Split cord malformation associated with spinal open neural tube defect

To illustrate the clinical and radiological findings of split cord malformation [SCM] in patients with spinal open neural tube defect [SONTD], and report the outcome of their treatment. A retrospective study of the clinical and radiological findings of 11 patients diagnosed with SCM, identified among 83 patients with SONTD at King Khalid University Hospital, in Riyadh, Saudi Arabia between 1995 and 2010. There were 6 girls and 5 boys; their age ranged from less than a year to 9 years [mean 4.2 years]. Six patients had type I SCM, and 5 patients type II SCM. The CT and MRI imaging showed characteristic bony, cartilaginous, or fibrous septum, and other SONTD-associated anomalies. Seven patients were graded A and B according to the Frankel grading score, and none of them required surgery, while worsening neurology led to surgical intervention in 3 patients, with clinical improvement after surgery, and one patient that underwent cord untethering remained stable. Split cord malformation is not uncommon among patients with SONTD. It tends to involve mainly the lumbar spine, and female predominance is more remarkable in type I. Neurological manifestations of SCM may be superimposed with SONTD. Surgery is effective for symptomatic patients, and not indicated in the severely disabled.

Agenesis of the corpus callosum associated with spinal open neural tube defect

To ascertain the incidence and clinical implications of agenesis of the corpus callosum [ACC] in spinal open neural tube defects [SONTD]. All cases of SONTD registered at the Spina Bifida Clinic in King Khalid University Hospital, Riyadh, Saudi Arabia between 1995 and 2010 were retrospectively reviewed, and mid-sagittal MRI of the corpus callosum [CC] area was analyzed in each case. Neurodevelopmental outcome was classified as poor in children with seizures, severe neurodevelopmental impairment, or death. Thirty-eight patients [45.8%] with ACC were identified among 83 cases with SONTD. Patients' age ranged between one and 16 years. Total ACC was found in 10 patients, partial ACC in 25, and in 3 patients, the CC was hypoplastic. Active hydrocephalus was an associated finding in 9 out of 10 patients with total ACC, 22 out of 25 with partial ACC, and in all patients with hypoplasia of the CC. Thirteen patients [34.2%] had normal intellectual function, whereas 24 patients presented with learning disability, epilepsy, or poor intellectual function; and one patient died of respiratory failure. Agenesis of the corpus callosum is found in a significant portion of patients with SONTD. When associated with hydrocephalus, its presence affects neuro-developmental outcome.

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.

Perinatal stroke in Saudi children. Clinical features and risk factors

To describe the clinical features and presentations of perinatal stroke in a prospective and retrospective cohort of Saudi children and ascertain the risk factors. Patients with perinatal stroke were identified from within a cohort of 104 Saudi children who were evaluated at the Division of Pediatric Neurology at King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, Saudi Arabia from July 1992 to February 2001 [retrospective study] and February 2001 to March 2003 [prospective study]. Neuroimaging for suspected cases of stroke consisted of cranial CT, MRI, or both. During the study period, 23 [22%] of 104 children [aged one month to 12 years] were diagnosed to have had perinatal stroke. The male:female ratio was 1.6:1. Ten [67%] of the 15 children who had unilateral ischemic involvement had their lesion in the left hemisphere. The presentation of the ischemic result was within 24-72 hours of life in 13 [57%] patients, and in 6 children [26%], motor impairment was recognized at or after the age of 4 months. Nine children [39%] had seizures at presentation. Pregnancy, labour, and delivery risk factors were ascertained in 18 [78%] cases. The most common of these included emergency cesarean section in 5 cases, and instrumental delivery in another 5. Screening for prothrombotic risk factors detected abnormalities in 6 [26%] patients on at least one test carried out between 2 months and 9 years of age. Four children [17%] had low protein C, which was associated with low protein S and raised anticardiolipin antibodies [ACA] in one patient, and low antithrombin III in another. Low protein S was detected in a 42-month-old boy. The abnormality in the sixth child was confined to raised ACA. The present study highlights the non-specific features by which stroke presents during the neonatal period. The data are in keeping with the potential role for inherited and acquired thrombophilia as being the underlying cause. However, the high prevalence of additional acquired antenatal and perinatal risk factors support a multifactorial disorder

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.

