RESUMEN
The acquired chronic demyelinating neuropathies include a growing number of disease entities that have characteristic, often overlapping, clinical presentations, mediated by distinct immune mechanisms, and responding to different therapies. After the discovery in the early 1980s, that the myelin associated glycoprotein (MAG) is a target antigen in an autoimmune demyelinating neuropathy, assays to measure the presence of anti-MAG antibodies were used as the basis to diagnose the anti-MAG neuropathy. The route was open for describing the clinical characteristics of this new entity as a chronic distal large fiber sensorimotor neuropathy, for studying its pathogenesis and devising specific treatment strategies. The initial use of chemotherapeutic agents was replaced by the introduction in the late 1990s of rituximab, a monoclonal antibody against CD20+ B-cells. Since then, other anti-B cells agents have been introduced. Recently a novel antigen-specific immunotherapy neutralizing the anti-MAG antibodies with a carbohydrate-based ligand mimicking the natural HNK-1 glycoepitope has been described.
Asunto(s)
Autoantígenos/inmunología , Enfermedades Autoinmunes Desmielinizantes SNC/inmunología , Glicoproteína Asociada a Mielina/inmunología , Polirradiculoneuropatía/inmunología , Adenina/análogos & derivados , Adenina/uso terapéutico , Animales , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Subgrupos de Linfocitos B/inmunología , Antígenos CD57/inmunología , Enfermedades Autoinmunes Desmielinizantes SNC/diagnóstico , Enfermedades Autoinmunes Desmielinizantes SNC/terapia , Epítopos/inmunología , Trastornos Neurológicos de la Marcha/inmunología , Humanos , Inmunosupresores/uso terapéutico , Inmunoterapia , Lenalidomida/uso terapéutico , Mamíferos , Ratones , Imitación Molecular , Vaina de Mielina/química , Vaina de Mielina/inmunología , Vaina de Mielina/ultraestructura , Fibras Nerviosas Mielínicas/inmunología , Fibras Nerviosas Mielínicas/patología , Enfermedad Autoinmune Experimental del Sistema Nervioso/inmunología , Paraproteinemias/inmunología , Paraproteínas/inmunología , Piperidinas/uso terapéutico , Intercambio Plasmático , Polirradiculoneuropatía/diagnóstico , Polirradiculoneuropatía/terapia , Nódulos de Ranvier/química , Nódulos de Ranvier/inmunología , Ratas , Rituximab/uso terapéuticoRESUMEN
Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare primary immunodeficiency disorder characterized by recurrent infections and low immunoglobulin levels due to variable combined immunodeficiency, and centromeric region instability, and facial dysmorphism. We describe a 12-year-old boy with recurrent respiratory tract infections, facial anomalies, scoliosis, and psychomotor retardation. He had recurrent pneumonia with low serum IgG and IgM levels during infancy and preschool age. Later at the age of 10, he developed recurrent ear infections. An IgA and IgM deficiency was found accompanied by a normal B-cell and T-cell count as well as an impaired candida-induced T-cell proliferation. Further evaluations revealed a missense mutation in the DNMT3B gene on chromosome 20. Chromosomal analysis showed a sunburst multi-radial feature on chromosome 1, which is a hallmark of ICF syndrome. The genetic mutation and chromosomal abnormality along with clinical findings are compatible with the diagnosis of ICF syndrome. To the best of our knowledge, this is the first time that scoliosis is observed in an ICF patient. The additional variable clinical symptoms in the case were the presence of spastic gait as well as hypogammaglobulinemia with immunoglobulin isotype switch at different ages.
