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BACKGROUND: In addition to other stroke-related deficits, the risk of seizures may impact driving ability after stroke. METHODS: We analysed data from a multicentre international cohort, including 4452 adults with acute ischaemic stroke and no prior seizures. We calculated the Chance of Occurrence of Seizure in the next Year (COSY) according to the SeLECT2.0 prognostic model. We considered COSY<20% safe for private and <2% for professional driving, aligning with commonly used cut-offs. RESULTS: Seizure risks in the next year were mainly influenced by the baseline risk-stratified according to the SeLECT2.0 score and, to a lesser extent, by the poststroke seizure-free interval (SFI). Those without acute symptomatic seizures (SeLECT2.0 0-6 points) had low COSY (0.7%-11%) immediately after stroke, not requiring an SFI. In stroke survivors with acute symptomatic seizures (SeLECT2.0 3-13 points), COSY after a 3-month SFI ranged from 2% to 92%, showing substantial interindividual variability. Stroke survivors with acute symptomatic status epilepticus (SeLECT2.0 7-13 points) had the highest risk (14%-92%). CONCLUSIONS: Personalised prognostic models, such as SeLECT2.0, may offer better guidance for poststroke driving decisions than generic SFIs. Our findings provide practical tools, including a smartphone-based or web-based application, to assess seizure risks and determine appropriate SFIs for safe driving.
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BACKGROUND AND PURPOSE: The value of intravenous thrombolysis (IVT) in eligible tandem lesion patients undergoing endovascular treatment (EVT) is unknown. We investigated treatment effect heterogeneity of EVT + IVT versus EVT-only in tandem lesion patients. Additional analyses were performed for patients undergoing emergent internal carotid artery (ICA) stenting. METHODS: SWIFT DIRECT randomized IVT-eligible patients to either EVT + IVT or EVT-only. Primary outcome was 90-day functional independence (modified Rankin Scale score 0-2) after the index event. Secondary endpoints were reperfusion success, 24 h intracranial hemorrhage rate, and 90-day all-cause mortality. Interaction models were fitted for all predefined outcomes. RESULTS: Among 408 included patients, 63 (15.4%) had a tandem lesion and 33 (52.4%) received IVT. In patients with tandem lesions, 20 had undergone emergent ICA stenting (EVT + IVT: 9/33, 27.3%; EVT: 11/30, 36.7%). Tandem lesion did not show treatment effect modification of IVT on rates of functional independence (tandem lesion EVT + IVT vs. EVT: 63.6% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 65.6% vs. 58.2%; p for interaction = 0.77). IVT also did not increase the risk of intracranial hemorrhage among tandem lesion patients (tandem lesion EVT + IVT vs. EVT: 34.4% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 33.5% vs. 26.3%; p for interaction = 0.15). No heterogeneity was noted for other endpoints (p for interaction > 0.05). CONCLUSIONS: No treatment effect heterogeneity of EVT + IVT versus EVT-only was observed among tandem lesion patients. Administering IVT in patients with anticipated emergent ICA stenting seems safe, and the latter should not be a factor to consider when deciding to administer IVT before EVT.
