RESUMO
BACKGROUND: Inflammatory responses in the cerebrospinal fluid (CSF) of patients with sporadic Creutzfeldt-Jakob disease (sCJD) remain elusive. METHODS: We conducted a case-control study, in which 14 patients with sCJD, 14 with noninflammatory neurological disorders, and 14 with autoimmune encephalitis were enrolled. We used the suspension array system to measure the concentrations of 27 cytokines in CSF. The cytokine titers of the three groups were compared, and the correlation between the relevant cytokine titers and clinical parameters was investigated in the patients with sCJD. RESULTS: Levels of the two cytokines interleukin (IL)-1 receptor antagonist and IL-17 were significantly elevated in the patients with sCJD compared with those in the patients with noninflammatory neurological disorders: IL-17 levels in sCJD were approximately ten times higher than in the noninflammatory neurological disorders (mean, 35.46 vs. 3.45 pg/ml; P < 0.001) but comparable to that in encephalitis (mean, 32.16 pg/ml). In contrast, levels of classical proinflammatory cytokines such as IL-12(p70) and tumor necrosis factor-α were increased only in encephalitis. Although not significant, IL-17 titers tended to be higher in the patients with shorter disease duration before CSF sampling (r = -0.452; P = 0.104) and in those with lower CSF total protein concentrations (r = -0.473; P = 0.086). CONCLUSIONS: IL-17 is significantly increased in CSF in sCJD, which can be an early event in the pathogenesis of sCJD.
Assuntos
Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Demência/líquido cefalorraquidiano , Interleucina-17/líquido cefalorraquidiano , Idoso , Estudos de Casos e Controles , Síndrome de Creutzfeldt-Jakob/imunologia , Demência/imunologia , Progressão da Doença , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by ventricular enlargement that deforms the corpus callosum, making the callosal angle (CA) small. The authors aimed to evaluate the clinical usefulness of the CA in different planes in iNPH. METHODS: Forty patients with iNPH were included in the study. As a control group, 241 patients with other neurological diseases and 50 healthy controls were included. The subjects had been seen at the authors' institutions from 2010 to 2020. The Timed Up and Go (TUG) test total time and Mini-Mental State Examination (MMSE) total score were evaluated. CAs were measured in the axial plane at the splenium and genu and in the coronal plane at the anterior commissure and posterior commissure by using 3-dimensional T1-weighted MR images. As other hydrocephalus parameters, the Evans index, frontal-occipital horn ratio, and third ventricular width were also measured in patients with iNPH. Associations between each CA or hydrocephalus parameter and clinical parameters were evaluated. The classification efficacy of each CA in differentiating between iNPH and other neurological diseases and healthy controls was evaluated. RESULTS: The CA at the splenium, but no other hydrocephalus parameters, was correlated with TUG total time or MMSE total score in patients with iNPH. Receiver operating characteristic analysis showed that a CA of 71.1° at the splenium has 90.0% sensitivity and 89.0% specificity in discriminating iNPH from other neurological diseases and healthy controls. Probabilistic tractography analysis showed that neuronal fibers via the splenium connect the superior parietal lobules, temporal lobes, and occipital lobes. CONCLUSIONS: The study results suggest that interhemispheric disconnections at the splenium are, at least in part, responsible for gait and cognitive disturbance in iNPH. The CA at the splenium is a unique morphological feature that correlates with gait and cognition in iNPH, and it is useful for discriminating iNPH from other neurological diseases and healthy controls.
