RESUMO
OBJECTIVE: To expand the spectrum of anti-IgLON5 disease by adding 5 novel anti-IgLON5-seropositive cases with bulbar motor neuron disease-like phenotype. METHODS: We characterized the clinical course, brain MRI and laboratory findings, and therapy response in these 5 patients. RESULTS: Patients were severely affected by bulbar impairment and its respiratory consequences. Sleep-related breathing disorders and parasomnias were common. All patients showed clinical or electrophysiologic signs of motor neuron disease without fulfilling the diagnostic criteria for amyotrophic lateral sclerosis. One patient regained autonomy in swallowing and eating, possibly related to immunotherapy. CONCLUSION: IgLON5 disease is an important differential diagnosis to evaluate in patients with bulbar motor neuron disease-like phenotype and sleep disorders. There is need for a deeper understanding of the underlying pathobiology to determine whether IgLON5 disease is an immunotherapy-responsive condition.
Assuntos
Autoanticorpos/sangue , Moléculas de Adesão Celular Neuronais/sangue , Doença dos Neurônios Motores/sangue , Doença dos Neurônios Motores/diagnóstico , Idoso , Autoanticorpos/imunologia , Moléculas de Adesão Celular Neuronais/imunologia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Imunoterapia/métodos , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/imunologia , Doença dos Neurônios Motores/terapia , SíndromeRESUMO
Peripheral nerve injuries remain challenging to treat despite extensive research on reparative processes at the injury site. Recent studies have emphasized the importance of immune cells, particularly macrophages, in recovery from nerve injury. Macrophage plasticity enables numerous functions at the injury site. At early time points, macrophages perform inflammatory functions, but at later time points, they adopt pro-regenerative phenotypes to support nerve regeneration. Research has largely been limited, however, to the injury site. The neuromuscular junction (NMJ), the synapse between the nerve terminal and end target muscle, has received comparatively less attention, despite the importance of NMJ reinnervation for motor recovery. Macrophages are present at the NMJ following nerve injury. Moreover, in denervating diseases, such as amyotrophic lateral sclerosis (ALS), macrophages may also play beneficial roles at the NMJ. Evidence of positive macrophages roles at the injury site after peripheral nerve injury and at the NMJ in denervating pathologies suggest that macrophages may promote NMJ reinnervation. In this review, we discuss the intersection of nerve injury and immunity, with a focus on macrophages.
Assuntos
Macrófagos/imunologia , Doença dos Neurônios Motores/imunologia , Junção Neuromuscular/imunologia , Traumatismos dos Nervos Periféricos/imunologia , Animais , Humanos , Doença dos Neurônios Motores/fisiopatologia , Regeneração Nervosa , Junção Neuromuscular/fisiologia , Junção Neuromuscular/fisiopatologia , Traumatismos dos Nervos Periféricos/fisiopatologiaRESUMO
Amyotrophic Lateral Sclerosis (ALS) patients express significant clinical heterogeneity that often hinders a correct diagnostic definition. Intracellular deposition of TDP-43, a protein involved in RNA metabolism characterizes the pathology. Interestingly, this protein can be detected in serum, wherein cognate naturally-occurring auto-antibodies (anti-TDP-43 NAb) might be also present, albeit they have never been documented before. In this exploratory study, we quantified the levels of both anti-TDP-43 NAb and TDP-43 protein as putative accessible markers for improving the ALS diagnostic process by using ELISA in N = 70 ALS patients (N = 4 carrying TARDBP mutations), N = 40 age-comparable healthy controls (CTRL), N = 20 motor neuron disease mimics (MN-m), N = 20 Alzheimer's disease (AD) and N = 15 frontotemporal lobar degeneration (FTLD) patients. Anti-TDP-43 NAb were found to be significantly increased in ALS patients compared to all the other groups (p < 0.001). On the other hand, the distribution of serum levels of TDP-43 protein was highly variable among the various groups. Levels were increased in ALS patients, albeit the highest values were detected in MN-m patients. NAb and protein serum levels failed to correlate. For the first time, we report that serum anti-TDP-43 NAb are detectable in human serum of both healthy controls and patients affected by a variety of neurodegenerative disorders; furthermore, their levels are increased in ALS patients, representing a potentially interesting trait core marker of this disease. Further studies are needed to clarify the exact role of the NAb. This information might be extremely useful for paving the way toward targeting TDP-43 by immunotherapy in ALS.
