Epilepsia, 38(3):266-270, 1997
Lippincott-Raven Publishers, Philadelphia
0 International League Against Epilepsy
Poststroke Late Seizures and Their Role in Rehabilitation
of Inpatients
Stefan0 Paolucci, *Giulia Silvestri, Sergio Lubich, Luca Pratesi, Marco Traballesi, and
*Gian Luigi Gigli
IRCCS S. Lucia, and *Department of Neurology, Tor Vergata University, Rome, Italy
Summary: Purpose: This study was designed to (a) identify
the prevalence of poststroke late seizures in a population of
patients admitted to rehabilitation of neurologic sequelae of
their first stroke, (b) recognize reliable prognostic factors as-
sociated with the occurrence of poststroke late seizures, and (c)
evaluate the impact of seizures on the results of rehabilitation
treatment.
Methods: In a prospective study of 306 consecutive patients
admitted to a rehabilitation hospital for sequelae of their first
stroke, we assessed the relation among 15 independent vari-
ables and the development of seizures by using multiple re-
gression analysis (forward stepwise). In addition, we evaluated
the impact of occurrence of poststroke seizures on both effi-
ciency and effectiveness of rehabilitation and length of stay.
Results: Poststroke late seizures occurred in 46 (15.03%)
patients, with a mean interval from stroke of 101.98 f 37.96
Stroke incidence is very high (200/100.000) in western
societies (l), and stroke is one of the most common
causes of death or disability. Despite the relatively low
incidence of epilepsy ( 6 9 % ) after cerebral stroke, be-
cause of its high incidence, stroke is one of the most
common causes of epilepsy (2-7). Epilepsy was defined
as a condition of recurring seizures, according to the
International League Against Epilepsy (8). This applies
particularly to the elderly, the age group most at risk for
stroke.
Patients with hemorrhagic stroke, cortical lesions, le-
sions involving more than one cerebral lobe, and persist-
ing paresis are at higher risk of developing seizures
(3,5,7,9-1 l).The higher incidence of epilepsy in patients
needing rehabilitation was confirmed by Kotila and Wal-
timo (12). Computed tomography (CT) scan is valuable
in the identification of patients at risk for developing
epilepsy, whereas EEG is not helpful in predicting the
Accepted September 13, 1996.
Address correspondence and reprint requests to D ~ G, , L, ~ i ~atl i
IRCCS S. Lucia, via Ardeatina, 306, 00179 Roma, Italy.
266
days. In multiple regression analysis, putaminal and lobar hem-
orrhages showed a significant positive association with the de-
velopment of seizures (p < 0.005), whereas high scores on the
Canadian Neurological Scale (CNS) (indicating less severe
strokes) and increasing age were negatively associated (p <
0.01 and p < 0.05, respectively). Patients with putaminal and
lobar hemorrhages and patients with severe stroke (CNS score
at admission, <7) were at significantly greater relative risk of
seizures [relative risk (RR) = 1.99, 95% confidence interval
(CI), 1.11-1.39; RR = 3.00, CI, 1.06-1.13; and RR = 2.41,
CI, 1.01-1.27, respectively). No significant association was
found between poststroke seizures and results of rehabilitation.
Conclusions: Poststroke late seizures occurred mainly in pa-
tients with putaminal and lobar hemorrhagic strokes but, if
treated, did not affect rehabilitation therapy. Key Words:
Stroke-Epilepsy-Rehabilitation.
occurrence of seizures (4-7,13). The risk of recurring
seizures is higher if the first seizures occur in the chronic
stage, compared with seizures occurring in the acute
phase after stroke (14-16). Despite the higher risk of
developing epilepsy among patients in need of rehabili-
tation for neurologic sequelae after stroke, the problem
of the consequences of epilepsy occurrence on rehabili-
tation programs and functional outcome has not been
addressed.
The aims of our study were (a) to identify the preva-
lence of poststroke late seizures among inpatients admit-
ted to rehabilitation for neurologic deficits, (b) to recog-
nize reliable prognostic factors associated with the oc-
currence of poststroke late seizures, and (c) to assess
their influence on the results of rehabilitative treatment.
METHODS
Subject selection
The study included 306 consecutive patients admitted
to our rehabilitation unit for neurologic sequelae of their
first stroke. The sample was not community based (pa-
 POSTSTROKE LATE SEIZURES AND REHABILITATION
tients were referred by general hospitals), and no selec-
tion was made before admission, except for the clinical
indication for physical rehabilitation. Stroke was de-
fined, according to the Stroke Data Bank (17), as a sud-
den, nonconvulsive, focal neurologic deficit persisting
for >24 h. The diagnosis of stroke was based on history,
clinical examination, and neuroradiologic findings [CT
scans or magnetic resonance imaging (MRI)]. Each pa-
tient underwent either a CT or a MRI examination, at
least.