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Procedimentos Endovasculares , Fibrinolíticos , Stents , Trombectomia , Ativador de Plasminogênio Tecidual , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Fibrinolíticos/administração & dosagem , Ativador de Plasminogênio Tecidual/administração & dosagem , Ativador de Plasminogênio Tecidual/uso terapêutico , Trombectomia/métodos , Procedimentos Endovasculares/métodos , Estenose das Carótidas/cirurgia , Idoso de 80 Anos ou mais , Administração Intravenosa , AVC Isquêmico/cirurgia , AVC Isquêmico/tratamento farmacológico , Resultado do Tratamento , Terapia Trombolítica/métodosRESUMO
BACKGROUND: Autoimmune encephalitis (AE) poses significant challenges in clinical management, requiring effective monitoring tools for therapeutic success and relapse detection. This study aims to assess the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) as compared to the modified Rankin scale (mRS) in evaluating AE patients and to determine the real-world adoption of the CASE score. METHODS: A retrospective cohort study was conducted on 20 AE patients, assessing clinical data including symptomatology, diagnostic findings, and therapeutic regimens. Furthermore, we performed a systematic review on the test performance criteria and the real-world use of the CASE score. RESULTS: The CASE score showed a higher sensitivity in detecting clinical changes compared to the mRS, with a significant correlation between the two scales throughout the disease course (r = 0.85, p < 0.01). A systematic review of 150 articles revealed widespread adoption of the CASE score, especially in Asian populations, demonstrating high reliability and internal consistency. DISCUSSION: Despite limitations such as retrospective design and small sample size, our findings underscore the CASE score's utility in both clinical practice and research settings. The CASE score emerges as a valuable tool for monitoring AE patients, offering improved sensitivity over existing scales like the mRS. Further validation studies in diverse populations are warranted to establish its broader applicability and inform future therapeutic interventions.
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Chronic pain poses a significant global socio-medical challenge causing significant costs. It is only since the mid-20th century that pain syndromes have been considered diseases in their own right. According to the definition of the International Association for the Study of Pain, pain is a complex, context-dependent-and hence modifiable-phenomenon. The philosophical view on pain is no less multi-facetted and allows for a wide range of viewpoints. This analysis aims at a characterisation of pain including a-mainly phenomenological and enactivist-philosophical perspective. The discourse will be guided by the concept of the limit(s) of the lived body: what is the relationship between pain and the perception of the lived body's boundaries? Does a reciprocal influence exist? And may the perception be modified in order to reduce the patient's suffering? These musings will also clarify that neurosciences and philosophy are not competing sciences, but rather inform each other.
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BACKGROUND: Epileptic seizures are a common manifestation of autoimmune encephalitis (AIE). Immunosuppression (IT) is an efficient therapeutic approach, particularly in AIE associated with antibodies against extracellular structures. The role of antiseizure medication (ASM) is less clear. However, it may be beneficial in disease refractory to IT or in chronic post-AIE epilepsy. METHODS: We conducted a systematic review assessing the PubMed and Cochrane databases to identify all reports on patients with epileptic seizures due to AIE in whom ASM was used and report it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. We included case series (minimum 3 eligible patients), retrospective and prospective observational studies, and randomized controlled trials. The main outcome assessed was therapeutic efficacy of ASM. Secondary outcomes comprise number, type, and adverse effects of ASM. Descriptive statistics were used. The level of evidence was assessed according to the Centre for Evidence-Based Medicine. RESULTS: We screened a total of 3371 studies and included 30 (7 prospective, 23 retrospective). The reports cover a total of 708 patients, the majority (72.5%) suffering from AIE with antibodies against extracellular structures. Type of AIE, seizure frequency, and number and type of ASM used were heterogenous. While most patients profited from IT and/or ASM, the effect of ASM could rarely be isolated. Nine studies report on patients who received ASM monotherapy or were on ASM for a relevant length of time before IT initiation or after IT failure. One study reports a significant association between seizure freedom and use of sodium channel inhibitors. However, levels of evidence were generally low. CONCLUSION: Few robust data exist on the particular efficacy of ASM in autoimmune epileptic seizures. While these patients generally seem to respond less well to ASM or surgical interventions, sodium channel blockers may have an additional benefit compared to other substances. However, levels of evidence are low and early IT remains the mainstay of AIE therapy. Future trials should address optimal ASM selection and dosing in AIE.
