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Immune Alterations Following Neurological Disorders: A Comparison of Stroke and Seizures.

ABSTRACT: Background: Granulocytes and monocytes are the first cells to invade the brain post stroke and are also being discussed as important cells in early neuroinflammation after seizures. We aimed at understanding disease specific and common pathways of brain-immune-endocrine-interactions and compared immune alterations induced by stroke and seizures. Therefore, we compared granulocytic and monocytic subtypes between diseases and investigated inflammatory mediators. We additionally investigated if seizure type determines immunologic alterations. Material and Methods: We included 31 patients with acute seizures, 17 with acute stroke and two control cohorts. Immune cells were characterized by flow cytometry from blood samples obtained on admission to the hospital and the following morning. (i) Monocytes subpopulations were defined as classical (CD14⁺⁺CD16^-), (ii) intermediate (CD14⁺⁺CD16⁺), and (iii) non-classical monocytes (CD14^dimCD16⁺), while granulocyte subsets were characterized as (i) "classical granulocytes" (CD16⁺⁺CD62L⁺), (ii) pro-inflammatory (CD16^dimCD62L⁺), and (iii) anti-inflammatory granulocytes (CD16⁺⁺CD62L^-). Stroke patient's blood was additionally drawn on days 3 and 5. Cerebrospinal fluid mitochondrial DNA was quantified by real-time PCR. Plasma High-Mobility-Group-Protein-B1, metanephrine, and normetanephrine were measured by ELISA. Results: HLA-DR expression on monocytes and their subpopulations (classical, intermediate, and non-classical monocytes) was reduced after stroke or seizures. Expression of CD32 was increased on monocytes and subtypes in epilepsy patients, partly similar to stroke. CD32 and CD11b regulation on granulocytes and subpopulations (classical, anti-inflammatory, pro-inflammatory granulocytes) was more pronounced after stroke compared to seizures. On admission, normetanephrine was upregulated in seizures, arguing for the sympathetic nervous system as inducer of immune alterations similar to stroke. Compared to partial seizures, immunologic changes were more pronounced in generalized tonic-clonic seizures. Conclusion: Seizures lead to immune alterations within the immediate postictal period similar but not identical to stroke. The type of seizures determines the extent of immune alterations.

SUBMITTER: Ruhnau J

PROVIDER: S-EPMC7280464 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Immune Alterations Following Neurological Disorders: A Comparison of Stroke and Seizures.

Ruhnau Johanna J Tennigkeit Johanna J Ceesay Sonya S Koppe Charlotte C Muszelewski Melissa M Grothe Sascha S Flöel Agnes A Süße Marie M Dressel Alexander A von Podewils Felix F Vogelgesang Antje A

Frontiers in neurology 20200602

<b>Background:</b> Granulocytes and monocytes are the first cells to invade the brain post stroke and are also being discussed as important cells in early neuroinflammation after seizures. We aimed at understanding disease specific and common pathways of brain-immune-endocrine-interactions and compared immune alterations induced by stroke and seizures. Therefore, we compared granulocytic and monocytic subtypes between diseases and investigated inflammatory mediators. We additionally investigated ...[more]

PMID: 32581999

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Project description:Background and Purpose: Stroke induces immediate profound alterations of the peripheral immune system rendering patients more susceptible to post-stroke infections. The precise mechanisms maintaining stroke-induced immune alterations (SIIA) remain unknown. High-Mobility-Group-Protein B1 (HMGB-1) is elevated for at least 7 days post-stroke and has been suggested to mediate SIIA. Patients with rapid clinical recovery of neurological deficits rarely develop severe infections. We therefore investigated whether rapid neurological recovery (either spontaneous or secondary to neurovascular recanalization therapy) alters the course of SIIA. National Institutes of Health Stroke Scale (NIHSS) served as surrogate marker for neurological improvement. Methods: Fluorescence-activated cell sorting was used to define leukocyte subpopulations. C-reactive protein (CRP), procalcitonin (PCT), HMGB-1, GM-CSF; IFN-?, IFN-?, IL-1?, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-17, IL-17F, IL-18, TNF-?, MIF, IL-8, MCP-1, MCP-4, MIP-3?, MIP-3?, Eotaxin, soluble IL-6 receptor, E-selectin, and P-selectin were analyzed by ELISA or Multiplex Assays. Serum miRNA expression changes were analyzed by qPCR. Results: Cellular parameters were similar in the improved and non-improved cohort on admission. In patients with rapid clinical recovery absolute and relative leukocyte, neutrophil, and lymphocyte numbers normalized promptly overnight. In contrast, HMGB-1 serum levels did not differ between the two groups. Nine miRNA were found to be differentially expressed between improved and non-improved patients. Conclusions: SIIA are detectable on admission of acute stroke patients. While it was assumed that post-stroke immunosuppression is rapidly reversed with improvement this is the first data set that shows that improvement actually is associated with a rapid reversal of SIIA demonstrating that SIIA require a constant signal to persist. The observation that HMGB-1 serum concentrations were similar in improved and non-improved cohorts argues against a role for this pro-inflammatory mediator in the maintenance of SIIA. Serum miRNA observed to be regulated in stroke in other publications was counter regulated with improvement in our cohort.

