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1.
J Neurol ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700563

RESUMO

OBJECTIVE: Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disease, and sometimes shows idiopathic normal pressure hydrocephalus (iNPH)-like presentations. We aimed to evaluate spinal tap responsiveness in patients with PSP, including the effect of sham spinal tap. METHODS: Eleven patients with PSP, ten with probable/definite iNPH, and eight control patients were prospectively enrolled. All participants underwent sham spinal tap and spinal tap procedures. Gait was evaluated using wearable inertial sensors. We defined "tap responders" as individuals with a 10% or more improvement from baseline in any of the gait parameters (timed up-and-go test total time, stride length, and velocity during straight walking under single-task and cognitive dual-task conditions). We compared the ratio of responders in patients with PSP to patients with iNPH and controls. RESULTS: The ratio of tap responders and the ratio of sham tap responders in patients with PSP were significantly higher than those in control patients, and not different from those in patients with iNPH. PSP patients with iNPH-like MRI features tended to respond to the spinal tap compared to those without such imaging features. Notably, one patient with PSP, who responded to the spinal tap beyond the effect of sham spinal tap, was treated by the shunt operation. CONCLUSION: This is the first prospective study to demonstrate tap and shunt responsiveness in patients with PSP while highlighting the placebo effects of the spinal tap in patients with PSP or iNPH. Our findings suggest that some PSP patients have impaired cerebrospinal fluid circulation, contributing to a distinct component of the clinical spectrum.

2.
Eur J Neurosci ; 59(6): 1332-1347, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38105486

RESUMO

Alzheimer's disease (AD) is associated with abnormal accumulations of hyperphosphorylated tau and amyloid-ß proteins, resulting in unique patterns of atrophy in the brain. We aimed to elucidate some characteristics of the AD's morphometric networks constructed by associating different morphometric features among brain areas and evaluating their relationship to Mini-Mental State Examination total score and age. Three-dimensional T1-weighted (3DT1) image data scanned by the same 1.5T magnetic resonance imaging (MRI) were obtained from 62 AD patients and 41 healthy controls (HCs) and were analysed by using FreeSurfer. The associations of the extracted six morphometric features between regions were estimated by correlation coefficients. The global and local graph theoretical measures for this network were evaluated. Associations between graph theoretical measures and age, sex and cognition were evaluated by multiple regression analysis in each group. Global measures of integration: global efficiency and mean information centrality were significantly higher in AD patients. Local measures of integration: node global efficiency and information centrality were significantly higher in the entorhinal cortex, fusiform gyrus and posterior cingulate cortex of AD patients but only in the left hemisphere. All global measures were correlated with age in AD patients but not in HCs. The information centrality was associated with age in AD's broad brain regions. Our results showed that altered morphometric networks due to AD are left-hemisphere dominant, suggesting that AD pathogenesis has a left-right asymmetry. Ageing has a unique impact on the morphometric networks in AD patients. The information centrality is a sensitive graph theoretical measure to detect this association.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Peptídeos beta-Amiloides/metabolismo , Mapeamento Encefálico , Envelhecimento , Imageamento por Ressonância Magnética/métodos
3.
Acta Neurol Belg ; 123(4): 1511-1517, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37273142

RESUMO

OBJECTIVE: If lesions in sporadic amyotrophic lateral sclerosis (ALS) originate from a single focal onset site and spread contiguously by prion-like cell-to-cell propagation at a constant speed, the lesion spread time should be proportional to the anatomical distance. We verify this model in the patients. METHODS: In 29 sporadic ALS patients with hand onset followed by spread to shoulder and leg, we retrospectively evaluated the inter/intra-regional spread time ratio: time interval of symptoms from hand-to-leg divided by that from hand-to-shoulder. We also obtained the corresponding inter-/intra-regional distance ratios of spinal cord from magnetic resonance imaging of 12 patients, and those of primary motor cortex from coordinates using neuroimaging software. RESULTS: Inter-/intra-regional spread time ratios ranged from 0.29 to 6.00 (median 1.20). Distance ratios ranged from 1.85 to 2.86 in primary motor cortex and from 5.79 to 8.67 in spinal cord. Taken together with clinical manifestations, of 27 patients with the requisite information available, lesion spreading was consistent with the model in primary motor cortex in 4 (14.8%) patients, and in spinal cord in only 1 (3.7%) patient. However, in more patients (12 of 29 patients: 41.4%), the inter-regional spread times in a long anatomical distance of hand-to-leg were shorter than or equal to the intra-regional spread times in a short anatomical distance of hand-to-shoulder. CONCLUSION: Contiguous cell-to-cell propagation at a constant speed might not play a major role at least in distant lesion spreading of ALS. Several mechanisms can be responsible for progression in ALS.