Assuntos
Esclerose Lateral Amiotrófica/imunologia , Anticorpos Anti-Idiotípicos/sangue , Autoanticorpos/sangue , Proteínas de Ligação a DNA/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/genética , Doença de Alzheimer/imunologia , Doença de Alzheimer/patologia , Esclerose Lateral Amiotrófica/sangue , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Anticorpos Anti-Idiotípicos/isolamento & purificação , Autoanticorpos/isolamento & purificação , Proteínas de Ligação a DNA/genética , Feminino , Demência Frontotemporal/sangue , Demência Frontotemporal/genética , Demência Frontotemporal/imunologia , Demência Frontotemporal/patologia , Degeneração Lobar Frontotemporal/sangue , Degeneração Lobar Frontotemporal/genética , Degeneração Lobar Frontotemporal/imunologia , Degeneração Lobar Frontotemporal/patologia , Humanos , Corpos de Inclusão/genética , Corpos de Inclusão/imunologia , Corpos de Inclusão/patologia , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/sangue , Doença dos Neurônios Motores/genética , Doença dos Neurônios Motores/imunologia , Doença dos Neurônios Motores/patologia , Mutação/genéticaAssuntos
Diagnóstico Diferencial , Doença dos Neurônios Motores/diagnóstico , Debilidade Muscular/diagnóstico , Oftalmoplegia/diagnóstico , Anticorpos Antinucleares , Raciocínio Clínico , Feminino , Humanos , Perna (Membro) , Pessoa de Meia-Idade , Doença dos Neurônios Motores/complicações , Doença dos Neurônios Motores/imunologia , Debilidade Muscular/complicações , Oftalmoplegia/complicaçõesRESUMO
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by neuronal degeneration and inflammation in the nerves. The role of the immune system has been concentrated by researchers in the etiopathogenesis of the disease. Given the inhibitory roles of regulatory T cells (Tregs), it is expected that increasing or activating their populations in patients with ALS can have significant therapeutic effects. Here we searched databases, including CENTRAL, MEDLINE, CINAHL Plus, clinicaltrials.gov, and ICTRP for randomized clinical trials (RCTs) and non-RCTs until March 2019. For preclinical studies, we searched PubMed, Scopus, and Google Scholar up to June 2019. We also included preclinical studies, due to the lack of clinical information available, which used Tregs (or directly targeting them) for treating mice models of ALS. We identified 29 records (CENTRAL 7, MEDLINE 4, CINAHL Plus 8, and clinicaltrials.gov 10) and removed 10 duplicated publications. After screening, we identified one RCT which had been published as an abstract, three non-RCTs, and four ongoing studies. We also identified 551 records (PubMed 446, Google Scholar 68, and Scopus 37) for preclinical studies and performed a meta-analysis. Finally, we found three papers that matched our inclusion criteria for preclinical studies. Results indicated the effectiveness of the application of Tregs in the treatment of ALS. Our meta-analysis on preclinical studies revealed that Tregs significantly prolonged survival in mice models of ALS. Overall, our analysis testified that exertion of Tregs in the treatment of ALS is a promising approach, that notwithstanding, requires further evaluations.
Assuntos
Esclerose Lateral Amiotrófica/imunologia , Inflamação/imunologia , Doença dos Neurônios Motores/imunologia , Linfócitos T Reguladores/imunologia , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Humanos , Inflamação/patologia , Doença dos Neurônios Motores/genética , Doença dos Neurônios Motores/patologia , Neurônios Motores/imunologia , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Qualidade de Vida , Linfócitos T Reguladores/patologiaRESUMO
INTRODUCTION: Motor neuron disease (MND) can occur in patients with cancer, but there is minimal evidence that this is more than by chance. We contrast two cases of motor neuronopathies occurring in the context of systemic malignancy and argue that in one case the cause was most likely paraneoplastic, while in the other it was not. CASE 1: A 61-year-old woman developed progressive walking difficulties over 9 months with weakness and stiffness in her legs. EMG showed fibrillations and positive sharp waves in multiple lower limb muscles bilaterally, with neurogenic units and a reduced recruitment pattern. An invasive ductal carcinoma of the breast was identified and she continued to deteriorate neurologically with worsening mobility, upper limb spasticity and fasciculations. She died approximately 26 months after symptom onset. CASE 2: A 57-year-old woman developed weight loss and weakness of her right arm without any sensory symptoms. At presentation, she had wasting and fasciculations in her right upper limb muscles, with normal reflexes, normal left upper limb and lower limb examination. Over the following week, she developed left upper limb weakness and fasciculations, brisk knee reflexes, and flexor plantar responses. Her EMG showed upper and lower limb denervation. She was found to have anti-Hu and anti-CV2 antibodies present in serum. A PET-CT showed active uptake in lymph nodes in the right hilum. Biopsy confirmed a small cell lung cancer. She had chemoradiation therapy and the tumour went into remission. She has remained well on follow-up 24 months later, regaining weight and strength after her chemotherapy. She continues to be monitored for cancer recurrence, but thus far appears to be in remission. CONCLUSION: In cases with rapidly progressive MND, particularly of upper limb onset, consideration should be given to testing anti-neuronal antibodies and searching for an occult tumour.
