Anatomical Venous Variants in Children With Cerebral Sinovenous Thrombosis.

Background and Purpose- Literature is sparse on the frequency and significance of anatomical venous variants (AVVs) in pediatric cerebral sinovenous thrombosis (CSVT). Methods- We retrospectively reviewed children with CSVT and controls undergoing computed tomography/magnetic resonance venography from January 2008 to 2014. Clinical features examined included raised intracranial pressure, risk factors, and treatment. Radiological features examined included CSVT location, presence and type of AVVs, hemorrhagic venous infarction, and venous collateralization. Clinical outcome was measured by the pediatric stroke outcome measure and radiological outcome by thrombus recanalization. Results- Fifty-one children with CSVT were identified. Twenty-two (43%) had AVVs at presentation. Nineteen (86%) had hypoplasia/absence of major dural sinus, 5 (23%) had persistent fetal structures, 3 (14%) had duplications/fenestrations, and 1 (5%) had disconnected superficial and deep venous systems. Controls had a slightly higher but nonsignificant prevalence 26 (51%) of AVVs. No significant clinical and radiological differences were observed between children with CSVT and AVVs compared with those with typical venous anatomy. Conclusions- AVVs are seen in many children with and without CSVT and do not seem to alter the presentation or clinical course. The influence of these variations on the brain's ability to tolerate venous congestion because of thrombosis merits further study.

Stroke recurrence in children with congenital heart disease.

OBJECTIVE: Pediatric arterial ischemic stroke (AIS) carries an important morbidity and mortality burden. Congenital heart disease (CHD) is among the most important risk factors for pediatric AIS. Data on stroke recurrence in childhood CHD are lacking, resulting in uncertainty regarding optimal strategies for preventing recurrence. METHODS: In the Canadian Pediatric Ischemic Stroke Registry-Toronto site, we identified children (birth to 18 years) with CHD diagnosed with AIS during 1992-2008. Data were abstracted from both stroke and cardiac surgery databases. Time-dependent outcomes (death and recurrent stroke) following sentinel stroke were parametrically modeled in competing risk analysis. Factors predicting stroke recurrence in parametric survival models were sought in parametric survival model analyses using backward variable selection of variables. RESULTS: A total of 135 patients (19 with recurrence, 116 without recurrence) were studied. In competing risk analysis, 10 years following sentinel stoke, 27% had experienced a stroke recurrence, 26% had died, and 47% were alive and free from recurrence. Stroke recurrence risk decreased over time from sentinel stroke. Approximately 50% of patients were receiving anticoagulation at recurrence. Significant factors associated with recurrence included the presence of a mechanical valve, prothrombotic condition, and an acute infection at the time of sentinel stroke. Hazard of mortality after recurrence was similar to mortality after sentinel stroke (hazard ratio, 1.3; p = 0.75). INTERPRETATION: Stroke recurrence was relatively common in neonates and children with CHD. Identified groups of patients at increased risk may require more aggressive secondary prophylaxis, especially in the early poststroke period.

Basilar artery strokes in children: good outcomes with conservative medical treatment.

AIM: To describe outcomes and outcome predictors in childhood basilar artery stroke (BAS). METHOD: We prospectively enrolled children with BAS with or without basilar artery occlusion (BAO) in the Toronto Children's Stroke Registry from 1992 to 2009. We assessed presenting features and outcomes including Pediatric Stroke Outcome Measure scores. RESULTS: Among 578 children with acute arterial ischemic stroke, 27 had BAS (4.6% including neonates, 6% excluding neonates). Twenty-four (14 males, 10 females) children met study criteria (mean age at stroke was 8 y 10 mo; range 0-17 y). Eleven children had BAO. Aspirin or anticoagulation was given to 15 children. None received tissue plasminogen activator or endovascular treatments. At mean follow-up (3 y 2 mo, range 1 mo-11 y 8 mo), 12 had a 'good outcome' (seven normal, five insignificant deficit) and 12 had 'poor outcome' (10 moderate or severe deficit, two acute deaths). Larger infarct size (≥50% of axial brainstem diameter) independently predicted poor outcome (p=0.02; odds ratio 21.2, 95% confidence interval 1.6-274.9) but not BAO, altered level of consciousness, or age. INTERPRETATION: Compared with adults, in childhood BAS death is rare and survivors frequently have good outcomes. Aggressive endovascular interventions may not be justifiable in this population.

