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Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease affecting the brain and spinal cord. Fatigue is a common disabling symptom from MS onset, however the mechanisms by which underlying disease processes cause fatigue remain unclear. Improved pathophysiological understanding offers potential for improved treatments for MS-related fatigue. MRI provides insights into in vivo neuroinflammatory activity and neurodegeneration, although existing evidence for imaging correlates of MS fatigue is mixed. We explore associations between fatigue and MRI measures in the brain and spinal cord to identify neuroinflammatory and regional neurodegenerative substrates of fatigue in early relapsing-remitting MS (RRMS). Recently diagnosed (<6 months), treatment-naive people with RRMS (n = 440) were recruited to a longitudinal multi-centre nationally representative cohort study. Participants underwent 3-Tesla brain MRI at baseline and one year. We calculated global and regional white and grey matter volumes, white matter lesion (WML) load and upper cervical spinal cord cross-sectional area levels C2-3, and assessed new/enlarging WMLs visually. Participants were classed as fatigued or non-fatigued at baseline according to the Fatigue Severity Scale (>/≤36). Disability and depression were assessed with the expanded-disability status scale and Patient Health Questionnaire, respectively. MRI measures were compared between fatigue groups, both cross-sectionally and longitudinally, using regression analyses. Higher disability and depression scores were observed for participants with fatigue, with a higher number of fatigued participants receiving disease-modifying treatments at follow-up. Structural MRI data for brain were available for n = 313 (45% fatigued) and for spinal cord for n = 324 (46% fatigued). Cervical spinal cord cross-sectional area 2-3, white and grey matter volumes decreased, and WML volume increased, over time for both groups (q < 0.05). However, no significant between-group differences in these measures were found either cross-sectionally or longitudinally (q > 0.05). The presence of new/enlarging WMLs (49% in fatigued; 51% in non-fatigued) at follow-up also did not differ between groups (q > 0.05). Our results suggest that fatigue is not driven by neuroinflammation or neurodegeneration measurable by current structural MRI in early RRMS. This novel negative finding in a large multi-centre cohort of people with recently diagnosed RRMS helps to resolve uncertainty in existing literature. Notably, we showed that fatigue is prevalent in patients without brain radiological relapse, who may be considered to have inactive disease. This suggests that symptom detection and treatment should remain a clinical priority regardless of neuroinflammatory disease activity. More sensitive objective biomarkers are needed to elucidate fatigue mechanisms in RRMS, and ultimately facilitate development of effective targeted treatments for this important 'hidden disability'.
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OBJECTIVES: After acute coronavirus disease-2019 (COVID-19), people often experience fatigue, "brain fog," or other central neurologic symptoms (neuro-post-acute SARS-CoV2, or "Neuro-PASC"). In this observational study we evaluated whether abnormalities noted on initial evaluation persist after at least another year. METHODS: Neuro-PASC research participants who had undergone comprehensive inpatient testing at the NIH Clinical Center returned after at least 1 year for follow-up assessments including symptoms rating scales, MRI, lumbar puncture for tests of the CSF, physiologic recordings during the Valsalva maneuver and head-up tilting (with serial plasma catechols and cardiac Doppler ultrasound during the tilting), blood volume measurement, skin biopsies to examine sympathetic innervation, and blood sampling for neuroendocrine and immunologic measures. RESULTS: 7 patients with Neuro-PASC (6 women, age range 42-63 years) underwent follow-up testing. 71% of initially abnormal test results remained abnormal at follow-up, including the pattern of CSF and serum oligoclonal bands, CSF indices of central catecholamine deficiency, baroreflex-cardiovagal dysfunction, the occurrence of tilt-evoked sudden hypotension, white matter hyperintensities on MRI, and adaptive responses in CSF. DISCUSSION: In Neuro-PASC most of the autonomic and immunologic abnormalities found initially are still present after more than a year.
