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THE CAUSES AND NEUROIMAGING FINDINGS IN PEDIATRIC ARTERIAL ISCHEMIC STROKE.

Byline: Shaila Ali, Muhammad Zia Ur Rehman and Tipu Sultan

ABSTRACT

Objective: To determine the causes of arterial ischemic stroke and neuroimaging findings in children.

Study Design: An observational, prospective, cross-sectional study.

Place and Duration of Study: Department of Paediatirc Neurology, Children's Hospital and Institute of Child Health, Lahore for a period of six months from Nov 2014 to Apr 2015.

Material and Methods: Children from 1 month to 18 years of age with radiologically confirmed arterial ischemic stroke, occurring 1st time in life, were included in the study. Arterial ischemic stroke (AIS) was confirmed on the basis of history, examination and neuroimaging findings of the brain. Further investigations were done according to the cause of arterial ischemic stroke and neuroimaging brain findings.

Results: A total of 72 patients of arterial ischemic stroke were identified over a period of 6 months. Among these, male predominance was found in 53 (73%) children. Outpatient department patients outnumbered the indoor patients with stroke in 38 (53%) children. Children between 1-5 years of age were the most affected ones (65%). Hemiplagia, fits, hemiparesis and aphasia were the most common presenting features affecting 60 (83%), 27 (38%), 14 (19%) and 8 (11%) children respectively. The commonest cause of arterial ischemic stroke was iron deficiency anemia, found in 30% (n=22) of the children followed by anemia due to other causes in 27% (n=20) and congenital heart diseases in 8.3% (n=6) of the children. On neuroimaging studies, parietal lobe was the most affected part of the brain in 23% of the children (n=16). Middle cerebral artery was the major artery affecting 57% (n=12) of the patients.

Conclusion: Iron deficiency anemia, anemia due to other causes and congenital heart diseases were common etiologies in children with arterial ischemic stroke in our study. Parietal lobe and middle cerebral artery were the most affected areas of the brain on neuroimaging.

Keywords: Aphasia, Arterial ischemic stroke, Hemiparesis, Hemiplegia, Iron deficiency anemia, Neuroimaging.

INTRODUCTION

Pediatric stroke is defined as an acute focal neurological deficit in a child lasting for >24 hours until proven otherwise. It can be ischemic or hemorrhagic depending on the cause. The ischemic varieties include arterial ischemic stroke (AIS) and cerebral sin venous thrombosis. The AIS is the focal ischemic brain injury leading to infraction due to occlusion of anterior, middle or posterior cerebral arteries or their branches. In hemorrhagic stroke there is intracranial hemorrhage without trauma1. Childhood arterial ischemic stroke is one of the serious and important causes of morbidity and mortality. Cerebrovascular accident (CVA) is the 10th leading cause of death in children in United States. Each year 1 in 4,000 newborns and 2000 older children are affected by stroke2. The incidence of AIS annually among infants in children ranges from 0.63 to 7.9/100,000 children per year3.

Over the past few decades, the incidence of stroke has become twice in low and middle income countries and has dropped to 40% in high income countries3-4. World health organization (WHO) carried out measurements including two important parameters of age and gender affecting the incidence and mortality rates of stroke. There was more than 10 fold difference in both parameters among different countries. Both were higher in low income countries (North Asia, Eastern Europe, Central Africa and South Pacific) as compared to high income countries (Western Europe, North America)4 Stroke incidence varies with age as infants are highest to be affected than children5. Non-Asian and white children were at lower risk of AIS than Asian and black children6. Similarly male children are at greater risk than female3,6.

The main causes of AIS in children are congenital and acquired heart diseases, central nervous system infections like meningitis/encephalitis, head trauma, sepsis, arrhythmias, sickle cell disease6, iron deficiency anemia1, disorder of coagulation, drug induced, autoimmune diseases like systemic lupus erythematosis, metabolic diseases (mitochondrial disorders), intracerebral vascular abnormalities (moya moya), Arterio-venous malformation and aneurysms7. Most population based studies on pediatric stroke were from continents other than Asia. There was lack of data of stroke among Asian children. In this study we tried to find out the causes and neuro-imaging findings of children presenting with AIS in a tertiary care center.