Assuntos
Hidrocefalia de Pressão Normal , Humanos , Hidrocefalia de Pressão Normal/diagnóstico , Corpo Caloso/diagnóstico por imagem , Cognição , Imageamento Tridimensional , MarchaRESUMO
OBJECTIVES: To elucidate the pathophysiology of urinary dysfunction in idiopathic normal-pressure hydrocephalus (iNPH) by single-photon emission computed tomography (SPECT) and statistical brain mapping. METHODS: Urinary symptoms were observed and N-isopropyl-p-[(123)I]-iodoamphetamine (IMP)-SPECT imaging was performed in 97 patients with clinico-radiologically definite iNPH. The patients included 56 men and 41 women; mean age, 74 years. The statistical difference in normalized mean tracer counts was calculated and visualized between patients with urinary dysfunction of severer degrees (>grade 2/4) and milder degrees (Assuntos
Lobo Frontal/irrigação sanguínea
, Lobo Frontal/diagnóstico por imagem
, Hidrocefalia de Pressão Normal/complicações
, Fluxo Sanguíneo Regional/fisiologia
, Incontinência Urinária/epidemiologia
, Transtornos Urinários/epidemiologia
, Idoso
, Idoso de 80 Anos ou mais
, Mapeamento Encefálico
, Transtornos Cognitivos/fisiopatologia
, Feminino
, Lobo Frontal/fisiopatologia
, Transtornos Neurológicos da Marcha/fisiopatologia
, Humanos
, Hidrocefalia de Pressão Normal/fisiopatologia
, Radioisótopos do Iodo
, Masculino
, Pessoa de Meia-Idade
, Estudos Retrospectivos
, Índice de Gravidade de Doença
, Tomografia Computadorizada de Emissão de Fóton Único
, Incontinência Urinária/fisiopatologia
, Transtornos Urinários/fisiopatologia
RESUMO
We report a case of a 62-year-old Japanese-Australian woman with progressive supranuclear palsy (PSP) who presented with prominent urinary retention, neurogenic changes in sphincter electromyography, and obstructive sleep apnea syndrome. Urodynamic study revealed a combination of detrusor overactivity during filling and underactivity during voiding. All these non-motor symptoms in PSP mimicked those of multiple system atrophy.
Assuntos
Apneia Obstrutiva do Sono/etiologia , Paralisia Supranuclear Progressiva/complicações , Paralisia Supranuclear Progressiva/diagnóstico , Retenção Urinária/etiologia , Diagnóstico Diferencial , Eletromiografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Paralisia Supranuclear Progressiva/fisiopatologia , Retenção Urinária/fisiopatologia , Urodinâmica/fisiologiaRESUMO
PURPOSE: To profile the detailed clinical features of sporadic amyotrophic lateral sclerosis (ALS) on large-scale samples in Japan. METHODS: We assessed the clinical features of sporadic ALS patients in Japan, based on the nationwide registration system of the Ministry of Health, Labor and Welfare of Japan. We described 3,428 new cases registered cases between 2003 and 2006 to analyze initial symptoms and related clinical features, 4,202 cases registered in the single year of 2005 to describe the cross-sectional overview of the ALS patients, and a total of 2,128 cases with tracheostomy positive pressure ventilation (TPPV) from all of the registration data from 2003 to 2006 to describe the features of ALS patients with TPPV. RESULTS: The patients with an older age at onset progressed more rapidly to the TPPV stage than those with a younger age at onset. The subpopulation of patients with long-standing TPPV showed ophthalmoplegia, while its appearance rate was less in the patients with an older age at onset than in those with a younger age at onset. Furthermore, age at onset strongly influenced the frequency of initial symptoms: dysarthria, dysphagia, neck weakness and respiratory disturbance were more frequent in patients with an older age at onset, while upper or lower limb weakness was observed more frequently in patients with a younger age at onset. In addition, those initial symptoms were still the most prominent at the follow-up stage, suggesting that the initial symptoms determine the major clinical features even in advanced illness. CONCLUSIONS: Our present study demonstrated that symptomatic features of ALS are strongly influenced by the age at onset by the large scale of samples.
Assuntos
Idade de Início , Esclerose Lateral Amiotrófica , Fatores Etários , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/terapia , Estudos Transversais , Feminino , Humanos , Japão , Masculino , Sistema de Registros , Estudos Retrospectivos , Canais de Cátion TRPV/genética , Traqueotomia/métodosRESUMO
This manuscript describes the first known case of a patient with multiple system atrophy whose parasympathetic dominant disturbance might have been associated with the relative constriction of the superior mesenteric artery, leading to nonocclusive mesenteric ischemia and subsequent portomesenteric venous gas with pneumatosis intestinalis on abdominal computed tomography approaching death.
