RESUMO
OBJECTIVE: To evaluate the efficacy and safety of intramuscular ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis (ALS). METHODS: 373 patients with ALS (El Escorial definite or probable; laboratory-supported probable; duration ≤36 months) were randomly assigned to placebo, 25 mg or 50 mg of methylcobalamin groups. The primary endpoints were the time interval to primary events (death or full ventilation support) and changes in the Revised ALS Functional Rating Scale (ALSFRS-R) score from baseline to week 182. Efficacy was also evaluated using post-hoc analyses in patients diagnosed early (entered ≤12 months after symptom onset). RESULTS: No significant differences were detected in either primary endpoint (minimal p value=0.087). However, post-hoc analyses of methylcobalamin-treated patients diagnosed and entered early (≤12 months' duration) showed longer time intervals to the primary event (p<0.025) and less decreases in the ALSFRS-R score (p<0.025) than the placebo group. The incidence of treatment-related adverse events was similar and low in all groups. CONCLUSION: Although ultra-high-dose methylcobalamin did not show significant efficacy in the whole cohort, this treatment may prolong survival and retard symptomatic progression without major side effects if started early. TRIAL REGISTRATION NUMBER: NCT00444613.
Assuntos
Esclerose Lateral Amiotrófica/tratamento farmacológico , Vitamina B 12/análogos & derivados , Idoso , Método Duplo-Cego , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Taxa de Sobrevida , Vitamina B 12/administração & dosagem , Vitamina B 12/uso terapêuticoRESUMO
A 69-year-old male (N.A.) with Creutzfeldt-Jakob disease showed pure autotopagnosia. We administered tests evaluating his ability to name his own body parts, to point to body parts (his own and examiner's), and to recognize positional relationships between his body parts by verbal questions and responses. We found impaired localization of the patient's own body parts by pointing and impaired recognition of positional relationships between his body parts. However, there was no impairment in naming his own body parts or in localizing the examiner's body parts. The results suggest a pure autotopagnosia in N.A. leading to an impairment of recognition of the spatial position of his body parts in a three-dimensional body representation within the egocentric reference frame. We were able to rule out the possibility that his pattern of performance could have been due to a disability in programming reaching movements of the arm.
Assuntos
Agnosia/patologia , Agnosia/psicologia , Síndrome de Creutzfeldt-Jakob/patologia , Síndrome de Creutzfeldt-Jakob/psicologia , Idoso , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
As there is a risk of MTCT of HTLV-1, the HSGP HTLV-1 MTCT was organized in 2011. To determine how many pregnant women are infected with HTLV-1 in Hokkaido, which is the northernmost and the second largest island in Japan with a population of 5,467,000 and 39,392 newborns in 2011, the HSGP HTLV-1 MTCT asked all facilities that may care for pregnant women in Hokkaido in July 2013 to provide information on the number of pregnant women who underwent screening for anti-HTLV-1 antibody using particle agglutination or chemiluminescent enzyme immunoassay, and the numbers of those with positive, equivocal, and negative test results in the screening and confirmation tests using western blotting or PCR methods in 2012, respectively. A total of 111 facilities participated in this study and provided information on 33,617 pregnant women who underwent screening in 2012, corresponding to approximately 85% of all pregnant women who gave birth in Hokkaido in 2012. Of 81 candidates for a confirmation test because of positive (n = 77) or equivocal (n = 4) results on screening, 63 (78%) underwent the confirmation test and, finally, 34 (0.1%) and 33,563 (99.8%) women were judged to be HTLV-1 carriers and non-carriers, respectively. It was concluded that the prevalence rate of HTLV-1 carriers was low, one per 1000 pregnant women in Hokkaido. Approximately 40 infants are born yearly to mothers infected with HTLV-1 in Hokkaido.
