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1.
Med Mycol ; 62(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38710585

RESUMO

Cryptococcus neoformans is the most common cause of fungal meningitis and is associated with a high mortality. The clinical significance of concurrent Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-negative patients with cryptococcal meningitis (CM) remains unclear. A retrospective cohort study was performed by analyzing CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA in these patients by metagenomic next-generation sequencing (mNGS) and compared 10-week survival rates among those with and without EBV DNA in CSF. Of the 79 CSF samples tested, 44.3% (35/79) had detectable viral DNA in CSF, while 55.7% (44/79) were virus-negative. The most frequent viral pathogen was EBV, which was detected in 22.8% (18/79) patients. The median number of CSF-EBV DNA reads was 4 reads with a range from 1 to 149 reads. The 10-week mortality rates were 22.2% (4/18) in those with positive CSF-EBV and 2.3% (1/44) in those with negative CSF-virus (hazard ratio 8.20, 95% confidence interval [CI] 1.52-81.80; P = 0.014), which remained significant after a multivariate adjustment for the known risk factors of mortality (adjusted hazard ratio 8.15, 95% CI 1.14-92.87; P = 0.037). mNGS can identify viruses that coexist in CSF of HIV-negative patients with CM. EBV DNA is most commonly found together with C. neoformans in CSF and its presence is associated with increased mortality in HIV-negative CM patients.


We retrospectively analyzed CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA by mNGS and compared 10-week survival rates among those with and without EBV DNA. Positive CSF-EBV DNA is associated with the increased mortality in HIV-negative CM patients.


Assuntos
DNA Viral , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Meningite Criptocócica , Humanos , Meningite Criptocócica/mortalidade , Meningite Criptocócica/líquido cefalorraquidiano , Meningite Criptocócica/microbiologia , Masculino , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , DNA Viral/líquido cefalorraquidiano , DNA Viral/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/líquido cefalorraquidiano , Idoso , Líquido Cefalorraquidiano/microbiologia , Líquido Cefalorraquidiano/virologia , Cryptococcus neoformans/genética , Cryptococcus neoformans/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Adulto Jovem , China/epidemiologia , Análise de Sobrevida
2.
Front Immunol ; 15: 1388667, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799430

RESUMO

Cerebellar ataxia is an uncommon and atypical manifestation of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, often accompanied by seizures, psychiatric symptoms, and cognitive deficits. Previous cases of isolated brainstem-cerebellar symptoms in patients with anti-NMDAR encephalitis have not been documented. This report presents a case of anti-NMDAR encephalitis in which the patient exhibited cerebellar ataxia, nystagmus, diplopia, positive bilateral pathological signs, and hemiparesthesia with no other accompanying symptoms or signs. The presence of positive CSF anti-NMDAR antibodies further supports the diagnosis. Other autoantibodies were excluded through the use of cell-based assays. Immunotherapy was subsequently administered, leading to a gradual recovery of the patient.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Autoanticorpos , Tronco Encefálico , Humanos , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Tronco Encefálico/patologia , Autoanticorpos/imunologia , Autoanticorpos/líquido cefalorraquidiano , Autoanticorpos/sangue , Feminino , Ataxia Cerebelar/etiologia , Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/imunologia , Cerebelo/patologia , Cerebelo/diagnóstico por imagem , Receptores de N-Metil-D-Aspartato/imunologia , Adulto , Imunoterapia , Masculino , Imageamento por Ressonância Magnética
3.
Sci Rep ; 14(1): 12486, 2024 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-38816506

