INTRODUCTION

 

Post stroke seizure is the most common neurologic sequelae of stroke¹.  Post stroke seizures are classified as early post stroke seizures, within 14 days of stroke and late post stroke seizures when occurring more than 2 weeks after stroke². The frequency of post stroke seizures reported in studies varied from 2.3%³ to 43%⁴ .There are different pathophysiological processes underlying early and late seizures after stroke, with a predominance of acute cellular biochemical disturbances in early seizures and epileptogenic gliotic scarring in late seizures⁵.Cortical site, severity, size of the lesion and site (parietal and temporal regions) were independent predictors of seizures occurrence⁶. Patients with Intracerebral and subarachnoid hemorrhage were at higher risk of seizure after stroke⁷. When seizures occur after stroke, they greatly increase the morbidity and mortality and further impair quality of life⁸. Experimental studies in laboratory animals suggest that, repeated seizures in the setting of cerebral ischemia significantly increases infarct size and can impair functional recovery⁹.Seizures worsen both medical and social prognosis and enhance the disability of both conditions.¹⁰

 

Aim of the work: To study the outcome of post stroke seizures, their effect on the functional disability and to evaluate the risk factors for their development.

 

PATIENTS AND METHODS

 

This study was conducted on 80 (49 males and 31 females) stroke patients aged ≥40 years (66 ischemic and 14 hemorrhagic). Patients were recruited from Neurology Department or Neurology outpatient clinic, Menoufiya University Hospital in the period from (January 2009 to May 2010). Patients were divided into two groups: Group A: patients who developed epileptic seizures for the first time after stroke occurrence (40 patients) with mean age (52.3±4.3) years, they were 22 males (55%) and 18 females (45%).The seizures were classified according to the ILAE   Classification of epileptic Seizures (1981) into generalized, partial (simple partial or complex partial) and partial with secondary generalization.  This group was subdivided into :( 1). (Early Post stroke seizures): those who had their first seizures within the first 2 weeks after stroke onset (9 patients:-2 hemorrhagic and 7 ischemic) and (2) (Late post stroke seizures): Those who had their first seizures after 2 weeks of stroke onset (31 patients:-7 hemorrhagic and 24 ischemic).They also were divided into 20 patients with single seizure and 20 patients with recurrent seizures (recurring seizures ≥ 2 attacks after stroke onset) with absence of other causes of epilepsy(20 patients). Group B: Composed of 40 patients who passed (≥2 years) from stroke occurrence without developing epileptic fits as control group, they were 5 hemorrhagic and 35 ischemic with mean age (51.7±3.6) years. They were 27 males (67.5%) and 13 females (32.5%).                         

Exclusion criteria: 1-Seizures before stroke onset. 2-other neurological and non neurological causes of seizures.3-family history of epilepsy. All patients included in the study were subjected to:

1)      Thorough history taking, complete general and neurological examinations

2)      Routine laboratory investigations including: Complete blood picture, blood sugar (fasting and 2 hours after meal), renal function tests (serum urea and creatinine), liver function tests (Transaminases, serum albumin, Prothrombin concentration, Prothrombin Time and International Normalized Ratio), serum electrolytes (sodium, calcium, magnesium) and lipid profile (serum cholesterol and Triglycerides).

3)      Assessment of neurological deficit and disability using 2 clinical scales: (I) Scandinavian Stroke scale (SSS): The assessment was done at the time of stroke onset to assess initial stroke severity before seizure occurrence. (II) Modified Rankin scale (MRS): The assessment of functional outcome is done twice, before seizure occurrence (retrospectively by history) and after control of seizures 

4)      EEG examination using the Nihon – Kohden 22-channels EEG machine according to the international 10-20 system. The EEG was done after 48 hours from the last epileptic spells. The EEG tracing were analyzed carefully as regard: changes in the background activity   and epileptic activity (focal, generalized or focal with secondary generalization).

5)      CT examination was performed for all patients included in this study. We determine the type (infarction, or hemorrhage) and site of the lesions; moreover, the greatest diameter on the CT slice showing the largest area involved was used to determine the size of the lesion at stroke onset. We also defined the lesion depth as cortical or subcortical. C.T was evaluated at stroke onset and after seizure occurrence to exclude recurrent stroke.

6)      Statistical methods: data were expressed as mean standard deviation for quantitative variables and as numbers and percentages for qualitative variables and analyzed by chi-square. Data were coded using SPSS version 11. P-value <0.05 was considered statistically significant.