Assuntos
Infecções por HTLV-I/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Complicações na Gravidez/epidemiologia , Adulto , Feminino , Anticorpos Anti-HTLV-I/imunologia , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Japão/epidemiologia , Gravidez , Complicações na Gravidez/imunologia , Complicações na Gravidez/virologia , Gestantes , Prevalência , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Interferon beta (IFNß) is standard therapy for multiple sclerosis (MS). The efficacy of intramuscular (IM) IFNß-1a (AVONEX(®)) was assessed in 25 Japanese patients with relapsing-remitting MS (RRMS). METHODS: Patients with RRMS not previously treated with IFNß or other disease-modifying therapies were included in this 36-week study. The primary outcome was the average total number of gadolinium-enhanced lesions detected on four brain MRI scans during the last 12 weeks of 24 weeks' treatment with IM IFNß-1a 30 µg once weekly compared with the number during the 12-week pre-treatment period. Lesions were counted by blinded investigators. RESULTS: IM IFNß-1a significantly decreased the median number of gadolinium-enhanced lesions from 2.5 to 0.3 (p < 0.0001) compared with pre-treatment values. The median number of new gadolinium-enhanced lesions also decreased significantly from 2.0 to 0.3 (p = 0.0002). Serum neopterin was induced in a manner similar to that observed previously in a Caucasian RRMS population. No new adverse events occurred during the study. CONCLUSION: This first study of IM IFNß-1a in Japanese patients with RRMS demonstrated a level of efficacy similar to that reported in Caucasian patients based on an assessment of pre-treatment and post-treatment gadolinium-enhanced lesions.
Assuntos
Encéfalo/patologia , Fatores Imunológicos/administração & dosagem , Interferon beta/administração & dosagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/patologia , Adolescente , Adulto , Povo Asiático , Feminino , Gadolínio , Humanos , Aumento da Imagem , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/farmacocinética , Injeções Intramusculares , Interferon beta-1a , Interferon beta/efeitos adversos , Interferon beta/farmacocinética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neopterina/análise , Adulto JovemRESUMO
The aim of this study was to investigate the effects of tandospirone on ataxia in various types of spinocerebellar degeneration (SCD). Fifteen milligram per day of tandospirone was administered to 39 patients with SCD (spinocerebellar atrophy (SCA) 1, five patients; SCA2, six patients; Machado-Joseph disease (MJD), 14 patient; SCA6, five patients; multiple system atrophy-cerebellar type (MSA-C), seven patients; and multiple system atrophy-Parkinson type (MSA-P), two patients). All patients were assessed before and 4 weeks after administration of the drug using the international cooperative ataxia rating scale total score (ARS), total length traveled (TLT) of body stabilometry, and a self-rating depression scale. Statistically, ARS showed a significant difference in MJD (p = 0.005) and SCA6 (p = 0.043). TLT also showed a significant difference in MJD (p = 0.002) and SCA6 (p = 0.043). Eight of 39 patients (SCA1, 1/5; SCA2, 0/6; MJD, 4/14; SCA6, 3/5; MSA-C, 0/7; and MSA-P, 0/2) showed more than a five point reduction in ARS, and 13 of 39 patients (SCA1, 0/5; SCA2, 1/6; MJD, 8/14; SCA6, 4/5; MSA-C, 0/7; and MSA-P, 0/2) showed a reduction of TLT. Our data indicate that the effects of tandospirone on ataxia are different between types of SCD. Therefore, tandospirone is useful for cerebellar ataxia in patients with MJD and SCA6.