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Doenças do Sistema Nervoso Autônomo , COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , COVID-19/complicações , COVID-19/imunologia , Feminino , Pessoa de Meia-Idade , Masculino , Adulto , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças do Sistema Nervoso Autônomo/imunologia , SARS-CoV-2 , SeguimentosRESUMO
OBJECTIVES: The incidence of autoimmune encephalitis (AIE) has risen in the last decade, yet recent studies are lacking. We compared the epidemiology of autoimmune and infectious encephalitis cases in Tel-Aviv Sourasky Medical Center (TASMC) between 2010 and 2020. METHODS: All encephalitis cases, aged 18 and above, admitted to TASMC between the years 2010 and 2020 were reviewed for demographic, clinical, laboratory, and imaging data and categorized based on etiology. RESULTS: Two hundred and twenty-five patients with encephalitis were identified. The most common identifiable cause was viral (42%), followed by autoimmune encephalitis (35%), bacterial (18%), and fungal/parasitic (5%). The incidence of AIE cases out of the yearly admitted cases increased substantially, from 3.8/100 K in 2010 to 18.8/100 K in 2020. The incidence of viral cases also increased while those of bacterial and fungal/parasitic infections remained stable. Patients with AIE were younger compared to infectious patients (p-value <0.001) and had lower markers of systemic and cerebrospinal fluid inflammation (p-value for all <0.001). Seizures were more common among AIE patients (p-value <0.001), yet one-year mortality rates were higher among infectious patients (p-value <0.001). INTERPRETATION: AIE incidence has risen significantly in our institution during the past decade, with current rates comparable to those of all infectious causes combined. Based on this cohort, clinical clues for an autoimmune etiology include a non-inflammatory cerebrospinal fluid profile, the presence of seizures, and temporal lobe imaging abnormalities (also common in herpetic encephalitis). In light of its rising incidence and the importance of early treatment, AIE should be considered in the differential diagnosis of all encephalitis cases.
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Introduction: Nontuberculous mycobacteria (NTM) mediated infections are important to consider in cases with neuroinflammatory presentations. We aimed to characterize cases of NTM with neurological manifestations at the National Institutes of Health (NIH) Clinical Center and review the relevant literature. Materials and methods: Between January 1995 and December 2020, six cases were identified. Records were reviewed for demographic, clinical, and radiological characteristics. A MEDLINE search found previously reported cases. Data were extracted, followed by statistical analysis to compare two groups [cases with slow-growing mycobacteria (SGM) vs. those with rapidly growing mycobacteria (RGM)] and evaluate for predictors of survival. NIH cases were evaluated for clinical and radiological characteristics. Cases from the literature were reviewed to determine the differences between SGM and RGM cases and to identify predictors of survival. Results: Six cases from NIH were identified (age 41 ± 13, 83% male). Five cases were caused by SGM [Mycobacterium avium complex (MAC) n = 4; Mycobacterium haemophilum n = 1] and one due to RGM (Mycobacterium abscessus). Underlying immune disorders were identified only in the SGM cases [genetic (n = 2), HIV (n = 1), sarcoidosis (n = 1), and anti-interferon-gamma antibodies (n = 1)]. All cases were diagnosed using tissue analysis. A literature review found 81 reports on 125 cases (SGM n = 85, RGM n = 38, non-identified n = 2). No immune disorder was reported in 26 cases (21%). Within SGM cases, the most common underlying disease was HIV infection (n = 55, 65%), and seizures and focal lesions were more common. In RGM cases, the most common underlying condition was neurosurgical intervention or implants (55%), and headaches and meningeal signs were common. Tissue-based diagnosis was used more for SGM than RGM (39% vs. 13%, p = 0.04). Survival rates were similar in both groups (48% SGM and 55% in RGM). Factors associated with better survival were a solitary CNS lesion (OR 5.9, p = 0.01) and a diagnosis made by CSF sampling only (OR 9.9, p = 0.04). Discussion: NTM infections cause diverse neurological manifestations, with some distinctions between SGM and RGM infections. Tissue sampling may be necessary to establish the diagnosis, and an effort should be made to identify an underlying immune disorder.
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Thromboembolic complications and excessive inflammation are frequent in severe COVID-19, potentially leading to long COVID. In non-COVID studies, we and others demonstrated that circulating Reelin promotes leukocyte infiltration and thrombosis. Thus, we hypothesized that Reelin participates in endothelial dysfunction and hyperinflammation during COVID-19. We showed that Reelin was increased in COVID-19 patients and correlated with the disease activity. In the severe COVID-19 group, we observed a hyperinflammatory state, as judged by increased concentration of cytokines (IL-1α, IL-4, IL-6, IL-10 and IL-17A), chemokines (IP-10 and MIP-1ß), and adhesion markers (E-selectin and ICAM-1). Reelin level was correlated with IL-1α, IL-4, IP-10, MIP-1ß, and ICAM-1, suggesting a specific role for Reelin in COVID-19 progression. Furthermore, Reelin and all of the inflammatory markers aforementioned returned to normal in a long COVID cohort, showing that the hyperinflammatory state was resolved. Finally, we tested Reelin inhibition with the anti-Reelin antibody CR-50 in hACE2 transgenic mice infected with SARS-CoV-2. CR-50 prophylactic treatment decreased mortality and disease severity in this model. These results demonstrate a direct proinflammatory function for Reelin in COVID-19 and identify it as a drug target. This work opens translational clinical applications in severe SARS-CoV-2 infection and beyond in auto-inflammatory diseases.