Assuntos
Neoplasias da Mama/complicações , Carcinoma Ductal de Mama/complicações , Neoplasias Pulmonares/complicações , Doença dos Neurônios Motores/complicações , Síndromes Paraneoplásicas do Sistema Nervoso , Carcinoma de Pequenas Células do Pulmão/complicações , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/patologia , Evolução Fatal , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Doença dos Neurônios Motores/etiologia , Doença dos Neurônios Motores/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapiaAssuntos
Progressão da Doença , Células Matadoras Naturais/metabolismo , Leucemia/diagnóstico , Leucemia/metabolismo , Doença dos Neurônios Motores/diagnóstico , Doença dos Neurônios Motores/metabolismo , Idoso , Humanos , Células Matadoras Naturais/imunologia , Leucemia/imunologia , Masculino , Doença dos Neurônios Motores/imunologia , Fatores de TempoRESUMO
OBJECTIVE: To present clinical, radiological, and pathological features of a cohort of patients with motor neuron involvement in association with anti-Ma2 antibodies (Ma2-Ab). METHODS: Retrospective case-series of patients with definite paraneoplastic neurological syndrome (PNS) and Ma2-Ab, and cases identified from a review of the literature. RESULTS: Among 33 Ma2-Ab patients referred between 2002 and 2016, we retrospectively identified three patients (9.1%) with a motor neuron syndrome (MNS). Seven additional cases were retrieved among the 75 Ma2-patients reported in the literature (9.3%). A total of ten patients are, therefore, described herein. MNS was evident as combined upper and lower MNS in four patients, isolated upper MNS in two, and isolated lower MNS in one; three patients were diagnosed with myeloradiculopathy. The most common MNS signs/symptoms were: hyperreflexia (80%), proximal weakness (60%), proximal upper-limb fasciculations (50%), head drop (40%), and dysarthria/dysphagia (30%). Brain MRI abnormalities included bilateral pyramidal tract T2-weighted/FLAIR hyperintensities (three patients). Spine MRI found bilateral, symmetric, T2-weighted signal abnormalities in the anterior horn in two patients. CSF examination was abnormal in nine patients. Cancer was found in seven patients (four testicular, two lung, and one mesothelioma). Eight patients underwent first-line immunotherapy. Second-line immunotherapy was adopted in all our patients and in none of those identified in the literature. Motor improvement was observed in 33% of our patients, and 20% in the literature series. CONCLUSIONS: Motor neuron involvement could complicate Ma2-Ab-associated PNS in almost 10% of patients and must be carefully studied to adapt treatment. This disorder differs from amyotrophic lateral sclerosis.
