Stroke in Saudi children. Epidemiology, clinical features and risk factors

To describe the epidemiology and clinical features of stroke in a prospective and retrospective cohort of Saudi children and ascertain the causes, pathogenesis, and risk factors.The Retrospective Study Group [RSG] included children with stroke who were evaluated at the Division of Pediatric Neurology, or admitted to King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia during the period July 1992 to February 2001. The Prospective Study Group [PSG] included those seen between February 2001 and March 2003. During the combined study periods of 10 years and 7 months, 117 children [61 males and 56 females, aged one month-12 years] were evaluated; the majority [89%] of these were Saudis. The calculated annual hospital frequency rate of stroke was 27.1/100,000 of the pediatric [1 month - 12 years] population. The mean age at onset of the initial stroke in the 104 Saudi children was 27.1 months [SD = 39.3 months] and median was 6 months. Ischemic strokes accounted for the majority of cases [76%]. Large-vessel infarcts [LVI, 51.9%] were more common than small-vessel lacunar lesions [SVLL, 19.2%]. Five patients [4.8%] had combined LVI and SVLL. Intracranial hemorrhage was less common [18.2%], whereas sinovenous thrombosis was diagnosed in 6 [5.8%] patients. A major risk factor was identified in 94 of 104 [89.4%] Saudi children. Significantly more hematologic disorders and coagulopathies were identified in the PSG compared to the RSG [p=0.001], reflecting a better yield following introduction of more comprehensive hematologic and coagulation laboratory tests during the prospective study period. Hematologic disorders were the most common risk factor [46.2%], presumed perinatal ischemic cerebral injury was a risk factor in 23 children [22.1%] and infectious and inflammatory disorders of the circulatory system in 18 [17.3%]. Congenital and genetic cerebrovascular anomalies were the underlying cause in 7 patients [6.7%] and cardiac diseases in 6 [5.8%]. Six patients [5.8%] had moyamoya syndrome, which was associated with another disease in all of them. Inherited metabolic disorders [3.8%] included 3 children with Leigh syndrome and a 29-month-old girl with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. Systemic vascular disease was a risk factor in 3 children [2.9%] including 2 who had hypernatremic dehydration; and post-traumatic arterial dissection was causative in 3 cases [2.9%]. Several patients had multiple risk factors, whereas no risk factor could be identified in 11 [10.6%]. Due to the high prevalence and importance of multiple risk factors, a comprehensive investigation, including hematologic, neuroimaging and metabolic studies should be considered in every child with stroke

Hematologic risk factors for stroke in Saudi children

To explore the hematologic risk factors for stroke in a cohort of Saudi children. We evaluated children at the Division of Pediatric Neurology at King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, during the periods July 1992 to February 2001 [retrospective study] and February 2001 to March 2003 [prospective study]. Investigations for suspected cases included neuroimaging, transcranial Doppler [TCD] for cases of sickle cell disease [SCO], and Duplex scan. Hemostatic assays included coagulation screening tests, tests of thrombin generation and fibrinolysis, coagulation inhibitors, and activated protein C resistance. During the study period, 104 Saudi children [aged one month to 12 years] with stroke were seen. The mean age of the cohort was 27.1 months [SD = 39.3 months] and median was 6 months. Ischemic strokes accounted for the majority of cases [76%]. A major risk factor was identified in 93 of 104 cases of stroke [89.4%]. Hematologic disorders were the most common [46.2%], followed by prothrombic disorders [31.7%]; microcytic hypochromic anemia [26%]; sickle cell disease [SCD], or SC beta-thalassemia, [11.5%], and factor IX deficiency [2.9%]. Raised anticardiolipin antibodies [13/49, 26.5%] was the most frequent abnormality. Deficiencies of the natural anticoagulants [protein S, protein C and antithrombin III] were as follows: protein S [15/70, 21.4%]; protein C [15/70, 21.4%] and combined deficiency of 2 or more inhibitors [9/70, 12.9%]. Activated protein C resistance has not been detected. Contrary to the findings of previous studies from Saudi Arabia, SCD is a common risk factor and is severe, as it resulted in multiple strokes. Moyamoya syndrome was diagnosed in 2 patients with SCD, one of whom had revascularization surgery [encephaloduroarteriosynangiosis]. Assessment of children with SCD at risk of stroke was helped by the introduction of TCD followed by neuroimaging, using MRI and magnetic resonance angiography. The study strongly highlights the importance of prothrombotic disorders and the severe phenotype of SCD as risk factors for stroke in Saudi children.