Asunto(s)
Centrómero , Inestabilidad Cromosómica , Cara/anomalías , Síndromes de Inmunodeficiencia , Escoliosis , Niño , ADN (Citosina-5-)-Metiltransferasas/genética , Trastornos Neurológicos de la Marcha/sangre , Trastornos Neurológicos de la Marcha/genética , Trastornos Neurológicos de la Marcha/inmunología , Humanos , Inmunoglobulinas/sangre , Síndromes de Inmunodeficiencia/sangre , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/inmunología , Masculino , Mutación Missense , Pelvis/anomalías , Escoliosis/sangre , Escoliosis/genética , Escoliosis/inmunología , ADN Metiltransferasa 3BRESUMEN
RATIONALE: Anti-IgLON5 disease was first described as a progressive antibody-associated encephalopathy, with multiple non-specific clinical symptoms including sleep dysfunction, bulbar symptoms, progressive supranuclear palsy-like syndrome, cognitive impairment, and a variety of movement disorders. This newly discovered disease presents with unremarkable or unspecific brain magnetic resonance imagings (MRI), and have poor responsiveness to immunotherapy. PATIENT CONCERNS: In this case, a 37-year-old man presented with 4-day history of gait instability, dysarthria, and oculomotor abnormalities. The initial neurologic examination revealed mild unsteady gait, subtle dysarthria, and left abducent paralysis. DIAGNOSIS: The patient was diagnosed with anti-IgLON5 disease, based on clinical features and positive anti-IgLON5 antibodies in serum. INTERVENTIONS: Initially, the patient was treated with high dosages of methylprednisolone and immunoglobulins.Outcomes: The symptoms of patient rapidly improved after high-dose intravenous methylprednisolone and immunoglobulins. CONCLUSIONS: In this paper, we report a new case of anti-IgLON5 disease with major symptoms of gait instability, dysarthria, and oculomotor abnormalities, with distinctive brain MRI findings, and responsive to immunotherapy.
Asunto(s)
Autoanticuerpos/sangre , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico por imagen , Moléculas de Adhesión Celular Neuronal/inmunología , Encefalitis/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Adulto , Autoanticuerpos/inmunología , Enfermedades Autoinmunes del Sistema Nervioso/tratamiento farmacológico , Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Encéfalo/diagnóstico por imagen , Disartria/diagnóstico por imagen , Disartria/tratamiento farmacológico , Disartria/inmunología , Encefalitis/tratamiento farmacológico , Encefalitis/inmunología , Trastornos Neurológicos de la Marcha/diagnóstico por imagen , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Trastornos Neurológicos de la Marcha/inmunología , Humanos , Masculino , Neuroimagen/métodos , Enfermedades del Nervio Oculomotor/diagnóstico por imagen , Enfermedades del Nervio Oculomotor/tratamiento farmacológico , Enfermedades del Nervio Oculomotor/inmunologíaRESUMEN
Repeated exposure to Group-A ß-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities.
Asunto(s)
Diencéfalo/inmunología , Trastornos Neurológicos de la Marcha/microbiología , Cojera Animal/microbiología , Trastorno de Movimiento Estereotipado/microbiología , Infecciones Estreptocócicas/inmunología , Streptococcus pyogenes , Animales , Conducta Animal , Diencéfalo/microbiología , Trastornos Neurológicos de la Marcha/inmunología , Cojera Animal/inmunología , Masculino , Ratones , Trastorno de Movimiento Estereotipado/inmunologíaRESUMEN
Subjects with severe motor and intellectual disability (SMID) are considered to be debilitated and at high risk of influenza infection. However, the safety and immunogenicity of pandemic H1N1 (pH1N1) vaccine in these subjects have not been reported. We measured the hemagglutination inhibition antibody titer and calculated the geometric mean titer ratio (GMTR), seroprotection rate, and seroconversion rate in 104 subjects with SMID (mean age±standard deviation 40.1±12.9 years), and in 179 healthcare workers (40.7±10.4 years) in a long-term care facility. Antibody responses after the first dose of pH1N1 vaccine among workers were greater than the European Medicines Evaluation Agency criteria and US Food and Drug Administration (FDA) criteria: the seroprotection rate was 79.9% (95% confidence interval (CI) 73.3-85.5), the seroconversion rate was 77.9% (95%CI: 70.8-84.0), and GMTR was 7.3 (95%CI: 6.9-7.8). Responses among subjects with SMID were lower than the FDA criteria: the seroprotection rate was 56.3% (95%CI: 46.2-66.1), the seroconversion rate was 54.1% (95%CI: 43.7-64.2), and GMTR was 5.4 (95%CI: 4.9-5.9). Any additional antibody response induced by the second dose of vaccine among subjects with SMID was limited. Multivariate analysis indicated that subjects with SMID had a significantly lower seroprotection rate (odds ratio (OR) 0.37, 95%CI: 0.20-0.66) and seroconversion rate (OR 0.34, 95%CI: 0.20-0.59) than healthcare workers. No serious adverse reaction was reported in either group. These results indicate that a single dose of pH1N1 vaccine does not induce sufficient immunity among subjects with SMID, and a second dose is likely to be ineffective because of diminished immunogenicity. Further study is required to determine if vaccination over consecutive influenza seasons can improve immunogenicity in subjects with SMID.