MATERIAL AND METHODS

It was an observational, prospective, cross-sectional study, conducted at the Neurology department of Childrens Hospital and The Institute of Child Health, Lahore, Pakistan. Children from 1 month to 18 years of age, having focal neurological deficit for >24 hours with radiologically confirmed AIS with 1st ever ischemic stroke were included in the study. Study was conducted during calendar year period November, 2014 - April, 2015 (a total duration of 6 months). Written informed consent was taken from the parents. Study was approved by the institutional review board. Patients were selected by non-probability convenience sampling technique. Sample size of 72 patients was calculated by using Open Epi sample size calculator, version 3, with 95% confidence level, 5% confidence limit (precision). Percentage of anticipated population (p) was 6% +- 5. The sample size was calculated by the following equation

Sample size n = [DEFF*Np(1-p)]/[(d2/Z21-[alpha]/2*(N-1)+p*(1-p)]

AIS was confirmed on the basis of history, examination and neuroimaging brain findings. Further investigations were done according to the cause of AIS and CT scan brain findings. The data was collected on proforma. Patients with central nervous system infection, trauma, space occupying lesion and re-current stroke were excluded from the study. Stroke was defined as sudden onset of a focal neurological deficit due to vascular cause lasting >24 hours. Arterial ischemic stroke is ischemia from blockage of 1 or more arteries supplying brain as detected radiologically by neuroimaging due to a thrombus or an embolus. Stroke symptoms include hemiparesis, hemiplegia, slurred speech, aphasia, seizures, worsening or sudden headaches, sudden loss of vision, abnormal eye movements, sudden loss of balance, difficulty in walking, dysphagia, change in mood, cognitive and personality changes2,7. Investigations vary from non-invasive to invasive modalities.

In younger children (<18 months of age) cranial ultrasonography was done. Other labs included work up for blood clotting disorder, Electroencephalography, Echocardio-graphy, Computed tomography scan brain, Magnetic resonance imaging, Magnetic resonance arteriography, according to history and examination specific labs were done2,7. Anemia was defined as Hemoglobin (Hb) <10 mg/dl in infants and <8 mg/dl in children, low Mean corpuscular volume is taken as (MCV) <56 in all ages groups. Iron deficiency was taken when S/iron level falls <40 ug/dl in infants and <50 ug/dl in children. The data was analyzed by using SPSS version 20. Quantitative variables like age was presented as mean and standard deviation while qualitative variables like MRA and MRI findings were presented in frequencies and percentages. Chi-square test (x2) was used to compare the variables. A p-value of 10 years

Iron deficiency###5###15###0###2###22(30.5%)

Idiopathic###1###10###6###2###19(26.3%)

Anemia(other causes)###2###15###2###1###20(27.7%)

CCHD###1###5###0###0###6(8.3%)

Down syndrome###0###2###3###0###5(7%)

Total###9###47###11###5###72

Table-II: Showing statistics of Hb, MCV and serum iron.

###Multiple,###Brainstem, basal ganglia,###Parietal lobe, Frontal

Causes###Temporal,###Caudate nucleus, thalamus,###lobe and internal

###Oocipital areas###Periventricular area###capsule

Anemia###20###0###0

Idiopathic###9###10###0

Iron deficiency###0###9###13

anemia

Down syndrome###0###0###5

CCHD###0###0###6

Total###29###19###24

Table-III: Showing the frequencies and association between the causes and radiological findings in arterial ischemic stroke in children.

###Statistics

###Age in months###HB###MCV###IROn

Mean###44.54###8.97###65.63###64.92

Std. Deviation###36.47###2.07###12.84###22.10

Minimum###3.00###4.60###37.00###24

Maximum###180.00###13.70###96.00###115

Table-IV: Comparison of different studies in different regions of the world on spectrum of arterial ischemic stroke in children.

###Our study###Mallick et al.###Dowling et al.###Maguire et al.###Chand et al.