Assuntos
Antígenos de Neoplasias/imunologia , Doença dos Neurônios Motores , Proteínas do Tecido Nervoso/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso , Radiculopatia , Doenças da Medula Espinal , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/imunologia , Doença dos Neurônios Motores/patologia , Doença dos Neurônios Motores/fisiopatologia , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/patologia , Síndromes Paraneoplásicas do Sistema Nervoso/fisiopatologia , Radiculopatia/imunologia , Radiculopatia/patologia , Radiculopatia/fisiopatologia , Estudos Retrospectivos , Doenças da Medula Espinal/imunologia , Doenças da Medula Espinal/patologia , Doenças da Medula Espinal/fisiopatologiaAssuntos
Anticorpos/metabolismo , Moléculas de Adesão Celular Neuronais/imunologia , Doença dos Neurônios Motores/imunologia , Doença dos Neurônios Motores/metabolismo , Doença dos Neurônios Motores/fisiopatologia , Eletromiografia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/diagnóstico por imagemRESUMO
Acquired myasthenia gravis (MG) is a prototype autoimmune disease of the neuromuscular junction, caused in most patients by autoantibodies to the muscle nicotinic acetylcholine receptor (AChR). There seem to be ethnic and regional differences in the frequency and clinical features of MG seronegative for the AChR antibody. This study aimed to describe the autoantibody profiles and clinical features of Korean patients with generalized MG seronegative for the AChR antibody. A total of 62 patients with a high index of clinical suspicion of seronegative generalized MG were identified from 18 centers, and we examined their sera for antibodies to clustered AChR, muscle-specific tyrosine kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (LRP4) by cell-based assays (CBA) and to MuSK by radioimmunoprecipitation assay (RIPA). We also included 8 patients with ocular MG, 3 with Lambert-Eaton myasthenic syndrome, 5 with motor neuron disease, and 9 with other diagnoses as comparators for the serological testing. Antibodies were identified in 25/62 (40.3%) patients: 7 had antibodies to clustered AChR, 17 to MuSK, and 2 to LRP4. Three patients were double seropositive: 1 for MuSK and LRP4, and 2 for MuSK and clustered AChR. The patients with MuSK antibodies were mostly female (88.2%) and characterized by predominantly bulbar involvement (70%) and frequent myasthenic crises (58.3%). The patients with antibodies to clustered AChR, including 2 with ocular MG, tended to have a mild phenotype and good prognosis.
Assuntos
Autoanticorpos/sangue , Miastenia Gravis/sangue , Miastenia Gravis/imunologia , Receptores Colinérgicos/imunologia , Adulto , Idoso , Estudos Transversais , Feminino , Seguimentos , Humanos , Proteínas Relacionadas a Receptor de LDL/imunologia , Síndrome Miastênica de Lambert-Eaton/sangue , Síndrome Miastênica de Lambert-Eaton/imunologia , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/sangue , Doença dos Neurônios Motores/imunologia , Ensaio de Radioimunoprecipitação , Receptores Proteína Tirosina Quinases/imunologia , República da Coreia , Estudos RetrospectivosRESUMO
Neuromuscular disorders may present and progress differently in women than in men. During pregnancy, medication adjustment, hormonal effects, and other alterations in physiology may influence the manifestation of a variety of neuromuscular disorders. The expression of existing conditions may change; previously asymptomatic conditions may be unmasked, or entirely new conditions may develop. Additionally, neuromuscular disorders and their treatments may have implications for the fetus. Such factors must be carefully considered when counseling and treating pregnant women and those considering pregnancy. This article reviews considerations specific to women and issues surrounding pregnancy in disorders of the neuromuscular junction, focal neuropathies, and acquired and inherited disorders of the nerve and muscle.
Assuntos
Doença dos Neurônios Motores , Doenças Musculares , Miastenia Gravis , Doenças do Sistema Nervoso Periférico , Complicações na Gravidez , Feminino , Humanos , Doença dos Neurônios Motores/complicações , Doença dos Neurônios Motores/tratamento farmacológico , Doença dos Neurônios Motores/imunologia , Doença dos Neurônios Motores/fisiopatologia , Doenças Musculares/complicações , Doenças Musculares/tratamento farmacológico , Doenças Musculares/imunologia , Doenças Musculares/fisiopatologia , Miastenia Gravis/complicações , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/imunologia , Miastenia Gravis/fisiopatologia , Doenças do Sistema Nervoso Periférico/complicações , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/imunologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/imunologia , Complicações na Gravidez/fisiopatologiaRESUMO
Multifocal motor neuropathy (MMN), an immune neuromuscular condition causing progressive weakness, usually responds to immune-mediated treatments, including intravenous immunoglobulin (IVIG). Fifteen patients with MMN receiving IVIG were enrolled in an open-label, single-center trial and switched to 20% subcutaneous immunoglobulin (SCIG) using a smooth transition protocol (ie, changing the therapy without interruption or impact on the intended outcome of the therapy). Patients received individualized training and support based on motivation and ability to learn, follow directions, and maintain compliance. Although some patients required assistance during the training phase, most managed self-infusion and reported satisfaction in managing therapy autonomously. Educating patients with neuropathies to self-infuse high-dose SCIG at home and with flexibility in dosing schedules was successfully demonstrated in this patient group.
