Laura L. Lehman

Leukoaraiosis and Sex Predict the Hyperacute Ischemic Core Volume

Background and Purpose— Leukoaraiosis (LA) and male sex have been associated with decreased cerebrovascular reactivity, which potentially adversely affects tissue viability in acute stroke. Therefore, we aimed to elucidate the contribution of LA-severity and sex to the extent of the hyperacute ischemic core volume after intracranial large artery occlusion. Methods— We analyzed data from 87 patients with acute intracranial large artery occlusion who had acute multimodal computed tomography-imaging. LA-severity was assessed using the van Swieten scale on noncontrast computed tomography. Computed tomography perfusion data were analyzed using automatic calculation of the mean transit time and hyperacute cerebral blood volume defects. Multivariate linear and logistic regression analyses were used to identify independent predictors of the hyperacute infarct-volume. Results— Severe LA (van Swieten Scale, 3–4; odds ratio, 43.22; 95% CI, 6.26–298.42; P<0.001) and male sex (odds ratio, 7.52; 95% CI, 1.38–40.86; P=0.020) were independently associated with a hyperacute cerebral blood volume-lesion >25 mL on multivariate logistic regression analysis. Multivariate linear regression analysis confirmed the association between severe LA (P<0.001) and male sex (P=0.01) with larger cerebral blood volume-lesions. There was no significant difference in the absolute or relative mean transit time-lesion volumes when stratified by LA-severity or sex. Women had significantly smaller cerebral blood volume-lesion volumes compared with men (P=0.036). Conclusions— Severe LA and male sex are associated with larger infarct cores, which adds to the notion that sex and LA alter the brain’s intrinsic susceptibility to acute cerebral ischemia. Future, larger studies are needed to confirm our observation that women have smaller core volumes and its significance.

Perinatal Arterial Ischemic Stroke: Presentation, Risk Factors, Evaluation, and Outcome

BACKGROUND Perinatal arterial ischemic stroke is as common as large vessel arterial ischemic stroke in adults and leads to significant morbidity. Perinatal arterial ischemic stroke is the most common identifiable cause of cerebral palsy and can lead to cognitive and behavioral difficulties that are amortized over a lifetime. METHODS The literature on perinatal arterial ischemic stroke was reviewed and analyzed. RESULTS Risk factors for perinatal arterial ischemic stroke include those that are maternal, neonatal, and placental. The most common clinical signs at presentation are seizures and hemiparesis. Evaluation should begin with thorough history acquisition and physical examination followed by magnetic resonance imaging of the brain, with consideration of magnetic resonance angiography of the head and neck, echocardiogram, and thrombophilia evaluation. Treatment beginning early to include physical, speech, and occupational therapies including constraint-induced movement therapy and close cognitive and developmental follow-up may be beneficial. Future treatments may include transcranial magnetic stimulation, hypothermia, and erythropoietin. CONCLUSIONS Perinatal arterial ischemic stroke comprises a group of arterial ischemic injuries that can occur in the prenatal, perinatal, and postnatal periods in term and preterm infants with different types of perinatal arterial ischemic stroke having different clinical presentations, risk factors, and long-term outcomes.

Changing ethnic disparity in ischemic stroke mortality in US children after the STOP trial.

IMPORTANCE A prior report showed higher stroke mortality in US black children compared with white children (1979-1998), a disparity likely due in part to sickle cell disease, which leads to a high risk of childhood ischemic stroke. We hypothesized that this disparity has diminished since the publication of the Stroke Prevention Trial in Sickle Cell Anemia (STOP trial) in 1998 demonstrating the efficacy of long-term blood transfusions for primary stroke prevention. OBJECTIVE To evaluate the demographics and secular trends in mortality from ischemic and hemorrhagic stroke (as a primary cause of death) in US children (<20 years) and determine if there has been a decrease in the disparity between white and black children since the publication of the STOP trial in 1998. DESIGN We used death certificate data from the National Center for Health Statistics, 1988 through 2007. SETTING United States. PARTICIPANTS Children who died in 1988 through 2007 in the United States. INTERVENTION Publication of the STOP trial. MAIN OUTCOME MEASURES Incidence rate ratios were calculated as the measure of relative risk. RESULTS Among 1.6 billion person-years of US children (1988-2007), there were 4425 deaths attributed to stroke, yielding an average of 221 deaths per year; 20% were ischemic; 67%, hemorrhagic; and 12%, unspecified. The relative risk of ischemic stroke mortality for black vs white children dropped from 1.74 from 1988 through 1997 to 1.27 from 1998 through 2007. The ethnic disparity in hemorrhagic stroke mortality, however, remained relatively stable between these 2 periods: black vs white relative risk, 1.90 (1988-1997) and 1.97 (1998-2007). CONCLUSIONS AND RELEVANCE The excess risk of death from ischemic, but not hemorrhagic, stroke in US black children has decreased over the past decade. This may be related to the implementation of an effective ischemic stroke prevention strategy for children with sickle cell disease.