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Doenças Autoimunes do Sistema Nervoso , Epilepsias Parciais , Humanos , Anticonvulsivantes/efeitos adversos , Epilepsias Parciais/induzido quimicamente , Epilepsias Parciais/tratamento farmacológico , Estudos Retrospectivos , Estudos Prospectivos , Convulsões/tratamento farmacológico , Doenças Autoimunes do Sistema Nervoso/induzido quimicamente , Doenças Autoimunes do Sistema Nervoso/tratamento farmacológico , Estudos Observacionais como AssuntoRESUMO
Chronic pain is a common disorder with enormous sociomedical importance. A major part of primary and secondary costs of illness is caused by the various pain syndromes. Nociception - the sensory perception of a painful stimulus - is a complex process relying on an intricate system of anatomical, neurophysiological and biochemical networks. This applies even more so to pain - the state of experiencing a nociceptive event, of interpreting it in terms of meaning for the affected individual and of suffering a range of emotions it elicits. This intricacy renders it obvious, that the empirical medical sciences alone cannot explain all aspects of pain. Hence, it has also become a focus of phenomenological research. One aspect of these investigations is the interaction of pain and the perception of the lived body's spatiality. The focus of this article will build on these concepts to develop a construct of the alteration of temporality caused by chronic pain and the effects this spells out for the affected subject. To this end, I will primarily draw on Merleau-Ponty's ideas of the lived body as well as on theories of enactivism and embodiment. I will also point out parallels to neuroscientific data, thereby demonstrating the proximity of phenomenology and neuroscience. A possible partial solution to the pain dilemma may be derived from psychology: techniques relying on cognitive behavioural intervention, awareness training, and existential analysis may provide alleviation to patients suffering from chronic pain.
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Dor Crônica , Filosofia Médica , Humanos , Dor Crônica/psicologia , Dor Crônica/terapiaRESUMO
OBJECTIVE: The purpose of this study was to identify risk factors for acute symptomatic seizures and post-stroke epilepsy after acute ischemic stroke and evaluate the effects of reperfusion treatment. METHODS: We assessed the risk factors for post-stroke seizures using logistic or Cox regression in a multicenter study, including adults from 8 European referral centers with neuroimaging-confirmed ischemic stroke. We compared the risk of post-stroke seizures between participants with or without reperfusion treatment following propensity score matching to reduce confounding due to treatment selection. RESULTS: In the overall cohort of 4,229 participants (mean age 71 years, 57% men), a higher risk of acute symptomatic seizures was observed in those with more severe strokes, infarcts located in the posterior cerebral artery territory, and strokes caused by large-artery atherosclerosis. Strokes caused by small-vessel occlusion carried a small risk of acute symptomatic seizures. 6% developed post-stroke epilepsy. Risk factors for post-stroke epilepsy were acute symptomatic seizures, more severe strokes, infarcts involving the cerebral cortex, and strokes caused by large-artery atherosclerosis. Electroencephalography findings within 7 days of stroke onset were not independently associated with the risk of post-stroke epilepsy. There was no association between reperfusion treatments in general or only intravenous thrombolysis or mechanical thrombectomy with the time to post-stroke epilepsy or the risk of acute symptomatic seizures. INTERPRETATION: Post-stroke seizures are related to stroke severity, etiology, and location, whereas an early electroencephalogram was not predictive of epilepsy. We did not find an association of reperfusion treatment with risks of acute symptomatic seizures or post-stroke epilepsy. ANN NEUROL 2021;90:808-820.
