1
2
3
4
Scientific Paper
University Department of Neurology, Sarajevo University
Clinical Center, Sarajevo, Bosnia and Herzegovina
Vuk Vrhovac Institute, University Clinic for Diabetes,
Endocrinology and Metabolic Diseases,
Dugi dol 4a, HR-10000 Zagreb, Croatia
Zenica Cantonal Hospital, Zenica, Bosnia and Herzegovina
Institute of Hemodialysis, Sarajevo University Clinical Center,
Sarajevo, Bosnia and Herzegovina
CORRELATION BETWEEN EARLY AND LATE EPILEPTIC
SEIZURES AND DIABETES MELLITUS DURING AND
AFTER STROKE
Azra Alajbegoviæ1, @eljko Metelko2, Salem Alajbegoviæ3, D‘elaludin Kantard‘iæ1,
Milan Bratiæ1, E. Suljiæ1, M. Hrnjica1, Halima Resiæ4
Key words: diabetes mellitus, epileptic seizures, stroke
SUMMARY
Diabetes mellitus is a well-known risk factor for
cerebrovascular diseases, but not so well-known for determining
early and late epileptic seizures during and after stroke. Early
and late epileptic fits recorded at the University Department of
Neurology in Sarajevo during a 10-year period (from January
1, 1989 until December 31, 1998) in 7001 stroke patients were
retrospectively evaluated so as to determine the impact of
diabetes on the onset of stroke and of the early and late epileptic
seizures. Out of 114 patients with epileptic seizures, 34 (29.8%)
had diabetes mellitus (7.9% type 1 and 20.2% type 2). The mean
age of patients was 60.0 years, with standard deviation of 12.52
years. The mean duration of diabetes was 10 years in patients
with late seizures, and 14.7 years in patients with early fits. In
the group of patients with early seizures, there were 19 patients
with diabetes mellitus (3 patients with type 1 and 12 patients
with type 2). In the group with late fits, there were 15 diabetics
(3 patients with type 1 and 11 patients with type 2).
Hyperglycemia was significantly more common in the group of
patients with early fits than in the group with late fits (60.9%).
The most frequent type of epileptic manifestations were partial
seizures with secondary generalization. Diabetes mellitus was
found to be a significant risk factor for the onset of stroke as well
as for the occurrence of early epileptic seizures during stroke
(p<0.1; χ2=3.472). There was no statistically significant effect
of diabetes on the onset of late epileptic seizures. The study
Diabetologia Croatica 31-3, 2002
showed no statistically significant difference between the patients
with normal and elevated blood glucose according to the type of
epileptic manifestations.
INTRODUCTION
Diabetes is the most common metabolic and
endocrine disease. According to the World Health
Organization (WHO), it is defined as a syndrome
consisting of a group of metabolic entities
characterized by chronic hyperglycemia as the result of
inadequate insulin resistance and/or resistance to its
biological effect (1). For many reasons (longer life span,
inheritage, reduced physical activity, unhealthy
nutrition, etc.) diabetes has reached epidemic
proportions (2,3). Between 2% and 5% of the adult
population of Europe suffer from diabetes (1,2,4). A
very frequent complication in diabetes is stroke.
According to Kannel, diabetes is four times more
common in stroke patients than in the general
population (5). Stroke is a focal neurologic dysfunction
of the central nervous system with acute onset as a
consequence of a pathologic disorder of vascular origin
(6,7). In diabetics, stroke is the result of diabetic
macroangiopathy (1,4).
According to the Framingham and Rochester studies,
diabetes has shown itself as an independent risk factor
for the occurrence of stroke; however, when combined
with congestive heart disease it is the least potential
173
A. Alajbegoviæ, @. Metelko, S. Alajbegoviæ, D‘. Kantard‘iæ, M. Bratiæ, E. Suljiæ, M. Hrnjica, H. Resiæ / CORRELATION BETWEEN EARLY
AND LATE EPILEPTIC SEIZURES AND DIABETES MELLITUS DURING AND AFTER STROKE
risk factor (8). According to Kuusisto et al. (9) and
Sadikario (10), it is the most potential risk factor for
the occurrence of stroke. Stroke is the leading cause of
death and the main cause of disablement in the adult
population of Europe (11,12). Helsinki declaration
from 1959 (13) identifies optimal care for patients and
evaluation of care for survivors (13-15), based on the
high mortality (8,9,17-20) and a variable degree of
disablement and need of 24-hour care in 60% of stroke
survivors.