Distinct Clinical and Radiographic Phenotypes in Pediatric Patients With Moyamoya.

BACKGROUND: Given the expanding evidence of clinico-radiological differences between moyamoya disease (MMD) and moyamoya syndrome (MMS), we compared the clinical and radiographic features of childhood MMD and MMS to identify predictors of ischemic event recurrence. METHODS: We reviewed a pediatric moyamoya cohort followed between 2003 and 2019. Clinical and radiographic characteristics at diagnosis and follow-up were abstracted. Comparisons between MMD and MMS as well as between MMD and two MMS subgroups (neurofibromatosis [MMS-NF1] and sickle cell disease [MMS-SCD]) were performed. RESULTS: A total of 111 patients were identified. Patients with MMD presented commonly with transient ischemic attacks (TIAs) (35 % MMD versus 13% MMS-NF1 versus 9.5% MMS-SCD; P = 0.047). Symptomatic stroke presentation (MMD 37% versus MMS-NF1 4% versus 33%; P = 0.0147) and bilateral disease at diagnosis (MMD 73% versus MMS-NF1 22 % versus MMS-SCD 67%; P = 0.0002) were uncommon in MMS-NF1. TIA recurrence was common in MMD (hazard ratio 2.86; P = 0.001). The ivy sign was absent on neuroimaging in a majority of patients with MMS-SCD (MMD 67% versus MMS-NF1 52% versus MMS-SCD 9.5%; P = 0.0002). Predictors of poor motor outcome included early age at diagnosis (odds ratio [OR] 8.45; P = 0.0014), symptomatic stroke presentation (OR 6.6; P = 0.019), and advanced Suzuki stage (OR 3.59; P = 0.019). CONCLUSIONS: Moyamoya exhibits different phenotypes based on underlying etiologies. Frequent TIAs is a common phenotype of MMD and symptomatic stroke presentation a common feature of MMD and MMS-SCD, whereas unilateral disease and low infarct burden are common in MMS-NF1. In addition, absence of ivy sign is a common phenotype in MMS-SCD.

Corticospinal tract pre-wallerian degeneration: a novel outcome predictor for pediatric stroke on acute MRI.

BACKGROUND AND PURPOSE: In neonatal arterial ischemic stroke, pre-Wallerian degeneration in descending corticospinal tracts (DCST) on diffusion MRI (DWI) predicts poor outcome. This signal has not been studied in older children. METHODS: A consecutive arterial ischemic stroke cohort (1 month to 18 years) with acute DWI and >12 months of follow-up were enrolled (SickKids Children's Stroke Program). DCST-DWI variables were quantified with a validated software technique and correlations to the Pediatric Stroke Outcome Measure were sought. RESULTS: Abnormal DCST-DWI signal was detected in 20 of 29 children (69%), with 85% having motor deficits on Pediatric Stroke Outcome Measure. DCST variables correlated with hemiparesis included: (1) any abnormal signal within the course of the DCST; (2) midbrain location; (3) percentage of peduncle; (4) vertical length; and (5) relative volume affected (all P<0.003). Unexpectedly, abnormal DWI signal was detected in the contralesional DCST in 7 children, all with severe hemiparesis. DCST signal abnormality increased over time, outlasted infarct DWI changes, and was difficult to appreciate on visual inspection. CONCLUSIONS: DCST-DWI signal is an acute predictor of motor outcome in childhood stroke and can help guide management. Previously unrecognized contralesional DCST signal predicts severe hemiparesis.