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COVID-19 , Camundongos , Animais , Humanos , Molécula 1 de Adesão Intercelular , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2 , Quimiocina CCL4 , Quimiocina CXCL10 , Interleucina-4 , InflamaçãoRESUMO
BACKGROUND AND OBJECTIVES: SARS-CoV-2 infection has been associated with a syndrome of long-term neurologic sequelae that is poorly characterized. We aimed to describe and characterize in-depth features of neurologic postacute sequelae of SARS-CoV-2 infection (neuro-PASC). METHODS: Between October 2020 and April 2021, 12 participants were seen at the NIH Clinical Center under an observational study to characterize ongoing neurologic abnormalities after SARS-CoV-2 infection. Autonomic function and CSF immunophenotypic analysis were compared with healthy volunteers (HVs) without prior SARS-CoV-2 infection tested using the same methodology. RESULTS: Participants were mostly female (83%), with a mean age of 45 ± 11 years. The median time of evaluation was 9 months after COVID-19 (range 3-12 months), and most (11/12, 92%) had a history of only a mild infection. The most common neuro-PASC symptoms were cognitive difficulties and fatigue, and there was evidence for mild cognitive impairment in half of the patients (MoCA score <26). The majority (83%) had a very disabling disease, with Karnofsky Performance Status ≤80. Smell testing demonstrated different degrees of microsmia in 8 participants (66%). Brain MRI scans were normal, except 1 patient with bilateral olfactory bulb hypoplasia that was likely congenital. CSF analysis showed evidence of unique intrathecal oligoclonal bands in 3 cases (25%). Immunophenotyping of CSF compared with HVs showed that patients with neuro-PASC had lower frequencies of effector memory phenotype both for CD4+ T cells (p < 0.0001) and for CD8+ T cells (p = 0.002), an increased frequency of antibody-secreting B cells (p = 0.009), and increased frequency of cells expressing immune checkpoint molecules. On autonomic testing, there was evidence for decreased baroreflex-cardiovagal gain (p = 0.009) and an increased peripheral resistance during tilt-table testing (p < 0.0001) compared with HVs, without excessive plasma catecholamine responses. DISCUSSION: CSF immune dysregulation and neurocirculatory abnormalities after SARS-CoV-2 infection in the setting of disabling neuro-PASC call for further evaluation to confirm these changes and explore immunomodulatory treatments in the context of clinical trials.
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Linfócitos T CD8-Positivos , COVID-19 , Feminino , Masculino , Humanos , COVID-19/complicações , SARS-CoV-2 , Encéfalo , CatecolaminasRESUMO
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Although various viruses have been proposed to contribute to MS pathology, the etiology of MS remains unknown. Since intrathecal antibody synthesis is well documented in chronic viral infection and neuroinflammatory diseases, we hypothesized whether the patterns of antigen-specific antibody responses associated with various viral exposures may define patients with CNS chronic immune dysregulation. The pan-viral antibody profiling in cerebrospinal fluid (CSF) and serum of patients with MS showed significant differences from those in healthy volunteers and a pattern of antibody responses against multiple viruses, including the previously identified Epstein-Barr virus. These findings demonstrate that virus-specific antibody signatures might be able to reflect disease-associated inflammatory milieu in CSF of subjects with neuroinflammatory diseases.
