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BACKGROUND: Sitting ability is an important prognostic factor for patients with acute stroke. However, the characteristics of trunk muscle activity and weight-bearing during sitting are unclear. RESEARCH QUESTION: Are trunk muscle activity and weight-bearing during static sitting associated with sitting ability in patients with acute stroke? METHODS: Trunk electromyography and sitting posturography were performed during static sitting in 20 patients with acute stroke. The electromyography measured the bilateral external oblique and erector spinae muscles. The symmetry of muscle activity between the paralyzed and non-paralyzed side was calculated using the Symmetry Index (SI) raw value and absolute value. The activity of each muscle during static sitting was calculated as the percent reference voluntary contraction (%RVC) normalized by the maximum contraction in the sitting position. Sitting posturography was used to calculate the weight-bearing pressure (%) on the paralyzed and non-paralyzed side, and the raw and absolute values of weight-bearing SI were calculated as a representative value. The trunk impairment scale (TIS) for sitting ability and the Berg balance scale (BBS) for basic balance ability were used as primary outcomes. RESULTS: None of the SI of electromyography for each trunk muscle correlated significantly with clinical performance tests. The %RVC of paralyzed and non-paralyzed external oblique muscle negatively correlated with TIS. The absolute SI of weight-bearing was negatively correlated with BBS. SIGNIFICANCE: This study showed that the amount, but not the symmetry, of external oblique muscle activity during sitting was associated with sitting ability. We also found that the symmetry of the weight-bearing was associated with sitting ability, not the direction, but the absolute amount of deviation. This suggests that it is important to focus on the amount of external oblique muscle activity and weight-bearing deviation during sitting as a measure of sitting ability in patients with acute stroke.
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The glymphatic system is considered to play a pivotal role in the clearance of disease-causing proteins in neurodegenerative diseases. This study employed MR diffusion tensor imaging (DTI) to evaluate glymphatic system function and its correlation with brain amyloid accumulation levels measured using [11C]Pittsburgh compound-B (PiB) PET/MRI. Fifty-six patients with mild cognitive impairment and early Alzheimer's disease (AD: 70 ± 11 y) underwent [11C]PiB PET/MRI to assess amyloid deposition and were compared with 27 age-matched cognitively normal volunteers (CN: 69 ± 10y). All participants were evaluated for cognitive function using the Mini Mental State Examination (MMSE) before [11C]PiB PET/MRI. DTI images were acquired during the PET/MRI scan with several other MR sequences. The DTI analysis along the perivascular space index (DTI-ALPS index) was calculated to estimate the functional activity of the glymphatic system. Centiloid scale was applied to quantify amyloid deposition levels from [11C]PiB PET images. All patients in the AD group showed positive [11C]PiB accumulation, whereas all CN participants were negative. ALPS-index for all subjects linearly correlated with PiB centiloid, MMSE scores, and hippocampal volume. The correlation between the ALPS-index and PiB accumulation was more pronounced than with any other biomarkers. These findings suggest that glymphatic system dysfunction is a significant factor in the early stages of Alzheimer's disease.
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Doença de Alzheimer , Biomarcadores , Disfunção Cognitiva , Sistema Glinfático , Imageamento por Ressonância Magnética , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Idoso , Masculino , Feminino , Tomografia por Emissão de Pósitrons/métodos , Imageamento por Ressonância Magnética/métodos , Biomarcadores/metabolismo , Imagem Multimodal/métodos , Sistema Glinfático/diagnóstico por imagem , Sistema Glinfático/metabolismo , Pessoa de Meia-Idade , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Imagem de Tensor de Difusão/métodos , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Tiazóis , Compostos de AnilinaRESUMO
This report presents a unique finding of an incidental right internal carotid artery dissection in an asymptomatic 69-year-old man. The report highlights the possible trigger and long-term outcomes of this condition. The patient had participated in Japanese archery competitions for many years. His medical history included hypertension and a prior ischemic stroke in the left lateral medulla, resulting in Wallenberg syndrome. During a routine visit, head magnetic resonance angiography revealed right internal carotid artery dissection. He was managed conservatively with antiplatelet therapy and close monitoring. Follow-up imaging after 10 years showed no changes, and the patient remained asymptomatic. Therefore, routine screening for incidental findings is important even in asymptomatic patients. Archery competitions may be a possible trigger for internal carotid artery dissection. The presence of re-entry in the lesion at the time of onset can be a predictor of a good long-term prognosis.