Assuntos
Imunoglobulinas Intravenosas/administração & dosagem , Infusões Subcutâneas/métodos , Doença dos Neurônios Motores/imunologia , Doença dos Neurônios Motores/terapia , Autoadministração/enfermagem , Humanos , Educação de Pacientes como Assunto , Método Simples-CegoRESUMO
Motor or motor-predominant neuropathies may arise from disease processes affecting the motor axon and/or its surrounding myelin. Lower motor neuron syndrome (LMNS) arises from a disease process affecting the spinal motor neuron itself. The term LMNS is more generally used, rather than motor neuronopathy, although both entities are clinically similar. Common features are muscle weakness (distal or proximal) with atrophy and hyporeflexia, but no sensory involvement. They can be acquired or hereditary. Immune-mediated neuropathies (multifocal motor neuropathy, motor-predominant chronic inflammatory demyelinating polyneuropathy) are important to identify, as effective treatments are available. Other acquired neuropathies, such as infectious, paraneoplastic and radiation-induced neuropathies are also well known. Focal LMNS is an amyotrophic lateral sclerosis (ALS)-mimicking syndrome especially affecting young adults. The main hereditary LMNSs in adulthood are Kennedy's disease, late-onset spinal muscular atrophy and distal hereditary motor neuropathies. Motor neuropathies and LMNS are all clinical entities that should be better known, despite being rare diseases. They can sometimes be difficult to differentially diagnose from other diseases, particularly from the more frequent ALS in its pure LMN form. Nevertheless, correct identification of these syndromes is important because their treatment and prognoses are definitely different.
Assuntos
Doença dos Neurônios Motores/fisiopatologia , Neuropatias Fibulares/fisiopatologia , Esclerose Lateral Amiotrófica/fisiopatologia , Humanos , Doença dos Neurônios Motores/imunologia , Doença dos Neurônios Motores/patologia , Atrofia Muscular Espinal/fisiopatologia , Neuropatias Fibulares/imunologia , Neuropatias Fibulares/patologiaRESUMO
Multifocal motor neuropathy (MMN) is a chronic immune-mediated disorder leading to slowly progressive muscle weakness and wasting. Current treatments are aimed at modulating the immune system in order to avoid further decline and to maintain functional status. Intravenous immunoglobulin (IVIg) is widely used in the treatment of immune-mediated disorders and is the only treatment approved for MMN. While patients do remain stable with maintenance IVIg treatment, most patients will slowly deteriorate over many years. The use of subcutaneous immunoglobulin (ScIg) is also gaining acceptance in this disease. The amount of axonal loss and the number of years without immunoglobulin (Ig) treatment appear to be associated with the permanence of weakness. We summarize the key literature to date that supports Ig use in the treatment of MMN.
Assuntos
Imunização Passiva/métodos , Polineuropatias/imunologia , Humanos , Doença dos Neurônios Motores/complicações , Doença dos Neurônios Motores/imunologia , Polineuropatias/complicaçõesAssuntos
Adenocarcinoma/diagnóstico , Autoanticorpos/imunologia , Doença dos Neurônios Motores/diagnóstico , Proteínas do Tecido Nervoso/imunologia , Degeneração Paraneoplásica Cerebelar/diagnóstico , Neoplasias da Próstata/diagnóstico , Adenocarcinoma/imunologia , Idoso , Humanos , Masculino , Doença dos Neurônios Motores/imunologia , Degeneração Paraneoplásica Cerebelar/imunologia , Neoplasias da Próstata/imunologiaRESUMO
BACKGROUND: The spectrum of autoimmune neurological diseases associated with voltage-gated potassium channel (VGKC)-complex antibodies (Abs) ranges from peripheral nerve disorders to limbic encephalitis. Recently, low titers of VGKC-complex Abs have also been reported in neurodegenerative disorders, but their clinical relevance is unknown. OBJECTIVE: The aim of the study was to explore the prevalence of VGKC-complex Abs in slow-progression motor neuron disease (MND). METHODS: We compared 11 patients affected by slow-progression MND with 9 patients presenting typical progression illness. Sera were tested for VGKC-complex Abs by radioimmunoassay. The distribution of VGKC-complex Abs was analyzed with the Mann-Whitney U test. RESULTS: The statistical analysis showed a significant difference between the mean values in the study and control groups. A case with long-survival MND harboring VGKC-complex Abs and treated with intravenous immunoglobulins is described. CONCLUSION: Although VGKC-complex Abs are not likely to be pathogenic, these results could reflect the coexistence of an immunological activation in patients with slow disease progression.