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Infecções por Vírus Epstein-Barr , Esclerose Múltipla , Humanos , Herpesvirus Humano 4 , Doenças Neuroinflamatórias , AntiviraisRESUMO
OBJECTIVE: The purpose of this study was to characterize the clinical, laboratory, and imaging findings of 10 patients with GATA2 deficiency who presented with early-onset ischemic stroke. METHODS: A retrospective chart review was conducted on a 127-patient cohort enrolled in the Natural History Study of GATA2 Deficiency and Related Disorders protocol at NIH between 2013 and 2021. All patients had a genetically confirmed GATA2 deficiency. Patients were included if they had evidence of an ischemic stroke through clinical evaluation and neuroimaging. Stroke diagnosis was confirmed through brain magnetic resonance imaging and/or CT. RESULTS: Ten patients between the ages of 15 and 38 years (4 males and 6 females) were identified with at least one ischemic stroke while 6 patients experienced recurrent strokes (7.9% overall, 10/127). Stroke etiology varied and included small vessel (n = 4), large vessel (n = 1), cardioembolic (n = 1), and undetermined (n = 4). Nine patients had lupus anticoagulant, and 2 patients had a history of recurrent deep vein thrombosis. DISCUSSION: We describe the clinical, laboratory, and imaging findings of 10 patients with GATA2 deficiency younger than 40 years who suffered one or more ischemic strokes , suggesting a link between GATA2 deficiency and stroke. This report emphasizes the need for further research to understand this unique vulnerability within this patient population.
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Isquemia Encefálica , Deficiência de GATA2 , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , AVC Isquêmico/complicações , Estudos Retrospectivos , Deficiência de GATA2/complicações , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/genética , Encéfalo , Isquemia Encefálica/etiologia , Isquemia Encefálica/genética , Fator de Transcrição GATA2/genéticaRESUMO
OBJECTIVES: Automated whole brain segmentation from magnetic resonance images is of great interest for the development of clinically relevant volumetric markers for various neurological diseases. Although deep learning methods have demonstrated remarkable potential in this area, they may perform poorly in nonoptimal conditions, such as limited training data availability. Manual whole brain segmentation is an incredibly tedious process, so minimizing the data set size required for training segmentation algorithms may be of wide interest. The purpose of this study was to compare the performance of the prototypical deep learning segmentation architecture (U-Net) with a previously published atlas-free traditional machine learning method, Classification using Derivative-based Features (C-DEF) for whole brain segmentation, in the setting of limited training data. MATERIALS AND METHODS: C-DEF and U-Net models were evaluated after training on manually curated data from 5, 10, and 15 participants in 2 research cohorts: (1) people living with clinically diagnosed HIV infection and (2) relapsing-remitting multiple sclerosis, each acquired at separate institutions, and between 5 and 295 participants' data using a large, publicly available, and annotated data set of glioblastoma and lower grade glioma (brain tumor segmentation). Statistics was performed on the Dice similarity coefficient using repeated-measures analysis of variance and Dunnett-Hsu pairwise comparison. RESULTS: C-DEF produced better segmentation than U-Net in lesion (29.2%-38.9%) and cerebrospinal fluid (5.3%-11.9%) classes when trained with data from 15 or fewer participants. Unlike C-DEF, U-Net showed significant improvement when increasing the size of the training data (24%-30% higher than baseline). In the brain tumor segmentation data set, C-DEF produced equivalent or better segmentations than U-Net for enhancing tumor and peritumoral edema regions across all training data sizes explored. However, U-Net was more effective than C-DEF for segmentation of necrotic/non-enhancing tumor when trained on 10 or more participants, probably because of the inconsistent signal intensity of the tissue class. CONCLUSIONS: These results demonstrate that classical machine learning methods can produce more accurate brain segmentation than the far more complex deep learning methods when only small or moderate amounts of training data are available (n ≤ 15). The magnitude of this advantage varies by tissue and cohort, while U-Net may be preferable for deep gray matter and necrotic/non-enhancing tumor segmentation, particularly with larger training data sets (n ≥ 20). Given that segmentation models often need to be retrained for application to novel imaging protocols or pathology, the bottleneck associated with large-scale manual annotation could be avoided with classical machine learning algorithms, such as C-DEF.