Assuntos
Esclerose Lateral Amiotrófica , Humanos , Esclerose Lateral Amiotrófica/diagnóstico , Estudos Retrospectivos , Mãos
4.
Transl Stroke Res ; 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37249762

RESUMO

This study aimed to identify the neuroanatomical predictors of oropharyngeal dysphagia and tube dependency in patients with supratentorial or infratentorial ischemic strokes. Patients with acute ischemic stroke were enrolled and were classified into 3 groups: right supratentorial (n = 61), left supratentorial (n = 89), and infratentorial stroke (n = 50). Dysphagia was evaluated by a modified water swallowing test and the Food Intake LEVEL Scale to evaluate oropharyngeal dysphagia and tube dependency, respectively. As two dysphagia parameters, we evaluated the durations from onset of stroke to (1) success in the modified water swallowing test and to (2) rating 7 points or above on the Food Intake LEVEL Scale: patients regained sufficient oral intake and were not tube-dependent. Voxel-based lesion-symptom mapping analysis was performed for a spatially normalized lesion map of magnetic resonance imaging to explore the anatomies that are associated with the two dysphagia parameters for each stroke group. The right precentral gyrus and parts of the internal capsule are associated with oropharyngeal dysphagia. The four supratentorial areas are associated with tube dependency. The dorsal upper medulla is associated with both oropharyngeal dysphagia and tube dependency. These results suggest that supratentorial stroke patients can be tube-dependent due to an impaired anticipatory phase of ingestion. The simultaneous damage in the four supratentorial areas: the inferior part of the precentral gyrus, lenticular nucleus, caudate head, and anterior insular cortex, predicts tube dependency. In contrast, infratentorial stroke patients can be tube-dependent due to oropharyngeal dysphagia caused by lesions in the dorsal upper medulla, damaging the swallowing-related nucleus.

5.
Int Med Case Rep J ; 16: 83-89, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36748025

RESUMO

Purpose: To report seven eyes of six patients diagnosed with corneal perforation and lacrimal canaliculitis in a single facility. Methods: Clinical records of patients with corneal perforation accompanied by lacrimal canaliculitis seen by the authors were reviewed. Results: Six patients (7 eyes) with corneal perforation accompanied by lacrimal canaliculitis were identified. All patients were female, and all were treated with topical antibiotics while five were receiving topical corticosteroids. Two patients had a history of dacryocystitis and three had systemic immune diseases. The corneal lesions did not respond to topical antibiotics but were effectively treated by removal of concretions in the lacrimal canaliculi and lacrimal duct drainage together with conjunctival autograft or corneal transplantation. Conclusion: Lacrimal canaliculitis is a risk factor for corneal perforation. When corneal perforation does not respond to antibiotics, lacrimal canaliculitis should be considered.

6.
Parkinsonism Relat Disord ; 108: 105322, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36822140

RESUMO

BACKGROUND: The sequence effect (SE) is characterized by the progressive decrement of movements and is often observed in Parkinson's disease (PD) patients. While acute effect of levodopa does not ameliorate the SE, the effect of long-term levodopa treatment for the SE remains unknown. OBJECTIVE: We aimed to elucidate the SEs during various gait conditions and their response to long-term levodopa treatment in drug-naïve PD patients. METHODS: Nineteen drug-naïve PD patients and 21 healthy controls were enrolled. Gait parameters were measured via wearable inertial sensors in the following conditions:1) straight walking, 2) circular walking: walking a circle of 1 m diameter in a clock-wise direction for 3 laps, 3) straight or circular walking under cognitive-motor dual-task (serial 7s subtractions). PD patients were evaluated at baseline, within 1 h after intravenous administration of levodopa, and after one, three, and six months treatment with levodopa. The SE was measured by a linear regression slope by plotting consecutive stride lengths over steps. Patients were also separately analyzed depending on laterality of symptoms. RESULTS: Long-term levodopa treatment ameliorated the SE only during single-task straight walking. The SE during circular walking was exacerbated after long-term levodopa treatment for right-side dominant patients. During dual-task straight walking, the SE at baseline was greater in right-side dominant PD patients. CONCLUSIONS: The SE only during single-task straight walking can be ameliorated by long-term levodopa treatment. However, the SE may be exaggerated by cognitive motor interference or by asymmetrical stride length with/without long-term levodopa treatment, depending on the laterality of symptoms.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Humanos , Levodopa/farmacologia , Caminhada/fisiologia , Marcha/fisiologia
7.
J Neurosurg ; 139(2): 481-491, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36670530