From the pathophysiologic point of view, stroke can
be ischemic (infarct) or hemorrhagic (intracerebral
hematoma or subarachnoid hemorrhage). The
symptomatology depends on the system involved by
the vascular incident. The symptoms of stroke in the
carotid system include hemiplegia, hemiparesis,
hemihypersthesia, various consciousness impairments,
amaurosis, and speech disorders such as dysarthria or
aphasia. Involvement of the vertebrobasilar system
shows the symptoms of bilateral weakness,
consciousness impairments, hemianopia, diplopia,
dysphasia, vertigo, ataxia, and nystagmus.
Epilepsy is a clinical phenomenon, a syndrome of
primary cerebral origin, which is characterized by
recurrent episodes during which continuous movement
or behavioral disturbances occur (21).
Epilepsy can occur as the first symptom of stroke
(associated seizure) during the acute stroke phase
(early epileptic seizure) within two weeks of the stroke
onset or as a consequence of stroke after 14 days or
later (late epileptic seizures). Acute phase of stroke
lasts for two weeks, so seizures in this acute phase are
called early seizures. Epileptic seizures arising after an
acute phase are called late seizures.
Cerebrovascular insult is a permanent damage of the
brain (22). The pathophysiologic basis of early
epileptic seizures are molecular changes that occur
primarily in ischemia and secondarily in hemorrhage.
The basis of late epileptic seizures are morphologic
changes following various types and subtypes of stroke.
The risk of epileptic seizures is associated with cortex
involvement, whereas deeper hemispheric or
infratentorial lesions less frequently lead to late
epilepsy.
174
The aim of the study was to determine the impact of
diabetes on the occurrence of early and late epileptic
seizures during and after stroke among patients
suffering from various types and subtypes of diabetes.
PATIENTS AND METHODS
The study included 167 patients with various
epileptic manifestations during and after stroke. Out of
7001 patients treated for stroke at the University
Department of Neurology, Sarajevo University Clinical
Center, during the 10-year study period, 111 had late
epileptic seizures and 56 early epileptic seizures. Data
on the presence of diabetes were available for 114
patients, whereas in 53 patients no such reliable data
were available and these patients were excluded from
statistical analysis. The diagnosis of stroke was
confirmed clinically and by computed tomography,
clearly specifying the type and subtype of stroke. The
study was retrospective in design, covering a 10-year
period (January 1, 1989 – December 31, 1998).
All patients with diabetes were tested for the type
and duration of diabetes. Glycemia was determined
and the effect of glycemia level on the occurrence of
early and late epileptic seizures was assessed on
admission, during clinical treatment, and at discharge
from the hospital.
RESULTS
Out of 7001 patients with stroke treated during the
10-year period at the University Department of
Neurology, Sarajevo University Clinical Center, there
were 167 patients with epileptic seizures (111 with
late seizures and 56 with early seizures). Diabetes data
were evaluated in 114 patients, whereas in 53 patients
no reliable data on their diabetes were available and
they were excluded from statistical analysis. On
statistical analysis, arithmetic mean, standard
deviation, t-test and χ2-test were used. Results are
presented in tables.
There were 34 diabetics (15 with late seizures and 19
with early seizures). There were significantly more
patients with type 2 than with type 1 diabetes. There
were significantly more patients with type 1 diabetes in
the group with early seizures as compared to the group
with late seizures. The group with early seizures
included significantly more diabetics than the group
A. Alajbegoviæ, @. Metelko, S. Alajbegoviæ, D‘. Kantard‘iæ, M. Bratiæ, E. Suljiæ, M. Hrnjica, H. Resiæ / CORRELATION BETWEEN EARLY
AND LATE EPILEPTIC SEIZURES AND DIABETES MELLITUS DURING AND AFTER STROKE
with late seizures (χ2=28.77;df=1, p<0.01). There
were statistically significantly more patients without
than with diabetes (χ2=18.561; df=1, p<0.01). Exact
data on diabetes duration were available in 21 patients.
According to Student’s t-test, difference in the mean
duration of diabetes between the groups with early and
late seizures was not statistically significant (t=1.062).
The mean patient age was 60.0 years, with standard
deviation of 12.52 years. The mean duration of diabetes
after stroke was 10.8±7.62 and 14.7±7.1 years in the
groups with late and early seizures, respectively
(Tables 1-3).
Based on the statistical analysis illustrated in Table 3,
it is evident that there was no statistically significant
difference in the number of patients with elevated
blood glucose at the time of admission (χ2=0.008;
n=1). Difference in the number of patients according
to the level of blood glucose and time of epileptic
seizure onset was not statistically significant at the
level of p<0.05 but was significant at a lower level
(p<0.1; χ2=3.472).
DISCUSSION
The population of diabetics have an increased
sensitivity to arteriosclerosis and stroke (3-5,24).