Botox treatment for migraine and chronic daily headache in adolescents.

Children and adolescents experience headaches as do adults and usually present with migraine and chronic daily or tension-type headaches. As some adolescents are unable to achieve headache relief after various treatment strategies, we currently provide botulinum toxin type A (Botox) injections as a clinical treatment (off-label use) in selected cases. Botulinum toxin type A by injection has been found to be effective in the treatment of headache disorders in adults. We treated 12 adolescents (aged 14 to 18 years) with Botox injections for migraine and chronic daily headache. Six patients (all female adolescents) were in long-term treatment and received Botox in the standard "migraine" and "follow-the-pain" patterns every 3 months. Effectiveness was evaluated using pain scales and a standardized quality-of-life survey at baseline and prior to each treatment session. Duration of treatment was 3-29 months. Each patient had 9-63 (average = 42) injections per treatment. All 6 long-term patients reported improvement in headache symptoms, with decreases on pain scales and an average of 33%-75% improvement in quality of life. Two long-term patients had complete relief of headaches between injection series. Four patients had only one series of injections with good results. Two patients had no improvement and refused additional injections. Side effects were mild ptosis (n = 1), blurred vision (n = 1), hematoma at neck injection site with tingling in one arm lasting 24 hours (n = 1), and burning sensations at all injection sites which lasted 1 week (n = 1). Our group findings warrant a controlled trial evaluation of Botox because it may be an effective treatment option for certain adolescents with intractable migraine and chronic daily headaches.

Nursing issues in caring for children with moyamoya vasculopathy and their families.

Moyamoya vasculopathy is a rare, progressive neurovascular condition that may cause recurrent transient ischemic attacks, ischemic strokes, hemorrhagic strokes, or neurologic decline in children. Children with moyamoya disease have no clear contributing etiology, but children with moyamoya syndrome have contributory diagnoses such as Down syndrome or neurofibromatosis. The concerns and lived experiences of children affected by this disease and their families have not been well explored or addressed in the nursing literature. Nurses who understand this lived experience increase their own knowledge of the disease so they can manage the complex medical issues, educate families about the disease, and provide emotional support.

Craniocervical arterial dissection in children: clinical and radiographic presentation and outcome.

Craniocervical arterial dissection is a recognized cause of arterial ischemic stroke in children. Whether children with craniocervical arterial dissection have dissection characteristics different from those of adults is unclear. A retrospective review of children, 1 month to 18 years of age, with dissection from two Canadian pediatric ischemic stroke registry centers was conducted. From 213 patients with arterial ischemic stroke, 16 (7.5%) were identified with dissection, 37.5% had warning symptoms, and 50% had a history of head or neck trauma. The clinical presentation included headache (44%), altered consciousness (25%), seizures (12.5%), and focal deficits (87.5%). Dissection involved extracranial vessels in 75% and anterior circulation in 56%. Follow-up included complete recovery in 43%, mild to moderate deficits in 44%, and severe deficits in 13%. Fourteen (87.5%) children received antithrombotic treatment. Follow-up angiography showed resolution of abnormalities in 60% of vessels. Total occlusion had the worst outcome for recanalization. In conclusion, the etiology of arterial dissection in the majority of children appears to be either trauma or idiopathic. Long-term angiography shows variable outcomes, depending on the initial findings. The relationship of angiographic outcomes with recurrent strokes requires further study in pediatric dissection. (J Child Neurol 2006;21:8-16).

Neurological complications of kernicterus.