RESUMO

Affections of the central nervous system (CNS) rarely occur in Lyme neuroborreliosis (LNB). CNS manifestations can have residual neurological symptoms despite antibiotic treatment. We explored the spectrum of CNS affections in patients with LNB in a tertiary care center in a region endemic for Lyme borreliosis. We retrospectively included patients treated at a tertiary care center from January 2020-December 2021 fulfilling the case criteria for LNB as stated in the current German guideline on LNB. Clinical data, cerebrospinal fluid (CSF) findings and MRI imaging were collected. We included 35 patients with LNB, 24 with early manifestations and 11 with CNS-LNB. CNS-LNB patients had encephalomyelitis (n = 6) or cerebral vasculitis (n = 5). Patients with early LNB and CNS-LNB differed regarding albumin CSF/serum quotient and total protein in CSF. Duration from onset of symptoms until diagnosis was statistically significantly longer in patients with encephalomyelitis. MRI findings were heterogeneous and showed longitudinal extensive myelitis, perimedullar leptomeningeal enhancement, pontomesencephalic lesions or cerebral vasculitis. CNS-LNB can present with a variety of clinical syndromes and MRI changes. No clear pattern of MRI findings in CNS-LNB could be identified. The role of MRI consists in ruling out other causes of neurological symptoms.


Assuntos
Neuroborreliose de Lyme , Imageamento por Ressonância Magnética , Humanos , Neuroborreliose de Lyme/diagnóstico por imagem , Neuroborreliose de Lyme/líquido cefalorraquidiano , Neuroborreliose de Lyme/diagnóstico , Imageamento por Ressonância Magnética/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Idoso , Sistema Nervoso Central/diagnóstico por imagem , Sistema Nervoso Central/patologia , Encefalomielite/diagnóstico por imagem , Encefalomielite/líquido cefalorraquidiano , Adulto Jovem , Vasculite do Sistema Nervoso Central/diagnóstico por imagem
4.
Fluids Barriers CNS ; 21(1): 47, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816737

RESUMO

BACKGROUND: Bidirectional reciprocal motion of cerebrospinal fluid (CSF) was quantified using four-dimensional (4D) flow magnetic resonance imaging (MRI) and intravoxel incoherent motion (IVIM) MRI. To estimate various CSF motions in the entire intracranial region, we attempted to integrate the flow parameters calculated using the two MRI sequences. To elucidate how CSF dynamics deteriorate in Hakim's disease, an age-dependent chronic hydrocephalus, flow parameters were estimated from the two MRI sequences to assess CSF motion in the entire intracranial region. METHODS: This study included 127 healthy volunteers aged ≥ 20 years and 44 patients with Hakim's disease. On 4D flow MRI for measuring CSF motion, velocity encoding was set at 5 cm/s. For the IVIM MRI analysis, the diffusion-weighted sequence was set at six b-values (i.e., 0, 50, 100, 250, 500, and 1000 s/mm2), and the biexponential IVIM fitting method was adapted. The relationships between the fraction of incoherent perfusion (f) on IVIM MRI and 4D flow MRI parameters including velocity amplitude (VA), absolute maximum velocity, stroke volume, net flow volume, and reverse flow rate were comprehensively evaluated in seven locations in the ventricles and subarachnoid spaces. Furthermore, we developed a new parameter for fluid oscillation, the Fluid Oscillation Index (FOI), by integrating these two measurements. In addition, we investigated the relationship between the measurements and indices specific to Hakim's disease and the FOIs in the entire intracranial space. RESULTS: The VA on 4D flow MRI was significantly associated with the mean f-values on IVIM MRI. Therefore, we estimated VA that could not be directly measured on 4D flow MRI from the mean f-values on IVIM MRI in the intracranial CSF space, using the following formula; e0.2(f-85) + 0.25. To quantify fluid oscillation using one integrated parameter with weighting, FOI was calculated as VA × 10 + f × 0.02. In addition, the FOIs at the left foramen of Luschka had the strongest correlations with the Evans index (Pearson's correlation coefficient: 0.78). The other indices related with Hakim's disease were significantly associated with the FOIs at the cerebral aqueduct and bilateral foramina of Luschka. FOI at the cerebral aqueduct was also elevated in healthy controls aged ≥ 60 years. CONCLUSIONS: We estimated pulsatile CSF movements in the entire intracranial CSF space in healthy individuals and patients with Hakim's disease using FOI integrating VA from 4D flow MRI and f-values from IVIM MRI. FOI is useful for quantifying the CSF oscillation.


