Ivanna Yau

A prospective outcome study of neonatal cerebral sinovenous thrombosis.

Neonatal cerebral sinovenous thrombosis is a frequent contributor to neonatal mortality and morbidity. Treatment is controversial, and reported clinical outcomes vary widely. Newborns with radiologically confirmed neonatal cerebral sinovenous thrombosis from 1992 to 2009 were prospectively followed in our Children’s Stroke Clinic for standardized outcomes, including the Pediatric Stroke Outcome Measure. Outcomes were available in 90 of 104 (87%) neonates. Early outcomes included cerebral sinovenous thrombosis-associated death (5) and thrombus propagation (15 [6 associated with new venous infarcts]). Lack of anticoagulation predicted propagation (RR = 13; P = .0007). Complete thrombus recanalization occurred in 90% by 3 months. Late outcomes (median, 2.5 years) were epilepsy (15) and neurological disability (50), which included moderate-severe language (43), sensorimotor (38), and cognitive/behavioral (24) deficits. Overall, 61% had poor outcome (death/any deficit). Concurrent neurological comorbidity at diagnosis (odds ratio = 2.8; P = .029) predicted poor outcome. Clinical trials are urgently needed to establish more effective treatment strategies.

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

To describe outcomes and outcome predictors in childhood basilar artery stroke (BAS).

A pediatric institutional acute stroke protocol improves timely access to stroke treatment

We aimed to evaluate whether an institutional acute stroke protocol (ASP) could accelerate the diagnosis and secondary treatment of pediatric stroke.

Evolution of a chronic dissecting aneurysm on magnetic resonance imaging in a pediatric patient

Clinical and imaging manifestations of the so-called partially thrombosed aneurysm (PTA) are different from those of the classic intracranial saccular aneurysm. Given some of their peculiar imaging features, it had been hypothesized that some PTAs occur due to repeated intramural hemorrhages. The authors present a case of PTA that evolved from an acute dissecting aneurysm as shown by serial imaging. A previously healthy 5-year-old boy had a sudden onset of left hemiparesis. Initial MRI sequences showed a perforating vessel infarction in the right basal ganglia area secondary to an acute distal middle cerebral artery (MCA) dissection as demonstrated on conventional angiography. Conservative management with close observation of this dissection was chosen, and serial MRI studies revealed layering of blood of various ages within the wall of an aneurysmal outpouching of the MCA, thereby leading to the imaging appearance of a PTA. The findings in this case indicate that some PTAs may be caused by repeated or chronic dissections, with blood entering the wall through an endothelial defect. Understanding the pathological mechanism underlying the formation of these aneurysms will help inform appropriate treatment strategies.

Current Concepts in Pediatric Stroke

Stroke is a relatively rare but rather significant cause of short- and long-term morbidity and mortality in children. It can be divided into three categories: arterial ischemic stroke (AIS), hemorrhagic stroke (HS) and cerebral sinovenous thrombosis (CSVT). This review focuses on AIS. The etiologies of pediatric AIS are diverse and different from those in adult stroke, chief among these being congenital heart disease, vasculopathies, hematological disorders and prothrombotic states. Additional factors might be related to the age group, ethnicity and geographic factors. Early recognition enables initiation of prompt therapy thereby reducing risk of further recurrence and complications.

Expanding the Spectrum of Methylmalonic Acid-Induced Pallidal Stroke: First Reported Case of Metabolic Globus Pallidus Stroke in Transcobalamin II Deficiency

UNLABELLED A 10-year-old boy with transcobalamin II (TCII) deficiency on oral cyanocobalamin therapy presented with acute right hemiparesis and sensory axonal neuropathy in the context of an intercurrent viral illness. MRI demonstrated unilateral globus pallidus stroke with normal MRA. Echocardiogram was normal. Methylmalonic acid in serum was mildly elevated at 10.29 μmol/L (normal < 0.37 μmol/L), which was an 18-fold increase from his previous baseline. The patient was switched to IM cyanocobalamin and serum methylmalonic acid levels normalized over 6 months to 0.01 μmol/L. After 4 months of IM cyanocobalamin therapy, the neuropathy had resolved. Repeat MRI 4 months after the sentinel stroke demonstrated a chronic-appearing contralateral globus pallidus stroke of uncertain timing. CONCLUSIONS We are describing the first case of metabolic stroke and peripheral neuropathy in TCII deficiency. The neuropathy was responsive to parenteral hydroxycobalamin. Unilateral globus pallidus stroke in the appropriate clinical context should not exclude a metabolic etiology as it may herald contralateral involvement and may provide an opportunity for early recognition and treatment. IM hydroxycobalamin should be strongly considered in all patients with TCII, particularly when they reach later childhood. This case highlights the selective vulnerability of the globus pallidus to increased levels of methylmalonic acid of various causes, which is important for both diagnosis and ultimately understanding the mechanisms of neurological injury in this group of conditions. Metabolic stroke may occur with lower levels of methylmalonic acid than previously reported in the context of an intercurrent bioenergetic stressor.