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Dissecação da Artéria Carótida Interna , Masculino , Humanos , Idoso , Dissecação da Artéria Carótida Interna/diagnóstico por imagem , Dissecação da Artéria Carótida Interna/etiologia , Seguimentos , Japão , Angiografia por Ressonância Magnética/efeitos adversosRESUMO
Nivolumab blocks inhibitors of T-cell activation and restores antitumor immunity but promotes T-cell activity in host tissues by blocking inhibition of the T-cell function, resulting in immune-related adverse effects. We herein report an 80-year-old man presenting with nivolumab-related myasthenia gravis with anti-muscular voltage-gated potassium channel-complex (Kv1.4) antibodies. On day 29 after nivolumab administration, he simultaneously developed rapidly progressing right ptosis and left facial paralysis. Nivolumab administration was discontinued. He subsequently presented with bulbar paralysis, dyspnea, and muscle weakness and received intravenous immunoglobulin, methylprednisolone, and plasma exchange. The severity of nivolumab-related myasthenia gravis with anti-Kv1.4 antibodies presented with diverse clinical findings.
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Blefaroptose , Miastenia Gravis , Miosite , Masculino , Humanos , Idoso de 80 Anos ou mais , Nivolumabe/efeitos adversos , Miastenia Gravis/induzido quimicamente , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , Miosite/induzido quimicamente , Miosite/diagnóstico , Miosite/tratamento farmacológico , Blefaroptose/induzido quimicamente , Debilidade Muscular/tratamento farmacológicoRESUMO
Background and objectives: Magnetic resonance imaging with arterial spin labeling (ASL) perfusion imaging is a noninvasive method for quantifying cerebral blood flow (CBF). We aimed to evaluate the clinical utility of ASL perfusion imaging to aid in the diagnosis of Creutzfeldt-Jakob disease (CJD). Methods: This retrospective study enrolled 10 clinically diagnosed with probable sporadic CJD (sCJD) based on the National CJD Research & Surveillance Unit and EuroCJD criteria and 18 healthy controls (HCs). Diffusion-weighted images (DWIs), CBF images obtained from ASL, N-isopropyl-(123I)-p-iodoamphetamine (123IMP)-single-photon emission computed tomography (SPECT) images, and 18F-fluorodeoxyglucose (18FDG)-positron emission tomography (PET) images were analyzed. First, the cortical values obtained using volume-of-interest (VOI) analysis were normalized using the global mean in each modality. The cortical regions were classified into DWI-High (≥ +1 SD) and DWI-Normal (< +1 SD) regions according to the DWI-intensity values. The normalized cortical values were compared between the two regions for each modality. Second, each modality value was defined as ASL hypoperfusion (< -1 SD), SPECT hypoperfusion (< -1 SD), and PET low accumulation (< -1 SD). The overall agreement rate of DWIs with ASL-CBF, SPECT, and PET was calculated. Third, regression analyses between the normalized ASL-CBF values and normalized SPECT or PET values derived from the VOIs were performed using a scatter plot. Results: The mean values of ASL-CBF (N = 10), 123IMP-SPECT (N = 8), and 18FDG-PET (N = 3) in DWI-High regions were significantly lower than those in the DWI-Normal regions (p < 0.001 for all); however, HCs (N = 18) showed no significant differences in ASL-CBF between the two regions. The overall agreement rate of DWI (high or normal) with ASL-CBF (hypoperfusion or normal) (81.8%) was similar to that of SPECT (85.2%) and PET (78.5%) in CJD. The regression analysis showed that the normalized ASL-CBF values significantly correlated with the normalized SPECT (r = 0.44, p < 0.001) and PET values (r = 0.46, p < 0.001) in CJD. Discussion: Patients with CJD showed ASL hypoperfusion in lesions with DWI hyperintensity, suggesting that ASL-CBF could be beneficial for the diagnostic aid of CJD.
