RESUMO
We report a case of acute prevertebral abscess caused by traumatic tooth fractures in a 77-year-old Japanese man. After being transferred to our hospital the patient was initially diagnosed with a neck hematoma; however, blood culture showed Streptococcus parasanguinis, an oral bacterium, and an MRI examination suggested prevertebral abscesses. Tooth fractures, severe periodontitis, and peri-implantitis with Streptococcus parasanguinis were observed. Antibiotics were administered and fractured teeth were extracted. The patient's condition then gradually improved. We concluded that bacteremia caused by traumatic tooth fractures induced the acute prevertebral abscesses.
Assuntos
Abscesso/etiologia , Bacteriemia/complicações , Doenças da Coluna Vertebral/etiologia , Fraturas dos Dentes/complicações , Abscesso/tratamento farmacológico , Idoso , Antibacterianos/uso terapêutico , Humanos , Masculino , Peri-Implantite/complicações , Periodontite/complicações , Doenças da Coluna Vertebral/tratamento farmacológicoRESUMO
Increased plasma homocysteinemia is considered a risk factor of dementia, including Alzheimer's disease (AD) and vascular dementia. However, the reason elevated plasma homocysteinemia increases the risk of dementia remains unknown. A pathological hallmark of AD is neurofibrillary tangles (NFTs) that consist of pathologically phosphorylated tau proteins. The effect of homocysteine (Hcy) on tau aggregation was explored using human neuroblastoma M1C cells that constitutively express human wild-type tau (4R0N) under the control of a tetracycline off system, primary mouse cultured neurons, and by inducing hyperhomocysteinemia in a mouse model of tauopathy (HHCy mice). A wide range of Hcy concentrations (10-1000 µM) increased total tau and phosphorylated tau protein levels. Hcy activated glycogen synthase kinase 3, and cyclin dependent kinase 5, major tau phosphokinases, and inactivated protein phosphatase 2A, a main tau phosphatase. Hcy exhibited cytotoxic effects associated with enhanced activation of caspase. Truncation of tau in the C-terminus, the cleavage site of caspase 3 (i.e., D421, detected by the TauC3 antibody) was also increased. Total tau, phosphorylated tau, as well as C-terminal cleaved tau were increased in the sarkosyl insoluble tau fraction. Hcy also increased the level of tau oligomers, as indicated by the tau oligomer complex 1 (TOC1) antibody that specifically identifies oligomeric tau species, in the tris insoluble, sarkosyl soluble fraction. The levels of TOC1-positive oligomeric tau were increased in brain lysates from HHCy mice, and treating HHCy mice with S-adenosylmethionine, an intermediate of Hcy, reduced the levels of oligomeric tau to control levels. These observations suggest that Hcy increases the levels of phosphorylated tau as well as truncated tau species via caspase 3 activation, and enhanced tau oligomerization and aggregation.
Assuntos
Doença de Alzheimer/metabolismo , Homocisteína/metabolismo , Hiper-Homocisteinemia/metabolismo , Agregação Patológica de Proteínas/metabolismo , Proteínas tau/metabolismo , Animais , Encéfalo/patologia , Linhagem Celular Tumoral , Quinase 5 Dependente de Ciclina/metabolismo , Modelos Animais de Doenças , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Emaranhados Neurofibrilares/metabolismo , Fosforilação , Proteína Fosfatase 2/antagonistas & inibidores , Tauopatias/metabolismo , Proteínas tau/genéticaRESUMO
BACKGROUND: Serum 1,5-anhydroglucitol (1,5-AG) levels are a measure that provides information on daily glycemic variations. We evaluated whether 1,5-AG could be a possible marker of acute ischemic stroke (AIS) or transient ischemic attacks (TIA) in patients with diabetes mellitus (DM). METHODS: We retrospectively reviewed electronic medical records of 5,294 AIS/TIA patients. Of the 5,294, 1,898 had diabetes and in 1,246, serum 1,5-AG levels were measured (group S). Group S was divided into 2 subgroups: hemoglobin A1c (HbA1c) <7% (S-low) and >7% (S-high). As controls, 394 outpatients with diabetes (group C) without AIS/TIA were likewise divided into subgroups, C-low and C-high according to HbA1c level. In each HbA1c subgroup, the association between serum 1,5-AG (≥14 vs. <14 µg/mL) and stroke was examined using multivariable logistic regression (MLR) with stepwise variable selection. In model 1, the OR and 95% CI was examined adjusted for age and gender. Known risk factors for stroke; hypertension, dyslipidemia, alcohol consumption, smoking, and estimated glomerular filtration rate were included in model 2. RESULTS: Overall, serum 1,5-AG levels were lower in group S than in group C. Serum 1,5-AG levels were low in subgroups S-high and C-high, showing no differences in mean values. However, mean serum 1,5-AG levels in S-low was statistically lower than that in C-low. MLR analysis showed that the OR for low (<14 µg/mL) 1,5-AG for stroke was statistically significant only in well-controlled diabetes (OR [95% CI] 2.19 [1.54-3.10]) in model 1 and (2.26 [1.56-3.28]) model 2. CONCLUSIONS: Low serum 1,5-AG levels could be a possible marker for AIS/TIA risk in patients with well-controlled DM.
