Acute childhood ischemic stroke: a pakistani tertiary care hospital experience
V O L .
Acute childhood ischemic stroke: a pakistani tertiar y care hospital experience
Prem Chand 0 1
Muhammad Matloob Alam 0 1
Aga Khan University, Karachi
0 National Medical Center , Karachi , Pakistan
1 Aga Khan University Hospital Karachi , pakistan
2 Department of Biological and Biomedical Sciences, Aga Khan University Hospital , Karachi , Pakistan
3 Department of Pediatrics and Child Health, Aga Khan University Hospital , Karachi , Pakistan
4 9221 3493 4294 Word count: 1631 (excluding references) Date of Submission:
ACUTE CHILDHOOD ISCHEMIC STROKE: A PAKISTANI
TERTIARY CARE HOSPITAL EXPERIENCE
Stroke is debilitating disease which has been increasingly
recognized in children in recent years, but diagnosis and
management can be difficult because of the diversity of
underlying risk factors and the absence of a uniform treatment
approach.1The incidence of ischemic stroke in USA ranges
from 0.56 to 2.4 per 100,000 children per year.4In the
Paediatric population, ischemic stroke occurs in 55% of all
strokes, the rest being hemorrhagic4, 5. In Contrary to adults
in whom ischemic stroke comprises 80% to 85% of all the
strokes cases.4, 5 Though hemiplegia is most common
clinical presentation in pediatric stroke as in adults but seizures
and fever are more common in pediatric strokes which
affecting 27% and 23% respectively of pediatric stroke
patient.6 Even when stroke presents acutely, delay in
diagnosis is common, limiting the opportunities for timely
interventions to improve outcome.4 Thrombolysis is standard
of care for acute ischemic stroke in adult patients which is to
be given within 4.5 hours of stroke onset7. Though the
experience of thrombolysis in pediatric stroke is limited but it
has to be given early8.However, it has been reported that in
about 1/3 of children with stroke present for medical
evaluation within 6 hours of symptom onset9, 10. Risk factor
profile of stroke is distinct from adult stroke and is more diverse
too. These include CNS infections, cardiac diseases
(congenital and acquired) vasculopathies (fibromuscular
dysplasia and moyamoya disease), vsculitidis, sickle cell
disease, coagulopathies and arterial dissection.1,11 In a local
study CNS Infections and cardiac diseases were most
common etiologic factors. 12There is great variability in the
use of antithrombotic and antiplatelet drugs after acute
ischemic stroke (AIS) in children.13 International Pediatric
Stroke group reported that of the 661 children with AIS, the
acute treatment consisted of anticoagulant alone in 27%,
antiplatelet therapy alone in 28%, and a combination of
anticoagulation and antiplatelet therapy in 16% of patients.
Anticoagulation was more likely to be used in children with
dissection and cardiac disease and less likely to be used in
patients with other risk factors 13. After an episode of cerebral
P A K I S T A N J O U R N A L O F N E U R O L O G I C A L S C I E N C E S
ischemia, children usually show substantial improvement in
the first 2 to 3 weeks and slower progress over the next several
months, however, many children are left with persistent
neurologic deficits.14 About 10% of children die during acute
period, and among the survivors, 70% are left with neurologic
deficits15 and approximately 15% to 20% have further
strokes.16, 17 Data on pediatric stroke from Pakistan is
scarce. Our objective is to describe the clinical features,
management and outcome of acute ischemic stroke in
pediatric patients admitted in a tertiary care university hospital
in Karachi, Pakistan.