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Isquemia Encefálica/complicações , Epilepsia/complicações , Convulsões/complicações , Convulsões/diagnóstico , Acidente Vascular Cerebral/complicações , Adulto , Idoso , Epilepsia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Convulsões/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: Stroke resulting from occlusion of the middle cerebral artery (MCA) can have devastating consequences, potentially leading to a loss of independence. This study aimed to investigate the relationship between the distance to the thrombus (DT) and both ischemic lesion volume (ILV) and clinical outcomes. METHODS: We retrospectively evaluated patients with thromboembolic MCA M1 segment occlusion who underwent neurovascular imaging followed by endovascular thrombectomy (EVT) at two comprehensive stroke centers over a 3-year period (2018-2020). Preinterventional computed tomography (CT) or magnetic resonance (MR) angiography was used to measure DT, defined as the distance from the carotidT bifurcation to the proximal surface of the M1 occlusion. Postinterventional CT or MR imaging was employed to determine the ILV and clinical outcomes were assessed using the modified Rankin scale (mRS) at 3 months. RESULTS: There were 346 patients evaluated. The median DT was 9.4â¯mm (interquartile range, IQR 6.0-13.7â¯mm) and the median ILV was 13.9â¯ml (IQR 2.2-53.1â¯ml). After adjustment, an increase in DT was associated with a decrease in odds for a larger ILV (odds ratio, OR 0.96, 95% confidence interval, CI 0.92-0.99, pâ¯= 0.041). Through this association, more distal thrombi were associated with good clinical outcome (mRS 0-2; clinical outcome available in 282 patients, pâ¯= 0.018). The ILV was inversely associated with better clinical outcome OR 0.52 (95% CI 0.40-0.67). CONCLUSION: Based on the findings, DT was identified as an independent albeit weak predictor for ILV and clinical outcomes in patients with MCA M1 occlusion who underwent EVT.
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Autoantibodies against contactin-associated protein 2 (Caspr2) not only induce limbic autoimmune encephalitis but are also associated with pain conditions. Here, we analyzed clinical data on pain in a large cohort of patients included into the German Network for Research in Autoimmune Encephalitis. Out of 102 patients in our cohort, pain was a frequent symptom (36% of all patients), often severe (63.6% of the patients with pain) and/or even the major symptom (55.6% of the patients with pain). Pain phenotypes differed between patients. Cluster analysis revealed two major phenotypes including mostly distal-symmetric burning pain and widespread pain with myalgia and cramps. Almost all patients had IgG4 autoantibodies and some additional IgG1, 2, and/or 3 autoantibodies, but IgG subclasses, titers, and presence or absence of intrathecal synthesis were not associated with the occurrence of pain. However, certain pre-existing risk factors for chronic pain like diabetes mellitus, peripheral neuropathy, or preexisting chronic back pain tended to occur more frequently in patients with anti-Caspr2 autoantibodies and pain. Our data show that pain is a relevant symptom in patients with anti-Caspr2 autoantibodies and support the idea of decreased algesic thresholds leading to pain. Testing for anti-Caspr2 autoantibodies needs to be considered in patients with various pain phenotypes.
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Autoanticorpos , Proteínas de Membrana , Proteínas do Tecido Nervoso , Fenótipo , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autoanticorpos/sangue , Autoanticorpos/imunologia , Estudos de Coortes , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Proteínas de Membrana/imunologia , Proteínas do Tecido Nervoso/imunologia , Dor/imunologia , Dor/etiologia , Dor/sangueRESUMO
BACKGROUND: Specific antiviral treatment is only available for a small subset of viral encephalitis (VE). Adjunctive steroids are used, but there is scant evidence evaluating its utility. We present a systematic review and meta-analysis on the outcome of steroid use in VE. METHODS: We conducted a systematic literature review and reported it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Two observational studies from unpublished or partially published data were added. For the meta-analysis, we employed the metaphor package of the statistical software R-4.3.1. RESULTS: We screened 378 studies and included 50. 155 patients were added from the Houston and Linz cohorts. Individual data were available for 281 persons, 120 (43%) of whom received steroids. The most common pathogens were herpes simplex virus 1, West Nile virus, and measles. Study designs and patient outcomes were heterogeneous. Only three of the trials report an advantage of steroid therapy. Steroid-induced side effects were scarce. Ten cohorts were included into the meta-analysis. For the pooled data, the null hypothesis could not be rejected (p = 0.245) using a random effects model, i.e., a benefit of steroid treatment on survival in VE could not be shown. CONCLUSIONS: Steroids as potent anti-inflammatory agents may act through a reduction of secondary inflammation-mediated damage. Our data do not support the use of steroids in VE. However, multiple shortcomings apply. Standardized controlled trials are needed to investigate optimal dosing and timing of steroid administration and to explore potential subgroups that could benefit.
