Background:
Information concerning longitudinal cognitive trajectories in multiple sclerosis (MS) is relatively scarce. Moreover, it is unclear which factors are associated with cognitive decline and ...what is the clinical impact of cognitive impairment (CI) in the long run.
Objective:
To investigate cognitive trajectories in relapsing–remitting multiple sclerosis (RRMS) patients, analyzing clinical and magnetic resonance imaging (MRI) predictors of cognitive decline.
Methods:
We enrolled 42 patients and 30 controls. They underwent brain MRI and clinical/neuropsychological evaluation at baseline and after 1, 2, and 6 years. We evaluated cognitive domains with principal component analysis and performed multivariable regression analyzing predictors of clinical/cognitive deterioration. We also performed repeated measures analysis to assess whether clinical progression was different according to CI at baseline.
Results:
A total of 23 (62.2%) patients deteriorated in combined cognitive domains after 6 years, most in processing speed and memory. The number of baseline impaired cognitive domains was strongly associated with 6-year cognitive (R2 = 0.452; p < 0.001) and Expanded Disability Status Scale (EDSS) deterioration (R2 = 0.263; p < 0.001). Patients with baseline CI in combined domains had worse clinical progression.
Conclusion:
Isolated CI tends to become more widespread, affecting memory and processing speed alongside. The extent of baseline CI was the best predictor of both clinical and cognitive deterioration after 6 years.
The cerebellum is an important site for cortical demyelination in multiple sclerosis, but the functional significance of this finding is not fully understood.
To evaluate the clinical and cognitive ...impact of cerebellar grey-matter pathology in multiple sclerosis patients.
Forty-two relapsing-remitting multiple sclerosis patients and 30 controls underwent clinical assessment including the Multiple Sclerosis Functional Composite, Expanded Disability Status Scale (EDSS) and cerebellar functional system (FS) score, and cognitive evaluation, including the Paced Auditory Serial Addition Test (PASAT) and the Symbol-Digit Modalities Test (SDMT). Magnetic resonance imaging was performed with a 3T scanner and variables of interest were: brain white-matter and cortical lesion load, cerebellar intracortical and leukocortical lesion volumes, and brain cortical and cerebellar white-matter and grey-matter volumes.
After multivariate analysis high burden of cerebellar intracortical lesions was the only predictor for the EDSS (p<0.001), cerebellar FS (p = 0.002), arm function (p = 0.049), and for leg function (p<0.001). Patients with high burden of cerebellar leukocortical lesions had lower PASAT scores (p = 0.013), while patients with greater volumes of cerebellar intracortical lesions had worse SDMT scores (p = 0.015).
Cerebellar grey-matter pathology is widely present and contributes to clinical dysfunction in relapsing-remitting multiple sclerosis patients, independently of brain grey-matter damage.
Background
The expression of serine protease granzyme-B (GzmB) by circulating CD8
+
T lymphocytes has been recently suggested as a biomarker for poor immunotherapy response and severe disability in ...patients with Neuromyelitis Optica spectrum disorders (NMOSD). In parallel, venous thromboembolism (VTE) has been reported mainly in NMOSD patients exhibiting transverse myelitis.
Case presentation
Here, we describe an Aquaporin-4 positive (AQP4-positive) NMOSD patient who showed short myelitis (SM) and experienced a fatal pulmonary thromboembolism/lower extremity deep vein thrombosis during anti-CD20 treatment. Flow cytometry analyses from the peripheral blood revealed an enhanced cytotoxic behavior through circulating CD8
+
GzmB
+
T, CD4
+
GzmB
+
T lymphocytes, and residual CD19
+
GzmB
+
B cells.
Conclusions
Fatal VTE may be a rare outcome, particularly in patients exhibiting SM, and may share poorly understood immunological mechanisms with AQP4-positive NMOSD severity.
