Poststroke Seizure and Epilepsy: A Review of Incidence, Risk Factors, Diagnosis, Pathophysiology, and Pharmacological Therapies

Abstract

Stroke is the most common cause of epilepsy and ultimately leads to a decrease in the quality of life of those affected. Ischemic and hemorrhagic strokes can both lead to poststroke epilepsy (PSE). Significant risk factors for PSE include age < 65 age less than 65 years, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), cortical involvement, and genetic factors such as TRPM6 polymorphism. The diagnosis of PSE is made by using imaging modalities, blood biomarkers, and prognostic criteria. Electroencephalography (EEG) is currently the gold standard to diagnose PSE, while new combinations of modalities are being tested to increase diagnostic specificity. This literature review uncovers a newly found mechanism for the pathology of poststroke epilepsy. The pathogenesis of early-onset and late-onset is characterized by sequelae of neuronal cellular hypoxia and disruption of the blood-brain barrier, respectively. Interleukin-6 is responsible for increasing the activity of glial cells, causing gliosis and hyperexcitability of neurons. Epinephrine, high-mobility group protein B1, downregulation of CD32, and upregulation of HLA-DR impact the pathology of poststroke epilepsy by inhibiting the normal neuronal immune response. Decreased levels of neuropeptide Y, a neurotransmitter, act through multiple unique mechanisms, such as inhibiting intracellular Ca2+ accumulation and acting as an anti-inflammatory, also implemented in the worsening progression of poststroke epilepsy. Additionally, CA1 hippocampal resonant neurons that increase theta oscillation are associated with poststroke epilepsy. Hypertensive small vessel disease may also have an implication in the temporal lobe epilepsy by causing occult microinfarctions. Furthermore, this review highlights the potential use of statins as primary prophylaxis against PSE, with multiple studies demonstrating a reduction in incidence using statins alone, statins in combination with antiepileptic drugs (AEDs), and statins with aspirin. The evidence strongly suggests that the second generation AEDs are a superior treatment method for PSE. Data from numerous studies demonstrate their relative lack of significant drug interactions, increased tolerability, and potential superiority in maintaining seizure-free status.

Injury-specific factors in the cerebrospinal fluid regulate astrocyte plasticity in the human brain

“… 7 ), and proliferating astrocytes are a likely origin for this. Also epilepsy or mood disorders following stroke or TBI have been linked to astroglia abnormalities 41 , 43 , as disease progression in Alzheimer’s disease 6 or chronic pain 42 . Indeed, proliferating astrocytes have specific molecular properties, as highlighted in previous preclinical mouse models 9 , 12 , 21 and here by GAL3 expression.…”

“…Much has been learned in recent years about the importance of the local environment and glial cells for disease progression and functional recovery 3,6,10,[41][42][43] . Here we discovered intracerebral hemorrhage as common denominator for eliciting reactive astrocyte proliferation and GAL3 upregulation in a wide range of pathologies.…”

Clinical approaches for poststroke seizure: a review

“…In late poststroke seizures, upregulation in endostatin and NCAM, and downregulation in S100B, Hsc70, and TNF-R1 in acute phase blood samples of stroke showed a high correlation ( 32 ). However the seizure risk for cerebral venous thrombosis is debatable, as some studies suggest an increase of up to 34%, whereas other studies indicate no association ( 33 – 35 ).…”

Inhibition of Neuron-Restrictive Silencing Factor (REST/NRSF) Chromatin Binding Attenuates Epileptogenesis

“…Epilepsy, the generation of apparently spontaneous seizures, is the third most common chronic brain disorder and exerts an enormous toll on human potential ( Committee, 2012 ). The epilepsies may derive from genetic factors, including increasingly recognized gene mutations ( EpiPM, 2015 ; Helbig et al, 2016 , 2018 ), or arise in the context of prior insults such as traumatic brain injury ( Pitkänen and Immonen, 2014 ), brain infection ( Patel et al, 2017 ), or stroke ( Chang et al, 2022 ; Phan et al, 2022 ). Because of the clear and causal association of insults and epileptogenesis, uncovering the mechanisms leading to an insult to the onset of epilepsy and the commonly associated cognitive and emotional problems is critical for the identification of preventative and therapeutic targets ( Committee, 2012 ).…”