8.4; 95% CI = 1.0 to 70.1; p = 0.05). Multivariate analysis (with covariates age, smoking, education, and occupation) showed an increased risk for current smokers of cigarettes (OR = 1.6; 95% CI = 1.0 to 2.5; p = 0.04). CONCLUSIONS: Occupation, education, and cigarette smoking are risk factors for amyotrophic lateral sclerosis, but only smoking appeared independently associated.
Assuntos
Esclerose Lateral Amiotrófica/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Ocupações/estatística & dados numéricos , Fumar/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Escolaridade , Meio Ambiente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Fatores de Risco , Distribuição por Sexo , Fumar/efeitos adversos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The best treatment for polyneuropathy associated with IgM monoclonal gammopathy (MGUS) is unknown. Oral cyclophosphamide combined with prednisone showed limited efficacy in a previous open label pilot study. We therefore performed a double-blind, randomized, placebo-controlled study of combined oral cyclophosphamide and prednisone in IgM MGUS polyneuropathy. METHODS: Thirty-five patients with progressive IgM MGUS polyneuropathy were included. After stratification for anti-MAG antibodies patients were randomized to oral cyclophosphamide 500 mg once daily for 4 days combined with oral prednisone 60 mg once daily for 5 days (treatment) (n = 16), or placebo (n = 19), repeated every 28 days for six times. Primary outcome was improvement of the Rivermead Mobility Index (RMI). Secondary outcomes were improvement of the modified Rankin scale, Medical Research Council and sensory sum scores, levels of M protein, EMG, and Short Form-36 scale after treatment. Patients were examined at 0, 6, 12, 18, and 24 months. RESULTS: After 6 months of treatment and at later follow-up, no difference in change of the RMI between the two groups was observed. Change of the Rankin scale was similar in both groups. Other outcome parameters showed more improvement in the treatment group: the MRC sum score improved more from 6 to 24 months after treatment; the sensory sum score improved more at 6 months; the SF 36 mean health change score and physical role score improved more; and the median nerve distal conduction (abductor pollicis brevis muscle) improved more in the treatment group. The most common adverse event was nausea. CONCLUSIONS: Compared with placebo treatment, this first double-blind randomized trial with cyclophosphamide and prednisone in IgM MGUS polyneuropathy showed no beneficial effect on the functional scales, but a beneficial effect on muscle strength and sensation was observed.
Assuntos
Ciclofosfamida/uso terapêutico , Imunoglobulina M , Paraproteinemias/complicações , Polineuropatias/tratamento farmacológico , Prednisona/uso terapêutico , Atividades Cotidianas , Idoso , Estudos Cross-Over , Ciclofosfamida/administração & dosagem , Dexametasona/uso terapêutico , Progressão da Doença , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Eletromiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/efeitos dos fármacos , Polineuropatias/etiologia , Prednisona/administração & dosagem , Qualidade de Vida , Sensação/efeitos dos fármacos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Non-systemic vasculitic neuropathy is a rare disabling disease that usually has a subacute onset of progressive or relapsing-remitting sensory or sensorimotor deficits. Asymmetry, pain and weakness are key features. The diagnosis can only be made by exclusion of other causes, the absence of systemic vasculitis or other rheumatic diseases, and the demonstration of vasculitis in a nerve or a combined nerve and muscle biopsy. There is a need for efficacious therapy to prevent disease progression and to improve prognosis. OBJECTIVES: To assess if immunosuppressive treatment in non-systemic vasculitic neuropathy reduces disability, and ameliorates neurological symptoms, and if such therapy can be given safely. SEARCH STRATEGY: The Cochrane Neuromuscular Disease Group Trials Register (March 2006), The Cochrane Library (Issue 1, 2006), MEDLINE, EMBASE, LILACS, and ISI were searched from January 1980 until April 2006. In addition, the reference lists of relevant articles, reviews and textbooks were handsearched. SELECTION CRITERIA: All randomised or quasi-randomised trials that examined the efficacy of immunosuppressive treatment for non-systemic vasculitic neuropathy at least one year after the onset of therapy were sought. Participants had to fulfill the following criteria: absence of systemic or neurological disease, exclusion of any recognised cause of the neuropathy by appropriate clinical or laboratory investigations, electrophysiological studies in agreement with axonal neuropathy, confirmation of vasculitis in a nerve or a combined nerve and muscle biopsy. The primary outcome measure was to be improvement in disability. Secondary outcome measures were to be change in the mean disability score, change in muscle strength measured with the Medical Research Council sum score, change in pain or other positive sensory symptoms, number of relapses, and adverse events. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed and extracted details of all potentially relevant trials. For included studies pooled relative risks and pooled weighted standardised mean differences were to be calculated to assess treatment efficacy. MAIN RESULTS: Fifty-nine studies were identified and assessed for possible inclusion in the review, but all were excluded because of insufficient quality or lack of relevance. AUTHORS' CONCLUSIONS: No adequate randomised or quasi-randomised controlled clinical trials have been performed on which to base treatment for non-systemic vasculitic neuropathy. Randomised trials of corticosteroids and other immunosuppressive agents are needed.
