Incidence of seizures following initial ischemic stroke in a community-based cohort: The Framingham Heart Study

Purpose We examined the incidence of seizures following ischemic stroke in a community-based sample. Methods All subjects with incident ischemic strokes in the Framingham Original and Offspring cohorts between 1982 and 2003 were identified and followed for up to 20 years to determine incidence of seizures. Seizure-type was based on the 2010 International League Against Epilepsy (ILAE) classification. Disability was stratified into mild/none, moderate and severe, based on post-stroke neurological deficit documentation according to the Framingham Heart Study (FHS) protocol and functional status was determined using the Barthel Index. Results An initial ischemic stroke occurred in 469 subjects in the cohort and seizures occurred in 25 (5.3%) of these subjects. Seizure incidence was similar in both large artery atherosclerosis (LAA) (6.8%) and cardio-embolic (CE) (6.2%) strokes. No seizures occurred following lacunar strokes. The predominant seizure type was focal seizure with or without evolution to bilateral convulsive seizure. One third of participants had seizures within the first 24 h from stroke onset and half of all seizures occurred within the first 30 days. On multivariate analysis, moderate and severe disability following stroke was associated with increased risk of incident seizure. Conclusions Seizures occurred in approximately 5% of subjects after an ischemic stroke. One third of these seizures occurred in the first 24 h after stroke and none followed lacunar strokes. Focal seizures with or without evolution in bilateral convulsive seizures were the most common seizure type. Moderate and severe disability was predictive of incident seizures

Postictal serotonin levels are associated with peri-ictal apnea.

ObjectiveTo determine the relationship between serum serotonin (5-HT) levels, ictal central apnea (ICA), and postconvulsive central apnea (PCCA) in epileptic seizures.MethodsWe prospectively evaluated video EEG, plethysmography, capillary oxygen saturation (SpO2), and ECG for 49 patients (49 seizures) enrolled in a multicenter study of sudden unexpected death in epilepsy (SUDEP). Postictal and interictal venous blood samples were collected after a clinical seizure for measurement of serum 5-HT levels. Seizures were classified according to the International League Against Epilepsy 2017 seizure classification. We analyzed seizures with and without ICA (n = 49) and generalized convulsive seizures (GCS) with and without PCCA (n = 27).ResultsPostictal serum 5-HT levels were increased over interictal levels for seizures without ICA (p = 0.01), compared to seizures with ICA (p = 0.21). In patients with GCS without PCCA, serum 5-HT levels were increased postictally compared to interictal levels (p < 0.001), but not in patients with seizures with PCCA (p = 0.22). Postictal minus interictal 5-HT levels also differed between the 2 groups with and without PCCA (p = 0.03). Increased heart rate was accompanied by increased serum 5-HT levels (postictal minus interictal) after seizures without PCCA (p = 0.03) compared to those with PCCA (p = 0.42).ConclusionsThe data suggest that significant seizure-related increases in serum 5-HT levels are associated with a lower incidence of seizure-related breathing dysfunction, and may reflect physiologic changes that confer a protective effect against deleterious phenomena leading to SUDEP. These results need to be confirmed with a larger sample size study

Neurovascular Unit Dysfunction with Blood-Brain Barrier Hyperpermeability Contributes to Major Depressive Disorder: A Review of Clinical and Experimental Evidence

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches

Neuroinflammation and Psychiatric Illness

Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological abnormalities occur in classical psychiatric disorders (for example, major depressive, bipolar, schizophrenia, and obsessive-compulsive disorders). Investigations into the pathophysiology of these conditions traditionally stressed dysregulation of the glutamatergic and monoaminergic systems, but the mechanisms causing these neurotransmitter abnormalities remained elusive. We review the link between autoimmunity and neuropsychiatric disorders, and the human and experimental evidence supporting the pathogenic role of neuroinflammation in selected classical psychiatric disorders. Understanding how psychosocial, genetic, immunological and neurotransmitter systems interact can reveal pathogenic clues and help target new preventive and symptomatic therapies