OBJECTIVE AND BACKGROUND: Prevention of bilirubin encephalopathy relies on the detection of newborns who are at risk of developing serious hyperbilirubinemia. The objective of this study was to reassess the clinical syndrome of kernicterus as neurodiagnostic studies have become more readily available and can be used to evaluate these infants. METHODS: The study population was neonates born at term or near term admitted to The Hospital for Sick Children in Toronto, Ontario, Canada, between January 1990 and May 2000. During the study period, there were 9776 admissions (average number of admissions per year--888 infants). The inclusion criteria were that patients had total serum bilirubin levels of >400 micromol/L at the time of diagnosis and no evidence of hypoxic ischemic encephalopathy. Records were reviewed to establish neurodevelopment outcomes. RESULTS: Twelve neonates (nine males) were identified. Bilirubin levels at the time of diagnosis ranged from 405 to 825 micromol/L. Causes of these elevated levels included glucose-6-phosphate dehydrogenase deficiency (seven patients), dehydration (three patients), sepsis (one patient), and was undetermined in one patient. Abnormal visual evoked potentials were found in three of nine patients and abnormal brainstem auditory evoked potentials in seven of ten patients. Abnormal electroencephalograms were documented in five patients studied. Brain magnetic resonance imaging results were abnormal in three of four patients. CONCLUSIONS: Magnetic resonance imaging typically showed an increased signal in the posteromedial aspect of the globus pallidus and was, therefore, useful in the assessment of the structural changes of chronic bilirubin encephalopathy after kernicterus.

Patterns of cerebral ischemia in children with moyamoya.

BACKGROUND: Moyamoya disease is characterized by progressive cerebrovascular stenosis with recurrent cerebral ischemic events. Transient ischemic attacks are often associated with hyperventilation in children with moyamoya, suggesting hypoperfusion rather than thrombotic vaso-occlusion as a prominent mechanism. The patterns of ischemia and severity of steno-occlusive disease in such children may elucidate these mechanisms. METHODS: Children, 1 month to 18 years, with moyamoya, observed over 11 years were analyzed. A study neuroradiologist reviewed all presurgical neuroimaging. Ischemic injury was categorized into cortical, subcortical, and watershed infarction. Angiographic findings were staged using a standardized method. RESULTS: Twenty children, 15 girls, median age 6.4 years, were included. All children had magnetic resonance imaging and angiography, and in 16, conventional angiography was available. All 40 hemispheres, in 20 children, were evaluated. The initial clinical presentation included neurological deficits in 17, recurrent transient ischemic attacks in 7, headache in 8, seizures in 8, and alteration in consciousness in 4 children. Infarcts were bilateral in 13 (65%) children (ischemia alone in 14, ischemic stroke with hemorrhagic transformation in two, and primary hemorrhage in two). Infarcts were cortical and/or subcortical in 13 (65%), both deep and cortical watershed in 11 (55%), and cortical watershed alone in 5 (25%) children. The predominant vascular territory involved was the middle cerebral artery. The internal carotid arterial system was involved in all, with stage IV being the most frequent angiographic stage. CONCLUSIONS: Ischemic injury in deep watershed zones is common in childhood moyamoya and may reflect non-vaso-occlusive ischemic mechanisms. Location and severity of vascular involvement may correlate with various patterns of ischemic infarction in moyamoya disease and requires further study.

Alternative therapy use by Chinese-Canadian children with stroke and cerebrovascular disease.

The use of alternative therapies in immigrant children with stroke and cerebrovascular diseases has not been reported. We identified immigrant and first-generation Chinese-Canadian children with stroke and cerebrovascular diseases in a pediatric stroke clinic and used standardized questionnaires to interview their parents about alternative therapy use. The chi-square test was used to assess the associations of parental educational level and foreign birth in the child with alternative therapy use. We identified 17 children, 9 boys and 8 girls. Six were immigrants to Canada and 11 were Canadian born. Nine of 17 families (53%) reported using alternative therapies. All 9 used Chinese herbs, but only 3 were able to report the names of specific preparations. Four families were using medications that had the potential to affect coagulation. Documentation of alternative therapy use was found in the medical charts of 3 of the 9 patients. Three families reported feeling uncomfortable discussing alternative therapy use with their physicians. We did not see an association between alternative therapy use and parental educational level or foreign birth in the child. Physicians should be aware that parents of children with stroke may be using alternative therapies to treat their children and may be unwilling or unable to report all therapies used.