RESUMO

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 , Marcha
8.
Hum Brain Mapp ; 44(3): 1193-1208, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36409700

RESUMO

Multiple sclerosis (MS) causes gait and cognitive impairments that are partially normalized by compensatory mechanisms. We aimed to identify the gait tasks that unmask gait disturbance and the underlying neural correlates in MS. We included 25 patients with MS (Expanded Disability Status Scale score: median 2.0, interquartile range 1.0-2.5) and 19 healthy controls. Fast-paced gait examinations with inertial measurement units were conducted, including straight or circular walking with or without cognitive/motor tasks, and the timed up and go test (TUG). Receiver operating characteristic curve analysis was performed to distinguish both groups by the gait parameters. The correlation between gait parameters and cortical thickness or fractional anisotropy values was examined by using three-dimensional T1-weighted imaging and diffusion tensor imaging, respectively (corrected p < .05). Total TUG duration (>6.0 s, sensitivity 88.0%, specificity 84.2%) and stride velocity during cognitive dual-task circular walking (<1.12 m/s, 84.0%, 84.2%) had the highest discriminative power of the two groups. Deterioration of these gait parameters was correlated with thinner cortical thickness in regional areas, including the left precuneus and left temporoparietal junction, overlapped with parts of the default mode network, ventral attention network, and frontoparietal network. Total TUG duration was negatively correlated with fractional anisotropy values in the deep cerebral white matter areas. Turning and multitask gait may be optimal to unveil partially compensated gait disturbance in patients with mild-to-moderate MS through dynamic balance control and multitask processing, based on the structural damage in functional networks.


Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico por imagem , Imagem de Tensor de Difusão , Equilíbrio Postural , Afinamento Cortical Cerebral , Estudos de Tempo e Movimento , Marcha , Caminhada
10.
Jpn J Ophthalmol ; 66(6): 579-589, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36181644

RESUMO

PURPOSE: To gain new insights into the etiology of blepharitis, we investigated the causative bacteria in patients with blepharitis and the effects of 1% azithromycin ophthalmic solution. STUDY DESIGN: A multicenter, prospective observational study. METHODS: After the subjects were diagnosed as having blepharitis they were administered 1% azithromycin ophthalmic solution for up to 14 days. Bacterial cultures and smear microscopic examinations of the eyelid margin were conducted at the initial visit, after administering eye drops, and 1 month after the end of eye drop administration. The minimum inhibitory concentrations (MICs) of azithromycin were measured. RESULTS: At the initial visit, the bacterial morphology determined by smear microscopic examinations coincided with that of strains isolated by culture taken from 22 of 45 patients. All detected bacteria were gram-positive, and Corynebacterium spp., Cutibacterium acnes, Staphylococcus epidermidis, Streptococcus spp., and Enterococcus faecalis were isolated most commonly. Compared with the initial visit the number of isolated strains per eye decreased significantly at 7 days after the start of eye drop administration and 1 month after the end of eye drop administration. The azithromycin MICs were temporarily increased after the start of eye drops but then decreased. CONCLUSION: Our study suggests that in blepharitis pathogenicity is characterized by increased strain numbers and amounts of indigenous bacteria. Administering a 1% azithromycin ophthalmic solution suppresses the number of bacterial strains within 1 month after the end of eye drop administration without increasing drug resistance.