Assuntos
Autoanticorpos/sangue , Doença dos Neurônios Motores/sangue , Doença dos Neurônios Motores/imunologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/tratamento farmacológico , Estudos RetrospectivosRESUMO
INTRODUCTION: Antibodies against cation channels, including voltage-gated potassium channel (VGKC) complex, voltage-gated calcium channel (VGCC), and ganglionic acetylcholine receptor (gAChR), are detected in subgroups of autoimmune disorders, and rarely occur in motor neuron disease (MND). METHODS: This investigation was a case-control study of 28 MND patients positive for cation channel antibodies in comparison with 56 age/gender/onset/diagnostic-category-matched MND patients without such antibodies. RESULTS: One or more cation channel antibodies were detected in 6.9% of MND patients, mostly at low titers. The rate of MND progression determined by the revised ALS Functional Rating Scale-revised (ALSFRS-R) and Kaplan-Meier survival analysis was statistically indistinguishable between the antibody-positive and control groups. Incidence rates of cancer and coexisting autoimmune disorders were similar between both groups, based on non-comprehensive screening. CONCLUSION: Cation channel antibodies in MND patients do not appear to affect disease progression. Routine testing for paraneoplastic antibodies is probably of limited usefulness in most MND patients. Muscle Nerve 54: 228-231, 2016.
Assuntos
Autoanticorpos/sangue , Canais Iônicos/imunologia , Doença dos Neurônios Motores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/imunologia , Doença dos Neurônios Motores/mortalidade , Estudos RetrospectivosRESUMO
Autoimmune neuropathies occur when immunologic tolerance to myelin or axonal antigens is lost. Even though the triggering factors and the underling immunopathology have not been fully elucidated in all neuropathy subsets, immunological studies on the patients' nerves, transfer experiments with the patients' serum or intraneural injections, and molecular fingerprinting on circulating autoantibodies or autoreactive T cells, indicate that cellular and humoral factors, either independently or in concert with each other, play a fundamental role in their cause. The review is focused on the main subtypes of autoimmune neuropathies, mainly the Guillain-Barré syndrome(s), the Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), the Multifocal Motor Neuropathy (MMN), and the IgM anti-MAG-antibody mediated neuropathy. It addresses the factors associated with breaking tolerance, examines the T cell activation process including co-stimulatory molecules and key cytokines, and discusses the role of antibodies against peripheral nerve glycolipids or glycoproteins. Special attention is given to the newly identified proteins in the nodal, paranodal and juxtaparanodal regions as potential antigenic targets that could best explain conduction failure and rapid recovery. New biological agents against T cells, cytokines, B cells, transmigration and transduction molecules involved in their immunopathologic network, are discussed as future therapeutic options in difficult cases. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
Assuntos
Síndrome de Guillain-Barré , Doença dos Neurônios Motores , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Autoanticorpos/imunologia , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/patologia , Humanos , Doença dos Neurônios Motores/imunologia , Doença dos Neurônios Motores/patologia , Proteínas do Tecido Nervoso/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologia , Linfócitos T/imunologia , Linfócitos T/patologiaRESUMO
A 42 years-old male noticed alopecia in 2006. Three years later, he had loss of hair in the whole body and weakness in the left upper limb. Prednisolone treatment failed to alleviate these symptoms. In 2011, he was diagnosed multifocal acquired demyelinating sensory and motor neuropathy and treated by intravenous immunoglobulin (IVIg), which improved muscle strength eventually. Three years later, he had remitting weakness of the limbs, and thus underwent again IVIg with amelioration of both alopecia and weakness in the limbs. Association of multifocal acquired demyelinating sensory and motor neuropathy and alopecia, and their improvement by immunomodulatory treatment strongly suggest a role of immunological pathomechanism.