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Anti-mitochondrial M2 antibody (AMA-M2)-positive myositis is an idiopathic inflammatory myopathy (IIM). Of all patients with myositis, 2.5-19.5% have AMA-M2 antibodies. However, the detailed distribution of muscles affected in AMA-positive myositis is unknown. Therefore, we examined lower muscle magnetic resonance imaging (MRI) findings of patients with AMA-positive myositis. Among the 63 patients with IIM at our institute, 5 (7.9%) were positive for AMA-M2 antibodies. However, one was also positive for anti-Jo1 antibodies; therefore, four patients were finally participated in this study. All patients had high-intensity MRI signals in the proximal muscles, including the gluteus maximus and iliopsoas muscles, and in the thigh muscles, including the vastus lateralis, vastus medialis, adductor magnus, and semimembranosus muscles. Lower leg muscles were relatively spared. Fascial edema was observed in all patients and was also present in the lower leg muscles. Subcutaneous edema was observed, particularly in the proximal portion of the lower limbs. In AMA-positive myositis, proximal muscles, including the gluteus maximus, vastus lateralis, adductor magnus, and the semimembranosus, were markedly affected, while the lower leg muscles were relatively preserved. Additionally, fascial edema was evident even in lower leg muscles. Therefore, muscle MRI can be a useful diagnostic aid for AMA-positive myositis.
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Extremidade Inferior , Miosite , Humanos , Extremidade Inferior/diagnóstico por imagem , Miosite/diagnóstico por imagem , Perna (Membro) , Músculo Quadríceps , Anticorpos , Imageamento por Ressonância MagnéticaRESUMO
Background: Left ventricular noncompaction (LVNC) is a rare inherited cardiomyopathy with a broad phenotypic spectrum. The genotype-phenotype correlations in fetal-onset LVNC have not yet been fully elucidated. In this report, we present the first case of severe fetal-onset LVNC caused by maternal low-frequency somatic mosaicism of the novel myosin heavy chain 7 (MYH7) mutation. Case presentation: A 35-year-old pregnant Japanese woman, gravida 4, para 2, with no significant medical or family history of genetic disorders, presented to our hospital. In her previous pregnancy at 33 years of age, she delivered a male neonate at 30 weeks of gestation with cardiogenic hydrops fetalis. Fetal echocardiography confirmed LVNC prenatally. The neonate died shortly after birth. In the current pregnancy, she again delivered a male neonate with cardiogenic hydrops fetalis caused by LVNC at 32 weeks of gestation. The neonate died shortly after birth. Genetic screening of cardiac disorder-related genes by next-generation sequencing (NGS) was performed which revealed a novel heterozygous missense MYH7 variant, NM_000257.3: c.2729A > T, p.Lys910Ile. After targeted and deep sequencing by NGS, the same MYH7 variant (NM_000257.3: c.2729A > T, p.Lys910Ile) was detected in 6% of the variant allele fraction in the maternal sequence but not in the paternal sequence. The MYH7 variant was not detected by conventional direct sequencing (Sanger sequencing) in either parent. Conclusions: This case demonstrates that maternal low-frequency somatic mosaicism of an MYH7 mutation can cause fetal-onset severe LVNC in the offspring. To differentiate hereditary MYH7 mutations from de novo MYH7 mutations, parental targeted and deep sequencing by NGS should be considered in addition to Sanger sequencing.
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PURPOSE: To investigate the relationship of the striatal dopamine transporter density to changes in the gray matter (GM) volume and cerebral perfusion in patients with Parkinson's disease (PD). METHODS: We evaluated the regional cerebral blood flow (CBF) and GM volume, concurrently measured using arterial spin labeling and T1-weighted magnetic resonance imaging, respectively, as well as the striatal specific binding ratio (SBR) in 123I-N-ω-fluoropropyl-2ß-carboxymethoxy-3ß-(4-iodophenyl)nortropane (123I-FP-CIT) single-photon emission computed tomography in 30 non-demented patients with PD (15 men and 15 women; mean age, 67.2 ± 8.8 years; mean Hoehn-Yahr stage, 2.2 ± 0.9). Voxel-wise regression analyses using statistical parametric mapping (SPM) were performed to explore the brain regions that showed correlations of the striatal SBR to the GM volume and CBF, respectively, with a height threshold of p < 0.0005 at the voxel level and p < 0.05 family-wise error-corrected at the cluster level. RESULTS: SPM analysis showed a significant positive correlation between the SBR and GM volume in the inferior frontal gyrus (IFG). Whereas, a positive correlation between the SBR and CBF was widely found in the frontotemporal and parietotemporal regions, including the IFG. Notably, the opercular part of the IFG showed significant correlations in both SPM analyses of the GM volume (r2 = 0.90, p < 0.0001) and CBF (r2 = 0.88, p < 0.0001). CONCLUSION: The voxel-wise analyses revealed the brain regions, mainly the IFG, that showed hypoperfusion and atrophy related to dopaminergic loss, which suggests that the progression of dopaminergic neurodegeneration leads to regional cortical dysfunction in PD.