Assuntos
Azitromicina , Blefarite , Humanos , Azitromicina/uso terapêutico , Soluções Oftálmicas , Antibacterianos/uso terapêutico , Resultado do Tratamento , Blefarite/diagnóstico , Blefarite/tratamento farmacológico , Bactérias , Protocolos Clínicos , Estudos Observacionais como Assunto , Estudos Multicêntricos como Assunto
11.
Mult Scler Relat Disord ; 67: 104077, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35926261

RESUMO

BACKGROUND: Different treatment strategies can have varying effects on disability and whole brain volume in patients with multiple sclerosis (MS). However, the association between regional brain volume and treatment efficacy is currently unclear. Our objective was to determine whether whole brain volume, as well as the regional volume of cortical and subcortical grey matter, differ with the administration of high-efficacy therapy (HET) versus low-efficacy therapy (LET). METHODS: We evaluated clinical data and change in regional brain volume in 44 patients with relapse-onset MS, who underwent HET (n = 19) or LET (n = 25). Regional brain volume was determined with three-dimensional T1-weighted magnetic resonance imaging using FreeSurfer. The association between volume change and treatment type was assessed via generalised linear mixed models (GLMMs). RESULTS: During the observation period (2.0 ± 0.16 years), the proportion of patients with a "no evidence of disease activity-3″ status was significantly greater in those who underwent HET versus LET (p = 0.012). HET was positively associated with volume changes in the cortex (ß = 0.64, p = 0.0499), left (ß = 0.98, p = 0.0033) and right (ß = 0.77, p = 0.019) caudate and right putamen (ß = 0.87, p = 0.0077), after adjusting for age, sex, and MS severity scores in the GLMMs. Further correction for multiple comparisons by false discovery rate revealed that HET was consistently associated with the volume changes of the left caudate (p = 0.049) and right putamen (p = 0.049). CONCLUSION: HET can improve the mid-term prognosis of Japanese patients with relapse-onset MS by reducing disease activity and regional brain volume loss.


Assuntos
Substância Cinzenta , Esclerose Múltipla , Humanos , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/patologia , Estudos de Coortes , Atrofia/patologia , Japão , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Recidiva
12.
Neuroimage Clin ; 35: 103100, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35780660

RESUMO

Working memory (WM) impairment is one of the most frequent cognitive deficits in Parkinson's disease (PD). However, it is not known how neural activity is altered and compensatory responses eventually fail during progression. We aimed to elucidate neural correlates of WM and compensatory mechanisms in PD. Eighteen cognitively normal PD patients (PD-CogNL), 16 with PD with mild cognitive impairment (PD-MCI), 11 with PD with dementia (PDD), and 17 healthy controls (HCs) were evaluated. Subjects performed an n-back task. Functional MRI data were analyzed by event-related analysis for correct responses. Brain activations were evaluated by comparing them to fixation cross or 0-back task, and correlated with n-back task performance. When compared to fixation cross, PD-CogNL patients had more activation in WM areas than HCs for both the 2- and 3-back tasks. PD-MCI and PDD patients had more activation in WM areas than HCs for the 0- and 1-back task. 2-back task performance was correlated with brain activations (vs. 0-back task) in the bilateral dorsolateral prefrontal cortex and frontal eye field (FEF) and left rostral prefrontal cortex, caudate nucleus, inferior/superior parietal lobule (IPL/SPL), and anterior insular cortex as well as anterior cingulate cortex. 3-back task performance was correlated with brain activations (vs. 0-back task) in the left FEF, right caudate nucleus, and bilateral IPL/SPL. Additional activations on top of the 0-back task, rather than fixation cross, are the neural correlates of WM. Our results suggest PD patients have two types of compensatory mechanisms: (1) Hyperactivation for different WM load tasks depending on their cognitive status. PD-CogNL have hyperactivation for moderate and heavy working memory load tasks while maintaining normal working memory performance. In contrast, PD-MCI and PDD have hyperactivation for control task and light working memory load task, leaving less neural resources to further activate for more demanding tasks and resulting in impaired working memory performance. (2) Bilateral recruitment of WM-related areas, in particular the DLPFC, FEF, IPL/SPL and caudate nucleus, to improve WM performance.


Assuntos
Disfunção Cognitiva , Doença de Parkinson , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Humanos , Imageamento por Ressonância Magnética , Transtornos da Memória , Memória de Curto Prazo/fisiologia , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem
13.
Am J Pathol ; 191(6): 1077-1093, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33705751