Assuntos
Ataxia/tratamento farmacológico , Ataxia/etiologia , Isoindóis/uso terapêutico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Agonistas do Receptor de Serotonina/uso terapêutico , Degenerações Espinocerebelares/complicações , Adulto , Idoso , Depressão/induzido quimicamente , Feminino , Humanos , Isoindóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Pirimidinas/efeitos adversos , Agonistas do Receptor de Serotonina/efeitos adversos , Degenerações Espinocerebelares/classificaçãoRESUMO
Typical absence seizures and isolated myoclonic seizures are both classified as age-related generalized seizures and are considered to be benign neurological manifestations. Concomitance of the two types of seizure is considered benign if it does not accompany other types of seizures or other neurological problems. We followed up a ten-year-old girl with isolated absence and myoclonic seizures whose family history of mental and neurological signs was initially not disclosed. After several years, the family history of neurological and mental problems was finally disclosed, and the diagnosis of dentato-rubro-pallido-luysian atrophy (DRPLA) was confirmed. The patient's clinical course was slowly progressive, and by age 21 she was in a nearly vegetative state. We would like to alert clinicians to consider DRPLA when diagnosing patients with absence and/or myoclonic seizures, even when they present the clinical features of benign epilepsies in the early stage.
Assuntos
Encefalopatias/complicações , Encefalopatias/patologia , Tronco Encefálico/patologia , Cerebelo/patologia , Epilepsias Mioclônicas/etiologia , Córtex Cerebral/patologia , Progressão da Doença , Eletroencefalografia/métodos , Epilepsias Mioclônicas/patologia , Saúde da Família , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Adulto JovemRESUMO
OBJECTIVES: We hypothesize that the regional pattern of blood flow reduction in the brain is different between tremor-dominant Parkinson's disease (PD) and postural instability gait difficulty (PIGD)-dominant PD. We therefore investigated the association of phenotypes in untreated PD with brain perfusion on SPECT using three-dimensional stereotactic surface projection (3D-SSP) technique. PATIENTS AND METHODS: Thirty-three patients who had PD without dementia (12 men and 21 women with a mean age of 67.1+/-6.4 years) were included in this study. Their symptoms were rated using the Unified Parkinson's Disease Rating Scale (UPDRS). Patients were grouped in two phenotypes: tremor and PIGD-dominant groups based on UPDRS components. Around the same time, all patients were examined by N-isopropyl-p[123I] iodoamphetamine single photon emission computed tomography (123I-IMP SPECT), and obtained images were analyzed with 3D-SSP using an image-analysis software, NEUROSTAT. Data on brain surface perfusion extracted by 3D-SSP analysis were compared between the PD patients and the normal control group. The same comparisons were made for subgroups of PD patients. RESULTS: Cerebral perfusion was decreased at the anterior cingulate cortex and primary visual cortex of the PD patients, and especially by the pixel-by-pixel comparison, perfusion was significantly decreased at the right anterior cingulate cortex compared with the normal controls. In the PIGD-dominant group, more severe hypoperfusion was seen at the same regions. In the tremor-dominant group, significant hypoperfusion was not seen compared with the normal controls. CONCLUSIONS: The regional pattern of blood flow reduction in the brain was found to be different between tremor-dominant PD and PIGD-dominant PD. These regional differences were considered to suggest different and disease-specific combinations of underlying pathophysiological and neurochemical processes.
Assuntos
Mapeamento Encefálico , Imageamento Tridimensional/métodos , Doença de Parkinson/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Idoso de 80 Anos ou mais , Feminino , Transtornos Neurológicos da Marcha/diagnóstico por imagem , Transtornos Neurológicos da Marcha/etiologia , Humanos , Inosina Monofosfato/farmacocinética , Isótopos de Iodo/farmacocinética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/classificação , Doença de Parkinson/complicações , Fenótipo , Tremor/diagnóstico por imagem , Tremor/etiologiaRESUMO
OBJECTIVE: The aim of the present study is to investigate the association of symptoms in Parkinson's disease (PD) with cerebral perfusion on single photon emission computed tomography (SPECT). The clinical features of PD were compared with SPECT images of the brain obtained by three-dimensional stereotactic surface projection (3D-SSP) analysis. PATIENTS AND METHODS: Thirty-eight patients who had PD without dementia (17 men and 21 women with a mean age of 68.6 +/- 4.7 years) were enrolled in this study. Their symptoms were rated using the unified Parkinson's disease rating scale (UPDRS). Within a week, all patients were examined by SPECT with 1-123, and reconstructed images were analyzed with 3D-SSP using an image-analysis software, iSSP ver. 3.5. Data on brain surface perfusion extracted by 3D-SSP analysis were compared between the PD patients and the normal control group. The same comparisons were made for subgroups of PD patients with severe symptoms, such as tremor, gait disturbance, bradykinesia, and the UPDRS motor score. RESULTS: Cerebral perfusion was decreased at the anterior cingulate cortex and occipital lobe of the PD patients compared with the normal controls. In the subgroups with severe gait disturbance and severe bradykinesia, additional hypoperfusion was seen at the lateral frontal association and lateral temporal association and the medial frontal gyrus, and by the pixel-by-pixel comparison, perfusion was significantly decreased (p < 0.05) at the medial frontal gyrus and anterior cingulate cortex compared with the normal control group. CONCLUSION: In PD patients, severe gait disturbance and bradykinesia may be correlated with hypoperfusion of the medial aspect of the frontal lobe. This suggests that functional disturbance of the supplementary motor area and other parts of the frontal lobe are involved in the development of gait disturbance and bradykinesia in PD.