Assuntos
Líquido Cefalorraquidiano , Imageamento por Ressonância Magnética , Humanos , Líquido Cefalorraquidiano/diagnóstico por imagem , Líquido Cefalorraquidiano/fisiologia , Adulto , Masculino , Feminino , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Adulto Jovem , Idoso , Hidrodinâmica , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/fisiopatologia , Hidrocefalia/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia
5.
Lakartidningen ; 1212024 May 31.
Artigo em Sueco | MEDLINE | ID: mdl-38818759

RESUMO

Technical developments have paved the way for the development of ultrasensitive analytical methods that allow for precise quantification of brain-specific proteins in blood samples. Plasma levels of amyloid ß, specifically the Aß42/40 ratio, are reduced in Alzheimer's disease (AD) and show concordance with brain amyloidosis assessed by PET, but the overlap with normal elderly may be too large for reliable use in clinical applications. Plasma phosphorylated tau (P-tau), especially a variant called P-tau217, is markedly increased in the early symptomatic stages of AD but remains normal in other neurodegenerative disorders. Total tau (T-tau) is measurable in blood and shows most promise as a biomarker for acute neuronal injury (e.g. acute traumatic or hypoxic brain injury), where T-tau shows a fast and dramatic increase but does not work well as an AD biomarker due to contributions to blood levels from peripheral tissues. Instead, a novel method for tau protein produced only in the CNS called brain-derived tau (BD-tau) shows promise as a biomarker for AD-type neurodegeneration. Neurofilament light (NFL) levels in blood correlate tightly with levels in CSF and reflect axonal injury irrespective of the underlying cause. Increased blood NFL concentration is found in several neurodegenerative disorders, including AD, but even more so in disorders such as motor neuron disease and frontotemporal dementia. Glial fibrillary acidic protein (GFAP) is expressed with activation of astrocytes, and is mildly increased in AD, but is also very high also in acute brain disorders. These blood tests show promise as tools to identify AD pathophysiology in the first assessment of patients with early cognitive symptoms, also in primary care, to guide clinical management and possible admission to the specialist clinic. A two-step model will result in a very high accuracy to either predict or exclude brain amyloidosis of the Alzheimer type.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Encéfalo , Proteínas de Neurofilamentos , Proteínas tau , Humanos , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Biomarcadores/sangue , Proteínas tau/sangue , Proteínas tau/líquido cefalorraquidiano , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Proteínas de Neurofilamentos/sangue , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Proteína Glial Fibrilar Ácida/sangue
8.
Acta Neurochir (Wien) ; 166(1): 234, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805034

RESUMO

PURPOSE: Progressive cerebral edema with refractory intracranial hypertension (ICP) requiring decompressive hemicraniectomy (DHC) is a severe manifestation of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH). The purpose of the study was to investigate whether a more pronounced cerebrospinal fluid (CSF) drainage has an influence on cerebral perfusion pressure (CPP) and the extent of EBI after aSAH. METHODS: Patients with aSAH and indication for ICP-monitoring admitted to our center between 2012 and 2020 were retrospectively included. EBI was categorized based on intracranial blood burden, persistent loss of consciousness, and SEBES (Subarachnoid Hemorrhage Early Brain Edema Score) score on the third day after ictus. The draining CSF and vital signs such as ICP and CPP were documented daily. RESULTS: 90 out of 324 eligible aSAH patients (28%) were included. The mean age was 54.2 ± 11.9 years. DHC was performed in 24% (22/90) of patients. Mean CSF drainage within 72 h after ictus was 168.5 ± 78.5 ml. A higher CSF drainage within 72 h after ictus correlated with a less severe EBI and a less frequent need for DHC (r=-0.33, p = 0.001) and with a higher mean CPP on day 3 after ictus (r = 0.2351, p = 0.02). CONCLUSION: A more pronounced CSF drainage in the first 3 days of aSAH was associated with higher CPP and a less severe course of EBI and required less frequently a DHC. These results support the hypothesis that an early and pronounced CSF drainage may facilitate blood clearance and positively influence the course of EBI.