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Encefalite Viral , Esteroides , Humanos , Esteroides/uso terapêutico , Anti-Inflamatórios , Encefalite Viral/tratamento farmacológicoRESUMO
BACKGROUND: Poststroke epilepsy (PSE) represents an important complication of stroke. Data regarding the frequency and predictors of PSE in patients with large-vessel occlusion stroke receiving mechanical thrombectomy (MT) are scarce. Furthermore, information on acute and preexisting lesion characteristics on brain MRI has not yet been systematically considered in risk prediction of PSE. This study thus aims to assess PSE risk after acute ischemic stroke treated with MT, based on clinical and MRI features. METHODS: In this multicenter study from two tertiary stroke centers, we included consecutive acute ischemic stroke patients who had received MT for acute intracranial large vessel occlusion (LVO) between 2011 and 2017, in whom post-interventional brain MRI and long term-follow-up data were available. Infarct size, affected cerebrovascular territory, hemorrhagic complications and chronic cerebrovascular disease features were assessed on MRI (blinded to clinical information). The primary outcome was the occurrence of PSE (> 7 days after stroke onset) assessed by systematic follow-up via phone interview or electronic records. RESULTS: Our final study cohort comprised 348 thrombectomy patients (median age: 67 years, 45% women) with a median long-term follow-up of 78 months (range 0-125). 32 patients (9%) developed PSE after a median of 477 days (range 9-2577 days). In univariable analyses, larger postinterventional infarct size, infarct location in the parietal, frontal or temporal lobes and cerebral microbleeds were associated with PSE. Multivariable Cox regression analysis confirmed larger infarct size (HR 3.49; 95% CI 1.67-7.30) and presence of cerebral microbleeds (HR 2.56; 95% CI 1.18-5.56) as independent predictors of PSE. CONCLUSION: In our study, patients with large vessel occlusion stroke receiving MT had a 9% prevalence of PSE over a median follow-up period of 6.5 years. Besides larger infarct size, presence of cerebral microbleeds on brain MRI predicted PSE occurrence.
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Arteriopatias Oclusivas , Isquemia Encefálica , Epilepsia , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Masculino , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/epidemiologia , AVC Isquêmico/complicações , Resultado do Tratamento , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Trombectomia/efeitos adversos , Trombectomia/métodos , Arteriopatias Oclusivas/complicações , Epilepsia/etiologia , Infarto , Hemorragia Cerebral/complicaçõesRESUMO
Importance: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk. Objective: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures. Design, Setting, and Participants: This cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022. Exposures: Type of acute symptomatic seizure. Main Outcomes and Measures: All-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke). Results: A total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy. Conclusions and Relevance: In this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up.
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Epilepsia , AVC Isquêmico , Estado Epiléptico , Acidente Vascular Cerebral , Adulto , Humanos , Masculino , Feminino , Idoso , Estudos de Coortes , Prognóstico , AVC Isquêmico/complicações , Epilepsia/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Estado Epiléptico/tratamento farmacológicoRESUMO
Anti-amyloidogenic processing of the amyloid precursor protein APP by α-secretase prevents formation of the amyloid-ß peptide, which accumulates in senile plaques of Alzheimer disease patients. α-Secretase belongs to the family of a disintegrin and metalloproteases (ADAMs), and ADAM10 is the primary candidate for this anti-amyloidogenic activity. We recently demonstrated that ADAM10 translation is repressed by its 5'-UTR and that in particular the first half of ADAM10 5'-UTR is responsible for translational repression. Here, we asked whether specific sequence motifs exist in the ADAM10 5'-UTR that are able to form complex secondary structures and thus potentially inhibit ADAM10 translation. Using circular dichroism spectroscopy, we demonstrate that a G-rich region between nucleotides 66 and 94 of the ADAM10 5'-UTR forms a highly stable, intramolecular, parallel G-quadruplex secondary structure under physiological conditions. Mutation of guanines in this sequence abrogates the formation of the G-quadruplex structure. Although the G-quadruplex structure efficiently inhibits translation of a luciferase reporter in in vitro translation assays and in living cells, inhibition of G-quadruplex formation fails to do so. Moreover, expression of ADAM10 was similarly repressed by the G-quadruplex. Mutation of the G-quadruplex motif results in a significant increase of ADAM10 levels and consequently APPsα secretion. Thus, we identified a critical RNA secondary structure within the 5'-UTR, which contributes to the translational repression of ADAM10.