Assuntos
Embolia Aérea/diagnóstico , Atrofia de Múltiplos Sistemas/complicações , Pneumatose Cistoide Intestinal/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Idoso , Embolia Aérea/etiologia , Evolução Fatal , Humanos , Imageamento por Ressonância Magnética , Masculino , Veias Mesentéricas , Atrofia de Múltiplos Sistemas/diagnóstico , Pneumatose Cistoide Intestinal/etiologia , Veia PortaRESUMO
AIM: To elucidate the mechanism of bladder dysfunction in idiopathic normal pressure hydrocephalus (iNPH) by a urodynamic study. METHODS: Forty-two patients with possible iNPH, who were diagnosed by clinical symptoms/signs (gait, cognitive, and urinary disorders) with typical imaging features (ventricular enlargement) and normal cerebrospinal fluid pressure, were enrolled. The subjects included 36 men and 6 women; mean age, 72 years (62-83 years). All patients underwent a urodynamic test according to the definitions and methods proposed by the International Continence Society. RESULTS: Lower urinary tract symptoms were seen in 93% of the patients, with storage symptoms (93%) being more common than voiding symptoms (71%); and urinary urgency (overactive bladder) (64%)/frequency (64%) being more common than urinary incontinence (57%). The mean values for the maximum flow rate and post-void residual (PVR) volume were 11.7 ml/sec and 42.1 ml, respectively. PVR >100 ml was noted in six patients (three men, three women; range, 100-228 ml). Although the majority of patients had normal bladder volume at the first sensation (mean 134 ml), bladder capacity was small (mean 200 ml) and detrusor overactivity was seen in 95% of patients. CONCLUSIONS: While incontinence can result secondarily from gait disturbance or dementia, detrusor overactivity mostly underlies urinary urgency/frequency and incontinence in iNPH.
Assuntos
Pressão do Líquido Cefalorraquidiano , Hidrocefalia de Pressão Normal/complicações , Bexiga Urinária Hiperativa/etiologia , Bexiga Urinária/fisiopatologia , Incontinência Urinária/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hidrocefalia de Pressão Normal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Bexiga Urinária Hiperativa/fisiopatologia , Incontinência Urinária/fisiopatologia , UrodinâmicaRESUMO
We present a case of anti-aquaporin-4 antibody-positive myelitis, which suggests the high-risk syndrome of neuromyelitis optica, whose modest clinical signs were in conspicuous contrast to the extensive spinal cord lesions demonstrated on magnetic resonance (MR) imaging. Follow-up MR imaging showed marked improvement of lesions. Interestingly, an anti-glutamate receptor antibody, which has been suggested to cause dysfunction of N-methy-D-aspartate receptor on neuron, was detected in the cerebrospinal fluid of the patient. We discuss the case and related literature.
Assuntos
Amnésia Retrógrada/imunologia , Aquaporina 4/imunologia , Autoanticorpos/sangue , Imageamento por Ressonância Magnética/métodos , Neuromielite Óptica/diagnóstico , Receptores de Glutamato/imunologia , Adulto , Amnésia Retrógrada/complicações , Autoanticorpos/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Encéfalo/patologia , Diagnóstico Diferencial , Feminino , Seguimentos , Doença de Hashimoto/complicações , Doença de Hashimoto/imunologia , Humanos , Interferon beta/uso terapêutico , Metilprednisolona/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/imunologia , Fármacos Neuroprotetores/uso terapêutico , Medula Espinal/patologiaRESUMO
Transient lesions at the splenium of the corpus callosum (SCC) have been reported after withdrawal of specific antiepileptic drugs (AED), though the pathophysiology of the lesions remains unclear. We examined and treated a schizophrenic patient who developed a transient SCC lesion after withdrawal of the AED, carbamazepine. Interestingly, the SCC lesion was accompanied by the onset of diabetes insipidus, a state of arginine-vasopressin (AVP) insufficiency. Because carbamazepine is shown to potentiate the effect of AVP, our case suggests that an insufficiency of AVP followed by withdrawal of AED could contribute to the pathogenesis of a transient SCC lesion.
Assuntos
Encefalopatias/induzido quimicamente , Encefalopatias/diagnóstico , Carbamazepina/efeitos adversos , Corpo Caloso/efeitos dos fármacos , Corpo Caloso/patologia , Síndrome de Abstinência a Substâncias/diagnóstico , Doença Aguda , Anticonvulsivantes/efeitos adversos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
OBJECTIVE: Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case-control series. METHODS: We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants. RESULTS: In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel-Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14-5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15-5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 × 10(-3)). INTERPRETATION: The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.
RESUMO
Psychiatric symptom can be a prominent feature early in Creutzfeldt-Jakob disease (CJD), which is also common in autoantibody-mediated limbic encephalitis. We hypothesized that anti-neuronal autoantibodies, especially those against N-methyl-D-aspartate glutamate receptors (NMDAR), can also be associated with CJD. Thirteen patients with CJD and 13 patients with limbic encephalitis were enrolled. Immunohistochemistry demonstrated that serum of CJD patients reacted with neuronal components of the rat hippocampus, indicating that those samples contained anti-neuronal antibodies. Enzyme-linked immunosorbent assay revealed that titers of antibodies against peptides of GluN2B subunit of NMDAR were significantly elevated in the serum and cerebrospinal fluid of CJD patients.