Assuntos
Isquemia Encefálica/etiologia , Desoxiglucose/sangue , Diabetes Mellitus/sangue , Ataque Isquêmico Transitório/etiologia , Acidente Vascular Cerebral/etiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/terapia , Regulação para Baixo , Registros Eletrônicos de Saúde , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Ataque Isquêmico Transitório/sangue , Ataque Isquêmico Transitório/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Fatores de TempoRESUMO
Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system, and also in the visceral organs. NIID has been considered to be a heterogeneous disease because of the highly variable clinical manifestations, and ante-mortem diagnosis has been difficult. However, since we reported the usefulness of skin biopsy for the diagnosis of NIID, the number of NIID diagnoses has increased, in particular adult-onset NIID. In this study, we studied 57 cases of adult-onset NIID and described their clinical and pathological features. We analysed both NIID cases diagnosed by post-mortem dissection and by ante-mortem skin biopsy based on the presence of characteristic eosinophilic, hyaline and ubiquitin-positive intanuclear inclusion: 38 sporadic cases and 19 familial cases, from six families. In the sporadic NIID cases with onset age from 51 to 76, dementia was the most prominent initial symptom (94.7%) as designated 'dementia dominant group', followed by miosis, ataxia and unconsciousness. Muscle weakness and sensory disturbance were also observed. It was observed that, in familial NIID cases with onset age less than 40 years, muscle weakness was seen most frequently (100%), as designated 'limb weakness group', followed by sensory disturbance, miosis, bladder dysfunction, and dementia. In familial cases with more than 40 years of onset age, dementia was most prominent (100%). Elevated cerebrospinal fluid protein and abnormal nerve conduction were frequently observed in both sporadic and familial NIID cases. Head magnetic resonance imaging showed high intensity signal in corticomedullary junction in diffusion-weighted image in both sporadic and familial NIID cases, a strong clue to the diagnosis. All of the dementia dominant cases presented with this type of leukoencephalopathy on head magnetic resonance imaging. Both sporadic and familial NIID cases presented with a decline in Mini-Mental State Examination and Frontal Assessment Battery scores. Based on these clinicopathological features, we proposed a diagnosis flow chart of adult-onset NIID. Our study suggested that the prevalence rate of adult-onset NIID may be higher than previously thought, and that NIID may be underdiagnosed. We should take NIID into account for differential diagnosis of leukoencephalopathy and neuropathy.
Assuntos
Demência/etiologia , Debilidade Muscular/etiologia , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/fisiopatologia , Adolescente , Adulto , Idade de Início , Idoso , Feminino , Humanos , Corpos de Inclusão Intranuclear/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/complicações , Linhagem , Adulto JovemRESUMO
BACKGROUND: The etiology of transient global amnesia (TGA) remains unclear. We studied the pathophysiology of TGA in 165 Japanese patients. SUBJECTS AND METHODS: TGA was diagnosed in hospitalized patients from 2004 to 2015. We analyzed clinical characteristics, magnetic resonance imaging findings, and maximum intima-media thickness of the common carotid artery, and the reflux of internal jugular venous (IJV) flow by ultrasonography, and statistically compared patients with TGA with age-matched and sex-matched patients who have had a transient ischemic attack (TIA), small-vessel occlusion (SVO), and normal controls (each group, N = 165). RESULTS: Patients with TGA showed lower prevalence of vascular risk factors than patients with TIA and SVO did. Eleven patients (6.7%) had 2 episodes of TAG, but specific clinical variables could not be recognized in these patients. The maximum intima-media thickness was significantly thinner in TGA (1.1 ± .7 mm) than in SVO (1.6 ± .9 mm; P = .001). The percentages of cases whose IJV flow reflux was increased by Valsalva maneuver showed no difference (P = .573) between TGA (26.0 %) and SVO (29.4%). MR diffusion-weighted imaging yielded small hyperintense signals in the hippocampus in 64 of 90 (71.1%) patients between 24 and 72 hours. Potential precipitating specific factors or events before the attacks could be recognized in 40 cases (24.2%) of 165 patients. CONCLUSION: Arterial ischemia and IJV flow reflux might not contribute to TGA pathophysiology. The vulnerability of the hippocampus to physical or emotional stress might be suspected as an underlying mechanism in some patients with TGA.