Asunto(s)
Trastornos Neurológicos de la Marcha/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Gripe Humana/virología , Discapacidad Intelectual/inmunología , Adulto , Anticuerpos Antivirales/sangre , Estudios de Cohortes , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Inmunización Secundaria/métodos , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estados Unidos , Vacunación/métodosRESUMEN
BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis has been recently reported as autoimmune/paraneoplastic encephalitis, affecting mostly young females. OBJECTIVE: To describe opsoclonus-myoclonus syndrome in association with anti-NMDAR antibodies. DESIGN: Case report. SETTING: Geneva University Hospital. Patient A 23-year-old woman with opsoclonus-myoclonus syndrome. RESULTS: Two weeks after an episode of gastroenteritis, the patient developed symptoms of depression associated with psychomotor slowing, progressive gait instability, and opsoclonus-myoclonus. Cerebrospinal fluid examination showed mild lymphocytic pleocytosis and intrathecal IgG synthesis with oligoclonal bands. The patient's condition worsened rapidly to an akinetic mutism, followed by a period of agitation, delirium, and hallucinations. These gradually subsided; however, a frontal behavior and executive dysfunction persisted 5 months after symptom presentation. No tumor was found. Anti-NMDAR antibodies were found in the cerebrospinal fluid. CONCLUSIONS: Opsoclonus-myoclonus may occur in patients with anti-NMDAR encephalitis. Prompt diagnosis of this disorder is important because after tumor removal and immunomodulatory therapies it has a relatively good prognosis.
Asunto(s)
Enfermedades Autoinmunes del Sistema Nervioso/fisiopatología , Encefalitis/inmunología , Encefalitis/fisiopatología , Síndrome de Opsoclonía-Mioclonía/inmunología , Síndrome de Opsoclonía-Mioclonía/fisiopatología , Receptores de N-Metil-D-Aspartato/inmunología , Mutismo Acinético/inmunología , Autoanticuerpos/análisis , Autoanticuerpos/líquido cefalorraquídeo , Enfermedades Autoinmunes del Sistema Nervioso/líquido cefalorraquídeo , Síntomas Conductuales/inmunología , Biomarcadores/análisis , Biomarcadores/líquido cefalorraquídeo , Trastornos del Conocimiento/inmunología , Delirio/inmunología , Trastorno Depresivo/inmunología , Progresión de la Enfermedad , Encefalitis/líquido cefalorraquídeo , Función Ejecutiva/fisiología , Femenino , Lóbulo Frontal/fisiopatología , Trastornos Neurológicos de la Marcha/inmunología , Gastroenteritis/complicaciones , Gastroenteritis/inmunología , Alucinaciones/inmunología , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Bandas Oligoclonales , Síndrome de Opsoclonía-Mioclonía/líquido cefalorraquídeo , Resultado del Tratamiento , Adulto JovenRESUMEN
The nature of the B-cell subsets associated with chronic hepatitis C virus related type II mixed cryoglobulinemia (HCV-MC) is unclear. We report the case of a 64-year-male with acute onset wrist drop and foot drop, secondary to HCV-MC related mononeuritis multiplex, who was treated with rituximab, an anti-CD20(+) antibody directed against B cells. We monitored the frequency of B-cell subsets in peripheral blood before and after rituximab, and correlated B-cell subset changes with clinical response. Significant improvements in his wrist and foot drop, as well as his vasculitic rash, depression and erectile dysfunction were evident within six days of starting rituximab and have persisted several months after B-cell recovery. More than 95% of CD20(+) B cells had disappeared from peripheral blood within 1 week, returning to baseline by week 21. CD20(+)CXCR3(+) frequency at baseline was similar to that at week 21. CD20(+)CD5(+), the human equivalent of B1 B cells and CD20(+)IgM(+)IgD(+), naïve B cells were increased. By contrast, CD20(+)CD27(+) memory cell frequency was reduced. These data suggest that CD27(+) memory B cells, but not CD5(+) and IgM(+)IgD(+) B cells may play a role in the clinical manifestations of cryoglobulinemia.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Crioglobulinemia/complicaciones , Trastornos Neurológicos de la Marcha/virología , Hepatitis C Crónica/complicaciones , Factores Inmunológicos/uso terapéutico , Neuropatía Radial/virología , Anticuerpos Monoclonales de Origen Murino , Crioglobulinemia/tratamiento farmacológico , Crioglobulinemia/inmunología , Crioglobulinemia/virología , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Trastornos Neurológicos de la Marcha/inmunología , Hepacivirus , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/virología , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Neuropatía Radial/tratamiento farmacológico , Neuropatía Radial/inmunología , RituximabRESUMEN
Polyethylene glycol-interferon alpha (PEG-IFNalpha) has been used as the standard treatment for hepatitis C virus (HCV) infection. There have been no previous reports of polyradiculoneuropathy with anti-ganglioside antibodies induced by PEG-IFNalpha-2b. We report a 59-year-old man who developed polyradiculoneuropathy during treatment with PEG-IFN alpha-2b for chronic HCV infection. Serum levels of anti-asialo-GM1 (GA1) and anti-GM1 antibodies were elevated. Cessation of therapy with double filtration plasmapheresis resulted in marked improvement in his symptoms accompanied by a reduction in the antibody level. PEG-IFN alpha-2b may induce peripheral neuropathy mediated by anti-GA1 and anti-GM1 antibodies.