Assuntos
Aneurisma Roto , Drenagem , Hemorragia Subaracnóidea , Humanos , Pessoa de Meia-Idade , Masculino , Hemorragia Subaracnóidea/cirurgia , Hemorragia Subaracnóidea/complicações , Feminino , Drenagem/métodos , Estudos Retrospectivos , Adulto , Aneurisma Roto/cirurgia , Aneurisma Roto/complicações , Idoso , Craniectomia Descompressiva/métodos , Lesões Encefálicas , Edema Encefálico/etiologia , Edema Encefálico/líquido cefalorraquidiano , Edema Encefálico/cirurgia , Líquido Cefalorraquidiano , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/cirurgia , Hipertensão Intracraniana/líquido cefalorraquidiano , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/complicações
9.
Sci Rep ; 14(1): 12235, 2024 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806521

RESUMO

Neuropsychological evidence of memory impairment represents the main feature of the clinical onset of typical Alzheimer's disease (AD). Rey's Auditory Verbal Learning Test (RAVLT) and Logical Memory (LM) are two tests both assessing verbal episodic memory, widely used in clinical practice. Our aim was to investigate the added value of their combined use in predicting cerebrospinal fluid (CSF) AD biomarkers positivity in a retrospective consecutive series of patients with mild cognitive impairment (MCI). 169 MCI patients were included. For all of them neuropsychological assessment and CSF analysis were available. According to CSF A/T/(N) profile, 109 were defined as MCI due to AD (A+T+), and 60 were non-AD MCI (A-T-). Logistic regression model and receiver-operating characteristic (ROC) curves were analyzed to evaluate the discriminatory power of single and combined sub-measures between AD and non-AD patients. The combination of RAVLT-del with LM could acceptably discriminate the two groups (AUC: 0.69, CI 95% 0.617-0.761, sens: 0.75, spec. 0.58, p < 0.001), while the single tests did not show sufficient discriminative performance. Our study shows that the combination of RAVLT delayed recall with LM better predicts the biological AD diagnosis (A+T+), showing a good discriminative power between MCI-AD from non-AD MCI. Since RAVLT and LM assess different components of verbal episodic memory, they should be considered as complementary, rather than interchangeable, tests.


Assuntos
Doença de Alzheimer , Biomarcadores , Disfunção Cognitiva , Memória Episódica , Testes Neuropsicológicos , Humanos , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Masculino , Feminino , Idoso , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Biomarcadores/líquido cefalorraquidiano , Estudos Retrospectivos , Pessoa de Meia-Idade , Curva ROC , Aprendizagem Verbal/fisiologia , Valor Preditivo dos Testes , Idoso de 80 Anos ou mais
10.
Fluids Barriers CNS ; 21(1): 40, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725029