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Doença de Parkinson , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Doença de Parkinson/patologia , Marcadores de Spin , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Perfusão , Tropanos , AtrofiaRESUMO
Oxidative stress imaging using diacetyl-bis (N4-methylthiosemicarbazone) (Cu-ATSM) was applied to the evaluation of patients with early Alzheimer's disease (eAD). Ten eAD patients (72 ± 9 years) and 10 age-matched healthy controls (HCs) (73 ± 9 years) participated in this study. They underwent dynamic PET/MRI using 11C-PiB and 64Cu-ATSM with multiple MRI sequences. To evaluate cerebral oxidative stress, three parameters of 64Cu-ATSM PET were compared: standardized uptake value (SUV), tracer influx rate (Kin), and a rate constant k3. The input functions were estimated by the image-derived input function method. The relative differences were analyzed by statistical parametric mapping (SPM) using SUV and Kin images. All eAD patients had positive and HC subjects had negative PiB accumulation, and MMSE scores were significantly different between them. The 64Cu-ATSM accumulation tended to be higher in eAD than in HCs for both SUV and Kin. When comparing absolute values, eAD patients had a greater Kin in the posterior cingulate cortex and a greater k3 in the hippocampus compared with lobar cortical values of HCs. In SPM analysis, eAD had an increased left operculum and decreased bilateral hippocampus and anterior cingulate cortex compared to HCs. 64Cu-ATSM PET/MRI and tracer kinetic analysis elucidated cerebral oxidative stress in the eAD patients, particularly in the cingulate cortex and hippocampus.
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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.
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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
A 51-year-old man was admitted to the hospital with a diagnosis of Listeria monocytogenes meningitis. Diffuse cerebral edema appeared after improvement of meningitis with appropriate treatment and worsened for two months. Due to brain herniation, brain tissue leaked through the incision made during the drain insertion in a hydrocephalus surgery. We found pathological evidence of significant neutrophil infiltration with a few lymphocytes without bacterial detection in the degraded brain tissue. The present case indicates that fatal cerebral edema with significant neutrophil infiltration may develop even after appropriate treatment for L. monocytogenes meningitis.
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Edema Encefálico , Hidrocefalia , Listeria monocytogenes , Meningite por Listeria , Masculino , Humanos , Pessoa de Meia-Idade , Meningite por Listeria/complicações , Meningite por Listeria/diagnóstico , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Infiltração de NeutrófilosRESUMO
PURPOSE: Corticobasal syndrome (CBS) and Parkinson's disease (PD) both present with asymmetrical extrapyramidal symptoms, often leading to a diagnostic dilemma. Patients with CBS frequently show cerebral blood flow (CBF) asymmetry alongside asymmetrical cortical atrophy. This study aimed to evaluate the clinical utility of arterial spin labeling (ASL) magnetic resonance imaging (MRI) to detect CBF asymmetry in patients with CBS. METHODS: We retrospectively investigated asymmetries of regional CBF and cortical volume, measured using ASL and T1-weighted MRI, in 13 patients with CBS and 22 age-matched patients with PD. Regional CBF and cortical volume values were derived from nine brain regions on each side. CBF and volume asymmetries were calculated as %difference in each region, respectively. RESULTS: CBF asymmetry showed significantly greater differences in seven of nine regions, such as the perirolandic area (- 8.7% vs. - 1.4%, p < 0.001) and parietal cortex (- 9.7% vs. - 1.3%, p < 0.001) in patients with CBS compared with patients with PD. In contrast, significant differences in volume asymmetry were observed in three regions included within the seven regions showing CBF asymmetry, which indicated that CBF asymmetry has greater sensitivity than volume asymmetry to detect asymmetricity in CBS. CONCLUSION: ASL imaging showed significant CBF asymmetry in a wider range of brain regions in patients with CBS, which suggests that noninvasive MRI with ASL imaging is a promising tool for the diagnosis of CBS, with advantages that include the simultaneous evaluation of asymmetrical hypoperfusion in addition to focal atrophy.