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Neoplasias Encefálicas , Aprendizado Profundo , Infecções por HIV , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Modelos Logísticos , Imageamento por Ressonância Magnética/métodosRESUMO
Background and Objectives: Various peripheral neuropathies, particularly those with sensory and autonomic dysfunction may occur during or shortly after acute COVID-19 illnesses. These appear most likely to reflect immune dysregulation. If similar manifestations can occur with the vaccination remains unknown. Results: In an observational study, we studied 23 patients (92% female; median age 40years) reporting new neuropathic symptoms beginning within 1 month after SARS-CoV-2 vaccination. 100% reported sensory symptoms comprising severe face and/or limb paresthesias, and 61% had orthostasis, heat intolerance and palpitations. Autonomic testing in 12 identified seven with reduced distal sweat production and six with positional orthostatic tachycardia syndrome. Among 16 with lower-leg skin biopsies, 31% had diagnostic/subthreshold epidermal neurite densities (≤5%), 13% were borderline (5.01-10%) and 19% showed abnormal axonal swelling. Biopsies from randomly selected five patients that were evaluated for immune complexes showed deposition of complement C4d in endothelial cells. Electrodiagnostic test results were normal in 94% (16/17). Together, 52% (12/23) of patients had objective evidence of small-fiber peripheral neuropathy. 58% patients (7/12) treated with oral corticosteroids had complete or near-complete improvement after two weeks as compared to 9% (1/11) of patients who did not receive immunotherapy having full recovery at 12 weeks. At 5-9 months post-symptom onset, 3 non-recovering patients received intravenous immunoglobulin with symptom resolution within two weeks. Conclusions: This observational study suggests that a variety of neuropathic symptoms may manifest after SARS-CoV-2 vaccinations and in some patients might be an immune-mediated process.
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BACKGROUND: Dramatic improvements in visualization of cortical (especially subpial) multiple sclerosis (MS) lesions allow assessment of impact on clinical course. OBJECTIVE: Characterize cortical lesions by 7 tesla (T) T2*-/T1-weighted magnetic resonance imaging (MRI); determine relationship with other MS pathology and contribution to disability. METHODS: Sixty-four adults with MS (45 relapsing-remitting/19 progressive) underwent 3 T brain/spine MRI, 7 T brain MRI, and clinical testing. RESULTS: Cortical lesions were found in 94% (progressive: median 56/range 2-203; relapsing-remitting: 15/0-168; p = 0.004). Lesion distribution across 50 cortical regions was nonuniform (p = 0.006), with highest lesion burden in supplementary motor cortex and highest prevalence in superior frontal gyrus. Leukocortical and white matter lesion volumes were strongly correlated (r = 0.58, p < 0.0001), while subpial and white matter lesion volumes were moderately correlated (r = 0.30, p = 0.002). Leukocortical (p = 0.02) but not subpial lesions (p = 0.40) were correlated with paramagnetic rim lesions; both were correlated with spinal cord lesions (p = 0.01). Cortical lesion volumes (total and subtypes) were correlated with expanded disability status scale, 25-foot timed walk, nine-hole peg test, and symbol digit modality test scores. CONCLUSION: Cortical lesions are highly prevalent and are associated with disability and progressive disease. Subpial lesion burden is not strongly correlated with white matter lesions, suggesting differences in inflammation and repair mechanisms.
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Pessoas com Deficiência , Esclerose Múltipla , Substância Branca , Adulto , Encéfalo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/patologia , Substância Branca/patologiaRESUMO
OBJECTIVE: We sought to characterize spinal cord atrophy along the entire spinal cord in the major multiple sclerosis (MS) phenotypes, and evaluate its correlation with clinical disability. METHODS: Axial T1-weighted images were automatically reformatted at each point along the cord. Spinal cord cross-sectional area (SCCSA) were calculated from C1-T10 vertebral body levels and profile plots were compared across phenotypes. Average values from C2-3, C4-5, and T4-9 regions were compared across phenotypes and correlated with clinical scores, and then categorized as atrophic/normal based on z-scores derived from controls, to compare clinical scores between subgroups. In a subset of relapsing-remitting cases with longitudinal scans these regions were compared to change in clinical scores. RESULTS: The cross-sectional study consisted of 149 adults diagnosed with relapsing-remitting MS (RRMS), 49 with secondary-progressive MS (SPMS), 58 with primary-progressive MS (PPMS) and 48 controls. The longitudinal study included 78 RRMS cases. Compared to controls, all MS groups had smaller average regions except RRMS in T4-9 region. In all MS groups, SCCSA from all regions, particularly the cervical cord, correlated with most clinical measures. In the RRMS cohort, 22% of cases had at least one atrophic region, whereas in progressive MS the rate was almost 70%. Longitudinal analysis showed correlation between clinical disability and cervical cord thinning. CONCLUSIONS: Spinal cord atrophy was prevalent across MS phenotypes, with regional measures from the RRMS cohort and the progressive cohort, including SPMS and PPMS, being correlated with disability. Longitudinal changes in the spinal cord were documented in RRMS cases, making it a potential marker for disease progression. While cervical SCCSA correlated with most disability and progression measures, inclusion of thoracic measurements improved this correlation and allowed for better subgrouping of spinal cord phenotypes. Cord atrophy is an important and easily obtainable imaging marker of clinical and sub-clinical progression in all MS phenotypes, and such measures can play a key role in patient selection for clinical trials.