RESULTS

 

In group A, there was higher incidence of late seizures, the incidence of early seizures was 22.5% and late seizures was 77.5% and the difference between the two subgroups was highly statistical significant (P<0.001). The incidence of recurrent seizures was 50% (20 patients) of them 4 patients  (20%) with early seizure onset and 16 patients (80%) with late seizure onset}  and the difference between the two subgroups was highly statistical significant (P<0.001). It was found  that the difference in age and gender between group A and B was not statistically significant (P>0.05). As regard clinical and laboratory risk factors as, hypertension, cardiac disorders, smoking, obesity, diabetes mellitus, hyperuricemia, and hyperlipidemia, the difference between the two groups was not statistical significant (P>0.05). As regard clinical presentations of the patients, only sensory deficit (superficial and deep sensory loss and cortical sensory loss) was statistically more prevalent in the seizure group (P<0.001). No significant difference was observed as regard type of sensory deficit between two groups (P>0.05) {27 patients (67.5%) of group A had superficial and deep sensory loss versus 22 patients (91.70 %) of group B. Cortical sensory loss was present  in 10 patients (25%) of group A while it was in 2 patients(8.3%) of group B. There was statistical significant difference as regard initial stroke severity using the Scandinavian stroke scale (SSS), (P<0.05) between seizure group and non-seizure group (Table 1) and between single seizure and recurrent seizure group (Table 2).

As regard assessment of the degree of functional disability by Modified Rankin scale (MRS), the study revealed statistically significant difference between seizure group and non seizure group (Table 3) and also revealed that functional disability increases significantly in group A after seizure occurrence (Table 4) but no significant difference as regard functional disability between patients with single and recurrent seizures or patients with early and late seizures (P>0.05).

As regard EEG findings, this study reported that, all patients (100%) of group A had abnormal EEG (either slowing or epileptic activity) while, 29 patients (72.5%) of group B showed EEG abnormality and this difference was statistically highly significant (P<0.001). Slowing occurred in 20 patients (50%) of group A and in 14 patients (35%) of group B, the difference was not statistically significant (P>0.05). Epileptiform activity either  spike discharges or sharp and slow wave complexes were found in 37 patients (92.5%) and 15 patients (37.5%) of group A and group B respectively and this difference was statistically highly significant (P<0.001), of them, it was focal in (12 of 37 patients)  (32.4%) of group A and 8 of 15  patients (53.3%) of group B and focal with secondary generalization in 19 patients (51.4%) and 5 patients (33.35%) in group A and group B respectively. The epileptic activity was generalized in 6 of 37 patients (16.2%) and 2 of 15 patients (13.3%).The difference between subtypes of epileptic activity was not statistically significant between both groups (P>0.05).

As regard focal epileptic activity (either focal or focal with secondary generalization) it was fronto-temporal in 17 patients (45.83%), temporo-occipital and parietal in 6 patients for each (19.35%), temporal and temporo-parietal in one patient for each (3.22%).

As regard C.T findings, there was significant difference between both groups regarding depth and the size of the lesion and only fronto-temporal and temporo-occipital lesions showed significant difference between both groups  (Tables 5 and 6).

As regard response to anti epileptic drugs, the response of patients with post stroke seizures to antiepileptic drugs and number of anti epileptic drugs used, there were 25 patients (62.5%) became seizure free of them  15 patients (60%) were on one anti epileptic drug and 10 patients (40%) were on two drugs, 8 patients (20%) improved as regard frequency and duration of seizures of them 5 patients were on one drug and 3 patients were on two drugs and 7 patients (17.5%) were not controlled on more than  one anti epileptic drug  as regard duration and frequency.

 

 

Table 1. Comparison of stroke severity between group A and group B assessed by Scandinavian Stroke Scale (SSS).

 

Grading of stroke severity by  (SSS)	Group (A) (N= 40)		Group (B) (N=40)		X2	P-value
	No	%	No	%
Mild stroke (40-58)	13	32.5	35	87.5	25.21	<0.001*
Moderate stroke (20-39)	11	27.5	5	12.5	2.81	>0.05
Severe stroke (0-19)	16	40	0	0	20.0	<0.001*

* significant at p<0.01

 

Table 2. Comparison of stroke severity    among group A between single and recurrent seizures groups assessed by Scandinavian Stroke Scale (SSS).

 

Grading of stroke severity by (SSS)	Group A (n=40)				X2	P-value
	With recurrent seizures (N=20)		Single seizure (N=20)
	No.	%	No.	%
Mild stroke (40-58)	3	15	10	50	5.58	<0.05*
Moderate stroke   (20-39)	5	25	6	30	0.13	>0.05
Severe stroke (0-19)	12	60	4	20	6.67	<0.05*

* significant at p<0.05            

 

Table 3. Comparison of the functional disability between group A and group B assessed by Modified Rankin Scale (MRS).