Cranial ultrasonography has a low sensitivity for detecting arterial ischemic stroke in term neonates.

The aim of this study was to investigate the sensitivity of cranial ultrasonography for detecting acute arterial ischemic stroke in term neonates. Thirty-six neonates with gestational age > or = 36 weeks who had cranial ultrasonography followed by computed tomography (CT) or magnetic resonance imaging (MRI) confirming arterial ischemic stroke were identified from a consecutive cohort study of all children diagnosed with arterial ischemic stroke by CT or MRI and seen at Chedoke McMaster Hospital between January 1992 and December 1998 or at The Hospital for Sick Children between January 1992 and December 2000. Cranial ultrasonography demonstrated focal abnormalities in 11 patients, giving the initial cranial ultrasonography a sensitivity of 30.56% for identifying neonates with infarction (95% CI 15.5-45.5%). The sensitivity of cranial ultrasonography performed in the two pediatric referral centers (Chedoke McMaster Hospital and Hospital for Sick Children; n = 19) was higher than that in community hospitals (n = 17) (47.3% versus 11.7%; P =.031). Neonates with suspected infarction should be evaluated with CT or MRI.

Neonatal arterial ischemic stroke and cerebral sinovenous thrombosis are more commonly diagnosed in boys.

The risk factors for arterial ischemic stroke and cerebral sinovenous thrombosis in neonates are not well understood. We looked at gender, birthweight, and gestational age in neonates with arterial ischemic stroke and cerebral sinovenous thrombosis to see if there were trends suggesting that these were risk factors. We identified neonates with a gestational age at birth > or = 36 weeks and a diagnosis of arterial ischemic stroke or cerebral sinovenous thrombosis made by computed tomography or magnetic resonance imaging during the neonatal period from a consecutive cohort study of children with arterial ischemic stroke and cerebral sinovenous thrombosis in Ontario. Data on gender, birthweight, and gestational age were obtained by health record review. Sixty-six children with neonatal arterial ischemic stroke were identified. Forty-one (62.1%; 95% CI 49.3-73.8%) were male. Thirty-two children with neonatal cerebral sinovenous thrombosis were identified. Twenty-five (78.1%; 95% CI 60.0-90.7%) were male. One male child was identified with both arterial ischemic stroke and cerebral sinovenous thrombosis. There was a trend toward higher than average birthweights among neonates with arterial ischemic stroke and a trend toward older gestational age in female neonates with arterial ischemic stroke. Our data suggest that neonatal arterial ischemic stroke and cerebral sinovenous thrombosis are more commonly diagnosed in boys. The slightly larger size of male neonates may be contributory in arterial ischemic stroke. It is not known whether boys are at higher risk of developing arterial ischemic stroke and cerebral sinovenous thrombosis or are simply more likely to present with symptoms resulting in diagnosis. These issues need further study.

Independent walking after neonatal arterial ischemic stroke and sinovenous thrombosis.

Few studies have examined walking after neonatal arterial ischemic stroke and sinovenous thrombosis. We looked at the development of walking in a retrospective and consecutive cohort study of 88 term and near-term neonates. We used Kaplan-Meier survival curves and Cox proportional hazards models to assess (1) sex, (2) stroke type (arterial ischemic stroke or sinovenous thrombosis), (3) number of cerebral hemispheres with infarction, and (4) presence of neonatal comorbidity as predictors of the probability over time of starting to walk independently. These variables were assessed as predictors of parent-reported gait normality using the chi-square test on 2 x 2 contingency tables. Seventy-five of 83 survivors (90.4%, 95% confidence interval = 81.9-95.7) walked with a median time of first steps at 13 months of age (95% confidence interval = 12-14). Only bilateral strokes were associated with a lower probability over time of initiating independent walking (hazard ratio = 0.41, P = .04). Parents reported normal gait for 58 of 75 walkers (77.3%, 95% confidence interval = 67.8-86.8). No variables predicted parent-reported gait normality. Our findings suggest that most survivors of neonatal arterial ischemic stroke and sinovenous thrombosis walk with a gait that appears normal to parents, but bilateral infarctions decrease the probability over time of starting to walk independently.