RESUMO

BACKGROUND: Parkinson's disease is characterized by dopamine-responsive symptoms as well as aggregation of α-synuclein protofibrils. New diagnostic methods assess α-synuclein aggregation characteristics from cerebrospinal fluid (CSF) and recent pathophysiologic mechanisms suggest that CSF circulation disruptions may precipitate α-synuclein retention. Here, diffusion-weighted MRI with low-to-intermediate diffusion-weightings was applied to test the hypothesis that CSF motion is reduced in Parkinson's disease relative to healthy participants. METHODS: Multi-shell diffusion weighted MRI (spatial resolution = 1.8 × 1.8 × 4.0 mm) with low-to-intermediate diffusion weightings (b-values = 0, 50, 100, 200, 300, 700, and 1000 s/mm2) was applied over the approximate kinetic range of suprasellar cistern fluid motion at 3 Tesla in Parkinson's disease (n = 27; age = 66 ± 6.7 years) and non-Parkinson's control (n = 32; age = 68 ± 8.9 years) participants. Wilcoxon rank-sum tests were applied to test the primary hypothesis that the noise floor-corrected decay rate of CSF signal as a function of b-value, which reflects increasing fluid motion, is reduced within the suprasellar cistern of persons with versus without Parkinson's disease and inversely relates to choroid plexus activity assessed from perfusion-weighted MRI (significance-criteria: p < 0.05). RESULTS: Consistent with the primary hypothesis, CSF decay rates were higher in healthy (D = 0.00673 ± 0.00213 mm2/s) relative to Parkinson's disease (D = 0.00517 ± 0.00110 mm2/s) participants. This finding was preserved after controlling for age and sex and was observed in the posterior region of the suprasellar cistern (p < 0.001). An inverse correlation between choroid plexus perfusion and decay rate in the voxels within the suprasellar cistern (Spearman's-r=-0.312; p = 0.019) was observed. CONCLUSIONS: Multi-shell diffusion MRI was applied to identify reduced CSF motion at the level of the suprasellar cistern in adults with versus without Parkinson's disease; the strengths and limitations of this methodology are discussed in the context of the growing literature on CSF flow.


Assuntos
Líquido Cefalorraquidiano , Imagem de Difusão por Ressonância Magnética , Doença de Parkinson , Humanos , Doença de Parkinson/líquido cefalorraquidiano , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Idoso , Imagem de Difusão por Ressonância Magnética/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Líquido Cefalorraquidiano/diagnóstico por imagem , Líquido Cefalorraquidiano/fisiologia , Movimento (Física)
11.
J Alzheimers Dis ; 99(3): 1077-1092, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38759016

RESUMO

Background: Although Lumipulse assays and conventional ELISA are strongly correlated, the precise relationship between their measured values remains undetermined. Objective: To determine the relationship between Lumipulse and ELISA measurement values. Methods: Patients who underwent cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker measurements and consented to biobanking between December 2021 and June 2023 were included. The relationship between values measured via Lumipulse assays and conventional ELISA were evaluated by Passing-Bablok analyses for amyloid-ß 1-42 (Aß42), total tau (t-tau), and phospho-tau 181 (p-tau 181). Studies using both assays were systematically searched for in PubMed and summarized after quality assessment. Results: Regression line slopes and intercepts were 1.41 (1.23 to 1.60) and -77.8 (-198.4 to 44.5) for Aß42, 0.94 (0.88 to 1.01) and 98.2 (76.9 to 114.4) for t-tau, and 1.60 (1.43 to 1.75) and -21.1 (-26.9 to -15.6) for p-tau181. Spearman's correlation coefficients were 0.90, 0.95, and 0.95 for Aß42, t-tau, and p-tau181, respectively. We identified 13 other studies that included 2,117 patients in total. Aß42 slope varied among studies, suggesting inter-lab difference of ELISA. The slope and intercept of t-tau were approximately 1 and 0, respectively, suggesting small proportional and systematic differences. Conversely, the p-tau181 slope was significantly higher than 1, distributed between 1.5-2 in most studies, with intercepts significantly lower than 0, suggesting proportional and systematic differences. Conclusions: We characterized different relationship between measurement values for each biomarker, which may be useful for understanding the differences in CSF biomarker measurement values on different platforms and for future global harmonization.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Ensaio de Imunoadsorção Enzimática , Fragmentos de Peptídeos , Proteínas tau , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Humanos , Biomarcadores/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Ensaio de Imunoadsorção Enzimática/métodos , Proteínas tau/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano
12.
J Alzheimers Dis ; 99(3): 883-885, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38759014

RESUMO

With the advent of therapeutics with potential to slow Alzheimer's disease progression the necessity of understanding the diagnostic value of plasma biomarkers is critical, not only for understanding the etiology and progression of Alzheimer's disease, but also for access and response to potentially disease modifying therapeutic agents. Multiple studies are currently assessing the sensitivity and specificity of plasma biomarkers in large cohorts such as the Alzheimer's Disease Neuroimaging Initiative. This study uses machine learning to predict the progression from mild cognitive impairment using plasma biomarkers in conjunction with well-established cerebrospinal fluid and imaging biomarkers of disease progression.