 

Grading of functional disability by (MRS)	Group(A) (N=40)		Group B) (N=40)		X2	P-value
	No.	%	No.	%
1. No significant disability	1	2.5	16	40	16.81	<0.001**
2. Slight disability	1	2.5	9	22.5	7.31	<0.001**
3. Moderate disability	7	17.5	4	10	0.95	>0.05
4.Moderately severe disability	20	50	10	25	5.33	<0.05*
5. Severe disability	11	27.5	1	2.5	9.8	<0.001**

* significant at p<0.05. ** significant at p<0.01

 

Table 4. Comparison of the functional disability before and after onset of post stroke seizures among group A assessed by (MRS).

 

Grading of functional disability by (MRS)	Group A(n=40)				X2	P-value
	Before onset of seizure (after stroke)		After onset of  seizure
	No.	%	No.	%
1.No significant disability	6	15	1	2.5	3.91	<0.05*
2.Slight disability	9	22.5	1	2.5	7.31	<0.001**
3.Moderately disability	15	37.5	7	17.5	4.01	<0.05*
4.Moderate severe disability	7	17.5	20	50	9.45	<0.001**
5.Severe disability	3	7.5	11	27.5	5.54	<0.05*

* significant at p<0.05. ** significant at p<0.01

 

 

 

Table 5. Type of the pathology, depth and size of the lesion in C.T scan of both groups.

 

Type of the pathology (in C.T scan)	Group A (N=  40 )		Group B (N=40  )		X2	P-value
	No.	%	No.	%
Intracerebral hemorrhage	9	22.5	5	12.5	1.39	>0.05
Infarction: Non-hemorrhagic Hemorrhagic Lacunar	31 26 4 1	77.5 83.8 12.9 3.2	35 29 2 4	82.5 87.90 9.10 3	0.31   1.15	>0.05   >0.05
Associated Brain atrophy	12	30	15	37.5	2.21	>0.05
Depth of the lesion: -                   Cortical extension -                   Deep only	34 6	85 15	20 20	50 50	9.58	<0.001**
Size of the lesion: Less than    1 cm in diameter 1cm to less than 3 cm 3cm to less than 5 cm 5cm or more	1 10 22 7	2.5 25 55 17.5	2 28 9 1	5 70 22.5 2.5	0.4 16.58 9.49 4.68	>0.05 <0.001** <0.001** <0.05*

* significant at p<0.05. ** significant at p<0.01

 

 

Table 6. Distribution of both groups A and B according to the site of the lesion on C.T scanning.

 

C.T findings	Group A (N=40 )		Group B (N=40 )		X2	P-value
	No.	%	No.	%
-                   Fronto-temporal -                   Parietal -                   Parieto-occipital -                   Temporal -                   Temporo-parietal -                   Occipital -           Basal ganglionic, internal capsule, thalamic(each alone or with each other) -                   Lacunar(multiple) -                   Temporo-occipital	11 4 6 0 13 0 1   1 4	27.5 10 15 0 32.5 0 2.5   2.50 10	0 5 7 3 9 3 9   4 0	0 12.5 17.5 7.5 22.5 7.5 22.5   10 0	12.75 0.13 0.09 3.12 1.0 3.12 7.31   0.35 4.21	<0.001** >0.05 >0.05 >0.05 >0.05 >0.05 <0.05*   >0.05 <0.05*

* significant at p<0.05. ** significant at p<0.01

DISCUSSION

 

Vascular risk factors studied as, age; gender; hypertension, diabetes mellitus, obesity smoking; cardiac diseases, hyperlipidemia and hyperuricemia showed no significant influence on the occurrence of post stroke seizures. A result that was reported by De Reuck et al.² and Li et al¹¹. However others suggested that, aging alone may have an epileptogenic  effect on the neurons ,as post stroke seizures are rare below the age of 40 years and its incidence increases rapidly with increasing age¹². Moreover, other studies reported the importance of gender as a risk factor, whereas Kotila and Waltimo⁴ found that, females developed post stroke seizures more than men, Davalos et al.¹³ and Giroud et al.¹⁴ reported the reverse. However, these findings were statistically not significant. Of 20 patients with recurrent  post stroke seizures, 16 patients (80%) had history of late onset seizures, while, 4 patients (20%) had early onset seizures. Therefore, late post stroke seizures was found to be a significant predictor for the recurrence and the subsequent development of epilepsy (P<0.001).The findings was confirmed by De Reuck et al.², however, the studies of So et al.¹²; Lamy et al.¹⁵ and Burn et al.¹⁶, reported that, the early onset seizures are the predictor of further recurrence and not the late onset. The present study disclosed a highly significant association between the occurrence of post stroke seizures and the presence of sensory deficit. This point was supported by Giroud et al.¹⁴ and El-Sayed et al.¹⁷. This may be explained by the assumption that, the presence of cortical sensory deficits indicates involvement of the cortical parietal region which may be (due to its low convulsive threshold), the cause for the increased epileptogenecity. Thus, one may say that the presence of cortical sensory deficit is one among factors predicting the occurrence of post stroke seizures and such finding has its therapeutic application, A stroke patient who had cortical sensory deficit may take antiepileptic drugs as a prophylaxis against the occurrence of post stroke seizures.¹⁸