RESUMO

Programmed cell death protein (PD)-1 is a coinhibitory molecule that suppresses immune response and maintains immune homeostasis. Moreover, the PD-1 pathway blocks cancers from being attacked by immune cells. Anti-PD-1 antibody therapy such as nivolumab improves survival in cancer patients. However, the occurrence of autoimmune inflammatory disorders in various organs has been increasingly reported as an adverse effect of nivolumab. Of the disorders associated with nivolumab, Sicca syndrome occurs in 3% to 11% of cases and has unknown pathologic mechanisms. Whether the absence of the PD-1 pathway causes functional and morphologic disorders in lacrimal glands was determined by analyzing PD-1 gene-knockout (Pdcd1-/-) mice. Histopathologic analysis showed that Pdcd1-/- mice developed dacryoadenitis beginning at 3 to 4 months of age, and deteriorated with age. Flow-cytometric analysis confirmed that cells infiltrating the affected lacrimal glands consisted mainly of CD3+ T cells and only a small proportion of CD19+ B cells. Among infiltrating T cells, the CD4+ Th-cell subset consisted of Th1 cells producing interferon-γ in an early stage of dacryoadenitis in Pdcd1-/- mice. Experiments of lymphocyte transfer from Pdcd1-/- into irradiated wild-type mice confirmed that CD4+ T cells from Pdcd1-/- mice induced dacryoadenitis. These results indicate that PD-1 plays an important role in the prevention of autoimmune inflammatory disorders in lacrimal glands caused by activated CD4+ Th1 cells.


Assuntos
Doenças Autoimunes/imunologia , Dacriocistite/imunologia , Dacriocistite/metabolismo , Receptor de Morte Celular Programada 1/deficiência , Células Th1/imunologia , Animais , Doenças Autoimunes/metabolismo , Autoimunidade/imunologia , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor de Morte Celular Programada 1/imunologia , Síndrome de Sjogren/imunologia
14.
J Neuroimmunol ; 351: 577466, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33370672

RESUMO

It is unclear whether brain atrophy in multiple sclerosis (MS) is associated with not only neuroinflammation but also systemic inflammation. Here we found that systemic inflammatory marker serum amyloid A (SAA) was moderately correlated with cortical volume in the patients with clinically isolated syndrome (CIS) and MS (r = -0.41, p = 0.019). SAA was also significantly correlated with T2 lesion volume (T2LV) even after adjusting for age, disease duration, and disease modifying therapy (p = 0.0050). Thus, systemic inflammation may be associated with cortical atrophy, possibly via an increase in the T2LV in patients with CIS/MS.


Assuntos
Encéfalo/patologia , Esclerose Múltipla/sangue , Esclerose Múltipla/patologia , Proteína Amiloide A Sérica/metabolismo , Adulto , Atrofia , Doenças Desmielinizantes/sangue , Doenças Desmielinizantes/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Amiloide A Sérica/análise
15.
J Neurol Sci ; 421: 117284, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33360732

RESUMO

Chronic progressive neuro-Behçet's disease (CPNBD) is characterized by slowly progressive cognitive decline, cerebellar ataxia, and brainstem atrophy without acute encephalomeningitis. To evaluate the progression of CPNBD during treatment, we conducted a retrospective, longitudinal comparative analysis of the clinical features and brain magnetic resonance imaging (MRI) in patients with CPNBD. We classified participants into three groups: NBD with acute encephalomeningitis alone (Group A, 8 patients with acute neuro-Behçet's disease [ANBD]), primary progressive CPNBD (Group B, 3 patients), and a combination of acute encephalomeningitis, and chronic progression (Group C, 2 patients). Routine laboratory tests and monthly rate of enlargement of the width of the third ventricle (ΔWTVm) and relative value of ΔWTVm to the transverse cerebral diameter (ΔWTVIm) were statistically evaluated. Although higher cell count values and interleukin-6 concentration in the cerebrospinal fluid were observed in ANBD, both ΔWTVm (p = 0.008) and ΔWTVIm (p = 0.008) were significantly larger in CPNBD phase than in the ANBD phase. Effective treatment for CPNBD seemed to reduce ΔWTVm and ΔWTVIm in some patients. Sequential evaluation of WTV in patients with CPNBD is a highly sensitive candidate biomarker of early diagnosis and treatment efficacy.