Arterial Wall Imaging in Pediatric Stroke

Background and Purpose— Arteriopathy is common in childhood arterial ischemic stroke (AIS) and predicts stroke recurrence. Currently available vascular imaging techniques mainly image the arterial lumen rather than the vessel wall and have a limited ability to differentiate among common arteriopathies. We aimed to investigate the value of a magnetic resonance imaging-based technique, namely noninvasive arterial wall imaging (AWI), for distinguishing among arteriopathy subtypes in a consecutive cohort of children presenting with AIS. Methods— Children with confirmed AIS and magnetic resonance angiography underwent 3-Tesla AWI including T1-weighted 2-dimensional fluid-attenuated inversion recovery fast spin echo sequences pre- and post-gadolinium contrast. AWI characteristics, including wall enhancement, wall thickening, and luminal stenosis, were documented for all. Results— Twenty-six children with AIS had AWI. Of these, 9 (35%) had AWI enhancement. AWI enhancement was associated with anterior circulation magnetic resonance angiography abnormality and cortical infarction in 8 of 9 (89%) children and normal magnetic resonance angiography with posterior circulation subcortical infarction in 1 (1 of 9; 11%) child. AWI enhancement was not seen in 17 (65%), 10 (59%) of whom had an abnormal magnetic resonance angiography. Distinct patterns of pre- and postcontrast signal abnormality were demonstrated in the vessel wall in the region of interest in children with transient cerebral arteriopathy, arterial dissection, primary central nervous system angiitis, dissecting aneurysm, and cardioembolic stroke. Conclusions— AWI is a noninvasive, high-resolution magnetic resonance AWI technique, which can be successfully used in children presenting with AIS. Patterns of AWI enhancement are recognizable and associated with specific AIS pathogeneses. Further studies are required to assess the additional diagnostic utility of AWI over routine vascular imaging techniques, in childhood AIS.

A novel mutation in the SerpinC1 gene presenting as unprovoked neonatal cerebral sinus venous thrombosis in a kindred.

Antithrombin (AT) deficiency has been associated with an increased risk of pediatric cerebral sinus venous thrombosis (CSVT); but few cases of neonatal CSVT have been reported. We describe two half‐siblings who presented with seizures in the first week of life and were found to have extensive CSVT with associated parenchymal and intraventricular hemorrhage. Both infants were found to have type 1 AT deficiency. Sequencing of the SerpinC1 gene revealed a novel heterozygous mutation on exon 5 (c.1009C > T p.Q337X). Both infants were treated with anticoagulation and had recanalization of the dural sinuses on follow up imaging. Pediatr Blood Cancer 2013; 60: 133–136.

Effectiveness of antiepileptic drug tapering in the pediatric epilepsy monitoring unit

OBJECTIVE Limited evidence on the relationship between antiepileptic drug (AED) tapering and the likelihood of a seizure during an Epilepsy Monitoring Unit (EMU) admission is available, and no evidence specific to the pediatric population has been published. Our study sought to determine whether AED tapering leads to increased seizure likelihood in a pediatric EMU setting. METHODS We performed a retrospective chart review of children admitted to the pediatric EMU at the Hospital for Sick Children in Toronto between June 1, 2014 and June 1, 2016. Data collected included demographics, reason for EMU referral, and epilepsy and medical characteristics. Among those with nondaily seizures, Kaplan-Meier curves were fit to compare probability of EMU seizure in those who were tapered fully from at least one AED to those not tapered. A Cox proportional hazards model was fit to evaluate this relationship after adjustment for subject sex, distance traveled to hospital, epilepsy duration, seizure frequency, time since last seizure, whether EMU referral was part of presurgical planning, magnetic resonance imaging (MRI) findings, and number of prescribed AEDs. An interaction between medication taper and number of prescribed AEDs was also included. Terms not significant at p < 0.3 were removed from the model, and the reduced model was recomputed. RESULTS Of the 281 children included in the study, 159 had nondaily seizures. Kaplan-Meier curves indicated fully tapering at least one AED was associated with increased likelihood of seizure during EMU; however, after adjustment for confounding variables, this association was not preserved. Abnormal MRI findings, referral for presurgical evaluation, and shorter (≤3 months) time since last seizure were associated with increased likelihood of seizure during EMU. SIGNIFICANCE Short-term AED tapering in pediatric patients may not be effective for increasing seizure likelihood in the EMU.

The role of surgery in refractory epilepsy secondary to polymicrogyria in the pediatric population

Polymicrogyria (PMG) is a common malformation of cortical development. Many patients with PMG will have medically refractory epilepsy but the role of epilepsy surgery is unclear. The objective of this study was to assess the efficacy of surgical resection/disconnection in achieving seizure control in pediatric patients with PMG.