This study showed significant association of initial stroke severity assessed by (SSS) and the occurrence of seizures after stroke also, it showed that, patients who developed recurrent seizures had severer stroke at the onset and the difference was statistically significant. This was in agreement with the results of Maurizio et al.⁶, Lamy et al.¹⁵, Cheung et al.¹⁹, who concluded that, the main predictors of post stroke seizures and epilepsy was the severity of the initial neurological impairment. This study confirmed the bad influence of seizures following stroke on the functional outcome, same results were previously recorded by Bladin et al.¹⁸. On assessment of seizure group before and after seizure occurrence,   significant worsening in functional disability compared to that before onset of seizure. Moreover, there was significant worsening of functional disability in recurrent seizure group compared to single seizure group, confirming the concept of De Reuck et al.², who notified that, recurrent seizures were more hazardous on stroke patients than single or infrequent ones, raising the matter of debate about if the worsening is due to recurrent ischemic events or it's the effect of the seizure itself on the damaged brain tissue. This study showed  statistically significant association between the occurrence of post stroke seizures and abnormal EEG records. Similar results were observed by El-Sayed et al.¹⁷ and Ryglewicz et al.²⁰, who observed EEG abnormalities in most patients with post stroke seizures.  Most of the focal EEG abnormalities (either focal slowing or focal epileptogenic activity) were mostly confined to temporal region , a finding which was confirmed by Ryglewicz et al.²⁰. This finding may be ascribed to vulnerability of this region to develop focal epileptogenic changes being the most ischemic area which can develops focal epilepsy¹⁶. This study failed to demonstrate statistically significant association (P>0.05) between post stroke seizures and stroke pathology on C.T, this finding is in agreement with El-Sayed et al.¹⁷. On the contrary, Furlan²¹ and Paolucci et al.²², noted post stroke seizures (either early or late) were more frequently seen in patients with cerebral hemorrhage than infarction, while Kotila and Waltimo⁴ reported the prevalence of cerebral infarction in the seizure group  .It was found in this study  that, a lesion of the cerebral cortex was significantly associated with the occurrence of post stroke seizures (P<0.001) regardless the nature of the vascular insult. (85%) of patients with seizures had cortical extension. This finding was in accordance with the work of So et al.¹² and Lo et al.²³, who documented the importance of cortical involvement for the development of post stroke seizures .However, it was also observed that post stroke seizures occurred in 6 patients (15%) with subcortical lesions. A similar finding was noticed by Giroud et al.¹⁴. This finding either ascribed to a sizable subcortical lesion with involvement of cortical zone or to a subcortical lesion with cortical cellular involvement which is too small to be detected by conventional C.T. On the contrast Mohr et al.²⁴, reported that, no subcortical lesions were associated with seizure due its low epileptogenecity. Furthermore, this study demonstrated that, fronto-temporal lesions were significantly higher in the seizure group (P<0.001). This finding was in agreement with that reported by Faught and petters²⁵, and Milandre et al.²⁶, who observed that, temporal lobe lesions are clinically associated with high susceptibility of epileptic seizures. This study showed that, more than one lobe were involved in 34 patients (85%) in patients with post stoke seizures, this was in agreement with Anthony and  Furlan²¹ who stated that, patients at high risk for development of post stroke seizures were those with lesions involving more than one lobe. Concerning the size of the vascular lesion as detected by C.T scan, the present study pointed out that a large sized lesion were associated with high incidence of post stroke seizures than smaller ones. This agrees with the work of Olsen²⁷. lacunar infarctions were observed only in one patient with post stroke seizures (2.5%). Similar figures were reported by Giroud et al.¹⁴ (1%) and Olsen²⁷ (2%). Although, seizures don't result from lacunar infarctions, it's likely that these lacunes reflect a more widespread cerebral vascular disease rather than being the direct cause of post stroke seizures.²⁸

 

Conclusion

Initial stroke severity, cortical, temporal and large sized lesions were predictors of post stroke seizures which had bad outcome on the functional disability of the stroke.

 

[Disclosure: Authors report no conflict of interest]

 

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