Acute Symptomatic Seizures Clinical and Experimental Studies

Abstract: Epilepsy is defined as a condition with recurrent unprovoked seizures. When seizures are believed to be provoked they fall into another category of situation-related seizures, i.e. acute symptomatic seizures (ASS). The definition of ASS is a clinical seizure occurring in close temporal relationship with an acute insult in the central nervous system (CNS), which may be metabolic, toxic, structural, infectious or inflammatory. The prognosis after unprovoked seizures and ASS differs with regard to risk of seizure recurrence and mortality.This thesis focuses on seizures occurring in relation to common dysmetabolic conditions and subarachnoid haemorrhage (SAH). Specifically, the occurrence of ASS in patients with different levels of hyponatraemia and hypoglycaemia was studied. Furthermore an experimental study in rodents was conducted to explore the relationship between chemically induced status epilepticus (SE) and hyponatraemia. In addition, seizures in relation to acute SAH were recorded and related to appearance of development of delayed cerebral ischemia (DCI). Finally, measurement of neurofilament light (NFL) and tau in the cerebrospinal fluid (CSF) was performed.In a large number of patients with hyponatremia a gradual increase (2.5 % – 11 %) in risk of seizures with declining sodium levels was noted. Seizures were the only neurologic manifestation of hyponatraemia in patients with moderately decreased sodium levels (> 115 mM).In a study of patients with hypoglycaemia, a notably low risk for seizures was found. Absolute risk for neurological symptoms at glucose < 2.0 mM (95% CI) was 0.25 (0.13-0.41). This is a finding of potentially great clinical relevance, since seizures in the presence of hypoglycaemia are often presumed to be acutely symptomatic.In the animal study of acute hyponatraemia on kainic acid (KA) induced status epilepticus (SE) the hyponatraemic animals displayed an increased frequency of epileptiform activity and had longer duration of seizures. These results support the clinical observations that hyponatraemia aggravates SE.In the study of patients with SAH seizures were frequent (36% of all patients) but did not predict the development of DCI. Measurement of the CSF biomarker tau at different time points revealed increased tau concentration between days 4 and 10, and may be associated with DCI.