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Medula Cervical , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Adulto , Atrofia/patologia , Medula Cervical/diagnóstico por imagem , Medula Cervical/patologia , Estudos Transversais , Avaliação da Deficiência , Progressão da Doença , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/patologia , Fenótipo , Medula Espinal/patologiaRESUMO
OBJECTIVE: To test the hypothesis that brain white matter hyperintensities (WMH) are more common in people living with HIV (PLWH), even in the setting of well-controlled infection, and to identify clinical measures that correlate with these abnormalities. METHODS: Research brain MRI scans, acquired within longitudinal studies evaluating neurocognitive outcomes, were reviewed to determine WMH load using the Fazekas visual rating scale in PLWH with well-controlled infection (antiretroviral therapy for at least 1 year and plasma viral load <200 copies/mL) and in sociodemographically matched controls without HIV (CWOH). The primary outcome measure of this cross-sectional analysis was increased WMH load, determined by total Fazekas score ≥2. Multiple logistic regression analysis was performed to evaluate the effect of HIV serostatus on WMH load and to identify MRI, CSF, and clinical variables that associate with WMH in the PLWH group. RESULTS: The study included 203 PLWH and 58 CWOH who completed a brain MRI scan between April 2014 and March 2019. The multiple logistic regression analysis, with age and history of tobacco use as covariates, showed that the adjusted odds ratio of the PLWH group for increased WMH load is 3.7 (95% confidence interval 1.8-7.5; p = 0.0004). For the PLWH group, increased WMH load was associated with older age, male sex, tobacco use, hypertension, and hepatitis C virus coinfection, and also with the presence of measurable tumor necrosis factor α in CSF. CONCLUSION: Our results suggest that HIV serostatus affects the extent of brain WMH. This effect is mainly associated with aging and modifiable comorbidities.
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Encéfalo/patologia , Infecções por HIV/patologia , Leucoaraiose/patologia , Substância Branca/patologia , Adulto , Estudos Transversais , Feminino , Humanos , Leucoaraiose/epidemiologia , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Cerebrospinal fluid (CSF) is essential for the medical workup of patients with neurological conditions and for disease-modifying clinical trials. Post- lumbar puncture (LP) headache is influenced by both operator and patient-related factors, including needle type and gauge, age, and gender. OBJECTIVES: We aimed to assess whether CSF volume measured based on pre-procedural brain MRI is associated with the risk of developing a post-LP headache. METHODS: In total, n = 117 participants (n = 58 Parkinson's disease patients, and n = 59 healthy controls) underwent an LP and CSF collection. Of those, n = 89 underwent MRI scans prior to the LP procedure acquiring high-resolution 3D magnetization-prepared rapid gradient echo (MP-RAGE) T1-weighted images using a 3 T MR scanner. Clinical and behavioral assessments were performed for all participants, and CSF was assessed for content. The T1-weighted images were segmented producing gray matter, white matter, and CSF probability maps. RESULTS: Thirteen participants (11.1%) experienced post-LP headache. They were younger (p = .033) and had lower CSF volumes (p = .040) compared to participants that did not develop a post LP headache. CONCLUSIONS: The results of this pilot study suggest that low CSF volumes might increase the risk for the occurrence of post-LP adverse events and should be taken into consideration when planning LP's.