Assuntos
Encéfalo/diagnóstico por imagem , Imageamento Tridimensional , Doença de Parkinson/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Idoso , Feminino , Lobo Frontal/irrigação sanguínea , Transtornos Neurológicos da Marcha/diagnóstico por imagem , Humanos , Hipocinesia/diagnóstico por imagem , Masculino , Pessoa de Meia-IdadeRESUMO
We evaluated the association of the platelet-activating factor receptor (PAFR) gene polymorphism (A224D) with the susceptibility and severity of multiple sclerosis (MS) in a Japanese population. DNA was collected from 162 Japanese patients with clinically definite 'conventional' MS (MS) and 245 healthy controls. The missense mutation A224D that impairs PAF-PAFR signaling was determined by polymerase chain reaction restriction fragment length polymorphism. The frequency of the AD/DD genotypes was significantly higher in MS patients (21.0%) than in healthy controls (13.5%) (p=0.045; odds ratio (OR), 1.71; 95% confidence interval (CI), 1.01-2.89). Moreover, the frequency of D allele in MS patients (11.7%) was also significantly higher than those in healthy controls (6.9%) (p=0.019; OR, 1.78; 95% CI, 1.10-2.89). These findings suggest that the PAFR gene missense mutation has a relation to the susceptibility for MS.
Assuntos
Suscetibilidade a Doenças , Esclerose Múltipla/genética , Glicoproteínas da Membrana de Plaquetas/genética , Polimorfismo Genético , Receptores Acoplados a Proteínas G/genética , Adulto , Distribuição de Qui-Quadrado , Intervalos de Confiança , Feminino , Frequência do Gene , Genótipo , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Razão de Chances , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Estatísticas não ParamétricasRESUMO
New diagnostic criteria for multiple sclerosis (MS) were recently proposed from the international panel on the diagnosis of MS, and they include exclusion criteria, such as lesions extending over more than two vertebral segments on spinal MRI and CSF pleocytosis of more than 50/mm3. We reviewed the clinical features of 158 patients who satisfied the diagnostic criteria for MS except for having the above atypical paraclinical findings. All patients exhibited two or more clinical attacks and objective clinical evidence of multiple lesions without any evidence of other disorders. Thirty-three (20.9%) patients had one or both atypical paraclinical findings. Twenty-one out of the 33 patients were classified as having optico-spinal MS (OSMS), and the other 12 as non-OSMS patients with atypical large expanding or destructive cerebral, cerebellar or brainstem lesions on MRI as well as one or both atypical paraclinical findings. Based on this heterogeneity in clinical findings in MS, there is an urgent need to develop a common general concept of the "MS" syndromes, and the ethnic-related heterogeneity should be considered in the revised criteria for the diagnosis of MS.