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Degeneração Corticobasal , Atrofia , Circulação Cerebrovascular/fisiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Marcadores de SpinRESUMO
Background: Early intervention for dementia patients is extremely important for the prevention of dementia. However, so far, it is not clear as to what kind of screening will be useful for the early detection of dementia. Objective: We aimed to investigate the relationship between the results of a short self-reporting yes/no survey selected in Kihon Checklist, developed by the Japanese Ministry of Health, Labor and Welfare to identify older adults who are at risk of requiring support/care, and other original items developed by Dementia Prevention Team, Fukui, Japan, and Mini-Mental State Examination (MMSE) scores, and determine the diagnostic efficacy of the self-reporting yes/no survey. Methods: Self-reporting yes/no surveys were conducted for 87,687 individuals aged ≥65 years, living in Fukui, Japan, and did not have Long-Term Care Insurance, Japan. According to the survey results, selected individuals were advised to visit a local hospital to be assessed with MMSE. Results: Individuals who could not make a call by looking up phone numbers and manage their own deposits and savings at the bank or automatic teller machine (ATM) had an increased risk of low MMSE score (≤23; odds ratio: 2.74 [1.89-3.97]; 95% confidence interval: 2.12 [1.46-3.07]). Conclusions: Self-reporting yes/no survey could effectively screen for dementia. Not being able to make a call by looking up phone numbers and not being able to manage their own deposits and savings at the bank or ATM are signs of dementia.
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PURPOSE: In patients with Wallenberg's syndrome who present with body lateropulsion (BL), whether the center of pressure (COP) position and velocity characterize postural dysregulation is unknown. We measured time-course changes in COP parameters in three BL patients. METHODS: Three patients with acute Wallenberg's syndrome presented with BL. COP was measured for time-course changes during first standing and every week thereafter. COP positions, which indicate the deviation in the center of gravity, were calculated. COP velocities associated with dynamic movements of the center of gravity were analyzed separately for the BL and non-BL sides. RESULTS: All patients showed that COP position shifted to the BL side in first standing and changed to the center over time. COP velocities to the BL side were fast in first standing. Two of the three patients had significantly faster COP velocities to the BL side than to the non-BL side (p < .05), and one did not. In all three cases, the faster COP velocities to the BL side decreased significantly after 2 weeks compared to the initial standing position (p < .001). The change seemed to be related to the time when independent walking became possible. CONCLUSIONS: Fast COP velocity to the BL side might reflect postural dysregulation in patients with BL. These findings might be useful information for devising effective rehabilitation in patients with BL.
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Síndrome Medular Lateral , Humanos , Gravitação , Movimento , Posição OrtostáticaRESUMO
Autoimmune basal ganglia encephalitis causes neurological symptoms such as parkinsonism associated with basal ganglia lesions. Here, we report a case of autoimmune basal ganglia encephalitis without retinal lesions or malignancy harboring anti-recoverin antibodies. The patient was a 67-year-old Japanese woman who developed anorexia, parkinsonism, and disturbance of consciousness 7 days before admission. Brain magnetic resonance imaging showed hyperintense bilateral basal ganglia lesions on fluid-attenuated inversion recovery images. 18F-fluorodeoxyglucose-positron emission tomography showed no malignancy in the trunk, and dopamine transporter single-photon emission computed tomography with dopamine transporters revealed reduced radiotracer uptake in the basal ganglia. Further, anti-recoverin IgG antibodies were detected in serum immunoblot. Based on the clinical and imaging findings, the patient was diagnosed with autoimmune basal ganglia encephalitis with anti-recoverin antibodies and administered high-dose immunoglobulins (HD-IVIG), which led to an improvement in clinical symptoms. Anti-recoverin antibodies are paraneoplastic antibodies that explicitly bind to Ca2+-binding proteins in the retina and cause retinopathy. This pathological sequence is defined as cancer-associated retinopathy (CAR). However, in our case, autoimmune basal ganglia encephalitis developed without CAR syndrome or malignancy. Clinicians should be aware of the possibility of autoimmune basal ganglia encephalitis showing anti-recoverin antibodies but no CAR syndrome or malignancy, which should be treated with HD-IVIG therapy.