Assuntos
Amnésia Global Transitória/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Veias Jugulares/fisiopatologia , Fluxo Sanguíneo Regional , Idoso , Amnésia Global Transitória/diagnóstico por imagem , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/fisiopatologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/epidemiologia , Angiografia Cerebral , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Veias Jugulares/diagnóstico por imagem , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Ultrassonografia DopplerRESUMO
BACKGROUND: Underweight patients have recently been reported as a group with a high risk of poststroke death. Anemia also increases mortality rates in stroke patients. However, the causal associations between body weight and anemia resulting in stroke-related death remain unclear. We examined the association of weight status and hemoglobin levels with 3-month mortality after ischemic stroke. METHODS: The study enrolled all consecutive patients with acute ischemic stroke and no history of stroke admitted to our hospital between January 2010 and December 2013. The patients were categorized into 4 body mass index (BMI) categories (underweight, normal-weight, overweight, and obese). Anemia was evaluated according to the World Health Organization criteria (men, <13 g/dL; women, <12 g/dL). RESULTS: A total of 1733 acute ischemic stroke patients (149 underweight, BMI < 18.5 kg/m2; 1076 normal-weight, BMI = 18.5-24.9 kg/m2; 436 overweight, BMI = 25-29.9 kg/m2; and 72 obese, BMI > 30 kg/m2) were included. Death within 3 months occurred in 65 patients (underweight, 10.1%; normal-weight, 3.4%; overweight, 2.3%; and obese, 5.6%). Compared to nonanemic patients, those with anemia (n = 329, 19.0%) had lower BMI (21.8 kg/m2 versus 23.7 kg/m2, P <.001) and higher mortality rates (9.1% versus 2.5%, P <.001). Underweight status was associated with 3-month mortality after adjusting for age, sex, comorbidities, and initial stroke severity. However, in the models that included laboratory findings, it was anemia status (odds ratio, 2.81; 95% confidence interval, 1.46-5.43), not underweight status, that was independently associated with 3-month mortality. CONCLUSION: Anemia on admission was associated with stroke mortality independent of underweight status.
Assuntos
Anemia/mortalidade , Isquemia Encefálica/mortalidade , Admissão do Paciente , Acidente Vascular Cerebral/mortalidade , Magreza/mortalidade , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/diagnóstico , Biomarcadores/sangue , Índice de Massa Corporal , Isquemia Encefálica/diagnóstico , Distribuição de Qui-Quadrado , Comorbidade , Feminino , Hemoglobinas/metabolismo , Humanos , Hipoalbuminemia/sangue , Hipoalbuminemia/diagnóstico , Hipoalbuminemia/mortalidade , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/diagnóstico , Obesidade/mortalidade , Obesidade/fisiopatologia , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Magreza/diagnóstico , Magreza/fisiopatologia , Fatores de TempoRESUMO
Tau aggregation and amyloid ß protein (Aß) deposition are the main causes of Alzheimer's disease (AD). Peroxisome proliferator-activated receptor γ (PPARγ) activation modulates Aß production. To test whether the PPARγ agonist pioglitazone (PIO) is also effective in preventing tau aggregation in AD, we used a cellular model in which wild-type tau protein (4R0N) is overexpressed (M1C cells) (Hamano et al., 2012) as well as primary neuronal cultures. PIO reduced both phosphorylated and total tau levels, and inactivated glycogen synthase kinase 3ß, a major tau kinase, associated with activation of Akt. In addition, PIO decreased cleaved caspase3 and C-terminal truncated tau species by caspase, which is expected to decrease tau aggregation. A fractionation study showed that PIO reduced high molecular-weight (120 kDa), oligomeric tau species in Tris Insoluble, sarkosyl-soluble fractions. Tau decrease was reversed by adding GW9662, a PPARγ antagonist. Together, our current results support the idea that PPARγ agonists may be useful therapeutic agents for AD.