Assuntos
Terapia de Imunossupressão/métodos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Vasculite/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Doenças do Sistema Nervoso Periférico/etiologia , Vasculite/complicaçõesRESUMO
BACKGROUND: To assess whether the premorbid dietary intake of fatty acids, cholesterol, glutamate or antioxidants was associated with the risk of developing amyotrophic lateral sclerosis (ALS). METHODS: Patients referred to our clinic during 2001-2002, who had definite, probable or possible ALS according to El Escorial criteria, without a familial history of ALS, were asked to participate in a case-control study (132 patients and 220 healthy controls). A food-frequency questionnaire was used to assess dietary intake for the nutrients of interest. Multivariate logistic regression analysis was performed with adjustment for confounding factors (sex, age, level of education, energy intake, body mass index and smoking). RESULTS: A high intake of polyunsaturated fatty acid (PUFA) and vitamin E was significantly associated with a reduced risk of developing ALS (PUFA: odds ratio (OR) = 0.4, 95% confidence interval (CI) = 0.2 to 0.7, p = 0.001; vitamin E: OR = 0.4, 95% CI = 0.2 to 0.7, p = 0.001). PUFA and vitamin E appeared to act synergistically, because in a combined analysis the trend OR for vitamin E was further reduced from 0.67 to 0.37 (p = 0.02), and that for PUFA from 0.60 to 0.26 (p = 0.005), with a significant interaction term (p = 0.03). The intake of flavonols, lycopene, vitamin C, vitamin B2, glutamate, calcium or phytoestrogens was not associated with the risk of developing ALS. CONCLUSION: A high intake of PUFAs and vitamin E is associated with a 50-60% decreased risk of developing ALS, and these nutrients appear to act synergistically.
Assuntos
Esclerose Lateral Amiotrófica/prevenção & controle , Gorduras Insaturadas na Dieta , Vitamina E , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/epidemiologia , Índice de Massa Corporal , Estudos de Casos e Controles , Ácidos Graxos Insaturados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Análise de Regressão , Medição de Risco , Fatores de RiscoRESUMO
We studied the efficacy of fludarabine in 16 patients with immunoglobulin M monoclonal gammopathy of unknown significance polyneuropathy in a prospective uncontrolled trial. The modified Rankin scale improved in 5/16 patients, all of whom had a demyelinating polyneuropathy. The motor conduction velocity improved by more than 10% in two or more nerves for four of five of these patients. Hematologic response in bone marrow occurred in three of five of these patients, whereas two of five already had small polyclonal B cell populations. There were no serious side effects.
Assuntos
Imunoglobulina M/sangue , Paraproteinemias/sangue , Paraproteinemias/tratamento farmacológico , Polineuropatias/sangue , Polineuropatias/tratamento farmacológico , Vidarabina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Paraproteinemias/complicações , Polineuropatias/complicações , Estudos Prospectivos , Vidarabina/uso terapêuticoRESUMO
The finding of conduction block (CB) on nerve conduction studies supports the diagnosis of potentially treatable immune-mediated neuropathies. CB in a number of axons may result in reduction of the compound muscle action potential (CMAP) on proximal versus distal stimulation (decrement). Decrement may also result from increased temporal dispersion (TD) as this leads to desynchronization and phase cancellation of the motor unit action potentials (MUAPs) out of which the CMAP is built up; polyphasia of MUAPs possibly yields additional decrement. To prove the occurrence of CB, decrement has to be larger than can be explained by increased TD or increased phase cancellation. This was established previously by simulations using MUAPs recorded in rats assuming maximal TD. Unfortunately, criteria based on human data and criteria for nerves with limited TD are not available. In the present study, criteria for CB were derived using simulations with thenar surface recorded MUAPs affected by collateral reinnervation that were obtained in patients with lower motor neurone disease (LMND). The effect of TD on decrement was determined for a wide range of TDs in the forearm segment of the median nerve and the segment distal to this. Our criteria for CB were based on area decrement because this was less influenced by TD and more by CB than amplitude decrement. The maximal area decrement in the forearm segment increased as TD in the forearm segment increased but decreased as TD in the distal segment increased. This suggests that, when desynchronization and phase cancellation occur in the distal segment due to TD, less phase cancellation and, therefore, less decrement can occur due to TD in the forearm. The finding that duration prolongation on proximal versus distal stimulation reflected TD within the forearm segment and that distal duration reflected TD in the distal segment allowed proposal of a more flexible set of criteria for forearm segments when TD in the forearm segment is limited or TD in the distal segment is pronounced. A separate investigation showed that the maximal TD in chronic inflammatory demyelinating polyneuropathy was within the range of our simulations, indicating that these were realistic. Our criteria were validated retrospectively in patients with multifocal motor neuropathy and patients with LMND. In the forearm segment of the median nerve, our criteria were more sensitive and equally specific for CB as compared with criteria for CB based on the study using rats. Our criteria have to be evaluated prospectively.