###(2008-9) UK###(2003-7) UK###(1992-2004)###(2009-15)

###Canada###Pakistan

Mean age###44 months###12 months###67 months###24 months###53 months

###No gender###No gender

M:F###3:1###difference###1.5:1###difference###3:1

Most common###Hemiplegia###Hemiplegia###Hemiplegia###Not seen###Seizure

Clinical feature

Most common###Iron deficiency###Not seen###Only cardiac###Iron deficiency###Cardiac

Cause###anemia###Pts seen###anemia

Cardiac causes###8.4%###23%###33.3%###excluded###28%

Territorial###MCA 57%###Not seen###MCA67%###Not seen###MCA56%

distribution

RESULTS

A total of 72 patients aged from 1 month to 18 years with AIS were identified over a period of 6 months. There was male pre-dominance with male to female ratio of 3:1. Patients were subdivided into 4 age groups. Majority of patients presented between 1-5 years of age followed by school going group between 5-10 years of age (table-I). A p-value was found to be not significant which shows weak relationship between causes and age of children with AIS (p<0.858). Chi-square test (x2) was used to compare the variables. A p-value of <0.05 was taken as statistically significant. The most common mode of presentation of patients was through OPD. Focal neurological deficit in the form of hemiplegia was the most common presentation in 60 (83%) patients followed by fits in 27 (38%) and hemiparesis in 14 (19%) children. Less common presentations included aphasia, headache, blindness/dysphagia followed by ataxia in 8 (11%), 5 (6.9%), 3 (4.16%) and 1 (1.4%) patient respectively.

Iron deficiency anemia was the most frequent cause of stroke in 22 (30.55%) children followed by anemia due to other causes (vitamin B 12 and folic acid deficiency, worm infestation, etc) in 20 children (27.7%) and idiopathic causes in 19 (26.3%) children. Among the congenital heart diseases, 6 (8.3%) patients with cyanotic congenital heart diseases (like tetrology of fallots and transposition of great arteries with ventricular septal defect) presented with stroke. In this study there were 5 patients with Down's syndrome who presented with stroke with no heart defects (fig-1). Table-I and fig-1 show causes of arterial ischemic stroke in different age groups Children between 1-5 years of age (mean= 44 months) with iron deficiency anemia had lower level of Hb (mean=8.9mg/dl), MCV (mean= 65) and serum iron (mean=64) as compared to other groups (table-II). All patients underwent neuroimaging with equal right to left cerebral hemisphere involvement with ratio of 1:1.

MRA was done in 22 cases in which there was suspicion of stroke involving specific arterial territorial involvement as indicated by CT/MRI brain. The most common single anatomically infracted area was the parietal lobe in 16 (22%) patients followed by the frontal lobe in 4 (5%) patients. Less commonly, there were few cases who had multiple, temporal and occipital lobe infarctions in 29 (collectively 40%) patients (fig-2). While the deeper structures including basal ganglia, internal capsule, brain stem, caudate nucleus and thalamus were involved in small number of 19 patients (collectively 26.3%) (fig-2). MRA was done in 22 patients (30.6%). The most commonly involved artery was middle cerebral artery (MCA) in 55% of cases (n=12) followed by internal carotid artery in 14% (n=3) and anterior cerebral artery in 9% (n=2) (fig-3).

Data was analyzed and p-value was found to be highly significant which shows strong relationship between causes and neuroimaging findings in children with AIS. (p<0.001) as shown in (table-III). Chi-square test was used to compare the variables. A p-value of <0.05 was taken as statistically significant.

DISCUSSION

Stroke is one of the oldest diseases known to mankind. It was found since the era of Hippocrates and Galen. In 17th century, Thomas Willis found a neonate with fits and the underlying cause was stroke. Therefore, he was the 1st person to provide documented evidence in medical literature8. AIS is an important cause of brain insult in children. Few prospective studies in children have been done especially in Asia. Children with AIS aged 1 month to 18 years were studied to evaluate the pattern of causes and radiological findings. The results of the current study showed male preponderance which is consistent with an international pediatric stroke study9. In that study 60% of boys predominated the girls regardless of age, and stroke subtype. That was in contrast to another study done by Mallick et al which showed no difference between the two genders5.