Materials and methods:
We conducted a retrospective chart review of all cases of acute
ischemic stroke, who were admitted in the pediatric ward of
Aga Khan University Hospital (AKUH), Karachi, Pakistan from
January 2007 till December 2012. Records were retrieved by
using ICD-9 coding system through our health information
management system. Patients aged below one month and
above 14 years were excluded. Patients in whom imaging was
not performed were also excluded. Other exclusion criteria
included patients with post traumatic or post anoxic brain
ischemia and with history of birth asphyxia, spinal and brain
trauma, GuillanBarre syndrome, poliomyelitis, these diseases
could result in seizures and other symptoms of interest on their
own and that would contaminate our data. The demographic,
clinical, laboratory, radiologic and pharmacologic data as well
as post discharge follow up was recorded on a structured
proforma.The data was analyzed on SPSS version 20.0 (IBM,
Chicago, USA). Summary statistics were used to describe the
cohort. Results were presented as mean and standard
deviation for continuous variables and frequencies and
percentage for categorical variables.The study was approved
by the institutional ethics review committee.
We identified a total of 29 pediatric patients with acute
ischemic stroke over a period of 5 years. Their mean age was
4.52 ± 4.1 years with seventy six percent over the age of one
year. Male to female ratio was 3:1. Mean duration of
symptoms at the time of presentation was 5.75±11.73.
Seizures, loss of consciousness, paresis were the commonest
clinical presentations followed by fever, vomiting, cranial nerve
palsy, delayed development, headache and blindness (figure
1). Out of the 21 patients who had seizures at presentation,
13 (62%) had generalized seizures, 7 (33%) had focal and 1
(5%) had myoclonic seizures. The cause of ischemic stroke
was identified in 22 patients and is shown in figure no.2. Past
history of stroke were present in only 2 (7%) patients and
positive family history of stroke were identified in only 1 (3.4%)
patient.Echocardiogram was performed in 13 patients that
revealed myocarditis in 5, tetralogy of Fallot, complex
congenital heart disease and ventricular septal defect one in
each. None of these patients had patent foramen ovale.
Ejection fraction was low in 4 patients (40% in one and
20-25% in 3). Prothrombotic workup was performed in 8
patients and 3 of these had hypercoagulopathy (protein S
deficiency in 2 and protein C deficiency in 1). CNS infections
were noted in three patients (2 meningitis, 1 encephalitis),
hematologic abnormalities noted in three patients (one each
had hemophagiclymphohistiocytosis, thalassemia major who
underwent bone marrow transplant and hereditary
spherocytosis), three had vasculopathies (moyamoya in one
and idiopathic vasculopathy in 2), 2 had possible
mitochondrial disorders and 2 had dehydration/hypovolemia.
All patients underwent brain imaging (4 had only CT scan of
head and 25 had either MRI brain or CT and MRI both).
Anterior circulation strokes were seen in 16 (55%), posterior
circulation strokes in 4 (14%) patients while in 9 (31%)
patients both circulations were effected. Twelve (41%) had
bilateral and 17 had (59%) unilateral strokes. Eight (28%)
received anticoagulation and 20 (69%) received aspirin.
Anti-seizure medications were given to 22 (76%) patients. All
children received supportive treatment acutely, with some
receiving physical, speech, or occupational therapy or a
combination of rehabilitation modalities. Mean length of stay
was 7±5 days. Eight (28%) patients died during the hospital
stay and 21 patients were sent home.In a univariate analysis,
multiple strokes and age below one year were associated with
higher mortality(Table no 1). Each of the survivor had at least
two follow up visits and their mean follow up period was 15
+/- 9.5 months (Range: 2-35). Four patients died during
follow up while 3 patients had complete recovery, and 14 of
17 (82%) patientshad residual neurologic deficit (motor,
cognitive deficits or both).