Assuntos
Simulação por Computador , Nervo Mediano/fisiopatologia , Doença dos Neurônios Motores/fisiopatologia , Condução Nervosa/fisiologia , Inibição Neural/fisiologia , Potenciais de Ação/fisiologia , Adulto , Idoso , Axônios/fisiologia , Feminino , Antebraço , Humanos , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/diagnóstico , Neurônios Motores/fisiologia , Músculo Esquelético/fisiopatologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/fisiopatologia , Tempo de ReaçãoRESUMO
BACKGROUND: Although polymyositis and dermatomyositis are regarded as treatable disorders, prognosis is not well known, as in the literature long-term outcome and prognostic factors vary widely. AIM: To analyse the prognostic outcome factors in polymyositis and adult dermatomyositis. METHODS: We determined mortality, clinical outcome (muscle strength, disability, persistent use of drugs and quality of life) and disease course and analysed prognostic outcome factors. RESULTS: Disease-related death occurred in at least 10% of the patients, mainly because of associated cancer and pulmonary complications. Re-examination of 110 patients after a median follow-up of 5 years showed that 20% remained in remission and were off drugs, whereas 80% had a polycyclic or chronic continuous course. The cumulative risk of incident connective tissue disorder in patients with myositis was significantly increased. 65% of the patients had normal strength at follow-up, 34% had no or slight disability, and 16% had normal physical sickness impact profile scores. Muscle weakness was associated with higher age (odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3 to 10.3). Disability was associated with male sex (OR 3.1; 95% CI 1.2 to 7.9). 41% of the patients with a favourable clinical outcome were still using drugs. Jo-1 antibodies predicted the persistent use of drugs (OR 4.4, 95% CI 1.3 to 15.0). CONCLUSIONS: Dermatomyositis and polymyositis are serious diseases with a disease-related mortality of at least 10%. In the long term, myositis has a major effect on perceived disability and quality of life, despite the regained muscle strength.
Assuntos
Polimiosite/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Dermatomiosite/complicações , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Avaliação da Deficiência , Progressão da Doença , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polimiosite/complicações , Polimiosite/tratamento farmacológico , Prognóstico , Qualidade de Vida , Análise de SobrevidaRESUMO
A late onset axonal Charcot-Marie-Tooth phenotype is described, resulting from a novel mutation in the myelin protein zero (MPZ) gene. Comparative computer modelling of the three dimensional structure of the MPZ protein predicts that this mutation does not cause a significant structural change. The primary axonal disease process in these patients points to a function of MPZ in maintenance of the myelinated axons, apart from securing stability of the myelin layer.
Assuntos
Axônios/patologia , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/patologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteína P0 da Mielina/genética , Fosfoproteínas/genética , Adulto , Idade de Início , Idoso , Biópsia , Doença de Charcot-Marie-Tooth/epidemiologia , Estudos de Coortes , Conexinas/genética , Análise Mutacional de DNA , Doenças Desmielinizantes/patologia , Feminino , Humanos , Masculino , Nervo Mediano/fisiopatologia , Pessoa de Meia-Idade , Proteínas da Mielina/genética , Condução Nervosa/fisiologia , Linhagem , Fenótipo , Mutação Puntual , Polimorfismo Conformacional de Fita Simples , Nervo Sural/patologia , Nervo Sural/fisiopatologia , Nervo Ulnar/fisiopatologia , Proteína beta-1 de Junções ComunicantesRESUMO
Sequence alterations in the promoter region of the vascular endothelial growth factor (VEGF) gene have been implicated in increasing the risk of developing ALS. VEGF promoter haplotypes were determined in 373 patients with sporadic ALS and 615 matched healthy controls in The Netherlands. No significant association between the previously reported at-risk haplotypes and ALS was found. Pooling our results with the previously studied population still showed a significant association with the AAG haplotype.
