Seizures in stroke patients.

The incidence of seizures increases with age. The etiology of most new-onset
seizures in patients > 40 years old is cerebrovascular disease. Epidemiological
studies have calculated the risk of post-stroke epilepsy for all stroke
patients to be 2.5 to 4%1-4. Depending on the type of stroke, the severity and
the location of the infarct or hemorrhage this percentage can increase to 62%
5. It is assumed that the occurrence of seizures diminishes quality of life,
but it has not been studied in this specific population so far. Quality of life
(QoL) in the general stroke population has been studied, but not related to the
occurrence of seizures. Furthermore, it is possible that neurological outcome
and cognition worsen after seizures6 7. Patients already damaged by stroke,
encounter another neurologic problem which may cause anxiety and depression.
Patients living at home may fear institutionalization.
Evaluating the problems encountered by stroke patients with seizures should be
done by making a comparison between stroke patients with and without seizures.

When stroke patients experience a first late seizure, they tend to be treated
with antiepileptic drugs. Finding the optimal antiepileptic treatment for these
patients is difficult as there is little evidence based information on AED
treatment in post-stroke epilepsy. This group of patients tends to be treated
chronically with one of the traditional antiepileptic drugs (AEDs), like
carbamazepine, phenytoin, phenobarbital, or valproate 8-10. These AEDs may
however have serious side effects in chronic use. The effect of co-medication
may be influenced. In this population in which poly-drug treatment is common
this is an important problem. Investigation of the impact of AED treatment on
side effects, cognition and quality of life seems valuable for clinical
practice. Some papers have reported which AEDs are used in this population,11
but more information on AED type, efficacy and tolerability is necessary.

All stroke patients are at risk for developing post-stroke epilepsy. When
prophylactic medication would become available in the future, identification of
stroke patients who are at the highest risk for developing post-stroke epilepsy
is important. The NMDA receptor, one of the glutamate receptors, seems to play
a role in the development of seizures. This receptor is formed by the NR1
subunit, together with one or more of the four different types of NR2 subunits
(NR2A-NR2D). The NR1 subunit of the NMDA receptor is coded by the GRIN1 gene.
Several polymorphisms of this gene are known. Rujescu et al (2005)12 determined
a single nucleotide polymorphism (G2108A) for the GRIN1 gene in alcoholics with
and without seizures and control patients. The A allele and A-containing
genotypes were over-represented in patients with withdrawal-induced seizures
compared to healthy volunteers and compared to alcoholics without a history of
seizures. Perhaps the GRIN1 gene polymorphism can serve as a risk factor for
the development of post-stroke seizures also.

Firstly, measurement of the impact of seizures in stroke patients by comparing
quality of life, cognitive function, disability, handicap, and mood between
stroke patients with and without seizures.
Secondly, recording information on treatment of post stroke seizures, including
AED treatment, information on seizure number and severity (efficacy), and side
effects (tolerability).
Thirdly, assessment of GRIN1 polymorphism in stroke patients with and without
seizures and in subjects without stroke of epilepsy to determine whether this
polymorphism is a risk factor for the development of post-stroke seizures.

Observational, cross-sectional study, with only one single observation moment.
In this observational study, two groups of patients will be included:
group 1 stroke patients with epilepsy,
group 2 matched stroke patients without seizures or epilepsy.

A third group consisting of subjects without stroke of seizures participates in
the DNA study.

When participating in the study, patients are asked to come to the outpatient
clinic to meet the study investigator. Patients are requested to perform a
reaction time test and information processing task (taking approximately 15
minutes for both tests). They fill in two quality of life questionnaires (ca.
10 minutes), a questionnaire about anxiety and depression (ca. 5 minutes), and
a questionnaire about side effects of the antiepileptic drug (ca. 15 minutes).
The study investigator records a modified Rankin score, Barthel index (ca. 5
minutes), and mini-mental state examination (ca. 10 minutes), and performs a
general history and neurological examination and records the NIHSS (ca. 10
minutes). To obtain DNA a mouth swab is taken.

In subjects without stroke or epilepsy a mouth swab is taken to obtain DNA.
This takes less than 5 minutes and is painless.