Assuntos
Doença de Alzheimer , Biomarcadores , Progressão da Doença , Aprendizado de Máquina , Proteínas de Neurofilamentos , Proteínas tau , Humanos , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Proteínas tau/sangue , Proteínas tau/líquido cefalorraquidiano , Idoso , Proteínas de Neurofilamentos/sangue , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Feminino , Masculino , Prognóstico , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Estudos de Coortes , Idoso de 80 Anos ou mais
14.
Brain Behav ; 14(5): e3534, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38702897

RESUMO

OBJECTIVE: This study aimed to explore the clinical characteristics and temporal disease course of patients with autoimmune encephalitis (AE) and paraneoplastic neurological syndrome (PNS) in Sweden. METHODS: Thirty-seven antibody-positive AE and PNS cases were identified in the Healthcare region Mid Sweden between 2015 and 2019. Clinical data were collected through a retrospective review of electronic health records. Patients were divided into three subgroups based on antibody type: neuronal surface antibodies (NSAbs), onconeural antibodies, and anti-GAD65 antibodies. RESULTS: Nineteen patients had NSAbs, 11 onconeural antibodies, and seven anti-GAD65 antibodies. Anti-LGI1 and anti-NMDAR were the most frequently detected NSAbs, with anti-NMDAR cases having an older-than-expected age distribution (median age 40, range 17-72). Only 11 of 32 (30%) of patients had findings suggesting encephalitis on initial MRI, but 28 of 31 (90%) had pathological findings on initial cerebrospinal fluid analysis. All patients but one had abnormal EEG findings. Median time to immunotherapy was comparable among the three subgroups, whereas patients with anti-LGI1, anti-CASPR2, and anti-IgLON5 had an eightfold longer time to immunotherapy than anti-NMDAR and anti-GABA-B (p = .0016). There was a seasonal variation in onset for patients with non-tumor-related NSAbs and anti-GAD65 antibodies, with most patients (72%) falling ill in spring or summer. CONCLUSION: Swedish patients with AE and PNS had similar clinical characteristics as previously described cohorts from other geographical regions except for anti-NMDAR encephalitis, with older onset than expected. The onset of non-tumor-related AE occurred predominantly in the warm seasons, and AE with a more insidious onset was associated with delayed treatment initiation.


Assuntos
Autoanticorpos , Encefalite , Doença de Hashimoto , Síndromes Paraneoplásicas do Sistema Nervoso , Humanos , Suécia/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/fisiopatologia , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Encefalite/imunologia , Estudos Retrospectivos , Adulto Jovem , Adolescente , Doença de Hashimoto/imunologia , Glutamato Descarboxilase/imunologia
15.
Alzheimers Res Ther ; 16(1): 99, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704569

RESUMO

BACKGROUND: Patients with sporadic cerebral amyloid angiopathy (sCAA) frequently report cognitive or neuropsychiatric symptoms. The aim of this study is to investigate whether in patients with sCAA, cognitive impairment and neuropsychiatric symptoms are associated with a cerebrospinal fluid (CSF) biomarker profile associated with Alzheimer's disease (AD). METHODS: In this cross-sectional study, we included participants with sCAA and dementia- and stroke-free, age- and sex-matched controls, who underwent a lumbar puncture, brain MRI, cognitive assessments, and self-administered and informant-based-questionnaires on neuropsychiatric symptoms. CSF phosphorylated tau, total tau and Aß42 levels were used to divide sCAA patients in two groups: CAA with (CAA-AD+) or without a CSF biomarker profile associated with AD (CAA-AD-). Performance on global cognition, specific cognitive domains (episodic memory, working memory, processing speed, verbal fluency, visuoconstruction, and executive functioning), presence and severity of neuropsychiatric symptoms, were compared between groups. RESULTS: sCAA-AD+ (n=31; mean age: 72 ± 6; 42%, 61% female) and sCAA-AD- (n=23; 70 ± 5; 42% female) participants did not differ with respect to global cognition or type of affected cognitive domain(s). The number or severity of neuropsychiatric symptoms also did not differ between sCAA-AD+ and sCAA-AD- participants. These results did not change after exclusion of patients without prior ICH. CONCLUSIONS: In participants with sCAA, a CSF biomarker profile associated with AD does not impact global cognition or specific cognitive domains, or the presence of neuropsychiatric symptoms.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Angiopatia Amiloide Cerebral , Testes Neuropsicológicos , Proteínas tau , Humanos , Feminino , Masculino , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Idoso , Estudos Transversais , Angiopatia Amiloide Cerebral/líquido cefalorraquidiano , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/etiologia , Fragmentos de Peptídeos/líquido cefalorraquidiano , Cognição/fisiologia , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética
16.
Front Cell Infect Microbiol ; 14: 1322847, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707513