Exclusion criteria included patients older than 79
years, previous cerebrovascular accidents, subarachnoid
hemorrhage, presence of other chronic neurologic (i.e.,
multiple sclerosis, amyotrophic lateral sclerosis, and
polyneuropathy) or disabling diseases (severe cardiac,
liver, or renal failure; cancer, limb amputation, etc.). Pa-
tients with a history of seizures before the stroke, at
stroke onset, or after stroke but before transfer to the
rehabilitation ward were excluded from the cohort.
Neurologic and functional assessment
To measure severity of stroke, we used the revised and
validated version (1 8) of the Canadian Neurological
Scale (CNS), proposed by Cot6 et al. in 1986 as impair-
ment scale (19), with a cut-off score of 11.5 for normal
patients.
Activities of daily living (ADL) status was measured
6y means of Barthel Index (20) (BI), the validity and
reliability of which has been well established (21). The
scale gives scores ranging from 0 to 100, with the top
score implying full functional independence, even if not
necessarily a normal status.
Specific mobility was monitored by means of River-
mead Mobility Index (22) (RMI; derived from the River-
mead Motor Assessment), which assesses the ability of
the patient through 15 common daily movements. The
scale, whose score ranges from 0 (totally unable) to 15,
proved to be valid and reliable for evaluating mobility
after stroke and head injury (22). It has recently been
used (in an earlier version, with a maximum score of 20)
in a randomized crossover trial in stroke rehabilitation
(23).
Individual physiotherapy, essentially based on Bo-
bath’s therapeutic exercises and adapted to the needs of
each patient, was performed for 60 min twice daily, 6
days a week. The stay in the rehabilitation hospital usu-
ally continued until clinical recovery was judged to be
stabilized, but in a few cases, discharge had to be delayed
because of nonmedical factors.
At admission all patients were submitted to CNS, BI,
and RMI, whereas at discharge, CNS was not used be-
cause the target of the rehabilitation was the functional
and not the neurologic recovery. All evaluations were
made by the same neurologic staff. We calculated reha-
bilitation results by using efficiency and effectiveness of
267
treatment (24). Efficiency is the amount of improvement
in the rating score of each scale divided by duration of
rehabilitation stay; it represents the average increase per
day obtained by therapy. Effectiveness reflects the pro-
portion of potential improvement achieved during reha-
bilitation, calculated by this formula: (Discharge score -
initial score)/(Maximum score - initial score) x 100.
Therefore if a patient achieves the top score after the
rehabilitation, effectiveness is 100%.
Data analysis and statistics
The incidence of seizures in each type of stroke and
the timing relative to stroke onset were recorded. A
1-year follow-up was performed in patients who had sei-
zures. In the other patients, the observation was stopped
after discharge, but patients were instructed to inform the
medical staff if seizure or any other relevant clinical
event occurred. Seizures have been classified according
to their respective clinical signs and electroencephalo-
graphic characteristics, as developed by the Commission
on Classification and Terminology of the International
League Against Epilepsy (8).
To evaluate reliable factors predicting the occurrence
of poststroke seizures, a multiple regression analysis
(forward stepwise) was performed by using as dependent
variable the development of seizures (coded as 1 = pre-
sent and 0 = absent) and 15 different independent vari-
ables. Independent variables were age, sex (coded as 1
= male and 2 = female), days elapsed from stroke to
admission, side of motor deficit (coded as 1 = right
hemiparesis/hemiplegia and 2 = left hemiparesis/
hemiplegia), stroke severity (CNS score at admission),
hypertension, diabetes, heart disease, middle cerebral ar-
tery infarction, deep lacunar lesions, vertebrobasilar
ischemia, infarctions in uncertain areas, lobar hemor-
rhages, putaminal hemorrhages, or thalamic hemor-
rhages. The last eleven variables were coded as 1 or 0,
according to the presence or absence of the event. Rela-
tive risks of occurrence of seizures were calculated ac-
cording to results of multivariate analysis.
To evaluate the relations between seizure occurrence,
clinical variables, and rehabilitation results, we per-
formed five other multiple regressions (forward step-
wise), by using as dependent variable, length of stay,
efficiency, and effectiveness on both BI and RMI, re-
spectively. Independent variables were the same as the
first analysis plus poststroke seizures, Broca’s aphasia,
global aphasia, and hemineglect. These four latter vari-
ables were coded as 1 or 0, according to the presence or
absence of the disorder.
Data analyses were performed by using the CSS/3
(Statsoft, Inc.) Statistical package.