Assuntos
Multimerização Proteica/efeitos dos fármacos , Tiazolidinedionas/farmacologia , Proteínas tau/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Camundongos Endogâmicos ICR , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neuroproteção/efeitos dos fármacos , PPAR gama/antagonistas & inibidores , PPAR gama/metabolismo , Fosforilação/efeitos dos fármacos , PioglitazonaRESUMO
BACKGROUND: The purpose of this study was to explore the relation between muscle MRI findings and weakness of the upper extremity muscles in patients with myotonic dystrophy type 1 (DM1). METHODS: Nineteen DM1 patients from 15 families were enrolled in this study. Muscle weakness was evaluated using the modified Medical Research Council scale. Subjects also underwent a genetic study and muscle MRI of the upper extremities. RESULTS: In patients with DM1, the flexor digitorum profundus (FDP), flexor pollicis longus, flexor digitorum superficialis (FDS), extensor pollicis, abductor pollicis longus (APL), lateral head of triceps brachii and infraspinatus (INF) muscles were frequently and severely affected. Muscle strength was significantly correlated with the severity of muscle MRI findings in the FDP, short head of biceps brachii (SBB), and medial head of triceps brachii muscles. Disease duration was correlated significantly with MRI findings in the FDP, FDS, long head of biceps brachii, INF, APL, and SBB muscles. Unexpectedly, the degree of trinucleotide expansion of myotonin protein kinase was not correlated with muscle MRI findings. CONCLUSION: Muscle MRI of the upper extremity is useful to detect affected muscles in DM1 patients.
Assuntos
Imageamento por Ressonância Magnética , Debilidade Muscular/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Distrofia Miotônica/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Extremidade Superior/diagnóstico por imagemRESUMO
BACKGROUND: It is important to determine the usage of anticoagulants by defining the actual risk of cardioembolic stroke in patients with old myocardial infarction. In the present study, we aimed to more precisely evaluate the risks of each segment associated with cardioembolic stroke using a 16-segment model. The usage of the plasma brain natriuretic peptide (BNP) associated with cardioembolic stroke was also evaluated in comparison with a left ventricle ejection fraction less than 40%. METHODS: There were a total of 190 ischemic stroke patients who had premorbid myocardial infarction. The study included a total of 143 ischemic stroke patients with old myocardial infarction who were available for evaluation and excluded patients with atrial fibrillation or acute myocardial infarction. Their left ventricle wall motion abnormality and the level of plasma BNP at their admission were analyzed. RESULTS: Hypertension and a plasma BNP level of 206.9 pg/mL or higher, determined from the receiver operating characteristic curve, were independently associated with cardioembolic stroke (χ(2) = 35.6, R(2) = .30, P < .001). Adjusting for these factors, statistically independent high risk was observed at the basal-inferior, basal-inferolateral, mid-anterior, mid-anteroseptal, apical-anterior, and apical-septal left ventricles. CONCLUSION: High plasma BNP levels and left ventricular wall motion abnormalities in the segments perfused with left anterior descending coronary artery or right coronary artery show a high risk for cardioembolic stroke in patients with old myocardial infarction. Considering these factors, it could be possible to more precisely define the risk of cardioembolic stroke and to perform appropriate antithrombotic treatments in old myocardial infarction patients.