Project description:Objective: Post-stroke epilepsy (PSE) is associated with increased morbidity and mortality. Stroke-associated acute symptomatic seizures are an important risk factor: 20.8-34.3% of these patients will go on to develop PSE. Identifying these "high risk" individuals may result in earlier PSE diagnosis, treatment, and avoidance of seizure-related morbidity. This study was to identify predictors of PSE development in patients with stroke-associated acute symptomatic seizures. Participants and Methods: This was a retrospective cohort study of 167 patients with stroke-associated acute symptomatic seizures admitted to the Neurology Department of a tertiary Hospital of China, from 1 May 2006 to 30 January 2020. Both those with primary ischemic stroke and intracerebral hemorrhage were included in the study. Patient demographics, medical history, stroke-associated, and seizure-related variables were evaluated with univariable analysis and multivariable Cox regression analysis. PSE was defined as unprovoked seizures occurring > 7 days post-stroke. Data points were extracted from medical records and supplemented by tele-interview. Results: Of the 167 patients with stroke-associated acute symptomatic seizures, 49 (29.3%) developed PSE. NIHSS score > 14 [hazard ratio (HR) 2.98, 95% CI 1.57-5.67], longer interval from stroke to acute symptomatic seizures (days 4-7 post-stroke) (HR 2.51, 95% CI 1.37-4.59) and multiple acute symptomatic seizures (HR 5.08, 95% CI 2.58-9.99) were independently associated with PSE development. This association remained in the sub-analysis within the ischemic stroke cohort. In the sub-analysis of the hemorrhagic stroke cohort, multilobar involvement (HR 4.80, 95% CI 1.49-15.39) was also independently associated with development of PSE. Further, we developed a nomogram to predict individual risk of developing PSE following stroke-associated acute symptomatic seizures. The nomogram showed a C-index of 0.73. Conclusion: More severe neurofunctional deficits (NIHSS score > 14), longer interval from stroke to acute symptomatic seizures (days 4-7 post-stroke), and multiple acute symptomatic seizures were independently associated with development of PSE in patients with stroke-associated acute symptomatic seizures. This knowledge may increase clinical vigilance for development of PSE, facilitating rapid diagnosis and treatment initiation, and subsequently reduce seizure-related morbidity.

Project description:BackgroundPerception is the ability to understand information from our senses. It allows us to experience and meaningfully interact with our environment. A stroke may impair perception in up to 70% of stroke survivors, leading to distress, increased dependence on others, and poorer quality of life. Interventions to address perceptual disorders may include assessment and screening, rehabilitation, non-invasive brain stimulation, pharmacological and surgical approaches.ObjectivesTo assess the effectiveness of interventions aimed at perceptual disorders after stroke compared to no intervention or control (placebo, standard care, attention control), on measures of performance in activities of daily living. SEARCH METHODS: We searched the trials registers of the Cochrane Stroke Group, CENTRAL, MEDLINE, Embase, and three other databases to August 2021. We also searched trials and research registers, reference lists of studies, handsearched journals, and contacted authors.Selection criteriaWe included randomised controlled trials (RCTs) of adult stroke survivors with perceptual disorders. We defined perception as the specific mental functions of recognising and interpreting sensory stimuli and included hearing, taste, touch, smell, somatosensation, and vision. Our definition of perception excluded visual field deficits, neglect/inattention, and pain.Data collection and analysisOne review author assessed titles, with two review authors independently screening abstracts and full-text articles for eligibility. One review author extracted, appraised, and entered data, which were checked by a second author. We assessed risk of bias (ROB) using the ROB-1 tool, and quality of evidence using GRADE. A stakeholder group, comprising stroke survivors, carers, and healthcare professionals, was involved in this review update.Main resultsWe identified 18 eligible RCTs involving 541 participants. The trials addressed touch (three trials, 70 participants), somatosensory (seven trials, 196 participants) and visual perception disorders (seven trials, 225 participants), with one (50 participants) exploring mixed touch-somatosensory disorders. None addressed stroke-related hearing, taste, or smell perception disorders. All but one examined the effectiveness of rehabilitation interventions; the exception evaluated non-invasive brain stimulation. For our main comparison of active intervention versus no treatment or control, one trial reported our primary outcome of performance in activities of daily living (ADL): Somatosensory disorders: one trial (24 participants) compared an intervention with a control intervention and reported an ADL measure. Touch perception disorder: no trials measuring ADL compared an intervention with no treatment or with a control intervention. Visual perception disorders: no trials measuring ADL compared an intervention with no treatment or control. In addition, six trials reported ADL outcomes in a comparison of active intervention versus active intervention, relating to somatosensation (three trials), touch (one trial) and vision (two trials). AUTHORS' CONCLUSIONS: Following a detailed, systematic search, we identified limited RCT evidence of the effectiveness of interventions for perceptual disorders following stroke. There is insufficient evidence to support or refute the suggestion that perceptual interventions are effective. More high-quality trials of interventions for perceptual disorders in stroke are needed. They should recruit sufficient participant numbers, include a 'usual care' comparison, and measure longer-term functional outcomes, at time points beyond the initial intervention period. People with impaired perception following a stroke should continue to receive neurorehabilitation according to clinical guidelines.