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The neuropathological hallmarks of Alzheimer's disease (AD) are senile plaques (SPs), which are composed of amyloid ß protein (Aß), and neurofibrillary tangles (NFTs), which consist of highly phosphorylated tau protein. As bio-metal imbalance may be involved in the formation of NFT and SPs, metal regulation may be a direction for AD treatment. Clioquinol (CQ) is a metal-protein attenuating compound with mild chelating effects for Zn2+ and Cu2+, and CQ can not only detach metals from SPs, but also decrease amyloid aggregation in the brain. Previous studies suggested that Cu2+ induces the hyperphosphorylation of tau. However, the effects of CQ on tau were not fully explored. To examine the effects of CQ on tau metabolism, we used a human neuroblastoma cell line, M1C cells, which express wild-type tau protein (4R0N) via tetracycline-off (TetOff) induction. In a morphological study and ATP assay, up to 10 µM CQ had no effect on cell viability; however, 100 µM CQ had cytotoxic effects. CQ decreased accumulation of Cu+ in the M1C cells (39.4% of the control), and both total and phosphorylated tau protein. It also decreased the activity of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) (37.3% and 60.7% levels of the control, respectively), which are tau kinases. Of note, activation of protein phosphatase 2A (PP2A), which is a tau phosphatase, was also observed after CQ treatment. Fractionation experiments demonstrated a reduction of oligomeric tau in the tris insoluble, sarkosyl soluble fraction by CQ treatment. CQ also decreased caspase-cleaved tau, which accelerated the aggregation of tau protein. CQ activated autophagy and proteasome pathways, which are considered important for the degradation of tau protein. Although further studies are needed to elucidate the mechanisms responsible for the effects of CQ on tau, CQ may shed light on possible AD therapeutics.
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Doença de Alzheimer/tratamento farmacológico , Clioquinol/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Emaranhados Neurofibrilares/efeitos dos fármacos , Multimerização Proteica , Proteínas tau/química , Proteínas tau/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Autofagia , Linhagem Celular Tumoral , Cobre/química , Humanos , Emaranhados Neurofibrilares/metabolismo , Fosforilação , Proteína Fosfatase 2/metabolismoRESUMO
Neurofibrillary tangles, which consist of highly phosphorylated tau protein, and senile plaques (SPs) are pathological hallmarks of Alzheimer's disease (AD). In swollen axons, many autophagic vacuoles are observed around SP in the AD brain. This suggests that autophagy function is disturbed in AD. We used a neuronal cellular model of tauopathy (M1C cells), which harbors wild type tau (4R0N), to assess the effects of the lysosomotrophic agent NH4Cl, and autophagy inhibitors chloroquine and 3 methyladenine (3MA). It was found that chloroquine, NH4Cl and 3MA markedly increased tau accumulation. Thus, autophagy lysosomal system disturbances disturbed the degradation mechanisms of tau protein. Other studies also revealed that tau protein, including aggregated tau, is degraded via the autophagy lysosome system. Phosphorylated and C terminal truncated tau were also reported to disturb autophagy function. As a therapeutic strategy, autophagy upregulation was suggested. Thus far, as autophagy modulators, rapamycin, mTOCR1 inhibitor and its analogues, lithium, metformin, clonidine, curcumin, nicotinamide, bexaroten, and torehalose have been proposed. As a therapeutic strategy, autophagic modulation may be the next target of AD therapeutics.