Assuntos
Técnicas de Apoio para a Decisão , Embolia Intracraniana/etiologia , Infarto do Miocárdio/complicações , Peptídeo Natriurético Encefálico/sangue , Acidente Vascular Cerebral/etiologia , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Fenômenos Biomecânicos , Distribuição de Qui-Quadrado , Estudos Transversais , Ecocardiografia , Feminino , Humanos , Hipertensão/complicações , Embolia Intracraniana/diagnóstico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Volume Sistólico , Regulação para Cima , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND: We undertook a multicenter cohort observational study to investigate the frequency and type of subsequent vascular events after an ischemic stroke and to compare the rates of vascular events between patients with and without hyperlipidemia. METHODS: This nationwide study was conducted in 19 hospitals participating in the Japan Standard Stroke Registry Study. We enrolled ischemic stroke patients, including those with a transient ischemic attack, who had not experienced any vascular events before enrollment after their ischemic stroke events. Each subject was observed prospectively from September 1, 2003, to October 1, 2005, or until a primary end point or death. Primary end points included subsequent fatal or nonfatal vascular events: stroke, angina pectoris, acute myocardial infarction, aortic aneurysm, or arteriosclerosis obliterans. RESULTS: A total of 449 patients (mean age, 67.6 years; 64.8% men) were enrolled in this study. Of the 41 vascular events observed during follow-up, 40 were stroke. The median observation period was 568 days. We found that patients with hyperlipidemia had a significantly higher rate of vascular events compared with those without hyperlipidemia according to the Kaplan-Meier method and the log-rank test (P = .013). Hyperlipidemia significantly increased the risk of vascular events (hazard ratio, 2.169 [1.125-4.312]; P = .021) according to the Cox proportional hazard model after adjusting for confounding factors (age, sex, days from ischemic stroke until enrollment, smoking habits, and daily drinking habits). CONCLUSIONS: This study demonstrated that stroke was the most common subsequent vascular event after ischemic stroke; the study also indicated that hyperlipidemia could be a risk factor for subsequent vascular events after ischemic stroke.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Ataque Isquêmico Transitório/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Idoso , Feminino , Humanos , Hiperlipidemias/complicações , Incidência , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/epidemiologia , Japão , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Prevenção Secundária , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND: Hashimoto's encephalopathy (HE) presents with a variety of neurologic and neuropsychiatric features. In this study, we investigated the clinical and immunological profiles of the cerebellar ataxic form of HE. METHODS: The clinical features, treatments, laboratory features, brain imaging, and serum anti-NH(2)-terminal of α-enolase autoantibodies (anti-NAE Abs), a useful diagnostic marker for HE, were investigated in 13 patients who presented with sporadic adult-onset cerebellar ataxia and fulfilled the HE diagnostic criteria (antithyroid Abs and responsiveness to immunotherapy). RESULTS: All of the patients presented with truncal ataxia, but nystagmus was uncommon (17%). Eight patients had an insidious onset that mimicked spinocerebellar degeneration (SCD), but brain imaging showed little or no cerebellar atrophy in all of the patients. Those patients with serum anti-NAE Abs (n = 8) did not have nystagmus and tended to respond better to immunotherapy than the anti-NAE Ab-negative patients. CONCLUSION: The present study suggests that insidious adult-onset and truncal ataxia are common in the cerebellar ataxic form of HE, which mimics SCD, but that nystagmus and severe cerebellar atrophy are uncommon. Antithyroid and anti-NAE Abs may be useful for diagnosing cerebellar ataxic HE.
Assuntos
Encefalopatias/diagnóstico , Ataxia Cerebelar/diagnóstico , Doença de Hashimoto/diagnóstico , Degenerações Espinocerebelares/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Encefalopatias/imunologia , Encefalopatias/patologia , Ataxia Cerebelar/imunologia , Ataxia Cerebelar/patologia , Diagnóstico Diferencial , Encefalite , Feminino , Doença de Hashimoto/imunologia , Doença de Hashimoto/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fosfopiruvato Hidratase/imunologia , Degenerações Espinocerebelares/imunologia , Degenerações Espinocerebelares/patologiaRESUMO
BACKGROUND/AIMS: To clarify the change of systemic redox states in patients carrying the A3243G mutation in mitochondrial DNA (A3243G), we evaluated oxidative stress and antioxidant activity in the serum of patients. METHODS: Oxidative stress and antioxidant activity in the serum samples obtained from 14 patients carrying A3243G and from 34 healthy controls were analyzed using the diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) tests, respectively. RESULTS: The mean d-ROMs level of all patients was significantly greater than that of the controls (p < 0.005), and the mean BAP/d-ROMs ratio of all patients was significantly lower than that of the controls (p < 0.02). In the patients with a history of stroke-like episodes (n = 10), both mean d-ROMs and BAP levels were increased compared with those of the controls (both p < 0.01). The mean BAP level of the patients without a history of stroke-like episodes (n = 4) was significantly decreased compared with that of the controls (p < 0.001), but the mean d-ROMs levels were not significantly different. CONCLUSION: d-ROMs and BAP tests indicated that patients carrying A3243G are always exposed to underlying oxidative stress, even at a remission state of stroke-like episodes.
