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.

On the functional and clinical aspects of vitamin E

Vitamin E is an essential nutrient for humans. It plays several important roles in the body as a powerful anti-oxidant and anti-thrombin. It also modulates the synthesis of prostacyclins and thromboxanes. Among its protective roles the most significant one is the protection of cellular membranes against increased haemolysis due to peroxidation. It protects the body from selenium deficiency and prevents nitrosamine formation. Deficiency of vitamin E produces haemolytic anaemia in the newborn and in infants up to several years of age. In children with cystic fibrosis and cholestasis it can lead to neuropathologic myopathic abnormalities and progressive neuromuscular disease. The deficiency also leads to thrombocytosis and hyperaggregability which can be reversed upon treatment with vitamin E. Vitamin E protects the newborn against bronchopulmonary dysplasia, respiratory distress syndrome and retrolental fibroplasia. In adults it has been tried as a treatment for intermittent claudication and respiratory distress syndrome. The drawback of the anti-oxidant activity of vitamin E is its effects in large doses on the normal functioning of polymorphonuclear leucoytes. It decreases H 2O 2 production, decreases the bactericidal power and results in an increased incidence of bacterial and candidal sepsis of necrotizing enterocolitis in the newborn receiving prophylactic vitamin E treatment for retinopathy of prematurity. In this paper, the functional and clinical aspects of vitamin E are presented and discussed

Cord blood hemostatic measurements in healthy Saudi full-term and low birth weight neonates

Measurement of coagulation parameters of prothrombin time [PT], partial thromboplastin time [PTT], thrombin time [TT], reptilase time [RT], plasma fibrinogen and antithrombin-III, [AT-III] and platelet aggregation responses to adenosine diphosphate [ADP] [20.0, 2.0 and 1.0 micro m] collagen, arachidonic acid and ristocetin [RIST] [1.5, 1.2 and 1.0 mg/ml] were performed in 59 low birth weight [LBW] infants and compared with similar measurements undertaken in full-term neonates [FTN]. All coagulation parameters were of similar magnitude in both FTN and LBW infants except AT-III which was significantly lower in the latter group [p<0.001]. Similarly, platelet aggregation responses to ADP [2.0 micro m, 20.0 micro m] and collagen were significantly reduced in LBW infants, while no significant differences were noted in ristocetin responses. Despite the markedly reduced levels of the measured haemostatic parameters in both groups especially the LBW infants, none of the subjects in the study displayed any bleeding disorder. The interpretation of abnormal coagulation tests in sick neonates, especially those with a bleeding disorder, becomes feasible, now that normal values for commonly employed haemostatic measurements are available

Normal reference levels of haemostatic variables in healthy Saudis

The normal levels of prothrombin time, partial thromboplastin time, thrombin time, reptilase time, fibrinogen, antithrombin III, plasminogen, alpha2-antiplasmin, vWF:RiCofactor, vWF:Ag, FVIII:C, FX, platelet count, FV, FVII and FIX, were determined in 1235 healthy Saudi males [n = 803] and females [n =432] aged 11 to 60 years. Females had shorter partial thromboplastin time and reptilase time, higher level of fibrinogen, antithrombin III [ATIII], plasminogen and platelet count, than males. FVIII:C, vWF:Ag and vWF:RiCof, and fibrinogen increased with advancing age. In females, ATIII and plasminogen dropped after the age of 50 years. The study confirmed higher factor VIII activity in individuals of group A and B than O. Smoking had no effect on haemostatic variables. The differences between these observations and those reported in the literature are highlighted and discussed. These data will represent the Saudi population reference values for these haemostatic parameters

Coagulation parameters in maternal and cord blood at delivery

A wide range of hemostatic variable were studied in 300 maternal/neonatal pairts at the time of delivery and also in 375 healthy nonpregnant women who served as control. There was significant prologation of the prothrombin time, partial thromboplastin time, and reptilase time in neonatal [cord] blood compared to maternal blood. The plasma levels of fibrinogen, antithrombin III, protein C, plasminogen, factors VIII coagulant and ristocetin cofactor activities, factors X, and platelet counts were significantly lower in neonatal than matyernal plasma. In contrast, the thrombin time, alpha2-antiplasmin, and serum fibrin degradation products showed comparable values for both mothers and neonates. von Willebrand factor antigen showed a more significant elevation in mothers than neonates; however, the ratio of von Willebrand factor antigen/factor VIII coagulant was similar in both [1.56 and 1.57, respectively]. There was a significant correlation only between factor VIII coagulant levels in mothers and their babies [r=0.69; P < 0.05] but not for the other hemostatic variables studied. The differences between our results and those reported in smaller published studies are discussed

Anemia of acute focal infection in children in the area of Riyadh

Chronic or acute systemic bacterial infection is usually associated with anemia. This study shows that anemia can also be associated with acute focal infections which are usually treated in outpatient clinics. A group of 682 children [aged 6 months to 12 years] were seen in a three-month period in the outpatient clinics of Suliemania Children's Hospital, Riyadh, with varying complications consisting of pharyngotonsillitis, otitis media, and sinusitis. Anemia [hemoglobin < 10.3 g] was detected in 36.5% of the children aged 6 to 11 months, 22.7% aged 12 to 35 months, and in 11.2% aged 3 to 12 years. Age [P<0.01] and duration of fever [P< 0.02] were found to have significant association with anemia

Smith-Lemli-Optiz syndrome in one Arab child: a case report

The first case of Smith-Lemli-Opitz syndrome from Saudi Arabia is described. The relevant literature is reviewed