Assuntos
Síndrome de Behçet , Terceiro Ventrículo , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/diagnóstico por imagem , Biomarcadores , Progressão da Doença , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos
16.
Exp Eye Res ; 199: 108190, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32798537

RESUMO

PURPOSE: To determine whether the CD27/CD70 pathway plays a significant role in corneal allograft rejection by investigating the effect of blocking the CD27/CD70 pathway by anti-CD70 antibody on corneal allograft survival. METHODS: Orthotopic penetrating keratoplasty was performed using C57BL/6 donor grafts and BALB/c recipients. Expression of CD27 and CD70 on rejected cornea was examined by immunohistochemistry. Corneal transplant recipients received intraperitoneal injection of anti-CD70 antibody (FR70) or control rat IgG. Alloreactivity was measured by mixed lymphoid reaction (MLR) in recipients administered control rat IgG and those administered anti-CD70 antibody. Corneal expression of IFN-γ and IL-12 was also examined in both groups. Graft opacity was assessed over an 8-week period and graft survival was evaluated using Kaplan-Meier survival curves. Proportion of CD4+CD44+ memory T cells in lymph nodes was measured by flow cytometry. RESULTS: CD4+CD27+ cells and CD11c+CD70+ cells were present in rejected cornea. Anti-CD70 antibody administration suppressed alloreactivity in corneal allograft recipients, and inhibited IFN-γ expression in recipient cornea (p < 0.05). Anti-CD70 antibody suppressed opacity score of recipient cornea and prolonged corneal allograft survival (p < 0.05). Proportion of CD4+CD44+ memory T cells in recipient lymph nodes was reduced by anti-CD70 antibody treatment. CONCLUSION: The CD27/CD70 pathway plays a significant role in corneal allograft rejection by initiating alloreactive Th1 cells and preserving memory T cells. Anti-CD70 antibody administration prolongs corneal allograft survival indicating the potential therapeutic effect of CD27/CD70 pathway blockade on corneal allograft rejection.


Assuntos
Ligante CD27/antagonistas & inibidores , Córnea/metabolismo , Transplante de Córnea , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/antagonistas & inibidores , Aloenxertos , Animais , Ligante CD27/biossíntese , Córnea/patologia , Modelos Animais de Doenças , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/biossíntese
17.
Mov Disord ; 35(6): 1037-1045, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32163636

RESUMO

BACKGROUND: Gait automaticity, which is impaired in patients with Parkinson's disease (PD), can be quantified by gait variability analysis. Among the 3 regions of the striatum (sensorimotor, executive, and limbic), the sensorimotor region may play a crucial role in motor automaticity in healthy individuals. However, neural correlates of impaired gait automaticity are poorly investigated in PD. OBJECTIVE: We aimed to examine the relationship between gait automaticity and striatal dopaminergic depletion in drug-naïve PD patients. METHODS: A total of 21 drug-naïve PD patients and 12 healthy controls were enrolled. Gait parameters were measured via wearable inertial sensors under fast-paced gait or cognitive dual-task conditions, and their respective coefficient of variation (CV) and dual-task cost were calculated. The extent of striatal dopaminergic depletion was evaluated by dopamine transporter (DAT) imaging with single-photon emission computed tomography using N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-[123 I]iodophenyl)nortropane. Correlation between DAT uptake and gait variables was analyzed using the region-of-interest analysis for the 3 right or left striatal regions and voxel-based analysis. RESULTS: PD had higher mean bilateral CV and dual-task cost of stride length than healthy controls. The mean bilateral CV of stride length was negatively correlated with DAT uptake in the bilateral executive regions of the striatum. Voxel-based analysis revealed a negative correlation between the mean bilateral CV of stride length and DAT uptake in the anteromedial striatum. CONCLUSIONS: Dopaminergic denervation in the anteromedial striatum, a part of the executive region, is associated with impaired gait automaticity in drug-naïve PD patients. This region may compensate for the posterior sensorimotor striatum, maintaining gait automaticity. © 2020 International Parkinson and Movement Disorder Society.


Assuntos
Doença de Parkinson , Preparações Farmacêuticas , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/metabolismo , Denervação , Dopamina , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Marcha , Humanos , Doença de Parkinson/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único
18.
Mult Scler Relat Disord ; 38: 101444, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31711001

RESUMO

A 25-year-old male presented with blurred peripheral vision and movement pain in his right eye. Fundus examination revealed unilateral disc swelling in his right eye with normal intracranial pressure. MRI showed remarkably high intensity in the optic nerve sheath and slightly high intensity in the optic nerve, indicating optic perineuritis (OPN). Anti-myelin oligodendrocyte glycoprotein (MOG) antibody was positive in both serum and cerebrospinal fluid. The patient responded promptly to corticosteroid treatment. OPN can be associated with the presence of anti-MOG antibody.