Assuntos
DNA Mitocondrial/genética , Síndrome MELAS/genética , Síndrome MELAS/fisiopatologia , Mutação/genética , Estresse Oxidativo/genética , Adolescente , Adulto , Alanina/genética , Antioxidantes/metabolismo , Feminino , Glicina/genética , Humanos , Peróxido de Hidrogênio/sangue , Síndrome MELAS/sangue , Masculino , Oxirredução , Espécies Reativas de Oxigênio/sangue , Estatísticas não Paramétricas , Adulto JovemRESUMO
Vitamin B12 deficiency is associated with cognitive impairment, hyperhomocysteinemia, and hippocampal atrophy. However, the recovery of cognition with vitamin B12 supplementation remains controversial. Of the 1716 patients who visited our outpatient clinic for dementia, 83 had vitamin B12 deficiency. Among these, 39 patients (mean age, 80.1 ± 8.2 years) had undergone Mini-Mental State Examination (MMSE) and laboratory tests for vitamin B12, homocysteine (Hcy), and folic acid levels. The hippocampal volume was estimated using the z-score of the MRI-voxel-based specific regional analysis system for Alzheimer's disease. This is multi-center, open-label, single-arm study. All the 39 patients were administered vitamin B12 and underwent reassessment to measure the retested for MMSE and Hcy after 21−133 days (median = 56 days, interquartile range (IQR) = 43−79 days). After vitamin B12 supplementation, the mean MMSE score improved significantly from 20.5 ± 6.4 to 22.9 ± 5.5 (p < 0.001). Hcy level decreased significantly from 22.9 ± 16.9 nmol/mL to 11.5 ± 3.9 nmol/mL (p < 0.001). Significant correlation was detected between the extent of change in MMSE scores and baseline Hcy values. The degree of MMSE score was not correlated with hippocampal atrophy assessed by the z-score. While several other factors should be considered, vitamin B12 supplementation resulted in improved cognitive function, at least in the short term, in patients with vitamin B12 deficiency.
Assuntos
Disfunção Cognitiva , Deficiência de Vitamina B 12 , Idoso , Idoso de 80 Anos ou mais , Atrofia , Cognição , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Suplementos Nutricionais , Ácido Fólico , Homocisteína , Humanos , Vitamina B 12 , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/tratamento farmacológico , VitaminasRESUMO
This report describes an episode of malignant hyperthermia (MH) in a 53-year-old Japanese man during general anesthesia that was triggered by isoflurane and succinylcholine. His past history and family history were unremarkable. From our analysis of ten exons, he had no recognizable mutation in the ryanodine receptor gene, but compatible with his MH reaction, he showed positive sensitivity to the Ca-induced Ca-release test. Histochemical and electron microscopic studies of muscle biopsy tissue demonstrated unusual "ring fibers," which have never before been reported to be associated with MH. The presence of ring fibers in this patient might indicate muscle regeneration, suggesting a recovery process from the MH episode.
Assuntos
Hipertermia Maligna/patologia , Músculo Masseter/patologia , Retículo Sarcoplasmático/ultraestrutura , Anestesia Geral/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Análise Mutacional de DNA , Humanos , Isoflurano/efeitos adversos , Masculino , Hipertermia Maligna/etiologia , Hipertermia Maligna/genética , Músculo Masseter/ultraestrutura , Microscopia Eletrônica , Pessoa de Meia-Idade , Miofibrilas/ultraestrutura , Fármacos Neuromusculares Despolarizantes/efeitos adversos , Rianodina , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Retículo Sarcoplasmático/patologia , Succinilcolina/efeitos adversosRESUMO
BACKGROUND: Cardiomyopathy is a life-threatening condition in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (known as MELAS). However, no effective therapy has been available until now. In the present study cardiac energetics and acute effects of L-arginine (Arg) were evaluated in MELAS patients. METHODS AND RESULTS: The 6 patients with MELAS (M-group) and 6 volunteers (C-group) underwent dynamic C-11 acetate positron emission tomography (PET) imaging. TCA-cycle metabolic rate (k(mono)), myocardial efficiency (double product (DP)/k(mono)), and myocardial blood flow (MBF) were determined before and after L-Arg administration. Baseline k(mono) showed a lower value in the M-group than in the C-group (0.051±0.013 vs 0.070±0.019min(-1), P=0.055). On the other hand, baseline DP/k(mono) was significantly greater in the M-group (1.69±5.9 vs 0.95±1.2×10(5), P=0.004). After L-Arg administration, 4 patients showed significant elevation of k(mono). No relationship was observed between the distribution of k(mono) elevation and the increase in MBF. CONCLUSIONS: The TCA cycle metabolic rate is markedly suppressed in MELAS patients, indicating a shift in energy production to the anaerobic pathway, leading to a paradoxical increase in myocardial efficiency. L-Arg can enhance TCA-cycle metabolism, regardless of its vasodilatation effect, and can be used as a treatment for patients with mitochondrial cardiomyopathy.