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Doenças do Sistema Nervoso , Cefaleia Pós-Punção Dural , Líquido Cefalorraquidiano , Humanos , Imageamento por Ressonância Magnética , Projetos Piloto , Cefaleia Pós-Punção Dural/diagnóstico por imagem , Cefaleia Pós-Punção Dural/etiologia , Punção Espinal/efeitos adversosRESUMO
OBJECTIVES: We aimed to estimate the frequency of epileptic seizures (ES) and psychogenic nonepileptic seizures (PNES) with atypical duration in our epilepsy monitoring unit (EMU), in order to raise awareness of atypical durations of both types of events. MATERIALS & METHODS: We retrospectively reviewed all consecutive video-electroencephalogram (vEEG) recordings in our medical center's EMU from January 2013 to December 2017 and identified patients with seizures with atypical duration. Short PNES were defined as those lasting fewer than 2â¯min and long ES as those lasting for more than 5â¯min. RESULTS: The files of 830 adult (age >16â¯years) patients were reviewed, of whom 26 patients (3.1%, mean age: 33.3⯱â¯9.8â¯years, 12 females) were diagnosed as having an unusual seizure duration. Among 432 patients with ES during monitoring, fourteen patients [3.2% (95% confidence interval (CI): 1.5%-5.0%), mean age: 33.0⯱â¯12.2, 5 females [had long ES durations (exceeding 5â¯min). In 64% of patients with long ES, the events were provoked by antiepileptic drug (AED) withdrawal during vEEG, 62% had focal lesion on brain imaging, and 64% had a frontotemporal or a temporal seizure focus. Among 223 patients diagnosed with PNES, 12 patients [5.4% (95% CI: 2.2%-8.6%), mean age: 33.6⯱â¯6.6, 7 females] had short PNES durations (less than 2â¯min) and demonstrated motor (9/12, 75%), altered responsiveness (6/12, 50%), and vocalization (5/12, 42%) as the most prominent clinical features. CONCLUSIONS: The data from our case files highlight two main considerations in the diagnosis of paroxysmal events: prolonged event can be due to ES, while short events can be psychogenic.
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Encéfalo/fisiopatologia , Eletroencefalografia/tendências , Transtornos Psicofisiológicos/fisiopatologia , Convulsões/fisiopatologia , Gravação em Vídeo/tendências , Adolescente , Adulto , Anticonvulsivantes , Estudos de Coortes , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicofisiológicos/diagnóstico , Estudos Retrospectivos , Convulsões/diagnóstico , Convulsões/psicologia , Fatores de Tempo , Gravação em Vídeo/métodos , Adulto JovemRESUMO
BACKGROUND: Management of partially-treated, community-acquired bacterial meningitis (PCBM) is commonly compromised by lack of microbiological diagnosis. We aimed to analyze the impact of FilmArray Meningitis-Encephalitis (FA-ME) PCR on the management of PCBM. METHODS: Comparison of treatment variables of PCBM cases between two periods, before (6.5 years, control group) and after (2 years, study group) the application of FA-ME PCR assay. RESULTS: The total duration of antimicrobial treatment in the study group (n = 8) was significantly shorter than the control group (n = 23) (9.5 ± 3.7 days vs. 15.2 ± 5 days, p = 0.007). The percentage of narrow-spectrum regimens was significantly higher in the study group (78 ± 11% vs. 40 ± 9%, p = 0.03). There was a significant difference in implementation of antimicrobial chemoprophylaxis for close contacts (4/8 (50%) vs. 1/23 (4%), p = 0.01). CONCLUSIONS: The use of FA-ME PCR provides significant benefits in the management of PCBM by shortening duration of antibiotic treatment, increasing the use of narrow-spectrum regimens, and allowing proper administration of antimicrobial chemoprophylaxis. TRIAL REGISTRATION: The study was approved and retrospectively registered by the Tel-Aviv Sourasky Medical Center ( 0378-17-TLV , 10/17/2017) and Rabin Medical Center ( 0270-18-RMC , 11/11/2018) Ethics committees and conforms to recognized standards.
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Encefalite/diagnóstico , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/tratamento farmacológico , Reação em Cadeia da Polimerase/métodos , Adulto , Antibacterianos/uso terapêutico , Quimioprevenção , Estudos de Coortes , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/prevenção & controle , Encefalite/genética , Feminino , Humanos , Israel , Masculino , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/prevenção & controle , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: We aimed to explore the diagnostic value, clinical correlates and electroencephalographic features of FIRDA (Frontal intermittent rhythmic delta activity). MATERIALS AND METHODS: We retrospectively reviewed reports from EEG studies done in adults at our tertiary center between January 2015 and May 2018. For cases demonstrating FIRDA, medical files were reviewed and each case was given a diagnostic category. EEG recordings were reviewed and electrophysiologic data were extracted including FIRDA characteristics (frequency, location, duration, and symmetry). Then, a statistical analysis was done to evaluate the relationship between the diagnostic categories and EEG variables. RESULTS: Ninety-four cases of FIRDA were found, with a frequency of 1.6% among inpatients. EEG recordings were available for review in 84 cases. FIRDA was asymmetric in 43 of these cases (49%), usually more prominent on the left (36/43, 84%). The diagnostic category groups included epilepsy (n = 39, 41%), other central nervous system (CNS) disease (n = 33, 35%), and systemic illness (n = 22, 23%). A significant difference in FIRDA location was found, as patients with epilepsy or other CNS disease, had a significantly higher probability for the delta activity to involve the temporal areas (frontotemporal location in 27/64 in these groups compared with 3/20 in the systemic illness group, P-value = .033). CONCLUSIONS: This study provides insights to the diagnosis underlying FIRDA, especially the high rate of epilepsy patients, and calls for further neurologic investigation of cases in which FIRDA involves the temporal areas since most of these cases were due to epilepsy or other CNS disease and not a systemic illness.