Assuntos
Corticosteroides/farmacologia , Autoanticorpos/metabolismo , Glicoproteína Mielina-Oligodendrócito/imunologia , Neurite Óptica/diagnóstico , Transtornos da Visão , Corticosteroides/administração & dosagem , Adulto , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Humanos , Imageamento por Ressonância Magnética , Masculino , Neurite Óptica/complicações , Neurite Óptica/tratamento farmacológico , Neurite Óptica/imunologia , Papiledema/diagnóstico por imagem , Papiledema/tratamento farmacológico , Papiledema/etiologia , Prednisolona/farmacologia , Transtornos da Visão/etiologia
19.
Sci Rep ; 9(1): 12821, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492880

RESUMO

The role of topical corticosteroids in management of Acanthamoeba keratitis (AK) remains controversial. Using a rabbit AK model, we investigated whether corticosteroid use is a risk factor of AK. Acanthamoeba (1 × 105/ml) was incubated with two densities of P. aeruginosa (PA; high-PA: 1 × 108/ml, low-PA: 3 × 105/ml) before corneal inoculation. Rabbit corneas were inoculated with Acanthamoeba alone or Acanthamoeba plus PA and administered levofloxacin and betamethasone sodium phosphate (BSP) eye drops for 5 or 7 days. Infected rabbit eyes were evaluated for clinical score and Acanthamoeba by histological examination. Acanthamoeba alone and BSP treatment did not produce keratitis. Corneas inoculated with Acanthamoeba plus low-PA treated immediately with levofloxacin and BSP remained clear with few infiltrates. Corneas inoculated with Acanthamoeba plus low-PA treated with levofloxacin immediately and BSP 12 h later developed severe keratitis. Corneas inoculated with Acanthamoeba plus high-PA treated immediately with levofloxacin and BSP also developed severe keratitis. Acanthamoebae were detected by PAS staining in corneas inoculated with Acanthamoeba plus high-PA treated with levofloxacin and BSP. Topical corticosteroids have the potential to aggravate AK when cornea is infected by Acanthamoeba with a critical number of bacteria or when corticosteroids are given after infection has established by Acanthamoeba with small number of bacteria.


Assuntos
Ceratite por Acanthamoeba/induzido quimicamente , Ceratite por Acanthamoeba/microbiologia , Acanthamoeba/fisiologia , Corticosteroides/efeitos adversos , Córnea/patologia , Soluções Oftálmicas/efeitos adversos , Pseudomonas aeruginosa/fisiologia , Animais , Antibacterianos/efeitos adversos , Betametasona/efeitos adversos , Córnea/microbiologia , Humanos , Coelhos
20.
J Neuroimmunol ; 334: 577003, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31306854

RESUMO

Olivary hypertrophy (OH) is the secondary degeneration of the inferior olivary nucleus (ION). It is observed one month after the onset of a primary lesion within the dento-rubro-olivary pathway and is usually associated with oculopalatal tremors. Here, we report two unique cases with rare autoimmune diseases leading to OH development with progressive cerebellar ataxia, both of which improved with steroid treatment. The first patient was a 59-year-old man with slowly progressive dysarthria and ataxic gait without palatal tremor. Anti-N-methyl-d-aspartate (NMDA) receptor antibody was positive in the CSF, supporting a diagnosis of anti-NMDA receptor encephalitis. The second patient was a 56-year-old man who developed dysarthria, ataxia, gait disturbance, and palatal tremor. He was diagnosed with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), based on presence of a punctate contrast-enhancing lesion in the middle cerebellar peduncle, pons, and cerebellum on magnetic resonance imaging (MRI). Brain MRI in both patients demonstrated high signal intensity regions in the bilateral IONs. Semi-quantitative volume analysis of MRI revealed significant reduction in ION volume after steroid treatment and accordingly cerebellar ataxia was improved in both cases. Clinical and radiological features of the two cases were unique, indicating potential novel etiologies in the pathophysiology of OH associated with cerebellar ataxia.


Assuntos
Glucocorticoides/uso terapêutico , Núcleo Olivar/efeitos dos fármacos , Núcleo Olivar/diagnóstico por imagem , Prednisolona/uso terapêutico , Glucocorticoides/farmacologia , Humanos , Hipertrofia/diagnóstico por imagem , Hipertrofia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisolona/farmacologia
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