There was a study done by Mallick et al which revealed that younger age, Asian race and black population had increased incidence of stroke5. That was parallel to our study in which children between 1-5 years of age were most affected ones. Presentation of stroke varies with the age. The younger patients present with subtle symptoms like irritability, reluctant to feed, vomiting and fits. While elder children present with hemiplegia, hemiparesis, headache, fits, visual loss, aphasia, ataxia and cranial nerve palsies10. Most of the patients in our study suffered from hemiplegia in 83% (n=60) followed by fits in 38% (n=27) of the patients. The finding of the current study is similar to a study conducted by Mallick et al in which 85% of children presented with focal neurological deficit5. In another study carried out by Abend et al, 22% of children with AIS presented with fits11. Iron deficiency anemia has a strong association with AIS in children12.

In the present study 30% of the children had iron deficiency anemia leading to stroke which was similar to a study done by Maquire showing low Hb, MCV and high platelet count12. Study done by Mackay et al revealed association of AIS with cardiac causes in 31% of the cases while no risk factor was found in 9% of the patients13. In a study conducted by an international pediatric stroke study group cardiac disorders were identified in almost 1/3rd of the children with AIS14. Both studies were in contrast to our study where 8.4% presented with CHD with AIS. In our study, 25%. Of the children fell under heading of idiopathic etiology of AIS despite of extensive investigations. It is not unusual, in another study done few years back, 17.7% of children had unknown etiology of AIS15. A large study was done at a tertiary care hospital in Karachi, over a period of five years but had small number of cases16, showing male predominance similar to our study.

Their age group differed having more cases between 5 to 11 years of children suffering from stroke. Most common presentation was fits (72%) followed by hemiplegia (62%) which was in reverse to the current study. Congenital cyanotic heart diseases also shared more cases (28%) as compared to our patients (8.4%)16. Another study conducted in 2010 at a tertiary care hospital in Lahore also showed more cases with tetrology of fallots suffered from cerebrovascular accidents (32%) in contrast to the current study17,18. The most common single anatomically infracted area was the parietal lobe in 16 (23%) which comes in MCA territory. The most common involved artery was middle cerebral artery (MCA) in 57% of cases (n=12). These findings are consistent with an another pediatric stroke study revealing the involvement of MCA territory in 67% of patients14. Similar findings are documented in a study done in Turkey in which MCA was affected in 43% of cases18,19.

The management of acute arterial ischemic stroke in children includes general and specific treatment along with preventive measures, physiotherapy and rehabilitation19. Outcome includes cerebral palsy, epilepsy, hemiparesis, hemiplegia, aphasia, behaviour, cognitive impairments and learning disorder20-22. Morbidity is 60-70% while death is 6-10%1. Our study shows that gender distribution, clinical presentations and territorial distribution on MRA are more or less similar to prior studies. However, differences are in age of presentation as compared to other studies. The main limitation of this study is small number of patients due to reduced time period. More case-control multicenter studies are needed including good number of patients over a period of years. But this study provides valuable information regarding main causes of AIS in children which can be preventable like iron deficiency anemia.

Key Message

Asia is a continent with developing countries, our children are more at risk of stroke. Neuroimaging has a basic role in diagnosis. Lot of research has to be done by neuro-radiologists, pediatric neurologists and neuro rehabilitation people to help these children.

CONCLUSION

Iron deficiency anemia is one of the common and preventable cause of AIS followed by anemia due to other causes in children. Parietal lobe was found to be the most commonly involved lobe due to infarction of the middle cerebral artery.

CONFLICT OF INTEREST

This study has no conflict of interest to be declared by any author.

REFERENCES

1. Kirton A, Deveber G. Paediatric stroke syndromes. Nelson text book of paediatrics. 19th edition SAUNDERS. Philadelphia: Kliegman RM, MD, Stanton B, MD, Geme J ST et al. 2012: 594 (19th edition); 2080-84.

2. The johns Hopkin University, the john Hopkins hospital and John Hopkins health system. All rights reserved Stroke- Pediatric 2014. www.hopkinmedicine.org/neurology_ neuro-surgery/centersclinics/Pediatricneurolgy/conditions/stroke_ Pediatric. html.

3. Smith SE. Annual incidence rates of arterial ischemic stroke in infants and children range from 0.6 to 7.9 www.uptodate.com/contents/ischemic/stroke-in-children-and-young-adults-etiology and clinical features of arterial ischemic stroke. This topic last updated: 2014.