Assuntos
Esclerose Lateral Amiotrófica/genética , Sistema Nervoso Central/metabolismo , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/fisiopatologia , Sequência de Bases/genética , Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiopatologia , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Testes Genéticos , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Países Baixos , Regiões Promotoras Genéticas/genética , Fatores Sexuais , Fator A de Crescimento do Endotélio Vascular/deficiênciaRESUMO
OBJECTIVE: To assess the frequency of hematologic malignancies at diagnosis and to determine the incidence and predictors of malignant transformation during follow-up in patients with polyneuropathy associated with monoclonal gammopathy. METHODS: Potential predictors of malignant transformation from medical history, hematologic, neurologic, and laboratory examination performed each 6 months were evaluated by univariable and multivariable Cox proportional hazard analysis. RESULTS: Of 193 patients with polyneuropathy associated with monoclonal gammopathy, 17 patients had a hematologic malignancy at diagnosis. The incidence rate of malignant transformation in 176 patients without a malignancy at diagnosis was 2.7/100 patient years. Weight loss, progression of the polyneuropathy, unexplained fever or night sweats, and M-protein level were independent predictors. CONCLUSIONS: Since hematologic malignancies occur frequently in polyneuropathy associated with monoclonal gammopathy, the authors suggest that all patients should be screened at diagnosis and subsequently during follow-up if malignant transformation is suspected.
Assuntos
Transformação Celular Neoplásica/imunologia , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/imunologia , Paraproteinemias/complicações , Paraproteinemias/epidemiologia , Polineuropatias/complicações , Polineuropatias/epidemiologia , Idoso , Estudos de Coortes , Conectina , Progressão da Doença , Feminino , Febre/imunologia , Febre/fisiopatologia , Seguimentos , Neoplasias Hematológicas/diagnóstico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/sangue , Proteínas Musculares/imunologia , Países Baixos/epidemiologia , Paraproteinemias/imunologia , Polineuropatias/imunologia , Valor Preditivo dos Testes , Redução de Peso/imunologiaRESUMO
OBJECTIVE: To assess whether lifetime physical activity during work and leisure time is associated with an increased risk of developing ALS and to determine the association between physical activity and duration or age at onset of disease. METHODS: Patients referred to our clinic during the 1-year period 2001 to 2002 who had definite, probable, or possible ALS according to El Escorial criteria, without a familial history of ALS, were asked to participate in the study. A case-control study was performed taking into account all occupational and leisure time activities of patients (n = 219) and controls (n = 254). Multivariate analysis included confounding factors (sex, age, level of education, body mass index, alcohol use, and smoking). Three quantitative measures of cumulative physical activity were calculated: until 1 year before the onset of disease (total physical activity), the last 10 years before the onset of disease (late physical activity), and until the age of 25 (early physical activity). In addition, a systematic review of all published data is presented. RESULTS: Smoking and alcohol use were independently associated with ALS (current smoking increased risk, OR = 1.8, 95% CI = 1.0 to 3.0, p = 0.03, ever/current alcohol use decreased risk, OR = 0.6, 95% CI = 0.3 to 0.9, p = 0.04). No significant association with occupational or leisure time physical activity was found (all ORs < or = 1.7), which was in agreement with most studies with the highest level of evidence in the systematic review. Higher leisure time activities were associated with an earlier age at onset: activity levels before age of 25 (p < 0.001, 7 years earlier), and activity during the last 10 years (p < 0.001, 3 years earlier). CONCLUSIONS: There is no association between physical activity and the risk of developing ALS.