Assuntos
Leucocitose/etiologia , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/patologia , Traumatismos da Medula Espinal/patologia , Adolescente , Adulto , Idoso , Proteínas do Líquido Cefalorraquidiano/metabolismo , Técnicas de Diagnóstico Neurológico , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Japão/epidemiologia , Leucocitose/líquido cefalorraquidiano , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Valores de Referência , Sensibilidade e Especificidade , Traumatismos da Medula Espinal/etiologiaRESUMO
OBJECTIVES: Cerebral blood flow was compared among patients with dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Parkinson's disease without dementia (PD), and Alzheimer's disease (AD) using three-dimensional stereotactic surface projection (3D-SSP) analysis. PURPOSE: We attempt to clarify the difference of reduction pattern on SPECT among patients having DLB, PDD, PD, AD. PATIENTS AND METHODS: Six patients with DLB, 7 patients with PDD who were matched with the DLB patients for age, unified Parkinson's disease rating scale-III (UPDRS-III) score, and degree of cognitive function disorders, 21 patients with PD who were matched with the DLB patients for age, UPDRS-III score, 12 patients with AD who were matched with the DLB patients for age and degree of cognitive function disorders, and 12 control subjects. All patients were examined by N-isopropyl-p[123I] iodoamphetamine single photon emission computed tomography (123I-IMP SPECT), and obtained images were analyzed with 3D-SSP using an image-analysis software, iSSP ver. 3.5. RESULTS: Although DLB and PDD showed similar cerebral perfusion reduction pattern at the lateral parietal association and lateral temporal association and precuneus on SPECT by the pixel-by-pixel comparison, greater perfusion reduction was observed in DLB than in PDD. Cerebral perfusion was decreased at the occipital lobe of the DLB patients compared with the AD patients. CONCLUSIONS: The regional pattern of blood flow reduction in the brain was found to be different among DLB, PD, and AD. Greater blood flow reduction was observed in DLB, although DLB and PDD showed similar reduction pattern. These regional differences were considered to suggest different and disease-specific combinations of underlying pathological and neurochemical processes.
Assuntos
Doença de Alzheimer/fisiopatologia , Circulação Cerebrovascular/fisiologia , Doença por Corpos de Lewy/fisiopatologia , Doença de Parkinson/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Imageamento Tridimensional , Iofetamina , Doença por Corpos de Lewy/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
OBJECTIVE: To investigate the efficacy and the rate of adverse events of chronic low-dose levodopa-carbidopa therapy in Japanese patients with Parkinson's disease (PD). PATIENTS AND METHODS: A total of 92 Japanese PD patients treated with low doses of levodopa from the outset were studied. Both disease-specific motor disabilities and quality of life (QOL) in the patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Parkinson's Disease 39 Quality of Life Questionnaire (PDQ39), respectively. RESULTS: In the overall patient group, the mean duration of treatment, the mean daily dose of levodopa, the disability scores and the motor scores of UPDRS were 6.2 years, 186.4 mg, 8.0 and 19.2, respectively. The rates of motor fluctuations, dyskinesias and hallucinations were 8.7%, 6.5% and 14.1%, respectively. The mean summary index of PDQ39 scores was 23.1. Patients with motor fluctuations showed a significantly earlier disease onset. Dose of levodopa, age at onset, and treatment duration were not associated with the occurrence of dyskinesias. Patients with hallucination had higher doses of levodopa and dopamine agonist. CONCLUSIONS: Our results demonstrate that chronic administration of a low-dose levodopa preparation can provide satisfactory benefit with a low incidence of motor complications, and can result in good QOL in Japanese patients with PD. The concomitant use of a small amount of dopamine agonist and amantadine from the outset has partly contributed to a reduced dose of levodopa and the lesser occurrence of motor complications.