Neurocognitive outcome after acute disseminated encephalomyelitis.

Cognitive dysfunction has been demonstrated in multiple sclerosis but has not been extensively studied after acute disseminated encephalomyelitis (ADEM). Because ADEM often presents with widespread demyelination, which may not completely resolve, these patients may be at risk for persistent cognitive dysfunction. The study objective was to explore the profile and severity of neurocognitive sequelae in pediatric ADEM. Children aged 6-15 years diagnosed with ADEM were invited to participate in a structured neurologic assessment, neuropsychological evaluation, and a follow-up magnetic resonance imaging. Nine of 15 children diagnosed with ADEM met the age criteria and six participated in the study. The mean age at presentation was 7.7 years; the mean duration of follow-up was 3.5 years. As a group, these children with prior ADEM performed within the average range on cognitive testing. However, a variety of mild cognitive deficits were demonstrated in each of the children, even in those whose magnetic resonance imaging studies had completely normalized. Four children demonstrated a cognitive profile of relatively poorer visuospatial/visuomotor function. The cognitive deficits observed in these children are similar but less severe than those previously reported in adults and children with multiple sclerosis, which may reflect the monophasic nature of ADEM, compared with the chronic, recurrent demyelination characteristic of multiple sclerosis.

Identical ATP1A3 mutation causes alternating hemiplegia of childhood and rapid-onset dystonia parkinsonism phenotypes.

BACKGROUND: Alternating hemiplegia of childhood and rapid-onset dystonia parkinsonism are two separate movement disorders with different dominant mutations in the same sodium-potassium transporter ATPase subunit gene, ATP1A3. PATIENT: We present a child with topiramate-responsive alternating hemiplegia of childhood who was tested for an ATP1A3 gene mutation. RESULTS: Gene sequencing revealed an identical ATP1A3 mutation as in three typical adult-onset rapid-onset dystonia parkinsonism cases but never previously described in an alternating hemiplegia of childhood case. CONCLUSION: The discordance of these phenotypes suggests that there are other undiscovered environmental, genetic, or epigenetic factors influencing the development of alternating hemiplegia of childhood or rapid-onset dystonia parkinsonism.

Mosaic microdeletion 18q21 as a cause of mental retardation.

We present the clinical and cytogenetic findings in an 8 year old girl with mental retardation, acquired microcephaly, delayed motor skills and stereotypical hand movements. Array comparative genomic hybridization identified a mosaic de novo deletion of approximately 7.505 Mb in chromosome region 18q21.1q21.31, resulting in the loss of one copy of the TCF4 gene as well as 29 other RefSeq genes. The deletion likely occurred early in development as this child has clinical symptoms affecting multiple organ systems, reminiscent of those observed in Pitt-Hopkins syndrome (PHS; OMIM 610954). This case represents the second known example of a mosaic deletion resulting in clinical symptoms consistent with Pitt-Hopkins syndrome, and illustrates the utility of genomic microarray analysis in detecting large mosaic imbalances that may otherwise be missed by G-band analysis.

Late complications of vertebral artery dissection in children: pseudoaneurysm, thrombosis, and recurrent stroke.

Craniocervical arterial dissection is an important cause of childhood arterial ischemic stroke, accounting for 7.5% to 20% of cases. Significant neurologic morbidity and mortality may result and recurrence risk may be higher than in adults. However, the natural history and long-term outcome of pediatric dissection are poorly studied. We report 3 cases of extracranial vertebral artery dissection with complications including pseudoaneurysm formation, recurrent stroke, and late spontaneous thrombosis of the dissected artery. These cases illustrate the dynamic processes involved in vascular injury and healing of vertebral artery dissection in children over years, with potential implications for long-term management and prevention of recurrence.