Asunto(s)
Antivirales/efectos adversos , Enfermedades Autoinmunes del Sistema Nervioso/inducido químicamente , Trastornos Neurológicos de la Marcha/inducido químicamente , Interferón-alfa/efectos adversos , Polietilenglicoles/efectos adversos , Polirradiculoneuropatía/inducido químicamente , Antivirales/uso terapéutico , Autoanticuerpos/biosíntesis , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Enfermedades Autoinmunes del Sistema Nervioso/terapia , Portadores de Fármacos , Quimioterapia Combinada , Gangliósido G(M1)/inmunología , Trastornos Neurológicos de la Marcha/inmunología , Trastornos Neurológicos de la Marcha/terapia , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Debilidad Muscular/inducido químicamente , Debilidad Muscular/inmunología , Debilidad Muscular/terapia , Plasmaféresis , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico , Polirradiculoneuropatía/inmunología , Polirradiculoneuropatía/terapia , Proteínas Recombinantes , Ribavirina/administración & dosificación , Ribavirina/uso terapéuticoRESUMEN
Multiple sclerosis (MS) is the most common demyelinating disease caused by an autoimmune inflammatory process in the central nervous system (CNS) and is associated with aberrant immune response to myelin selfantigens. Coexistence of MS with other autoimmune disorders, including connective tissue disorders including systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and scleroderma have been reported previously. In the present article we report the coexistence of MS, familial mediterranean fever and ankylosing spondylitis in a patient and review the clinical presentation, neurologic findings, cerebrospinal fluid and radiologic characteristics and treatment options. We further discuss the immunopathogenetic mechanisms for a possible association between MS and autoimmune disorders.
Asunto(s)
Enfermedades Autoinmunes/complicaciones , Enfermedades del Tejido Conjuntivo/complicaciones , Fiebre Mediterránea Familiar/complicaciones , Esclerosis Múltiple/complicaciones , Espondilitis Anquilosante/complicaciones , Actividades Cotidianas , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/fisiopatología , Autoinmunidad/genética , Autoinmunidad/inmunología , Encéfalo/inmunología , Encéfalo/patología , Análisis por Conglomerados , Enfermedades del Tejido Conjuntivo/inmunología , Enfermedades del Tejido Conjuntivo/fisiopatología , Progresión de la Enfermedad , Fiebre Mediterránea Familiar/inmunología , Fiebre Mediterránea Familiar/fisiopatología , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Trastornos Neurológicos de la Marcha/inmunología , Trastornos Neurológicos de la Marcha/fisiopatología , Humanos , Interferón beta/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Mitoxantrona/uso terapéutico , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/fisiopatología , Paraparesia/inmunología , Paraparesia/fisiopatología , Espondilitis Anquilosante/inmunología , Espondilitis Anquilosante/fisiopatología , Insuficiencia del TratamientoRESUMEN
Autonomic disturbances are common in patients with paraneoplastic syndromes associated with type-1 antineuronal nuclear autoantibodies (ANNA-1), although pupillary disturbances are infrequent. The authors describe a patient with ANNA-1 associated paraneoplastic sensory neuronopathy and bilateral Adie's pupils.