Intrathecal immunoglobulin synthesis in an oligoclonal pattern is the most common immunologic abnormality detected in MS patients. Various treatments, such as immunomodulators and immunosuppressors, ...have not been found to modify it. Natalizumab hinders migration of encephalitogenic T-cells into the central nervous system (CNS), reducing inflammatory response. Its impact on CSF oligoclonal bands (OCBs) has not been demonstrated. This report describes its effect in four out of six patients with multiple sclerosis after a mean of 10 infusions: the CSF was negative for OCBs at the second lumbar puncture. In conclusion, natalizumab treatment can reduce CSF OCBs to undetectable levels, although the clinical significance of this observation is not yet known.
Emerging evidence of antibody-independent functions, as well as the clinical efficacy of anti-CD20 depleting therapies, helped to reassess the contribution of B cells during multiple sclerosis (MS) ...pathogenesis.
To investigate whether CD19
B cells may share expression of the serine-protease granzyme-B (GzmB), resembling classical cytotoxic CD8
T lymphocytes, in the peripheral blood from relapsing-remitting MS (RRMS) patients.
In this study, 104 RRMS patients during different treatments and 58 healthy donors were included. CD8, CD19, Runx3, and GzmB expression was assessed by flow cytometry analyses.
RRMS patients during fingolimod (FTY) and natalizumab (NTZ) treatment showed increased percentage of circulating CD8
GzmB
T lymphocytes when compared to healthy volunteers. An increase in circulating CD19
GzmB
B cells was observed in RRMS patients during FTY and NTZ therapies when compared to glatiramer (GA), untreated RRMS patients, and healthy donors but not when compared to interferon-β (IFN). Moreover, regarding Runx3, the transcriptional factor classically associated with cytotoxicity in CD8
T lymphocytes, the expression of GzmB was significantly higher in CD19
Runx3
-expressing B cells when compared to CD19
Runx3
counterparts in RRMS patients.
CD19
B cells may exhibit cytotoxic behavior resembling CD8
T lymphocytes in MS patients during different treatments. In the future, monitoring "cytotoxic" subsets might become an accessible marker for investigating MS pathophysiology and even for the development of new therapeutic interventions.
Gut microbiome in neuropsychiatric disorders MEJÍA-GRANADOS, Diana Marcela; VILLASANA-SALAZAR, Benjamín; COAN, Ana Carolina ...
Arquivos de neuro-psiquiatria,
02/2022, Letnik:
80, Številka:
2
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
Background:
Neuropsychiatric disorders are a significant cause of death and disability worldwide. The mechanisms underlying these disorders include a constellation of structural, ...infectious, immunological, metabolic, and genetic etiologies. Advances in next-generation sequencing techniques have demonstrated that the composition of the enteric microbiome is dynamic and plays a pivotal role in host homeostasis and several diseases. The enteric microbiome acts as a key mediator in neuronal signaling via metabolic, neuroimmune, and neuroendocrine pathways.
Objective:
In this review, we aim to present and discuss the most current knowledge regarding the putative influence of the gut microbiome in neuropsychiatric disorders.
Methods:
We examined some of the preclinical and clinical evidence and therapeutic strategies associated with the manipulation of the gut microbiome.
Results:
targeted taxa were described and grouped from major studies to each disease.
Conclusions:
Understanding the complexity of these ecological interactions and their association with susceptibility and progression of acute and chronic disorders could lead to novel diagnostic biomarkers based on molecular targets. Moreover, research on the microbiome can also improve some emerging treatment choices, such as fecal transplantation, personalized probiotics, and dietary interventions, which could be used to reduce the impact of specific neuropsychiatric disorders. We expect that this knowledge will help physicians caring for patients with neuropsychiatric disorders.
ABSTRACT The Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological ...Diseases (BCTRIMS) provide recommendations in this document for vaccination of the population with demyelinating diseases of the central nervous system (CNS) against infections in general and against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. We emphasize the seriousness of the current situation in view of the spread of COVID-19 in our country. Therefore, reference guides on vaccination for clinicians, patients, and public health authorities are particularly important to prevent some infectious diseases. The DCNI/ABN and BCTRIMS recommend that patients with CNS demyelinating diseases (e.g., MS and NMOSD) be continually monitored for updates to their vaccination schedule, especially at the beginning or before a change in treatment with a disease modifying drug (DMD). It is also important to note that vaccines are safe, and physicians should encourage their use in all patients. Clearly, special care should be taken when live attenuated viruses are involved. Finally, it is important for physicians to verify which DMD the patient is receiving and when the last dose was taken, as each drug may affect the induction of immune response differently.