Assuntos
Esclerose Lateral Amiotrófica/epidemiologia , Atividade Motora , Adulto , Idade de Início , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Atividades de Lazer , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Ocupações , Razão de Chances , Fatores de Risco , Fumar/epidemiologia , Esportes , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To determine the outcome in patients with ulnar neuropathy at the elbow (UNE) treated surgically or conservatively, and the prognostic value of clinical, sonographic, and electrophysiologic features. METHODS: After a median follow-up of 14 months, 69 of 84 patients initially included in a prospective blinded study on the diagnostic value of sonography in UNE were re-evaluated. The patients underwent renewed systematic clinical and sonographic examination. Patients were scored as having a poor (stable or progressive symptoms) or favorable (complete remission of symptoms or improvement) outcome. RESULTS: Of the 74 initially affected arms, 12 (16%) had a complete remission, 21 (28%) improved, 25 (34%) remained stable, and 16 (22%) had progression. Surgically treated patients (28 arms) had a more favorable outcome than those treated conservatively (p = 0.03). After surgery, the mean ulnar nerve diameter decreased from 3.2 to 2.9 mm (p = 0.03), while this was not seen after conservative treatment. Multiple logistic regression analysis showed that more outspoken nerve enlargement found during sonography at the time of the diagnosis was associated with a poor outcome (OR: 2.9, p = 0.009). Furthermore, the presence of a motor conduction block (OR: 0.2, p = 0.03) and motor velocity slowing across the elbow (OR: 0.1, p = 0.01) were associated with a favorable outcome. CONCLUSION: More pronounced ulnar nerve thickening at the time of the diagnosis is associated with poor outcome at follow-up, especially in conservatively treated cases, while electrodiagnostic signs of demyelination on testing indicate favorable outcome.
Assuntos
Cotovelo/inervação , Neuropatias Ulnares/diagnóstico , Neuropatias Ulnares/cirurgia , Adulto , Eletrodiagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Resultado do Tratamento , Nervo Ulnar/diagnóstico por imagem , Neuropatias Ulnares/diagnóstico por imagem , UltrassonografiaRESUMO
The incidence of amyotrophic lateral sclerosis (ALS) is higher among men than women but rises in women after the menopause. Estrogens may play a protective role. Treatment with estrogens has been shown to be neuroprotective in models of several neurodegenerative diseases. We therefore determined the effect of ovariectomy on female G93A mSOD1 transgenic mice, and the effect of subsequent treatment with 17beta-estradiol (E2). Ovariectomy led to a significant acceleration of disease progression of the mice, and high-dose E2 treatment significantly delayed disease progression of ovariectomized G93A mSOD1 transgenic mice. We conclude that treatment with E2 may also delay disease progression of post-menopausal women with ALS.
Assuntos
Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/fisiopatologia , Estradiol/farmacologia , Fármacos Neuroprotetores/farmacologia , Ovariectomia , Esclerose Lateral Amiotrófica/patologia , Animais , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Camundongos , Camundongos Transgênicos , Fenótipo , Superóxido Dismutase/genética , Superóxido Dismutase-1RESUMO
Hyper-creatine-kinase(CK)-aemia in patients without neurological abnormalities may be sign of a subclinical neuromuscular disorder. Initial screening of patients with hyper-CK-aemia must include careful history taking and a neurological examination. Appropriate blood tests to exclude aeanthocytosis and glycogen storage disease type II must be done. The diagnostic value of a skeletal muscle biopsy and electromyography is small. A muscle biopsy to exclude dystrophinopathy is indicated if the CK activity exceeds 5 times the upper limit of the normal range. If the results of initial screening are normal, patients with idiopathic hyper-CK-aemia fare quite well at 7-year follow-up. Also, standardized exercise tests in these patients have provided no evidence of increased muscle vulnerability. Thus, in most of these patients, hyper-CK-aemia probably does not reflect disease.
Assuntos
Creatina Quinase/sangue , Doenças Neuromusculares/diagnóstico , Biópsia , Diagnóstico Diferencial , Humanos , Anamnese , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Exame Neurológico , Doenças Neuromusculares/sangue , Doenças Neuromusculares/enzimologia , Valores de ReferênciaRESUMO
Myasthenia gravis (MG) susceptibility is partially determined by allelic heterogeneity of immune-modulatory genes. IgG receptors (FcgammaR) link the humoral and cellular branches of the immune system, and regulate immune responses and inflammation. Three FcgammaR subclasses (FcgammaRIIa, FcgammaRIIIa, and FcgammaRIIIb) exhibit functional polymorphisms, which affect efficiency of FcgammaR-mediated functions. FcgammaRIIa genotypes, but not FcgammaRIIIa and FcgammaRIIIb genotypes, were differentially distributed among 107 MG patients as compared to 239 healthy controls (Pz.Lt;0.01), with a relative increase of the FcgammaRIIa-R/R131 genotype (Odds ratio 2.4, 95% confidence interval 1.4-3.9). These data suggest that the FcgammaRIIa-R/R131 genotype is a marker for susceptibility to MG.