Assuntos
Acetatos/metabolismo , Arginina/administração & dosagem , Cardiomiopatias , Metabolismo Energético/efeitos dos fármacos , Síndrome MELAS , Tomografia por Emissão de Pósitrons , Acetatos/administração & dosagem , Adulto , Isótopos de Carbono/administração & dosagem , Isótopos de Carbono/farmacocinética , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/metabolismo , Ciclo do Ácido Cítrico/efeitos dos fármacos , Circulação Coronária/efeitos dos fármacos , Feminino , Humanos , Síndrome MELAS/diagnóstico por imagem , Síndrome MELAS/metabolismo , Masculino , Pessoa de Meia-Idade , RadiografiaRESUMO
The purpose of this study was to investigate the relationship of muscle MRI findings and gait disturbance in myotonic dystrophy type 1 (DM1) patients. Thirteen patients with DM1 were evaluated by manual muscle strength test and muscle MRI of the lower limb. All DM1 patients presenting with foot drop showed high intensity signals in the tibialis anterior muscles on T1-weighted imaging (p < 0.001). The patients presenting with gait disturbance showed high intensity signals in the semimembranosus, vastus intermedius and gastrocnemius medialis muscles, too. Disturbance of the gastrocnemius lateralis muscles was mild in all DM1 patients. The patients without gait disturbance showed no abnormalities, especially in tibialis anterior muscles on muscle MRI. Muscle MRI is useful for the detection of pathological muscles in DM1 patients with gait disturbance.
Assuntos
Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/patologia , Músculo Esquelético/patologia , Distrofia Miotônica/complicações , Distrofia Miotônica/patologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
Although folate deficiency was reported to be associated with hyperhomocysteinemia, influence of folate supplementation on cognition remains controversial. Therefore, we explored the effects of folate supplementation on the cognition and Homocysteine (Hcy) level in relatively short periods in patients with folate deficiency and cognitive impairment. Enrolled 45 patients (mean age of 79.7 ± 7.9 years old) with folate deficiency (<3.6 ng/mL) with cognitive impairment underwent Mini-Mental State Examination (MMSE), and laboratory examinations, including folate, vitamin B12, and Hcy. The degree of hippocampal atrophy in MRI was estimated using a voxel-based specific regional analysis system for Alzheimer's disease (VSRAD). Patients were administrated folate (5 mg/day), then Hcy, and MMSE score were re-examined after 28 to 63 days. Mean Hcy significantly decreased from 25.0 ± 18.0 to 11.0 ± 4.3 nmol/mL (p < 0.001). Average MMSE scores also significantly changed from 20.1 ± 4.7 to 22.2 ± 4.3 (p < 0.001). The degree of change in the MMSE score and basic Hcy or Hcy change was significantly positively correlated, while degree of hippocampal atrophy in MRI did not. Although several factors should be taken into account, folate supplementation ameliorated cognitive impairment, at least for a short period, in patients with folate deficiency.
Assuntos
Cognição , Disfunção Cognitiva/sangue , Disfunção Cognitiva/psicologia , Suplementos Nutricionais , Deficiência de Ácido Fólico/psicologia , Ácido Fólico/administração & dosagem , Ácido Fólico/farmacologia , Homocisteína/sangue , Idoso , Idoso de 80 Anos ou mais , Atrofia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/tratamento farmacológico , Feminino , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/dietoterapia , Hipocampo/patologia , Humanos , Masculino , Testes de Estado Mental e Demência , Fatores de Tempo , Resultado do TratamentoRESUMO
Neurofibrillary tangles, one of the pathological hallmarks of Alzheimer's disease, consist of highly phosphorylated tau proteins. Tau protein binds to microtubules and is best known for its role in regulating microtubule dynamics. However, if tau protein is phosphorylated by activated major tau kinases, including glycogen synthase kinase 3ß or cyclin-dependent kinase 5, or inactivated tau phosphatase, including protein phosphatase 2A, its affinity for microtubules is reduced, and the free tau is believed to aggregate, thereby forming neurofibrillary tangles. We previously reported that pitavastatin decreases the total and phosphorylated tau protein using a cellular model of tauopathy. The reduction of tau was considered to be due to Rho-associated coiled-coil protein kinase (ROCK) inhibition by pitavastatin. ROCK plays important roles to organize the actin cytoskeleton, an expected therapeutic target of human disorders. Several ROCK inhibitors are clinically applied to prevent vasospasm postsubarachnoid hemorrhage (fasudil) and for the treatment of glaucoma (ripasudil). We have examined the effects of ROCK inhibitors (H1152, Y-27632, and fasudil [HA-1077]) on tau protein phosphorylation in detail. A human neuroblastoma cell line (M1C cells) that expresses wild-type tau protein (4R0N) by tetracycline-off (TetOff) induction, primary cultured mouse neurons, and a mouse model of tauopathy (rTG4510 line) were used. The levels of phosphorylated tau and caspase-cleaved tau were reduced by the ROCK inhibitors. Oligomeric tau levels were also reduced by ROCK inhibitors. After ROCK inhibitor treatment, glycogen synthase kinase 3ß, cyclin-dependent kinase 5, and caspase were inactivated, protein phosphatase 2A was activated, and the levels of IFN-γ were reduced. ROCK inhibitors activated autophagy and proteasome pathways, which are considered important for the degradation of tau protein. Collectively, these results suggest that ROCK inhibitors represent a viable therapeutic route to reduce the pathogenic forms of tau protein in tauopathies, including Alzheimer's disease.