Increased values of blood glucose lead to an increased
risk of vascular disorders (24). In our study, the
population of diabetics accounted for 29.8% of the total
sample, which was significantly higher than the results
reported by Giroud et al. (25) and Arboix et al. (26). The
higher rate of diabetics in our group of patients with
stroke and epileptic seizures could be explained by the
higher quality care for diabetics, higher educational
level and better health education for the general
population regarding nutrition and lifestyle in general
in the respective countries.
An increase in the level of blood glucose worsens
ischemic brain damage and makes the recovery from
stroke more difficult. Because of the increased lactate
level in ischemic tissue with local acidosis due to
anaerobic glycolysis, it is an imperative to prevent
hyperglycemia in stroke, irrespective of whether
diabetes or hyperglycemia induced by the liver
(glucose uptake) is present. In these hyperglycemias,
besides the already disturbed quantity, the quality of
the blood that distorts the synergy between constant
cerebral flow and brain cell metabolism is impaired. It
Diabetologia Croatica 31-3, 2002
Table 1. Patient distribution according to the presence
of diabetes mellitus and stroke induced early/late
epileptic seizures
Patient category
Late
seizures
Total
Early
seizures
N
%
n
%
n
%
Study samp le
114
100
68
100
46
100
Wi thout di ab etes
80
70.2
53
77.9
27
58.7
Wi th di ab etes:
total
34
29.8
15
22.1
19
41.3
typ e I
9
7.9
3
4.4
6
13.0
typ e II
23
20.2
11
16.2
12
26.1
2
1.7
1
1.5
1
2.2
typ e unknow n
Table 2. Stroke induced early/late epileptic seizures
according to diabetes duration
N o. of p ati ents
Mean di ab etes
durati on (yrs)
Standard devi ati on
Late seizures
6
Early seizures
15
10.8
14.7
7.62
7.11
Table 3. Glycemia on admission to hospital
Glycemia on
admission
(mMol/l)
Study samp le
Total
Late seizures Early seizures
N
%
n
%
n
%
100
123
100
77
100
46
2.8
–
–
–
–
–
–
2.9 – 5.9
62
50.4
44
57.1
18
39.1
6.0
61
49.6
33
42.9
28
60.9
primarily leads to functional and later to morphologic
cell impairment due to hypoxia and later anoxia. The
Na-K pump is distorted and the concentration of
anaerobic glycolysis products is the pathophysiologic
basis for these seizures (27). Hyperglycemia as well as
hypoglycemia lead to an increased risk of brain edema,
which is within the first 24 hours cytocidal and later
vasoactive. Unregulated diabetes leads to the
possibility of diabetic coma (ketoacidotic or
hypersomolar), which is the basis for the occurrence of
new microinfarcts or microhemorrhage (5,24).
The prevalence of hyperglycemia was significantly
higher in the group of patients with early seizures
(60.9%) because this group included significantly more
diabetics, which was statistically significant at a lower
175
A. Alajbegoviæ, @. Metelko, S. Alajbegoviæ, D‘. Kantard‘iæ, M. Bratiæ, E. Suljiæ, M. Hrnjica, H. Resiæ / CORRELATION BETWEEN EARLY
AND LATE EPILEPTIC SEIZURES AND DIABETES MELLITUS DURING AND AFTER STROKE
level of confidence. Glycemia higher than 6 mMol/l was
recorded in 60.9% of patients, which is in accordance
with the results of Neufeld et al. (28).
In the group of patients with late seizures, 57.l% had
normal glycemia at the time of admission, confirming
that the morphologic changes in the brain in this group
of patients followed the pattern of epileptogenic focus,
and that glycemia did not significantly influence the
discharge of nervous cells which produces various
epileptic seizures (29,30).
factor that can lead to the occurrence of early epileptic
seizures. It is an imperative to prevent hyperglycemia
in the acute phase of stroke, as a prevention of early
epileptic seizures. Considering late epileptic seizures,
it appears that diabetes has no major effect on their
occurrence, although changes in the blood glucose level
(hypo- and hyperglycemia) can be a preceding factor
for epileptic discharge of morphologic brain changes
after stroke, in terms of their awakening and behavior
according to the type of epileptogenic focus.
CONCLUSION
In our sample, diabetes mellitus was shown to be a
significant risk factor for the occurrence of stroke. In
diabetics with stroke, hyperglycemia is a significant
REFERENCES
1.
Pemovska G. Šeæerna bolest i mo‘dani udar.
Medicus 2001;10:35-40.
2.
Bokonjiæ R. Mo‘dani udar. 2nd ed. Sarajevo:
Svjetlost, 1986:25-41.
3.
Gavranoviæ M. Klinièka gerijatrija. Sarajevo:
Meðunarodni centar za mir, 1997:75-79.
4.