Assuntos
Autoanticorpos/imunologia , Síndrome de Creutzfeldt-Jakob/imunologia , Receptores de N-Metil-D-Aspartato/imunologia , Idoso , Idoso de 80 Anos ou mais , Animais , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/sangue , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Feminino , Hipocampo/imunologia , Hipocampo/metabolismo , Humanos , Encefalite Límbica/sangue , Encefalite Límbica/imunologia , Encefalite Límbica/metabolismo , Masculino , Pessoa de Meia-Idade , Ratos , Receptores de N-Metil-D-Aspartato/sangue , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
Objectives To assess the utility of the display standardisation of diffusion-weighted MRI (DWI) and to compare the effectiveness of DWI and fluid-attenuated inversion recovery (FLAIR) MRI for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). Design A reliability and agreement study. Setting Thirteen MRI observers comprising eight neurologists and five radiologists at two universities in Japan. Participants Data of 1.5-Tesla DWI and FLAIR were obtained from 29 patients with sCJD and 13 controls. Outcome measures Standardisation of DWI display was performed utilising b0 imaging. The observers participated in standardised DWI, variable DWI (the display adjustment was observer dependent) and FLAIR sessions. The observers independently assessed each MRI for CJD-related lesions, that is, hyperintensity in the cerebral cortex or striatum, using a continuous rating scale. Performance was evaluated by the area under the receiver operating characteristics curve (AUC). Results The mean AUC values were 0.84 (95% CI 0.81 to 0.87) for standardised DWI, 0.85 (95% CI 0.82 to 0.88) for variable DWI and 0.68 (95% CI 0.63 to 0.72) for FLAIR, demonstrating the superiority of DWI (p<0.05). There was a trend for higher intraclass correlations of standardised DWI (0.74, 95% CI 0.66 to 0.83) and variable DWI (0.72, 95% CI 0.62 to 0.81) than that of FLAIR (0.63, 95% CI 0.53 to 0.74), although the differences were not statistically significant. Conclusions Standardised DWI is as reliable as variable DWI, and the two DWI displays are superior to FLAIR for the diagnosis of sCJD. The authors propose that hyperintensity in the cerebral cortex or striatum on 1.5-Tesla DWI but not FLAIR can be a reliable diagnostic marker for sCJD.
RESUMO
Idiopathic normal pressure hydrocephalus (iNPH) is an elderly dementia caused by abnormal metabolism in the cerebrospinal fluid (CSF). The tap test is the current basis for confirming iNPH, but it shows very low sensitivity, indicating that many patients who might be cured by a shunt operation will be missed. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we found two transferrin isoforms: one had a unique N-glycan (Tf-1) whereas the other had N-glycan similar to that of serum transferrin (Tf-2). Glycan analyses revealed that Tf-1 had branching (biantennary) asialo- and agalacto-complex type N-glycans (N-acetylglucosamine [GlcNAc]-terminated glycans), which carried bisecting ß1,4-N-acetylglucosamine and core α1,6-fucose. To examine glycoform whether changes in iNPH, we introduced the Tf-2/Tf-1 ratio as a diagnostic index, which minimized blot-to-blot variations in measurement. The Tf-2/Tf-1 ratios of iNPH patients are significantly higher than those of controls (p = 0.0019) and Alzheimer's patients (p = 0.0010). This suggests that the Tf-2/Tf-1 ratio could distinguish iNPH from Alzheimer's disease, and possibly other dementias. In conclusion, glycoform analysis has diagnostic potential in neurological diseases.