Assuntos
Antiparkinsonianos/administração & dosagem , Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Idoso , Amantadina/administração & dosagem , Antiparkinsonianos/efeitos adversos , Agonistas de Dopamina/administração & dosagem , Discinesia Induzida por Medicamentos/etiologia , Alucinações/induzido quimicamente , Humanos , Japão , Levodopa/efeitos adversos , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Qualidade de Vida , Estudos Retrospectivos , Fatores de TempoRESUMO
We evaluated the clinical courses of 216 patients with multiple sclerosis (MS) diagnosed according to the recommended diagnostic criteria of McDonald et al (10). Sixty-five patients clinically displaying selective involvement of the optic nerves and spinal cord were classified as opticospinal MS (OS-MS), while the other 151 showing disseminated involvement of the central nervous system were classified as conventional MS (C-MS). The disease duration did not differ significantly between the two subtypes (11.2 years vs. 11.5 years). In addition to a higher age of onset, female preponderance and higher Kurtzke's expanded disability status scale (EDSS) scores, the OS-MS patients showed a markedly lower frequency of secondary progressive MS than the C-MS patients (4.6% vs. 29.1%, p=0.0001). The EDSS scores of the C-MS patients were significantly correlated with the disease duration, while those of the OS-MS patients were not. Among the C-MS patients, the frequency of secondary progressive MS was significantly more common in patients with a disease duration of more than 10 years than in those with a shorter duration. These results suggest that the irreversible disability in OS-MS is determined by relapses, rather than by chronic progression, whereas C-MS has a similar clinical course to MS in Westerners.
Assuntos
Esclerose Múltipla/etiologia , Adulto , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/classificação , Esclerose Múltipla/fisiopatologia , Nervo Óptico/fisiopatologia , Estudos Retrospectivos , Medula Espinal/fisiopatologia , Fatores de TempoRESUMO
A patient with an atypical presentation of herpes simplex virus (HSV) encephalitis mimicking acute cerebral infarction was reported. A 48-year-old man developed left-sided hemiparesis, convulsive seizures, and loss of consciousness. Brain magnetic resonance imaging revealed high intensity areas in the right frontal to parietal lobes on T2-weighted and diffusion-weighted images. Soon after admission with suspected cerebral infarction of the right middle cerebral artery region, the patient had high fever with frequent seizures and severe loss of consciousness. Laboratory findings including cerebrospinal fluid established a diagnosis of HSV encephalitis, and a state of apalic syndrome persisted despite aggressive antiviral therapy.
Assuntos
Encefalite por Herpes Simples/diagnóstico , Encéfalo/patologia , Infarto Cerebral/diagnóstico , Diagnóstico Diferencial , Encefalite por Herpes Simples/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: We previously discovered spinocerebellar ataxia type 14 (SCA14) in a single Japanese family with an autosomal dominant neurodegenerative disorder characterized by cerebellar ataxia and intermittent axial myoclonus. The latter manifestation is selectively observed in patients with early onset. We mapped the locus to chromosome 19q13.4-qter, but the etiologic gene was not known. Recently, a mutation in the protein kinase C gamma gene (PRKCG) was identified in a US family of English and Dutch ancestry with autosomal dominant SCA whose disease mapped to a region overlapping that of the SCA14 locus. Different PRKCG mutations were found in another family with SCA and in a sporadic case from the United States. Axial myoclonus was not observed in any of these US families. OBJECTIVES: To determine whether a mutation in the PRKCG gene is responsible for SCA14 and to investigate the prevalence of PRKCG mutations in Japanese patients with autosomal dominant SCA. PATIENTS AND METHODS: Direct nucleotide sequencing analysis of the 18 coding exons of the PRKCG gene was performed in the 19 members of the original Japanese family with SCA14 and in 24 Japanese probands with SCA. After identifying a PRKCG mutation, DNA samples from 72 patients with multiple system atrophy and 50 healthy individuals were examined for the mutation as controls. RESULTS: Sequence analysis revealed a novel missense mutation, Gln127Arg, in all affected members of the family with SCA14. This mutation was not found in 122 control individuals. No mutations in the PRKCG gene were detected in the group of 24 probands with SCA of unknown type. CONCLUSIONS: These findings document that SCA14 is caused by mutations in the PRKCG gene. The observation that all 4 PRKCG mutations identified in patients with SCA to date are located in exon 4 suggests a critical role for this region of the gene in cerebellar function. Mutations in the same region of the gene can result in myoclonus in some families but not in others.