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Doença de Alzheimer/patologia , Autofagia , Tauopatias/patologia , Proteínas tau/metabolismo , Doença de Alzheimer/metabolismo , Animais , Humanos , Tauopatias/metabolismoRESUMO
BACKGROUND: Hashimoto's encephalopathy with serum anti-NH2-terminal of α-enolase (NAE) antibodies occasionally displays clinical symptoms such as cerebellar ataxia and parkinsonism. We studied the frequency of anti-NAE antibodies in patients with Parkinson-plus syndrome. METHODS: We examined the positive rates of anti-NAE antibodies in 47 patients with multiple system atrophy (MSA), 29 patients with Parkinson's disease (PD), eight patients with corticobasal syndrome (CBS), and 18 patients with progressive supranuclear palsy (PSP) using conventional immunoblot analysis. RESULTS: Positive anti-NAE antibody rates of 31.9%, 10.3%, 50.0%, and 11.1% were reported in the MSA, PD, CBS, and PSP patients, respectively. The duration from onset to a wheelchair-bound state in seropositive MSA patients tended to be shorter than that in seronegative MSA patients. CONCLUSIONS: Anti-NAE antibodies are detected in some patients clinically diagnosed with MSA and CBS. Although its pathophysiological significance remains uncertain, serum anti-NAE antibodies might represent a prognostic marker in the clinical course of MSA.
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Atrofia de Múltiplos Sistemas , Doença de Parkinson , Paralisia Supranuclear Progressiva , Humanos , Atrofia de Múltiplos Sistemas/epidemiologia , Doença de Parkinson/epidemiologia , Fosfopiruvato Hidratase , Prevalência , Paralisia Supranuclear Progressiva/epidemiologiaRESUMO
This report describes a 59-year-old woman who presented with progressive encephalomyelitis with rigidity and myoclonus (PERM)-like symptoms and severe dysautonomia, including orthostatic hypotension, sinus bradycardia, dysuria, and prolonged constipation. Her neurological symptoms improved after immunotherapy, but the dysautonomia persisted. Anti-ganglionic acetylcholine receptor (gAChR) α3 subunit antibodies, which are frequently identified in patients with autoimmune autonomic ganglionopathy, were detected in the pre-treatment serum. The central distribution of the nicotinic acetylcholine receptors, a target of anti-gAChR antibodies, and immunotherapeutic efficacy observed in this case indicate that anti-gAChR α3 subunit antibodies are associated with the PERM-like features accompanied by autonomic manifestations.
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Encefalomielite , Mioclonia , Autoanticorpos , Encefalomielite/complicações , Encefalomielite/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Rigidez Muscular , Mioclonia/complicações , Mioclonia/diagnóstico , Receptores ColinérgicosRESUMO
Mitochondrial diseases (MDs) are occasionally difficult to diagnose. Growth differentiation factor 15 (GDF15) has been reported as a biomarker useful for not only diagnosing MDs, but also evaluating disease severity and therapeutic efficacy. To enable the measurement of serum GDF15 concentrations at medical institutions, we developed a new latex-enhanced turbidimetric immunoassay (LTIA) as an automated diagnostic indication test for MDs. We also examined the equivalency of specificity and sensitivity in measuring serum GDF15 concentrations between a commercially available enzyme-linked immunosorbent assay (ELISA) kit and a novel LTIA device in patients with MDs, disease controls, and healthy controls. A clinical performance study used a newly developed LTIA device and an existing ELISA kit to measure the concentrations of GDF15 in 35 MD patients, 111 disease controls, and 86 healthy controls. The median (first quartile-third quartile) of serum GDF15 concentrations measured with the LTIA device was significantly higher (P < .001) in MD patients (1389.0 U/mL [869.5-1776.0 U/mL]) than in healthy controls (380.5 U/mL [330.2-471.8 U/mL]); the interquartile ranges did not overlap between MD patients and healthy controls. The areas under the curve in disease and healthy controls were 0.812 (95% confidence interval [CI]: 0.734-0.886) and 0.951 (95% CI: 0.910-0.992), respectively. The automated, high-throughput technology-based LTIA device has definite advantages over the ELISA kit in shorter processing time and lower estimated cost per sample measurement. The LTIA device of GDF15 may be a sufficiently reliable, frontline, diagnostic indicator of individuals with suspected MDs in the general population.