Project description:BackgroundLinks between dissociation and functional neurological disorder (FND)/conversion disorder are well-established, yet the pathophysiology of dissociation remains poorly understood. This MRI study investigated structural alterations associated with somatoform and psychological dissociation in FND. We hypothesized that multimodal, paralimbic cingulo-insular regions would relate to the severity of somatoform dissociation in patients with FND.MethodsFreeSurfer cortical thickness and subcortical volumetric analyses were performed in 26 patients with motor FND and 27 matched healthy controls. Patients with high dissociation as measured by the Somatoform Dissociation Questionnaire-20 (SDQ) or Dissociative Experiences Scale (DES) were compared to controls in stratified analyses. Within-group analyses were also performed with SDQ and DES scores in patients with FND. All cortical thickness analyses were whole-brain corrected at the cluster-wise level.ResultsPatients with FND and high somatoform dissociation (SDQ > 35) showed reduced left caudal anterior cingulate cortex (ACC) cortical thickness compared to controls. In within-group analyses, SDQ scores inversely correlated with left caudal ACC cortical thickness in patients with FND. Depersonalization/derealization scores positively correlated with right lateral occipital cortical thickness. Both within-group findings remained statistically significant controlling for trait anxiety/depression, borderline personality disorder and post-traumatic stress disorder, adverse life events, and motor FND subtypes in post-hoc analyses.ConclusionUsing complementary between-group and within-group analyses, an inverse association between somatoform dissociation and left caudal ACC cortical thickness was observed in patients with FND. A positive relationship was also appreciated between depersonalization/derealization severity and cortical thickness in visual association areas. These findings advance our neuropathobiological understanding of dissociation in FND. Hum Brain Mapp 39:428-439, 2018. © 2017 Wiley Periodicals, Inc.

Project description:Infiltrating T-lymphocytes from the peripheral blood into the central nervous system (CNS) play a dynamic role in the development of a neurological immune-mediated diseases. HAM/TSP is a chronic progressive inflammatory neurological disorder associated with human T-cell lymphotropic virus type I (HTLV-I) infection. In this chronic myelopathy, virus-infected circulating T-cells infiltrate the CNS and an immune response is initiated against the components of CNS. As the HTLV-I proviral load (PVL) has been used as the best clinical marker for patient diagnostic with HAM/TSP, we hypothesized there might be a signature on T-cell receptor (TCR) clonal repertoire in these patients, which could distinguish HAM/TSP patients from the healthy population, as well as from patients with a more heterogeneous CNS-reactive inflammatory disease as multiple sclerosis (MS). With this in mind, we applied an innovative unbiased molecular technique – unique molecular identifier (UMI) library-strategy to investigate with high accuracy the TCR clonal repertoire by high throughput sequencing (HTS) technology. cDNA-TCR β-chain libraries were sequenced from 2 million peripheral mononuclear cells (PBMCs) in 14 HAM/TSP patients, 34 MS patients and 20 healthy controls (HC). To address whether the clonal expansion correlates with the patient’s PVL level, analysis of longitudinal TCR repertoire was performed in 2 HAM/TSP patients. Over 5.6 million TCR sequences were generated per sample on HiSeq 2500 Illumina system and analyzed through the molecular identifier groups-based error correction pipeline (MiGEC). Bioinformatic analysis showed that clones with more than 8 reads had a lower coefficient of variation (CV) and then could be used with confidence to evaluate the TCR clonal expansion. While HAM/TSP patients showed the higher clonal T-cell expansion compared to MS and HC, increase of the TCR clonal expansion was inversely correlated with the diversity of TCR repertoire in all subject’s group. In addition, correlation of the PVL with TCR clonal expansion was observed in HAM/TSP patients at longitudinal time-points. Surprisingly, MS patients showed a higher diversity of TCR repertoire along with a very slight clonal T-cell expansion in comparison to either HAM/TSP patients or HC. Despite of the higher TCR clonal expansion in HAM/TSP patients, a non-shared or “private” TCR repertoire was observed in these patients. No clones that shared the same CDR3 amino acid sequences were seen in HC and MS patients. However, a cluster of related CDR3 amino acid sequences were observed for 18 out of 34 MS patients when evaluated by phylogenetic tree analysis. It suggestes that a TCR-repertoire signature might characterize patients with MS. Our findings suggest that even though a unique TCR-b repertoire shapes the immune response in patients with neurological immune-mediated disease, a relatedness on clonal T-cell repertoire exist in MS.

Dataset Information

Immune Alterations Following Neurological Disorders: A Comparison of Stroke and Seizures.

Publications

Immune Alterations Following Neurological Disorders: A Comparison of Stroke and Seizures.

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