Asunto(s)
Anticuerpos Antineoplásicos/inmunología , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Carcinoma de Células Pequeñas/complicaciones , Neoplasias Pulmonares/complicaciones , Síndromes Paraneoplásicos del Sistema Nervioso/fisiopatología , Pupila Tónica/fisiopatología , Anciano , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/inmunología , Azatioprina/uso terapéutico , Carcinoma de Células Pequeñas/inmunología , Trastornos Neurológicos de la Marcha/diagnóstico , Trastornos Neurológicos de la Marcha/inmunología , Trastornos Neurológicos de la Marcha/fisiopatología , Ganglios Parasimpáticos/inmunología , Ganglios Parasimpáticos/patología , Ganglios Parasimpáticos/fisiopatología , Humanos , Inmunosupresores/uso terapéutico , Iris/inervación , Iris/fisiopatología , Neoplasias Pulmonares/inmunología , Masculino , Nervio Oculomotor/inmunología , Nervio Oculomotor/patología , Nervio Oculomotor/fisiopatología , Enfermedades del Nervio Oculomotor/diagnóstico , Enfermedades del Nervio Oculomotor/inmunología , Enfermedades del Nervio Oculomotor/fisiopatología , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/inmunología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Pupila , Trastornos de la Sensación/diagnóstico , Trastornos de la Sensación/inmunología , Trastornos de la Sensación/fisiopatología , Pupila Tónica/diagnóstico , Pupila Tónica/inmunología , Resultado del TratamientoRESUMEN
BACKGROUND: Celiac disease (CD) is a chronic inflammatory enteropathy resulting from sensitivity to ingested gluten. Neurologic complications are estimated to occur in 10% of affected patients, with ataxia and peripheral neuropathy being the most common problems. The incidence and clinical presentation of patients with CD-associated peripheral neuropathy have not previously been investigated. OBJECTIVE: To determine the incidence of CD in patients with neuropathy and to characterize the clinical presentation. METHODS: The records of 20 patients with neuropathy and biopsy-confirmed CD were reviewed. RESULTS: Six of the 20 patients had neuropathic symptoms alone without gastrointestinal involvement, and neuropathic symptoms preceded other CD symptoms in another 3 patients. All patients had burning, tingling, and numbness in their hands and feet, with distal sensory loss, and nine had diffuse paresthesias involving the face, trunk, or lumbosacral region. Only two had weakness. Results of electrophysiologic studies were normal or mildly abnormal in 18 (90%) of the patients. Sural nerve biopsies, obtained from three patients, revealed mild to severe axonopathy. Using the agglutination assay, 13 (65%) of the patients were positive for ganglioside antibodies. Excluding patients who were referred with the diagnosis of celiac neuropathy, CD was seen in approximately 2.5% of all neuropathy patients and in 8% of patients with neuropathy and normal electrophysiologic studies seen at our center. CONCLUSION: CD is commonly associated with sensory neuropathy and should be considered even in the absence of gastrointestinal symptoms.
Asunto(s)
Enfermedad Celíaca/complicaciones , Trastornos Neurológicos de la Marcha/etiología , Parestesia/etiología , Adulto , Anciano , Anciano de 80 o más Años , Especificidad de Anticuerpos , Biopsia , Enfermedad Celíaca/dietoterapia , Enfermedad Celíaca/inmunología , Femenino , Trastornos Neurológicos de la Marcha/inmunología , Gangliósidos/inmunología , Gliadina/inmunología , Glútenes/efectos adversos , Humanos , Inmunoglobulina A/inmunología , Masculino , Persona de Mediana Edad , Parestesia/inmunología , Estudios Retrospectivos , Nervio Sural/patología , Transglutaminasas/inmunologíaRESUMEN
Rett syndrome (RTT) is neurodevelopmental disorder with the onset at critical period of postnatal ontogenesis and age dependent occurrence of clinical manifestations. The aim of the present study was to investigate possible correlations of the age of disease onset with clinical manifestations at the stage 3 of illness and neurobiological parameters. The study was carried out in 38 girls with classical RTT, aged from 3 to 7 years, and twenty and eighteen patients with the disease onset before and after the age of one year were divided into the groups 1 and 2 (Gr1 and Gr2), respectively. Quantitative EEG (QEEG) and measurement of the serum levels of autoantibodies (AAB) to nerve growth factor (NGF) were performed. Clinically, speech and motor functions were significantly more severely affected in the Gr1 than in the Gr2. In QEEG, spectral density of theta activity was significantly higher in Gr1 than in the Gr2. The titer of AAB to NGF was significantly increased in comparison with healthy controls, and the titer in Gr2 was higher than in Gr1. The data obtained suggests that patients with the classical RTT can be divided into subgroups according to the age of disease onset and genetic factors such as mosaicism of MeCP2 mutation may be associated with the heterogeneity of phenotype in RTT patients.