RESUMO

The aetiology of chronic aseptic meningitis is difficult to establish. Candida meningitis in particular is often diagnosed late, as cerebrospinal fluid (CSF) work-up and imaging findings are nonspecific. A 35-year-old patient with chronic aseptic meningitis, for which repeated microbiological testing of CSF was unrevealing, was finally diagnosed with Candida albicans (C. albicans) meningitis with cauda equina involvement using metagenomic next-generation sequencing (mNGS). This report highlights the diagnostic challenges and the difficulties of treating shunt-associated fungal meningitis.


Assuntos
Candida albicans , Sequenciamento de Nucleotídeos em Larga Escala , Meningite Fúngica , Metagenômica , Humanos , Adulto , Candida albicans/genética , Candida albicans/isolamento & purificação , Meningite Fúngica/diagnóstico , Meningite Fúngica/microbiologia , Meningite Fúngica/tratamento farmacológico , Metagenômica/métodos , Candidíase/diagnóstico , Candidíase/microbiologia , Candidíase/líquido cefalorraquidiano , Masculino , Doença Crônica , Antifúngicos/uso terapêutico , Meningite Asséptica/diagnóstico
17.
Nat Commun ; 15(1): 3676, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693142

RESUMO

Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer's disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing reference proteins which improved the diagnostic accuracy of key CSF AD biomarkers. Our reference protein method attenuates the risk for false positive findings, and improves the sensitivity and specificity of CSF biomarkers, with broad implications for both research and clinical practice.


Assuntos
Doença de Alzheimer , Biomarcadores , Proteínas do Líquido Cefalorraquidiano , Humanos , Biomarcadores/líquido cefalorraquidiano , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Proteínas do Líquido Cefalorraquidiano/análise , Proteínas do Líquido Cefalorraquidiano/metabolismo , Masculino , Feminino , Sensibilidade e Especificidade , Idoso , Encefalopatias/líquido cefalorraquidiano , Encefalopatias/diagnóstico , Pessoa de Meia-Idade , Peptídeos beta-Amiloides/líquido cefalorraquidiano
18.
J Prev Alzheimers Dis ; 11(3): 672-683, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706283