Vertebral artery dissection leading to stroke caused by violent neck tics of Tourette syndrome.

Tourette syndrome is a childhood onset neuropsychiatric disorder characterized by involuntary or urge-driven motor and vocal tics. When tics cause impairment or pain, medical treatment is often recommended.1 We present a patient with Tourette syndrome who had treatment-refractory violent neck tics. We propose that the frequent violent neck tics caused a vertebral artery dissection leading to right pontine and bilateral cerebellar infarcts. ### Case report. An 18-year-old man with Tourette syndrome, obsessive compulsive disorder, and depression with violent neck tics was transferred to our institution after having right pontine and bilateral cerebellar infarcts. Imaging was consistent with a right vertebral artery dissection and basilar artery occlusion. Two days prior to hospital admission the patient had symptoms of dizziness plus tingling, headache, and left-sided numbness. In the emergency department, the head CT was negative, and he was discharged. Two days later, he presented again with signs consistent with a posterior circulation stroke including left hemiparesis, left facial droop, diplopia, and dysarthria. His head CT was originally interpreted as normal; however, on further examination, cerebellar infarcts were identified as well as abnormally dense basilar and right vertebral arteries (figure, A and B). Brain MRI showed evidence of right pontine and bilateral cerebellar infarcts (figure, C and D). The magnetic resonance arteriogram showed occlusions of the right vertebral and …

Pathways for Neuroimaging of Childhood Stroke.

BACKGROUND The purpose of this article is to aid practitioners in choosing appropriate neuroimaging for children who present with symptoms that could be caused by stroke. METHODS The Writing Group members participated in one or more pediatric stroke neuroimaging symposiums hosted by the Stroke Imaging Laboratory for Children housed at the Hospital for Sick Children in Toronto, Ontario, Canada. Through collaboration, literature review, and discussion among child neurologists with expertise diagnosing and treating childhood stroke and pediatric neuroradiologists and neuroradiologists with expertise in pediatric neurovascular disease, suggested imaging protocols are presented for children with suspected stroke syndromes including arterial ischemic stroke, cerebral sinovenous thrombosis, and hemorrhagic stroke. RESULTS This article presents information about the epidemiology and classification of childhood stroke with definitions based on the National Institutes of Health Common Data Elements. The role of imaging for the diagnosis of childhood stroke is examined in depth, with separate sections for arterial ischemic stroke, cerebral sinovenous thrombosis, and hemorrhagic stroke. Abbreviated neuroimaging protocols for rapid diagnosis are discussed. The Writing Group provides suggestions for optimal neuroimaging investigation of various stroke types in the acute setting and suggestions for follow-up neuroimaging. Advanced sequences such as diffusion tensor imaging, perfusion imaging, and vessel wall imaging are also discussed. CONCLUSIONS This article provides protocols for the imaging of children who present with suspected stroke.

Potential Eligibility for Recombinant Tissue Plasminogen Activator Therapy in Children: A Population-Based Study:

Intravenous recombinant tissue plasminogen activator is an established therapy for adults with ischemic stroke. In this Greater Cincinnati/Northern Kentucky population-based study, 8% were eligible. However, no established therapy exists for children with acute ischemic stroke. Accordingly, investigators assessed rates of eligibility for recombinant tissue plasminogen activator therapy among children (<18 years of age) in the same population to aid planning of future clinical trials. The investigators identified 29 pediatric ischemic strokes during 3 separate study periods (1993-1994, 1999, and 2005) and determined potential eligibility for recombinant tissue plasminogen activator therapy based on 2007 American Heart Association guidelines for adults. Depending on how relative contraindications were considered, 1 to 3 cases (3%-10%) met eligibility criteria. On the basis of national pediatric stroke incidence rates extrapolated from our population, it is estimated that up to 178 children might be eligible for intravenous recombinant tissue plasminogen activator therapy annually in the United States. Thus, recruitment for clinical studies is likely to be challenging and requires a concerted multicenter effort.

Predictors of Stroke After Transient Ischemic Attack in Children.

Background and Purpose— Transient ischemic attack (TIA) in children has received far less attention compared with TIA in adults. The risk factors of stroke after TIA in children are relatively unknown. We aimed to determine the percentage of children who have stroke after TIA and the risk factors associated with stroke after TIA. Methods— We searched the medical records at Boston Children’s Hospital for the year 2010 to find children who were evaluated for TIA to determine associated risk factors of stroke after TIA. We included children who were evaluated in 2009 through 2010 for TIA and had magnetic resonance imaging. We examined follow-up imaging through August 2014 for subsequent stroke. Logistic regression was used to calculate odds ratios for factors in our cohort who are associated with stroke after presentation with TIA. Results— We identified 63 children who experienced a TIA. The mean time of imaging follow-up was 4.5 years after TIA presentation. Of the 63 children, 10 (16%) developed radiological evidence of ischemic cerebral injury within the follow-up period. Four of the 10 (6%) demonstrated diffusion abnormalities on magnetic resonance imaging at TIA presentation, whereas 8 (13%) had a stroke after their TIA. Arteriopathy, female sex, and autoimmune disorders were significantly associated with stroke after TIA. Conclusions— In our cohort of children, stroke occurred after TIA at a rate similar to that seen in adults, but the risk factors for stroke after TIA in children are different.