Assuntos
Mutação de Sentido Incorreto , Proteína Quinase C/genética , Ataxias Espinocerebelares/classificação , Ataxias Espinocerebelares/genética , Adulto , Idoso , Arginina , Sequência de Bases/genética , Estudos de Casos e Controles , Glicina , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
Vitamin D-binding protein (DBP) is known to function as an immunomodulatory factor, as well as the main carrier of vitamin D. We analyzed the frequencies of two polymorphisms (codon 416 and codon 420) in the DBP gene through a case-control study involving 107 Japanese patients with multiple sclerosis (MS) and 109 healthy controls. None of these polymorphisms showed any association with the occurrence of MS. Furthermore, no association was observed between the DBP polymorphisms and the age at disease onset. These results suggest that DBP does not contribute to the development of MS in Japanese.
Assuntos
Adjuvantes Imunológicos/genética , Esclerose Múltipla/genética , Polimorfismo Genético , Proteína de Ligação a Vitamina D/genética , Adulto , Idade de Início , Feminino , Frequência do Gene , Genótipo , Humanos , Japão , Masculino , Esclerose Múltipla/imunologia , FenótipoRESUMO
Osteopontin (OPN) exhibits pleiotropic functions and abundant transcripts for OPN are present in brains of patients with multiple sclerosis (MS). The aim of this study was to investigate the role of OPN genes in the pathogenesis of MS. Polymorphisms at the 8090th, 9250th and 9583rd positions in OPN were detected by PCR-RFLP from DNAs of 116 MS Japanese patients and 124 healthy controls. The C/C genotype at the 8090th position in exon 6 was more prevalent in MS than in control (p<0.0001), and C allele was more prevalent in MS than in control (p<0.0001, OR=2.57, 95% CI=1.65-4.00). For the 9583rd position polymorphism in exon 7, patients with G/G genotype (age; 32.1+/-12.5 years, mean+/-S.D.) showed a later disease onset than G/A (age; 25.9+/-7.8 years, p=0.01) and A/A (age; 25.2+/-8.9 years, p=0.01) genotypes. There were no significant correlations between OPN gene polymorphisms and disease progression. Our results suggest that the 8090th polymorphism might be associated with susceptibility to MS, while the 9583rd polymorphism might be associated with age of onset of MS.
Assuntos
DNA/genética , Predisposição Genética para Doença/genética , Esclerose Múltipla/genética , Polimorfismo Genético/genética , Sialoglicoproteínas/genética , Adulto , Sequência de Bases/genética , Encéfalo/imunologia , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Cromossomos Humanos Par 4/genética , DNA/sangue , Análise Mutacional de DNA , Progressão da Doença , Éxons/genética , Feminino , Testes Genéticos , Genótipo , Humanos , Japão , Masculino , Esclerose Múltipla/sangue , Mutação/genética , OsteopontinaRESUMO
We investigated PvuII and XbaI polymorphism in the estrogen receptor gene (ERG) and HLA-DRB1*1501 positivity in 116 conventional multiple sclerosis (MS) patients and 101 healthy controls in a Japanese population. Logistic analysis revealed independent associations of [P] allele in the profiles for PvuII (p=0.0005, adjusted odds ratio (aOR)=3.17) and DRB1*1501 (p=0.0089, aOR=2.61) with conventional MS. Synergistic elevated risk of MS due to interaction between the [P] allele and HLA-DRB1*1501 allele was found among female patients (odds ratio=16.0; 95% CI=3.99-63.8, p<0.0001). The [P] allele-positive patients with disease duration of more than 5 years had a significantly higher progression index (PI) of disability (p=0.0230) and a worse ranked MS severity score (p=0.0152) than their non-[P] counterparts.