RESUMO

BACKGROUND: We aimed to explore whether the relationships of blood pressures (BPs) with Alzheimer's disease (AD) endophenotypes varied by usage of antihypertensive drugs (AHDs). METHODS: A total of 765 non-demented older adults (mean age: 74.4 years; female: 43.1%) with a self-reported history of hypertension were followed for 6 years. Multiple linear regression and linear-mixed effect models were used to investigate the interaction effects of five categories of AHDs (angiotensin-converting enzyme inhibitors [ACEI], angiotensin II receptor blockers [ARBs], ß-blocker, calcium channel blockers [CCB], diuretic) with BPs (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse pressure [PP]) on AD core pathology and neurodegenerative markers. RESULTS: After Bonferroni correction, significant interaction effects of BPs with AHDs were observed. Elevated SBP or PP in late-life was associated with higher levels of cerebral Aß burden (diuretic alone/ß-blocker × SBP), higher levels of CSF tau proteins (diuretic × SBP/PP, ARBs/CCB × SBP), and lower volume of entorhinal region (ß-blocker × SBP, diuretic × PP) only among hypertensive patients who received no anti-hypertensive treatments, while these associations became compromised or null for users of specific AHDs except for ACEI. Compared to taking other classes of AHDs, elevated SBP in late-life was associated with lower cerebral Aß burden in diuretic users (padjusted = 0.08) and was associated with higher CSF tau proteins in ACEI alone users (padjusted = 0.03). Longitudinal data validated the above-mentioned interaction effects on changes of cerebral Aß burden (padjusted < 0.05), CSF tau proteins (padjusted < 0.10), and brain atrophy (padjusted < 0.05). CONCLUSIONS: The relationships of late-life BP with AD pathology and neurodegeneration could be modified by anti-hypertensive treatments and varied by AHD classification. These findings provide preliminary evidence for tailored BP management strategy for preventing AD among late-life hypertensive adults.


Assuntos
Doença de Alzheimer , Anti-Hipertensivos , Pressão Sanguínea , Hipertensão , Humanos , Idoso , Feminino , Masculino , Hipertensão/tratamento farmacológico , Doença de Alzheimer/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Proteínas tau/líquido cefalorraquidiano , Proteínas tau/metabolismo , Biomarcadores/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Peptídeos beta-Amiloides/metabolismo , Idoso de 80 Anos ou mais , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico
19.
Cephalalgia ; 44(5): 3331024241248203, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38690635

RESUMO

BACKGROUND: Idiopathic intracranial hypertension is a secondary headache disorder potentially causing visual loss. Neurofilament light chain is a candidate, prognostic biomarker, but further studies of neuronal biomarkers are needed. Our objective was to investigate neurofilament light chain in cerebrospinal fluid (cNfL) and plasma (pNfL), amyloid-beta 42 (Aß-42), total-tau and phosphorylated-tau in cerebrospinal fluid in new-onset idiopathic intracranial hypertension. METHODS: Prospective case-control study including new-onset idiopathic intracranial hypertension and age, sex and BMI matched controls. Biomarkers were compared between patients and controls and related to papilledema, visual fields and opening pressure. RESULTS: We included 37 patients and 35 controls. Patients had higher age-adjusted cNfL (1.4 vs. 0.6 pg/mL, p-adjusted < 0.001), pNfL (0.5 vs. 0.3 pg/mL, p-adjusted < 0.001) and total-tau/Aß-42 (0.12 vs. 0.11, p-adjusted = 0.039). Significant, positive linear correlations were found between cNfL, pNfL, total-tau/Aß-42 and opening pressure. Patients with severe papilledema had elevated cNfL compared to mild-moderate papilledema (median cNfL: 4.3 pg/mL (3.7) versus 1.0 pg/mL (1.4), p-adjusted = 0.009). cNFL was inversely associated with perimetric mean deviation (r = -0.47, p-adjusted < 0.001). CONCLUSIONS: cNfL, pNfL and total-tau/Aß-42 were elevated in new-onset idiopathic intracranial hypertension. cNfL was associated with severity of papilledema and visual field defects at diagnosis. This indicates early axonal damage. Neurofilament light chain is a candidate biomarker for disease severity.


Assuntos
Biomarcadores , Proteínas de Neurofilamentos , Pseudotumor Cerebral , Humanos , Feminino , Masculino , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Proteínas de Neurofilamentos/sangue , Adulto , Pseudotumor Cerebral/diagnóstico , Pseudotumor Cerebral/líquido cefalorraquidiano , Pseudotumor Cerebral/sangue , Pseudotumor Cerebral/complicações , Estudos Prospectivos , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Estudos de Casos e Controles , Pessoa de Meia-Idade , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Peptídeos beta-Amiloides/sangue , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Proteínas tau/sangue
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