RESUMO O DC de Neuroimunologia da ABN e o BCTRIMS trazem, nesse documento, as recomendações sobre vacinação da população com doenças desmielinizantes do sistema nervoso central (SNC) contra infecções em geral e contra o coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2), causador da COVID-19. Destaca-se a gravidade do atual momento frente ao avanço da COVID-19 em nosso País, o que torna mais evidente e importante a criação de guia de referência para orientação aos médicos, pacientes e autoridades de saúde pública quanto à vacinação, meio efetivo e seguro no controle de determinadas doenças infecciosa. O DCNI/ABN e o BCTRIMS recomendam que os pacientes com doenças desmielinizantes do SNC (ex., EM e NMOSD) sejam constantemente monitorados, quanto a atualização do seu calendário vacinal, especialmente, no início ou antes da mudança do tratamento com uma droga modificadora de doença (DMD). É importante também salientar que as vacinas são seguras e os médicos devem estimular o seu uso em todos os pacientes. Evidentemente, deve ser dada especial atenção às vacinas com vírus vivos atenuados. Por fim, é importante que os médicos verifiquem qual DMD o paciente está em uso e quando foi feita a sua última dose, pois cada fármaco pode interagir de forma diferente com a indução da resposta imune.
Neuropsychiatric symptoms in Alzheimer's disease (AD) are prevalent, however their relationship with patterns of cortical atrophy is not fully known. Objectives To compare cortical atrophy's patterns ...between AD patients and healthy controls; to verify correlations between neuropsychiatric syndromes and cortical atrophy. Method 33 AD patients were examined by Neuropsychiatric Inventory (NPI). Patients and 29 controls underwent a 3T MRI scanning. We considered four NPI syndromes: affective, apathy, hyperactivity and psychosis. Correlations between structural imaging and neuropsychiatric scores were performed by Freesurfer. Results were significant with a p-value < 0.05, corrected for multiple comparisons. Results Patients exhibited atrophy in entorhinal cortices, left inferior and middle temporal gyri, and precuneus bilaterally. There was correlation between affective syndrome and cortical thickness in right frontal structures, insula and temporal pole. Conclusion Cortical thickness measures revealed atrophy in mild AD. Depression and anxiety symptoms were associated with atrophy of right frontal, temporal and insular cortices.
Objective Cognitive dysfunction is common in multiple sclerosis. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was developed to assess cognitive functions most-frequently impaired ...in multiple sclerosis. However, normative values are lacking in Brazil. Therefore, we aimed to provide continuous and discrete normative values for the BRB-N in a Brazilian population sample. Methods We recruited 285 healthy individuals from the community at 10 Brazilian sites and applied the BRB-N version A in 237 participants and version B in 48 participants. Continuous norms were calculated with multiple-regression analysis. Results Mean raw scores and the 5th percentile for each neuropsychological measure are provided, stratified by age and educational level. Healthy participants' raw scores were converted to scaled scores, which were regressed on age, sex and education, yielding equations that can be used to calculate predicted scores. Conclusion Our normative data allow a more widespread use of the BRB-N in clinical practice and research.
The plasmacytoid dendritic cells (pDCs) express a high level of Toll-like receptor 9 (TLR-9), which recognizes viral DNA. Activated via TLR-9, pDCs also secrete large amounts of type I interferon ...which are involved either in stimulation or down regulation of immune response in multiple sclerosis (MS). In the present study, we determinate pDCs levels by flow cytometry in Cerebrospinal Fluid (CSF) and Peripheral Blood from MS patients in relapsing and in remitting phases of the disease, comparing with other non-inflammatory diseases (OND). We provide evidence that MS patients in relapse without any treatment have a significantly (p < 0.01) higher percentage of pDCs in CSF than do patients in remission or those with OND. No change in the percentage of pDCs was observed in the peripheral blood of any of these patients. The increase of pDCs in central nervous system during relapse may be explained either by a virus infection or a down regulatory process.
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