Cardiac diseases as a risk factor for stroke in Saudi children

To ascertain the role of cardiac diseases as a risk factor for stroke in a cohort of Saudi children who were evaluated in a retrospective and prospective study. Children with cardiac diseases were identified from within a cohort of 104 Saudi children who presented with stroke. They were seen as inpatients in the Pediatric Wards or evaluated at the Outpatient Clinics of the Division of Pediatric Neurology [DPN], and the Division of Pediatric Cardiology at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia during the periods July 1992 to February 2001 [retrospective study] and February 2001 to March 2003 [prospective study]. A comprehensive form for clinical, neuroimaging, neurophysiological and laboratory data retrieval was designed and completed for each patient. Cardiac evaluation included 12-lead ECG and serial echocardiograms. Cardiac catheterization and 24-hour ambulatory ECG [Holter] were conducted on clinical discretion. Cardiac diseases were the underlying risk factor for stroke in 6 [5.8%] of the 104 children [aged one month to 12 years]. The patients [4 males and 2 females] were evaluated at the DPN at a mean age of 5.3 years [range = 1 - 8 years; median 6.5 years]. Onset of stroke was at a mean age of 34 months [range = 4 months - 8 years; median = 30 months]. Five patients had stroke in association with congenital heart disease [CHD], whereas the sixth had restrictive cardiomyopathy. The identified CHD consisted of membranous ventricular septal defect in a 5-year-old boy who had moyamoya syndrome and sickle cell beta - thalassemia, asymptomatic patent ductus arteriosus [PDA] in a 17-month-old girl, atrioventricular canal defect and PDA in an 8-year-old boy who also had Down syndrome, partial anomalous pulmonary venous drainage in a one-year-old boy, and Tetralogy of Fallot in an 8-year-old boy. The latter patient developed hemiparesis secondary to a septic embolus, which evolved into brain abscess involving the right fronto-parietal region. This was successfully managed surgically. The sixth patient was an 8 1/2 -year-old girl who had hemiparesis and complex partial seizure in association with restrictive cardiomyopathy. Serial echocardiograms depicted resolution of the cardiac abnormalities within 5 years and subsequent normal findings. Cardiac diseases, as a group, constitute a significant risk factor for stroke in Saudi children. Early diagnosis of these diseases is important to prevent further recurrences of stroke, and because some of them are potentially curable.

Moyamoya syndrome as a risk factor for stroke in Saudi children. Novel and usual associations

To report on moyamoya syndrome [MMS] as a risk factor for stroke in a prospective and retrospective cohort of Saudi children. The usual and novel associations of MMS in this cohort will also be described. Children with stroke were evaluated at the Division of Pediatric Neurology at 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, biochemical, and serological tests. Neuroimaging included CT, MRI, magnetic resonance angiography [MRA], single photon computerized tomography [SPECT] brain scan and conventional cerebral angiography. Moyamoya syndrome was the underlying risk factor for stroke in 6 [5.8%] of the 104 children [aged one month to 12 years]. They were 4 females and 2 males. Their first cerebral ischemic event occurred at a mean age of 45 months [median = 44 months, range 17-66 months]. In all 6 cases, MMS was associated with an underlying hematologic abnormality or other diseases. Protein C deficiency was identified in one girl and protein S deficiency in another. Two patients had respectively, sickle cell disease [SCD] and sickle cell-B-thalassemia [S beta-thalassemia], which had been associated in the latter with membranous ventricular septal defect. Adams-Oliver syndrome [AOS, OMIM 100300] was associated with MMS in an 18-month-old girl. A 4-year-old boy had wrinkly skin syndrome [WSS, OMIM 278250] phenotype. The association of MMS and protein C deficiency was first reported in this cohort of patients, whereas the association of the syndrome with WWS and AOS has not, hitherto, been described. The 3 patients who had MMS associated with protein C deficiency, SCD, and AOS underwent successful revascularization surgery in the form of encephaloduroarteriosynangiosis. Moyamoya syndrome constitutes an important risk factor of stroke in Saudi children. Comprehensive clinical evaluation and investigations, including screening for thrombophilia and neuroimaging studies, are required for the primary diagnosis of the disease and for unraveling other diseases associated with MMS. This will help in managing these patients and in guiding genetic counseling for their families.

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

Stroke from cervicocephalic arterial dissection in Saudi children

Cervicocephalic arterial dissection [CCAD] is an important, but rarely recognized, cause of stroke in children. We describe 3 cases of CCAD who were diagnosed during a study on childhood stroke which included 104 patients. A high index of suspicion and targeted investigations are needed for the diagnosis and management of CCAD in childhood.

Fluid-fluid level in Langerhans cell histiocytosis of the skull

We present a case of solitary eosinophilic granuloma in the skull of a 6-year-old Saudi boy. This osteolytic lesion has fluid-fluid level on CT and MRI. We are presenting a rare radiological finding of eosinophilic granuloma

Imaging findings of neuro-Behcet disease

To study the neuroimaging findings of neuro-Behcet's disease [NBD] in Saudi patients and to discuss the radiological differential diagnosis. The clinical data and radiological findings on CT, MRI and cerebral angiography of 16 patients with NBD attending King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia, from January 1990 to February 2003 were reviewed. Out of 16 patients with NBD, 11 patients [68.75%] had cerebral venous thrombosis predominantly involving superior sagittal sinus causing intracranial hypertension, while 5 patients [31.25%] had symptoms and signs related to brain parenchymal involvement predominantly affecting brainstem. Pattern of distribution of brain parenchymal lesions in NBD might help to differentiate it from other vasculitides as well as from demyelinating disease such as multiple sclerosis. Cerebral venous thrombosis is a common manifestation of NBD