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Regiões 5' não Traduzidas/fisiologia , Proteínas ADAM/biossíntese , Secretases da Proteína Precursora do Amiloide/biossíntese , Proteínas de Membrana/biossíntese , Conformação de Ácido Nucleico , Biossíntese de Proteínas/fisiologia , Proteínas ADAM/genética , Proteína ADAM10 , Secretases da Proteína Precursora do Amiloide/genética , Células HEK293 , Humanos , Proteínas de Membrana/genética , MutaçãoRESUMO
BACKGROUND: For most viral encephalitides, therapy is merely supportive. Intravenous immunoglobulins (IVIG) have been used as a prophylactic and therapeutic approach. We conduct a systematic review on the safety and efficacy of IVIG in viral encephalitis. METHODS: We conducted a systematic review assessing PubMed, Cochrane Database, Biosis Previews and the ClinicalTrials.gov website to identify all reports on patients with viral encephalitis treated with IVIG as of May 31, 2019. The main outcomes assessed were therapeutic efficacy and safety. For an increased homogeneity of the population, atypical viral infections were excluded, as were reports on prophylactic IVIG use, intrathecal application of immunoglobulins, or use of antibody-enriched IVIG-preparations. Data were extracted from published studies. Descriptive statistics were used. RESULTS: We included a total of 44 studies (39 case reports). The case reports cover a total of 53 patients. Our search retrieved two prospective and three retrospective studies. These show heterogeneous results as to the efficacy of IVIG therapy. Only one study reports a significant association between IVIG-use and death (odds ratio 0.032; 95% confidence interval 0.0033-0.3024; p = 0.0027). None of the studies report significant differences in the number of serious adverse events. CONCLUSION: Data on the efficacy of IVIG-therapy is heterogeneous. While it seems generally safe, evident superiority compared to supportive treatment has not been demonstrated so far. Future trials should also investigate the optimal dosing and timing of IVIG and their benefit in the immunosuppressed.
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Encefalite Viral , Viroses , Encefalite Viral/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Neuroimaging studies have indicated abnormalities in cortico-striatal-thalamo-cortical circuits in patients with obsessive-compulsive disorder compared with controls. However, there are inconsistencies between studies regarding the exact set of brain structures involved and the direction of anatomical and functional changes. These inconsistencies may reflect the differential impact of environmental and genetic risk factors for obsessive-compulsive disorder on different parts of the brain. To distinguish between functional brain changes underlying environmentally and genetically mediated obsessive-compulsive disorder, we compared task performance and brain activation during a Tower of London planning paradigm in monozygotic twins discordant (n=38) or concordant (n=100) for obsessive-compulsive symptoms. Twins who score high on obsessive-compulsive symptoms can be considered at high risk for obsessive-compulsive disorder. We found that subjects at high risk for obsessive-compulsive disorder did not differ from the low-risk subjects behaviourally, but we obtained evidence that the high-risk subjects differed from the low-risk subjects in the patterns of brain activation accompanying task execution. These regions can be separated into those that were affected by mainly environmental risk (dorsolateral prefrontal cortex and lingual cortex), genetic risk (frontopolar cortex, inferior frontal cortex, globus pallidus and caudate nucleus) and regions affected by both environmental and genetic risk factors (cingulate cortex, premotor cortex and parts of the parietal cortex). Our results suggest that neurobiological changes related to obsessive-compulsive symptoms induced by environmental factors involve primarily the dorsolateral prefrontal cortex, whereas neurobiological changes induced by genetic factors involve orbitofrontal-basal ganglia structures. Regions showing similar changes in high-risk twins from discordant and concordant pairs may be part of compensatory networks that keep planning performance intact, in spite of cortico-striatal-thalamo-cortical deficits.