RESULTS
All patients but one were white. Sex distribution was
equal between men and women. Mean age was 63.61 f
Epilepsia, Vol. 38, No. 3, 1997
268
11.45 years (median, 67 years), and mean interval be-
tween stroke and admission was 54.13 f 36.3 1 days (me-
dian, 47 days). The length of this interval is because in
Italy, the number of beds available in rehabilitation is
considerably lower than the potential demand. Before
stroke, none of the patients was institutionalized.
Clinical and neuroradiologic diagnosis was of isch-
emic stroke in 247 (80.72%) of 306 patients, and of
cerebral hemorrhage in 59 (19.28%); 161 (52.61%) pa-
tients had a right hemiparesis or hemiplegia, whereas 145
(47.39%) were affected by a left-sided motor deficit.
Hemorrhagic patients were younger (F = 5.51; p =
0.02) than ischemic patients (60.45 k 12.26 years vs.
64.32 f 11.16 years).
Among ischemic strokes, 144 (58.3%) of 247 were
infarcts in the territory of the middle cerebral artery
(MCA), 57 (23.08%) were deep lacunar infarcts, 17
(6.88%) were infarcts in vertebrobasilar territory, and the
remaining 29 (1 1.74%) were of uncertain localization.
Among hemorrhagic lesions, 29 (49.15%) were lobar, 14
(23.73%) putaminal, and the remaining 16 (27.12%)
were thalamic.
In all patients, the presence of hypertension, diabetes,
heart disease (i.e., previous myocardial infarction, atrial
fibrillation) or of other risk factors was recorded. Mean
length of stay in rehabilitation hospital was 122.66 f
30.66 days. Seizures occurred in 46 (15.03%) patients,
with a mean interval from stroke of 101.98 k 37.96 days.
Seven ( 15.22%) patients had generalized tonic-clonic
seizures, probably of focal origin; the remaining 38 had
partial seizures (simple partial or complex partial). All
patients received anticonvulsant drugs, 38 with carba-
mazepine monotherapy and seven (15.22%) with poly-
therapy. In consideration of the lesional substrate of epi-
leptogenicity in this group of patients, antiepileptic treat-
ment was started immediately after the first seizure.
TABLE 1. Demographic and neuroradiologic characteristics of the sample
Gender
Female
Male
Age
646
46-55
5545
6&75
275
Ischemic strokes
MCA territory
Lacunar deep infarcts
Border or uncertain areas
VB territory
Hemorrhagic strokes
htaminal
Thalamic
Lobar
MCA, middle cerebral artery; VB, vertebrobasilar.
Epilepsia, Vol. 38, No. 3, 1997
S. PAOLUCCI ET AL.
Despite this, 12 (26.09%) patients had a second seizure
during their stay in rehabilitation hospital, and this per-
centage increased to 89.13% at 1 year after discharge
from the hospital.
Table 1 shows medical, demographic, and neuroradio-
logic findings of the sample, divided according to the
occurrence of seizures.
Patients with seizures showed at admission a greater
severity of stroke, with an impairment score (CNS) sig-
nificantly lower than that of patients without seizures
(5.04 k 1.98 vs. 6.18 f 2.14; z = -3.245; p < 0.005). In
addition, the prevalence of hemorrhagic lesions was sig-
nificantly higher (x2 = 8.36; p < 0.01) in patients with
seizures than in patients without seizures.
In multiple regression analysis, the first significant
predictive variable (p < 0.005) to enter the equation was
putaminal hemorrhages, followed by lobar hemorrhages,
with p positive regression coefficients (p = 0.183 and p
= 0.145, respectively). The other significant variables
were CNS score at admission (severity of stroke) (p =
-0.153; p < 0.01) and age (p = -0.103; p < 0.05), both
with a p negative regression coefficient.
In this model, days of interval between stroke and
admission, hypertension, and deep lacunar lesions were
not significant, whereas sex, side of motor deficits, dia-
betes, heart disease, MCA infarctions, infarctions with
uncertain localization, vertebrobasilar ischemia, and tha-
lamic hemorrhages did not enter the equation. As shown
in Table 2, patients with putaminal and lobar hemor-
rhages and patients with severe stroke (CNS score at
admission <7) had a significantly higher RR of occur-
rence of seizures (RR = 1.99,95% CI, 1.11-1.39; RR =
3.00, CI, 1.06-1.13; and RR = 2.41, CI, 1.01-1.27,
respectively).
In the other five multiple regressions analyses with
functional measures as dependent variables (length of
n With seizures (% of no.)
153 22 (14.38)
153 24 (15.69)
31 8 (25.81)
31 7 (22.58)
79 12 (15.19)
135 18 (13.33)
30 l(3.33)
144 21 (14.58)
50 7 (12.29)
28 l(3.57)
16 l(6.25)
14 4 (28.57)
16 l(6.25)
29 11 (37.93)
 POSTSTROKE LATE SEIZURES AND REHABILITATION
TABLE 2. Relative risks of occurrence of seizures
Putaminal hemorrhages
Lobar hemorrhages
Seventy of stroke (CNS score <7 vs. 2 7 )
Age (<46 vs. 246)
Any group was compared with all other patients.