Neoangiogenesis and Blood-brain Barrier Dysfunction in Human TSC Brain Lesions

Introduction: Tuberous sclerosis complex (TSC) is a genetic disorder characterized by the presence of multiple benign tumors throughout the body and brain. Patients with TSC experience severe cognitive dysfunction and therapy-resistant seizures, which can be associated with refractory epilepsy and poor developmental outcomes. We hypothesize that neoangiogenesis, disruption of the blood-brain barrier, and leakage of serum proteins into the brain parenchyma play vital roles in the pathogenesis of TSC. Methods: In order to assess blood-brain barrier integrity, cortical tissue samples from TSC patients with intractable seizures, non-TSC patients with therapy-resistant epilepsy, and control subjects were immunolabeled for the serum protein fibrinogen, the adherens junction protein V-cadherin, and the tight junction protein occludin. Lectin was used to visualize blood vessels. Quantification was performed to assess average blood vessel segment length and branching. The fraction of membrane-associated V-cadherin and occludin, relative to the blood vessel surface area represented by lectin, was also analyzed. Results: The average length of blood vessel segments and the average number of branch nodes were significantly increased in TSC compared to epilepsy and control. The average surface area fraction of V-cadherin and occludin was significantly decreased in TSC compared to control. In addition, fibrinogen staining outside of the blood vessels was extensive in both TSC and epilepsy. These results confirm our hypothesis, suggesting blood-brain barrier dysfunction in TSC, with disease-specific neoangiogenic mechanisms in TSC. Discussion: Our results show increased blood-brain barrier permeability and increased vascular proliferation in TSC. These findings are likely due to decreased expression of tight junctions and adherens junctions in TSC cortical tissue. These results suggest that antiangiogenic therapies targeting the blood-brain barrier may offer a novel approach to preventing epileptogenesis in patients with TSC

Incidence of Epilepsy and Seizures Over the First 6 Months After a COVID-19 Diagnosis: A Retrospective Cohort Study

BACKGROUND: The relationship between COVID-19 and epilepsy is uncertain. We studied the potential association between COVID-19 and seizures or epilepsy in the six months after infection. METHODS: We applied validated methods to an electronic health records network (TriNetX Analytics) of 81 million people. We closely matched people with COVID-19 infections to those with influenza. In each cohort, we measured the incidence and hazard ratios (HRs) of seizures and of epilepsy. We stratified data by age and by whether the person was hospitalized during the acute infection. We then explored time-varying HRs to assess temporal patterns of seizure or epilepsy diagnoses. RESULTS: We analyzed 860,934 electronic health records. After matching, this yielded two cohorts each of 152,754 patients. COVID-19 was associated with an increased risk of seizures and epilepsy compared to influenza. The incidence of seizures within 6 months of COVID-19 was 0.81% (95% CI, 0.75-0.88; HR compared to influenza 1.55 (1.39-1.74)). The incidence of epilepsy was 0.30% (0.26-0.34; HR compared to influenza 1.87 (1.54-2.28)). The HR of epilepsy after COVID-19 compared to influenza was greater in people who had not been hospitalized and in individuals aged under 16 years. The time of peak HR after infection differed by age and hospitalization status. CONCLUSIONS: The incidence of new seizures or epilepsy diagnoses in the six months following COVID-19 was low overall, but higher than in matched patients with influenza. This difference was more marked in people who were not hospitalized, highlighting the risk of epilepsy and seizures even in those with less severe infection. Children appear at particular risk of seizures and epilepsy after COVID-19 providing another motivation to prevent COVID-19 infection in pediatric populations. That the varying time of peak risk related to hospitalization and age may provide clues as to the underlying mechanisms of COVID-associated seizures and epilepsy

Idiopathic Generalized Epilepsy: Misunderstandings, Challenges, and Opportunities

The idiopathic generalized epilepsies (IGE) make up a fifth of all epilepsies, but <1% of epilepsy research. This skew reflects misperceptions: diagnosis is straightforward, pathophysiology is understood, seizures are easily controlled, epilepsy is outgrown, morbidity and mortality are low, and surgical interventions are impossible. Emerging evidence reveals that patients with IGE may go undiagnosed or misdiagnosed with focal epilepsy if EEG or semiology have asymmetric or focal features. Genetic, electrophysiologic, and neuroimaging studies provide insights into pathophysiology, including overlaps and differences from focal epilepsies. IGE can begin in adulthood and patients have chronic and drug-resistant seizures. Neuromodulatory interventions for drug-resistant IGE are emerging. Rates of psychiatric and other comorbidities, including sudden unexpected death in epilepsy, parallel those in focal epilepsy. IGE is an understudied spectrum for which our diagnostic sensitivity and specificity, scientific understanding, and therapies remain inadequate

Stiripentol in D ravet syndrome: Results of a retrospective U . S . study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100157/1/epi12303.pd