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Encéfalo/fisiopatologia , Doenças em Gêmeos/fisiopatologia , Rede Nervosa/fisiopatologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Adolescente , Adulto , Análise de Variância , Mapeamento Encefálico , Cognição , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Inquéritos e Questionários , GêmeosRESUMO
This paper reports on the process of the Swiss national strategy to define and implement eHealth. Switzerland is a federal political organization with 26 cantons that are autonomous for the health legal framework. Switzerland must also provide support for four national languages. Thus, this experience addresses many challenges that are experienced at the European level in a much larger scale. Also, Switzerland benefits from the major projects ongoing in Europe, such as epSOS, to define its own strategy.
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Conscientização , Sistemas Computacionais , Consenso , Informática Médica/organização & administração , Desenvolvimento de Programas , SuíçaRESUMO
OBJECTIVES: Enterovirus (EV) is a frequent cause of encephalitis. The optimal therapeutic approach remains a matter of debate. We present the case of an immunosuppressed patient with EV encephalitis treated successfully with intravenous immunoglobulin (IVIG) and report the results of a systematic review on the characteristics of EV encephalitis, as well as the safety and efficacy of IVIG therapy. METHODS: A systematic review was conducted using the PubMed, Cochrane Database, BIOSIS Previews, and ClinicalTrials.gov databases to identify all reports on patients with EV encephalitis as of December 31, 2020. The main outcomes assessed were the efficacy and safety of the respective therapeutic approach. RESULTS: A total of 73 articles were included: one prospective trial, one retrospective and prospective case series, one purely retrospective case series, and 70 case reports. The case reports included a total of 101 patients. Immunosuppressed patients were at higher risk of contracting EV encephalitis and experiencing a fatal course. Hypogammaglobulinaemia particularly predisposes to EV disease, even with a moderate reduction in serum IgG levels. IVIG therapy in the immunosuppressed may confer a survival advantage. CONCLUSIONS: IVIG therapy is rarely associated with severe adverse events and may be considered in immunosuppressed patients with EV encephalitis. Future trials should investigate the optimal IVIG dosing and route of application, the benefit of antibody-enriched IVIG preparations, and the serum immunoglobulin level that should trigger prophylactic replacement.
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Encefalite Viral , Infecções por Enterovirus , Enterovirus , Encefalite Viral/tratamento farmacológico , Infecções por Enterovirus/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Estudos RetrospectivosRESUMO
Post-stroke Epilepsy (PSE) is one of the most common forms of acquired epilepsy, especially in the elderly population. As people get increasingly older, the number of stroke patients is expected to rise and concomitantly the number of people with PSE. Although many patients are affected by post-ischemic epileptogenesis, not much is known about the underlying pathomechanisms resulting in the development of chronic seizures. A common hypothesis is that persistent neuroinflammation and glial scar formation cause aberrant neuronal firing. Here, we summarize the clinical features of PSE and describe in detail the inflammatory changes after an ischemic stroke as well as the chronic changes reported in epilepsy. Moreover, we discuss alterations and disturbances in blood-brain-barrier leakage, astrogliosis, and extracellular matrix changes in both, stroke and epilepsy. In the end, we provide an overview of commonalities of inflammatory reactions and cellular processes in the post-ischemic environment and epileptic brain and discuss how these research questions should be addressed in the future.