Assuntos
Doença de Alzheimer/metabolismo , Inibidores Enzimáticos/farmacologia , Proteólise/efeitos dos fármacos , Quinolinas/farmacologia , Tauopatias/metabolismo , Quinases Associadas a rho/antagonistas & inibidores , Proteínas tau/metabolismo , Doença de Alzheimer/tratamento farmacológico , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Células Cultivadas , Modelos Animais de Doenças , Humanos , Camundongos , Emaranhados Neurofibrilares/metabolismo , Fosforilação/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tauopatias/tratamento farmacológico , Quinases Associadas a rho/fisiologiaRESUMO
BACKGROUND AND AIM: The relationship between Helicobacter pylori infection and body mass index (BMI) and dyspeptic symptoms is controversial. We investigated the changes in BMI and dyspeptic symptoms after H. pylori eradication among stages of atrophic gastritis classified according to the serum pepsinogen (PG) I/II ratio. METHODS: One hundred and sixty-three H. pylori-positive patients underwent eradication therapy for H. pylori. Serum PG I and II concentrations were measured before treatment, and the PG I/II ratio was classified into three groups: PG I/II ratio <2.0, PG I/II ratio >or=2.0 and <4.0, and PG I/II ratio >or=4.0 were considered to be low, middle, and high, respectively. Their BMI and abdominal symptoms were checked before, 1 and 5 years after treatment, and these changes were investigated among the three groups. RESULTS: The mean BMI changes 1 year after treatment in the low PG I/II ratio group were significantly higher than those in other groups. Most abdominal symptoms in the high PG I/II ratio group were most severe before eradication but improved significantly after eradication. CONCLUSIONS: The effects of H. pylori eradication on BMI and dyspeptic symptoms may be different according to the serum PG I/II ratio before eradication.
Assuntos
Dispepsia/tratamento farmacológico , Gastrite Atrófica/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Adulto , Índice de Massa Corporal , Dispepsia/sangue , Dispepsia/microbiologia , Feminino , Gastrite Atrófica/sangue , Gastrite Atrófica/microbiologia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Pepsinogênios/sangueRESUMO
The patient was a 53-year-old woman with an 18-year history of recurrent oral aphtae, genital ulcers and folliculitis-like erupsions without mucocutaneus symptoms. She was admitted to our hospital for headache, and presented with meningeal irritation, dysarthria and right pyramidal signs. Brain MRI showed abnormal intensities extending from the right midbrain to the bilateral corona radiata, accompanied by contrast enhancement. She was diagnosed as having an incomplete form of neuro-Behçet disease (NBD) based on the diagnostic criteria for NBD. However, the HLA-type was defined as B54 and Cw1, which is common and specific in neuro-Sweet disease (NSD). Oral administration of prednisolone was markedly effective for the neurological symptoms and improved radiological findings, suggesting NSD rather than NBD as the clinical diagnosis for this patient Since she presented with clinical features that appeared in both diseases, the definitive diagnosis was clinically difficult. While tapering the dosage of prednisolone, we carefully observed the appearance of skin lesions and erythema nodosum appearing on her right lower leg. Skin biopsy demonstrated the features of erythema nodosum: lobular panniculitis with the accumulation of neutrophils and lymphocytes with necrotic fatty cells in the subcutaneous area, which was compatible with skin lesions in NBD. In our case, pathological findings of the skin lesion were required to differentiate between NBD and NSD, indicating the need for careful follow-up of dermatologic signs appearing in such a case.