Assuntos
Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/diagnóstico , Polissacarídeos/líquido cefalorraquidiano , Transferrina/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissacarídeos/química , Ligação Proteica , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Transferrina/químicaRESUMO
We have established high-throughput lectin-antibody ELISAs to measure different glycans on transferrin (Tf) in cerebrospinal fluid (CSF) using lectins and an anti-transferrin antibody (TfAb). Lectin blot and precipitation analysis of CSF revealed that PVL (Psathyrella velutina lectin) bound an unique N-acetylglucosamine-terminated N-glycans on "CSF-type" Tf whereas SSA (Sambucus sieboldiana agglutinin) bound α2,6-N-acetylneuraminic acid-terminated N-glycans on "serum-type" Tf. PVL-TfAb ELISA of 0.5 µL CSF samples detected "CSF-type" Tf but not "serum-type" Tf whereas SSA-TfAb ELISA detected "serum-type" Tf but not "CSF-type" Tf, demonstrating the specificity of the lectin-TfAb ELISAs. In idiopathic normal pressure hydrocephalus (iNPH), a senile dementia associated with ventriculomegaly, amounts of the SSA-reactive Tf were significantly higher than in non-iNPH patients, indicating that Tf glycan analysis by the high-throughput lectin-TfAb ELISAs could become practical diagnostic tools for iNPH. The lectin-antibody ELISAs of CSF proteins might be useful for diagnosis of the other neurological diseases.
RESUMO
The concept of limbic encephalitis has changed over time. Since the introduction of "limbic encephalitis" (LE) in 1968, LE was thought to almost always be associated with carcinoma; this belief led to the coining of the term "paraneoplastic limbic encephalitis" (PLE). In the 1990s, antineuronal antibodies, including anti-Hu and anti-Ta/Ma2, were detected; this supported the hypothesis of an autoimmune mechanism for PLE. The prognosis of patients with PLE was, however, poor. Since 2001, there have been reports of patients with LE exhibiting antibodies to the voltage-gated potassium channel; this observation is intriguing because in such cases the encephalitis was usually independent of carcinoma, and its clinical course was often reversible. Since the 1990s, cases of non-herpetic acute limbic encephalitis have been reported in Japan. In some of these cases, an autoantibody to GluRepsilon2 (NR2B) has been detected; GluRepsilon2 is a subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor found in the limbic forebrain. A postulated pathophysiologic role of this antibody led to the concept of autoantibody-mediated acute reversible LE (AMED-ARLE). In 2007, some patients with ovarian teratoma developed encephalitis and exhibited antibodies to the NMDA receptor; this antibody is thought to recognize NR1/NR2 heteromers. Later, anti-NMDA receptor antibodies were also detected in some Japanese patients who had been previously diagnosed with juvenile acute non-herpetic encephalitis. Currently, limbic encephalitis is categorized into 3 groups: limbic encephalitis caused by virus infection, autoantibody-mediated limbic encephalitis (AMLE), and limbic encephalitis with autoimmune disease. In AMLE, antibodies to cytoplasmic antigens cause classical PLE (type I). In contrast, antibodies to cell membrane antigens often cause reversible limbic encephalitis in patients with (PLE type II) or without tumors (AMED-ARLE).
Assuntos
Encefalite Límbica , Autoanticorpos , Doenças Autoimunes/complicações , História do Século XX , Humanos , Encefalite Límbica/classificação , Encefalite Límbica/etiologia , Encefalite Límbica/história , Encefalite Límbica/fisiopatologia , Sistema Límbico/anatomia & histologia , Sistema Límbico/fisiologia , Receptores de N-Metil-D-Aspartato/imunologia , Viroses/complicaçõesRESUMO
We reviewed the clinical, electrophysiological an laboratory findings, plus the therapeutics and evolution of patients with motor-dominant Chronic inflammatory demyelinating polyneuropathy (CIDP) and compared them with those of other CIDP patients. Among 12 consecutive CIDP patients, we identified five patients with motor-dominant CIDP. The five patients with motor-dominant CIDP initially presented with weakness of the upper limbs. Cervical magnetic resonance imaging (MRI) examinations of the patients with motor-dominant CIDP showed that the most affected lesions are the cervical nerve roots and brachial plexus. The clinical course of these patients was relapsing-remitting, and they improved markedly after treatment by intravenous immunoglobulin (IVIg) infusion or plasmapheresis. However, they did not improve in response to corticosteroid therapy during the acute phase of relapses. The relapses frequently occurred within 2 years, but rarely occurred after that. The score in the modified Rankin disability scale (mRDS) at the last follow-up period was statistically lower for the patients with motor-dominant CIDP than for the other CIDP patients (P < 0.002). The characteristic clinical features, responsiveness to treatment, and prognosis suggest that motor-dominant CIDP is a distinct subtype of CIDP, with a specific immunological background. Repeated IVIg therapy is required to maintain the motor functions of patients with motor-dominant CIDP. We consider that treatment for recurrence prevention as an alternative to IVIg therapy is very important for patients with motor-dominant CIDP.