Infectious and inflammatory disorders of the circulatory system as risk factors for stroke in Saudi childern

To report on the role of infectious and inflammatory disorders as risk factors for stroke in a prospective and retrospective cohort of Saudi children. Children, who presented with stroke, were evaluated at the Division of Pediatric Neurology or admitted to King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia during the periods July 1992 to February 2001 [retrospective study] and February 2001 to March 2003 [prospective study]. Investigations for suspected cases included hemostatic assays, microbiological and serological tests. Neuroimaging included cranial CT, MRI, magnetic resonance angiography [MRA], magnetic resonance venography [MRV] and single photon emission computed tomography [SPECT] brain scan. Of the 104 Saudi children with stroke, seen during the combined study periods of 10 years and 7 months, infectious and inflammatory disorders of the circulatory system were the identified risk factor in 18 [17.3%]. Five children had stroke following acute bacterial meningitis at ages ranging between 5-21 months. The causative organism was identified in 3 of them and consisted of Haemophilus influenzae [in a 5-month-old girl], Streptococcus pneumoniae [in a 21-month-old girl complicated by subdural empyema and sinovenous thrombosis], and Staphylococcus aureus in a 6-month-old boy who had an underlying chronic granulomatous disease. Unspecified meningitis/meningoencephalitis affected 4 patients, whereas 3 children had an underlying congenital infection as a cause for their stroke. Two of the latter 3 children were diagnosed to have congenital toxoplasmosis, and the third had congenital rubella syndrome. Two girls had stroke following septicemia at ages of one and 2 months. Neurobrucellosis caused stroke in 2 boys at the ages of 4 1/2 and 4 years. In both patients, neuroimaging revealed lacunar and other infarcts involving mainly the deep cerebral nuclei, secondary to occlusion of small penetrating end arteries. Two patients presented with cerebrovascular disease following systemic lupus erythematosus. These were a 12-year-old girl and a 5-year-old boy. Several of the infectious diseases that caused stroke in this cohort of Saudi children are potentially preventable through childhood immunization programs or other maternity health programs. In particular, immunogenic conjugate vaccines against the 3 most common organisms causing acute bacterial meningitis [Haemophilus influenzae type b, Neisseria meningitidis and defined serotypes of Streptococcus pneumoniae] are needed to protect the young [<2 years] who are mostly affected.

Congenital and genetic cerebrovascular anomalies as risk factors for stroke in Saudi children

To explore the role of and report on congenital and genetic cerebrovascular anomalies as risk factors for stroke in a prospective and retrospective cohort of Saudi children. Children with stroke were evaluated at the Division of Pediatric Neurology [DPN], or were seen as inpatients in the Pediatric Wards at King Khalid University Hospital [KKUH], Riyadh, Kingdom of Saudi Arabia during the periods July 1992 to February 2001 [retrospective study] and February 2001 to March 2003 [prospective study]. Stroke work-up for each suspected case included hemostatic assays, serological, biochemical and neurophysiological tests. Neuroimaging modalities included routine skull X-rays, CT, MRI, magnetic resonance angiography [MRA] and conventional cerebral angiography. Of 104 children with stroke, congenital and genetic cerebrovascular anomalies were the underlying risk factor in 7 [6.7%]. The patients were evaluated at the DPN at a mean age of 66 months [range = 8 months to 11 years, median = 6 years]; and they had stroke at a mean age of 48 months [range = 2 months to 10 years, median = 8 months]. Four patients had stroke in association with neurocutaneous syndromes. Two had Sturge-Weber syndrome [SWS], one had Klippel-Trenaunay syndrome associated with SWS, and the fourth had neurofibromatosis type 1. Two patients had intracranial hemorrhage secondary to ruptured aneurysm. A girl [aged 9 years and 4 months] had left posterior cerebral artery aneurysm. She was diagnosed to have autosomal dominant polycystic kidney disease following renal ultrasonography. She died 5 months later despite surgical intervention [clipping of aneurysm]. The second child was an 8-month-old boy who presented with subarachnoid and intraventricular hemorrhage [IVH] following ruptured anterior communicating artery aneurysm. He recovered with no residual symptoms following successful clipping of the aneurysm. Arteriovenous malformation [AVM] caused IVH in a 7-year-old boy who reported to hospital 5 hours after onset of headache, vomiting, drowsiness, and dizziness. Following drainage of the IVH and stabilization of the patient, the AVM was successfully embolized 6 weeks later. As a group, congenital and genetic cerebrovascular anomalies constitute a significant risk factor for stroke in Saudi children. Recognition of these diseases is important since some are treatable and because other family members may be at risk.