4. Johnston SC, Mendis S, Mathers CD. Global variation in stroke burden and mortality: Estimates from monitoring, surveillance and modeling. Lancet Neurol 2009; 8(4): 345-54.

5. Mallick AA, Ganesan V, Kirkham FJ, Fallon P, Hedderly T, McShane T et al. Childhood arterial ischemic stroke incidence, presenting features and risk factors: A prospective population based study. Lancet Neurol 2014; 13(1): 35-43.

6. Lo W, Stephens J, Fermendez S. Paediatric strokes in united states and the impact of risk factors. Child neurol 2009; 24(2): 194-203.

7. Johnston MV, Coni A. Acute stroke syndromes. 601. Volume 2. 18th ed. Kliegman RM, Behrman RE, Geme J ST, Stanton B.; 2008. pp. 2508-12.

8. Williams AN. Winner of the young physician's section of the Gowers prize 2000. Too good to be true? Thomas Willis-neonatal convulsins, childhood stroke and infanticide in seventeenth century England. Seizures 2001; 10(7): 471-83.

9. Golomb MR, Fullerton HJ, Nowak- Gotti U, DeveberG. Inter-national pediatirc stroke study group [Make pre-dominance in childhood ischemic stroke: Findings from the IPSS.] Stroke 2009; 40(1): 52-7.

10. Delsing BJ, Catsman-Berrevoets CE, Appel IM. Early prognostic indicators of outcome in ischemic childhood stroke. Peadiatric Neurol 2001; 24(4): 283-9.

11. Abend N, Beslow LA, Smitr SE, Kessler SK, Vossough A, Mason S, et al. Seizures as a presenting symptom of AIS in childhood. J Pediatr 2011; 159(3): 479-83.

12. Maquire JL, Deveber G, Pankin PC. Association between Iron deficiency anemia and stroke in young children. Pediatrics 2007; 120(5): 1053-7.

13. Mackay MT, Wiznitzer M, Benedict SL, Lee KJ, Deveber GA. Arterial ischemic stroke risk factors: The international pediatric stroke study. Ann Neurol 2011; 69(1): 130-40.

14. Dowling MM, Hynan LS, Lo W, Mc Clure C, Yaqer JY, Dlamin N. International paediatric Stroke study group. Int J stroke 2013; 8 (Suppl A-100): 39-44.

15. Siddiqi TS, Rehman AU, Ahmed B. Etiology of strokes and hemiplegia in children presenting at ayub teaching hospital, Abbottabad. J Ayub Med Coll Abbottabad 2006; 18(2): 60-3.

16. Chand P, Ibrahim S, Matloob A, Arain F, Khealani B. Acute childhood ischemic stroke; A Pakistani tertiary care hospital experience. Pak J Neurol Sci 2016; 11(1): 3-6.

17. Aftab S, Usman A, Sultan T. Frequency of cerebrovascular accidents and brain abcess in children with tetrology of fallots. Pak J Neurol Sci 2015; 10(2): 23-6.

18. Yimenicioglu S, Yakut A, Ekici A, Carman KB, Kocak O et al. Evaluation of pediatric stroke patients. J Clin Case Rep 2015; 5(12): 1-4.

19. Pappachan J, Kirkham FJ, Pappachan J, Kirkham FJ. Cerebro-vascular disease and stroke. Arch Dis Child 2008; 93(10): 890-8.

20. Ganesan V, Hogan A, Shack N, Gordon A, Isaacs E, Kirkham FJ. Outcome after ischemic stroke in childhood [PubMed]. Dev Med Child Neurol 2000; 42(7): 455-61.

21. Steinlin M, Roellin K, Schroth G. Long-term follow-up after stroke in childhood. Eur J Pediatr 2004; 163(4-5): 245-50.

22. Lee JC, Lin KL, Wang HS, Chou ML, Hung PC, Hsieh MY et al. Seizures in childhood ischemic stroke in Taiwan. Brain Dev 2009; 31(4): 294-9.
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Publication:Pakistan Armed Forces Medical Journal
Article Type:Clinical report
Geographic Code:9PAKI
Date:Dec 31, 2018
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