This study presents a detailed report of the patients who
presented to Aga Khan University Hospital with ischemic stroke
during a 5 year period. Mean age of our patients was 4.5±4.2
(median 3) years and there was male predominance. An
Indian study reported mean age of about 11 years while
international pediatric stroke study (IPSS) reported median
age of about 5 years.13,18 Though the age of our patients
was relatively younger but we noted male preponderance
which has been reported by a hospital based in India and the
multicenter IPSS13,19 The relatively younger age group at
presentation (mean 39 months) has been reported earlier
from Pakistan3. Selection bias is always a possibility in
hospital based studies specially the retrospective ones but
possibility of the fact that stroke in our country occurs at
younger age cannot be excluded. In Pakistan adult stroke has
been reported to occur about a decade earlier than that
P A K I S T A N J O U R N A L O F N E U R O L O G I C A L S C I E N C E S
reported from West.20,21 We noted that cardiac disorders
(congenital or acquired) were the most common causes of
stroke in our patients followed by CNS infections,
hypercoagulopathies, hematological diseases and
vasculopathies. This finding that is consistent with previous
reports.1, 3, 11, 12, 18, and 22 Previous studies reported
that hemiplegia was the most common clinical presentation
followed by seizures in such patients.3, 6, 18However; our
data showed that seizures were more common manifestation
followed closely by hemiplegia. One reason could be that our
patient presented to the hospital early, before the onset of
more advance symptoms such as hemiplegia. The treatment
for ischemic strokes most commonly reported in other studies
consists of anticoagulants, antiplatelets or a combination of
both of these.13a similar strategy was noted in our patients,
however, in IPSS anticoagulation and antiplatelet were used in
almost equal number of the patients while most of our
patients received antiplatelet agent. This simply reflects
variations in stroke management among the treating
physicians. Though there is robust evidence for specific
treatment in stroke patients with sickle cell disease,
moyamoya disease but for rest of patients the evidence and
recommendations are of relatively low level.1 The mortality
rate among our patients in acute period (during index
hospitalization; mean hospital stay was 7±5 days) was 28%
which is significantly higher than earlier reports which
mentioned mortality below 10%.13,16, 17,18 Similarly,
post-discharge mortality of our patients was also high i.e. 14%
of the survivors died during the mean follow up period of
15±9.5 days. The high mortality rate is probably multifactorial.
Most of our patients had bilateral multiple strokes which has
been reported as poor prognostic factor.13 Cardiac disorders
were most common etiologic factors in our patients and these
are reported to be more frequently associated with bilateral
strokes.22 Young age and fever at presentation have also
been reported as poor prognostic factors in long term.23
Mean age of our patients was relatively young comparative to
the age reported in literature and about 40% of our patients
had fever at presentation. Thesemight be the contributory
factors to poor outcome in our patients. Additionally, lack of
trained neurologists (most of pediatric stroke patients are
managed by general pediatricians), lack of stroke units and
lack of pediatric focused rehabilitation services, all might be
contributory. Previous studies have reported that among the
patients who survive after a stroke 70% has persistent
neurological deficits.16, 17 we also noted residual neurologic
deficits in 82% of the patients.Our study shows that clinical
presentation, etiologic factors and prophylactic management
is more or less similar to prior reported literature, however,
significant differences were also noted including relatively
younger age at onset, high immediate and long term mortality.
The establishment of multicenter pediatric stroke database
study in Pakistan is needed to further evaluate our findings.
The study was conducted at Aga khan University Hospital,
Karachi, Pakistan The results were presented at 6th pediatric
neurology conference in Pakistan. We acknowledge Ms. Hina
Tejani for assistance in making tables and graphs.
The study was approved by the institutional ethical review
committee No: 2817-Ped-ERC-13
P A K I S T A N J O U R N A L O F N E U R O L O G I C A L S C I E N C E S
Conflict of interest: Author declares no conflict of interest.
Funding disclosure: Nil
Dr. Prem Chand: Study concept and design, protocol writing, data collection, data
analysis, manuscript writing, manuscript review
Dr. Shahnaz Ibrahim: Study concept and design, data analysis, manuscript writing, manuscript review
Dr. Muhammad Matloob Alam: data collection, data analysis, manuscript writing, manuscript review
Dr. Fazal Arain: data analysis, manuscript writing, manuscript review
Dr. Bhojo Khealani: Study concept and design, manuscript writing, manuscript review
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