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Encefalopatias/diagnóstico , Encefalopatias/fisiopatologia , Ritmo Delta/fisiologia , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Neurosyphilis is a rare disease that until the 2000s was almost eradicated due to population awareness of HIV and efficient treatment. Since then, the prevalence of the entity is rising due to risk-associated behaviour such as unprotected intercourse. Neurosyphilis is still a difficult entity to diagnose especially when combined with acute HIV infection which can influence the usual clinical course of disease. In rare occasions, both acute HIV and early syphilis infection can present as mono or multiple cranial nerve palsies. This case demonstrates a rare manifestation of misdiagnosed early syphilis infection combined with acute HIV infection in a 34-year-old man with prior history of unprotected sex with men.
Assuntos
Antibacterianos/uso terapêutico , Doenças dos Nervos Cranianos/microbiologia , Paralisia Facial/microbiologia , Infecções por HIV/imunologia , Perda Auditiva/microbiologia , Neurossífilis/microbiologia , Penicilina G/uso terapêutico , Adulto , Doenças dos Nervos Cranianos/diagnóstico por imagem , Doenças dos Nervos Cranianos/fisiopatologia , Disartria/microbiologia , Disartria/fisiopatologia , Paralisia Facial/fisiopatologia , Infecções por HIV/fisiopatologia , Perda Auditiva/fisiopatologia , Homossexualidade Masculina , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Neurossífilis/tratamento farmacológico , Neurossífilis/fisiopatologia , Resultado do Tratamento , Sexo sem ProteçãoAssuntos
Fatores Imunológicos/uso terapêutico , Rituximab/uso terapêutico , Vasculite do Sistema Nervoso Central/tratamento farmacológico , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vasculite do Sistema Nervoso Central/diagnóstico , Vasculite do Sistema Nervoso Central/fisiopatologiaRESUMO
BACKGROUND: Myocarditis is a life-threatening heart disease characterized by myocardial inflammation, necrosis, and chronic fibrosis. While mast cell inhibition has been suggested to prevent fibrosis in rat myocarditis, little is known about its effectiveness in attenuating cardiac remodeling and dysfunction in myocarditis. Thus, we sought to test the hypothesis that mast cell inhibition will attenuate the inflammatory reaction and associated left ventricular (LV) remodeling and dysfunction after fulminant autoimmune myocarditis. Methods and RESULTS: To induce experimental autoimmune myocarditis, we immunized 30 rats with porcine cardiac myosin (PCM) twice at a 7-day interval. On day 8 animals were randomized into treatment with either an intraperitoneal (IP) injection of 25mg/kg of cromolyn sodium (n = 13) or an equivalent volume (â¼0.5 mL IP) of normal saline (n = 11). All animals were scanned by serial echocardiography studies before treatment (baseline echocardiogram) and after 20 days of cromolyn sodium (28 days after immunization). Furthermore, serial cardiac magnetic resonance was performed in a subgroup of 12 animals. After 20 days of treatment (28 days from first immunization), hearts were harvested for histopathological analysis. By echocardiography, cromolyn sodium prevented LV dilatation and attenuated LV dysfunction, compared with controls. Postmortem analysis of hearts showed that cromolyn sodium reduced myocardial fibrosis, as well as the number and size of cardiac mast cells in the inflamed myocardium, compared with controls. CONCLUSIONS: Our study suggests that mast cell inhibition with cromolyn sodium attenuates adverse LV remodeling and dysfunction in myocarditis. This mechanism-based therapy is clinically relevant and could improve the outcome of patients at risk for inflammatory cardiomyopathy and heart failure.