CNS, Canadian Neurological Scale; CI, confidence interval.
stay, efficiency, and effectiveness on both BI and RMI),
development of epileptic seizures entered into all but one
equation but was never significant. Seizures did not enter
into analysis with efficiency on RMI as dependent vari-
able. Multiple R2 were 0.188 (length of stay); 0.038 and
0.242 (both efficiency); and 0.390 and 0.336 (both ef-
fectiveness). In all analyses, CNS score at admission
(severity of stroke) was the most powerful prognostic
factor, positively correlated with rehabilitation results,
and negatively, with length of stay. Relevant prognostic
factors were also hemineglect, days of interval before
admission, and age.
DISCUSSION
In our study, the percentage of patients developing late
seizures after a first stroke (15.03%) is higher than those
usually reported in similar studies conducted on unse-
licted patient populations (2-7). This is probably be-
cause our case series was selected for the need of reha-
bilitation, usually for permanent language or motor defi-
cits, indicating a higher severity of stroke. Higher
prevalences of late seizures were found by other authors
in patients with permanent neurologic deficits (7) or
needing rehabilitation (12).
From our data, patients at risk for developing late sei-
zures are younger patients affected by severe strokes
with hemorrhagic lesions. In particular, putaminal and
lobar hemorrhages are significantly associated with sei-
zures. However, in our series, younger age is a weak
predicting factor, showing only a slight association (p <
0.05) with occurrence of seizures at multivariate analy-
sis. In fact, relative risk of seizures in younger patients
(younger than 46 years) compared with the older patients
did not reach statistical significance. We have been un-
able to find this association in other studies on poststroke
late seizures. A tentative explanation of the slight asso-
ciation of seizures with younger age could be found in
the generally weaker epileptogenicity of older brains.
Altogether our findings indicate that younger patients
with putaminal and lobar hemorrhagic lesions in need of
rehabilitation constitute a group that should be carefully
monitored to examine a possible development of epi-
lepsy.
At 1-year follow-up, the percentage of patients with
recurrence of seizures, for whom it is possible to speak of
269
Relative risks 95% CI
1.99 1.1 1-1.39
3.00 1.06-1.13
2.41 1.01-1.27
1.87 0.98-1.23
a true epileptic condition, is very high (89.13% of the
group with seizures). This percentage, which could have
been even higher if a treatment had not been started
immediately, is in accordance with data from literature,
indicating that epilepsy developed in 90% of patients
with late poststroke seizures, compared with 35% of pa-
tients with early seizures (16).
Similar to other previous studies, a higher prevalence
(27.12%) of late seizures was found among patients with
hemorrhagic lesions (3,5,7,9,10). In ischemic strokes,
this was only 12.15%, with the higher frequency in MCA
lesions. All but one of MCA lesions associated with sei-
zures were observed in cortical lesions.
The most important results in terms of risk factors
predicting seizure development are putaminal and lobar
hemorrhages, followed by severity of stroke and younger
age. Therefore the relevant role of cortical hemorrhages
is independent of the severity of stroke. In our series, the
effect of younger age is partially dependent of the other
variables, because hemorrhagic patients were signifi-
cantly younger than ischemic patients. On the contrary,
the percentage of thalamic hemorrhages was higher
among patients without seizures, indicating that purely
deep lesions are less at risk for the development of sei-
zures.
The most interesting findings of our study concern the
poor impact of the late seizures on rehabilitation and
functional outcome. In fact, no significantly association
was found in multiple regression analyses with length of
stay and efficiency and effectiveness on both BI and
RMI. The assessment of these three parameters permits a
global evaluation of rehabilitation results.
Relevant prognostic factors were severity of stroke
(CNS score at admission), hemineglect, days of interval
before admission, and age. In our series, the development
of seizures is not associated with a worsening of func-
tional outcome. Because worsening of neurologic status
is not uncommon in patients with poststroke seizures,
especially after seizures of longer duration (25), we won-
der if the lack of negative consequences on functional
outcome in our series could be interpreted as an effect of
the immediate phmacologic treatment. In this case,
treatment after late poststroke seizures should be started
as soon as possible. In addition, the presence of groups
more at risk for developing seizures suggests the interest
Epilepsia, Vol. 38, No. 3, 1997
2 70 S. PAOLUCCI ET AL.
in prospective studies with prophylactic treatment of pa-
tients.
Acknowledgment: This study was supported by a fund of
the Italian Ministry of Health.
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