Metelko @, Lipovac V, @mire J, Škrabalo Z, Prašek
M, Graniæ M. Šeæerna bolest. In: Vrhovac B, et al.,
eds. Interna medicina. Vol. 2. Zagreb: Naprijed,
1991:1308-1328.
5.
Kannel WB. Epidemiology of cerebrovascular
disease. Edinburgh: Churchill Livingstone, 1976.
6.
Radojièiæ B. Bolesti nervnoga sistema. Beograd:
Elit Medica, 1996:956-1013.
7.
Scheinberg P. Controversies in the management of
cerebral vascular disease. Neurology 1988;38:1609.
8.
Davis PH, Dambrosia JM, Schoenberg BS, et al.
Risk factors for ischaemic stroke: a prospective
study in Rochester, Minnesota. Ann Neurol
1987;22:319-327.
9.
Kuusisto J, et al. Non insulin dependent diabetes
and metabolic control are important predictors of
stroke in elderly subjects. Stroke 1994;25:11571164.
176
10. Sadikario S. Cerebrovaskularna bolest kaj
dijabetosot. In: Elementarna dijabetologija, Vol. 3.
:1997:61.
11. Korv J, Rosse E. Stroke epidemiology. Neurol Croat
1994;43 (Supl 3):3.
12. Grad A. Implementation of the Helsinborg
declaration in Central and East Europe: is it
realistic? Acta Clin Croat 1998;37:53-57.
13. WHO Regional Office for Europe, European
Stroke Council. Pan European Consensus Meeting
on Stroke Management. Helsinborg, Sweden,
November 8-10, 1995:1-44.
14. Thorvaldson P. Stroke incidence, case fatality, and
mortality in the WHO MONICA Project. Stroke
1995;26:361-367.
15. European Ad Hoc Consensus Group. Optimizing
intensive care in stroke: a European perspective.
Cerebrovasc Dis 1997;7:113-128.
16. Bonita R, Beaglehole R, Asplund K. International
trends in stroke mortality 1970 - 1985. Stroke
1990;21:989-992.
17. Ryglewicz D. Stroke epidemiology in Poland. Acta
Clin Croat 1998;37:80-83.
18. @van B. Epidemiology of stroke in the Republic of
Slovenia. Acta Clin Croat 1998;37:95-97.
A. Alajbegoviæ, @. Metelko, S. Alajbegoviæ, D‘. Kantard‘iæ, M. Bratiæ, E. Suljiæ, M. Hrnjica, H. Resiæ / CORRELATION BETWEEN EARLY
AND LATE EPILEPTIC SEIZURES AND DIABETES MELLITUS DURING AND AFTER STROKE
19. Sacco RL, Wolf PHA, et al. Subarachnoid and
intracerebral hemorrhage. Natural history,
prognosis and precursive factors in the
Framingham study. Neurology 1984;34:847.
20. Sach AL.Subarachnoidal hemorrhage. In: Harisson
MJG, Duklen ML, et al., eds. Cerebral vascular
disease. London: Butterworth, 1983.
21. Gavranoviæ M. Dijagnostika i lijeèenje epilepsija.
Sarajevo: Svjetlost, 1988:5-116.
22. Lechtenderg R. Seizure recognition and
treatment. New York, Edinburgh, London,
Melbourne: Churchill Livingstone, 1990:73-74.
23. Sacco RL, Benjamin EJ, Broderick JP, et al. Risk
factors for stroke. Stroke 1997;28:1507-1517.
24. Pemov P. Cerebrovaskularna bolest, savremena
dijagnostika i terapija vo medicinata 2000.
Priruènik za lekari, 2000:1488-1494.
Diabetologia Croatica 31-3, 2002
25. Giroud M, Gras P, Foyolle H, Andre N, Soichot P,
Dumas R. Early seizures after stroke. A study of
1640 cases. Epilepisia 1994;35:959-964.
26. Arboix A, Comes E, Massons J, Garcian L, Olivers
M. Relevance of early seizures for inhospital
mortality in acute cerebrovascular disease.
Neurology 1996;47:1429-1435.
27. Meldrum BS, Porter RJ. Current problems in
epilepsy. New anticonvulant drugs. London: John
Libbey, 1980.
28. Neufeld MY, Vishnevskaya S, Traves TA, et al.
Periodical lateralized epileptiform dischages
(PLEDS) following stroke are associated with
metabolic abnormalities. Electroencephalogr Clin
Neurophysiol 1997;102:295-298.
29. Poeck N. Neurologija. Zagreb: Školska knjiga,
1994:100-200.
30. Hauser WA, Hersdorffer DA. Epilepsy: frequency,
causes and consequences. New York: Epilepsy
Foundation of America – Demos, 1990.
177