Epilepsy in Stroke as De Novo Independent Nosology Unit – Physiology, Pathogenesis, Histology, Clinical Picture, Diagnosis, and Treatment – A Systematic Review

Abstract

INTRODUCTION: Early seizures are considered complications of stroke, and late seizures are a type of structural epilepsy. If they are separated as a new independent nosology unit, the problem in the diagnostic – treatment approach will be solved. PHYSIOLOGY: Cerebral blood flow is regulated by local factors such as carbon dioxide and oxygen content. Brain activity is also an important factor in the regulation of the volume speed of the blood – with locally increased neuronal activity, the local blood flow increases. Neurons in the CNS are subject to a variety of effects mediated by membrane receptors of two types – ionotropic and metabotropic. PATHOGENESIS: Early seizures are due to transient biochemical dysfunctions, while late seizures are due to gliosis changes affecting neuronal excitability. HISTOLOGY: The highlighted histopathological aspects confirm and support the results of clinical and radiological studies with dead nervous tissue, replaced by numerous newly formed capillaries, and surrounded by lipid-laden macrophages. CLINICAL PICTURE: This is represented by a complex combination of excitatory epileptic manifestations and residual focal symptoms depending on the localization of the lesion. LABORATORY DIAGNOSTICS: A very typical group of patients with post-stroke seizures have a high risk of recurrence when some of the studied biomarkers for this are available in the blood. In summary, the additional expanded package of studies of stroke patients should include screening diagnostics for the risk of epileptic seizures, namely: IL-6, IL-1β, TNF, Mg2+, Ca2+, CD40L, and Hsc70. IMAGING: Transient periodic MRI abnormalities have been demonstrated, possibly as a result of cerebral edema induced by seizure activity. Routine MRI in stroke patients is recommended. TREATMENT: It is possible that rt-PA may increase the risk of early seizures after stroke. Levetiracetam (LEV) as a neuroprotective agent in stroke has been proposed as the drug of first choice, based on safety and efficacy profiles. The usual practice is to treat recurrent early-onset seizures with short-term (3–6 months) treatment with antiepileptic drugs. CONCLUSIONS: Separation of stroke-epilepsy as a new independent nosology entity will solve the diagnostic-treatment problems in this area by changing the minimum package for laboratory tests, as well as routine MRI in patients with clinical evidence of stroke. LEV is the first-line agent for the treatment of these patients, in combination with correction of registered laboratory parameters.

Risk Factors Associated with Epilepsy Related to Cerebrovascular Disease: A Systematic Review and Meta-Analysis

“…Additionally, the presence of the CD40/CD40L system, associated with seizure susceptibility, further contributes to inflammatory mechanisms. 41,42 In the clinical field, the studies included in this meta-analysis have not shown evidence supporting the prophylactic use of antiseizure medications in the post stroke setting. Serafini et al 32 suggested that patients with hemorrhagic stroke could benefit from the antiseizure drugs; Tanaka et al 34 evaluated different families of antiepileptic drugs and conclude that valproic acid does not improve prognosis; and Yamada et al 36 mentioned that prophylactic antiepileptic therapy of short duration could be beneficial in high-risk patients with intracerebral hematomas, or with at least two factors identified in their study.…”

“…Additionally, the presence of the CD40/CD40L system, associated with seizure susceptibility, further contributes to inflammatory mechanisms. 41 , 42 …”