Stroke due to mitochondrial disorders in Saudi children

To report on the clinical and biochemical features of patients who presented with stroke due to mitochondrial disorders amongst a prospective and retrospective cohort of Saudi children. Children, who presented with stroke, were evaluated at the Division of Pediatric Neurology, or admitted to King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia, during the periods July 1992 to February 2001 [retrospective study] and February 2001 to March 2003 [prospective study]. Open muscle biopsies were obtained from patients suspected to have mitochondrial disorders, and examined using conventional histological and histochemical techniques. Biochemical, molecular pathological investigations, or both, of muscle could be arranged for only some of the patients. Mitochondrial disorders were the underlying risk factor for stroke in 4 [3.8%] of 104 children [aged one month to 12 years]. Three patients [one male and 2 females] had Leigh syndrome [LS] and one had mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes [MELAS]. At the time of stroke, the 3 children with LS were 11 months, 15 months, and 7 years old. They presented with psychomotor regression and seizures. Muscle histology and histochemistry showed mild non-specific changes but no ragged red fibers. Biochemical analysis of muscle [in one patient] revealed deficiency of pyruvate dehydrogenase complex. Analysis of mitochondrial DNA [mtDNA], [the other 2 patients] was negative for the 2 point mutations [T-G and T-C] at nucleotide position 8993, and for two T-C point mutations [at positions 8851 and 9176 of the ATPase 6 gene] that have been described in patients with LS. The girl with MELAS syndrome presented with a stroke-like episode at the age of 29 months and had focal brain lesions in the medial aspect of the left occipital and temporal lobes, and in the posteromedial aspect of the left thalamus, which resolved within 7 weeks. She had raised cerebrospinal fluid lactate but no ragged red fibers on muscle histochemistry. Biochemical assay of muscle homogenate showed reduction in respiratory chain complexes I, III and IV. Mutation screening of mtDNA at nucleotides 3243 [tRNA Leu[UUR] and 8344 [tRNA Lys] was negative. Mitochondrial disorders constitute a risk factor for stroke in Saudi children. However, demanding and highly specialized investigations are needed to confirm the diagnosis. These are better performed at supraregional centers where facilities for clinical, biochemical and molecular work-up are available

Stroke from systemic vascular disorders in Saudi children. the devastating role of hypernatremic dehydration

Systemic vascular disorders, leading to childhood stroke, include volume depletion or systemic hypotension and hypernatremic dehydration. We describe 3 cases of stroke following systemic vascular disorders. These were diagnosed during a prospective and retrospective study on childhood stroke, which included 104 patients. Post-gastroenteritis hypernatremic dehydration is an important, potentially preventable, cause of stroke in Saudi children

management of acute severe asthma in a pediatric intensive care unit

The hospitalization and mortality rates incurred from acute childhood asthma continue to rise in the past decade. The purpose of this study is to examine the outcome, morbidity and the management of children admitted with acute asthma to our pediatric intensive care unit [PICU] and compare it with those described in the literature. Medical records of all children admitted with acute severe asthma to PICU at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia over an 8-year period [1994-2001] were reviewed. Fifty-six patients were analyzed. The male to female ratio was 1.3:1 and the mean age was 3.6 +/- 2.8 years. The mean duration of symptoms prior to admission was 2 +/- 1.5 days with 39.3% <24 hours. A positive family history of allergy was present in two third of patients. The average stay in PICU was 2 +/- 0.9 days. Seventy-three% of patients received prophylaxis bronchodilator therapy before hospital admission including inhaled steroid in 62%. All the patients received nebulized salbutamol and intravenous corticosteroid. Two third of our patients received nebulized ipratropium bromide and 62% intravenous aminophylline. From arterial blood gases analysis, 46.4% had hypercapnia [PaCO2 >45 mm Hg]. None of our patients required mechanical ventilation. Only 2 patients developed pneumomediastinum with pneumothorax that has resolved spontaneously without intervention. There were no deaths among our 56 patients admitted to PICU. We conclude that the mortality and morbidity in children with severe asthma, who require PICU admissions are minimal, provided optimal early use of bronchodilators and intravenous steroids. Using this approach, it could also be possible to avoid mechanical ventilation and shorten the duration of hospital admission

Congenital central hypoventilation syndrome: diagnosis and the challenge of management

Congenital central hypoventilation syndrome is a rare disease characterized by a lack of automatic, but with intact, voluntary control of breathing. Patients with this disease need assisted ventilation mostly during sleep. To the best of our knowledge our patient is the first case reported among Saudi and Arab children. Since these patients need special respiratory care with difficulties in family adaptation, reappraisal is needed of the available therapeutic option in the kingdom, including the availability of adequate support for home ventilation at different regions