Pathways for Neuroimaging of Neonatal Stroke

PURPOSE To provide consensus-based, suggested imaging protocols to facilitate the accurate and timely diagnosis of a neonate with symptoms concerning for stroke. METHODS The Writing Group, an international collaboration of pediatric neurologists and neuroradiologists with expertise in perinatal and childhood stroke, participated in a series of pediatric stroke neuroimaging symposia. These discussions, in conjunction with extensive literature review, led to a consensus for imaging protocols to guide practitioners in the diagnosis of neonatal stroke subtypes as defined by the National Institute of Neurological Disorders and Stroke Common Data Elements. The epidemiology, clinical presentation, and associated risk factors for arterial ischemic stroke, cerebral sinovenous thrombosis, and hemorrhagic stroke are reviewed, with a focused discussion regarding the role of neuroimaging for each subtype. RESULTS In a neonate with suspected stroke, magnetic resonance imaging is the preferred modality, given the lack of X-irradiation, superior anatomic resolution, and sensitivity for acute ischemia. Core recommended sequences include diffusion-weighted imaging and apparent diffusion coefficient mapping to diagnose acute ischemia, gradient-recalled echo or susceptibility-weighted imaging to detect intracranial blood and its breakdown products, and T1- and T2-weighted imaging to assess for myelination, extra-axial blood, and edema. Magnetic resonance angiography of the brain may be useful to detect vascular abnormalities, with venography if venous sinus thrombosis is suspected. The application of more novel sequences, as well as the utility of follow up-imaging, is also discussed.

Placental Pathology in Neonatal Stroke: A Retrospective Case-Control Study

Objective To assess the association of placental abnormalities with neonatal stroke. Study design This retrospective case‐control study at 3 academic medical centers examined placental specimens for 46 children with neonatal arterial or venous ischemic stroke and 99 control children without stroke, using a standard protocol. Between‐group comparisons used χ2 and Fisher exact t test. Correlations used Spearman correlation coefficient. Results Case placentas were more likely than controls to meet criteria for ≥1 of 5 major categories of pathologic abnormality (89% vs 62%; OR, 5.1; 95% CI, 1.9–14.0; P = .0007) and for ≥2 categories (38% vs 8%; OR, 7.3; 95% CI, 2.9–19.0; P < .0001). Fetal vascular malperfusion occurred in 50% of cases and 17% of controls (OR, 4.8; 95% CI, 2.2–10.5; P = .0001). Amniotic fluid inflammation occurred in 46% of cases with arterial ischemic stroke vs 25% of controls (OR, 2.6; 95% CI, 1.1–6.1; P = .037). There was evidence of a “stress response” (meconium plus elevated nucleated red blood cells) in 24% of cases compared with 1% of controls (OR, 31; 95% CI, 3.8–247.0; P < .0001). Conclusions Placental abnormality was more common in children with neonatal stroke compared with controls. All placental findings represent subacute‐to‐chronic intrauterine stressors. Placental thrombotic processes were associated with both arterial and venous stroke. Our findings provide evidence for specific mechanisms that may predispose to acute perinatal stroke. Amniotic fluid inflammation associated with neonatal arterial ischemic stroke deserves further investigation.

Transient Focal Neurologic Symptoms Correspond to Regional Cerebral Hypoperfusion by MRI: A Stroke Mimic in Children

SUMMARY: Children who present with acute transient focal neurologic symptoms raise concern for stroke or transient ischemic attack. We present a series of 16 children who presented with transient focal neurologic symptoms that raised concern for acute stroke but who had no evidence of infarction and had unilateral, potentially reversible imaging features on vascular and perfusion-sensitive brain MR imaging. Patients were examined with routine brain MR imaging, MRA, perfusion-sensitive sequences, and DWI. Fourteen (88%) children had lateralized MRA evidence of arterial tree pruning without occlusion, all had negative DWI findings, and all showed evidence of hemispheric hypoperfusion by susceptibility-weighted imaging or arterial spin-labeling perfusion imaging at presentation. These findings normalized following resolution of symptoms in all children who had follow-up imaging (6/16, 38%). The use of MR imaging with perfusion-sensitive sequences, DWI, and MRA can help to rapidly distinguish children with conditions mimicking stroke from those with acute stroke.