Cerebral palsy after perinatal arterial ischemic stroke.

The frequency of cerebral palsy, degree of disability, and predictors of disability were assessed in children in a perinatal arterial stroke database. Risk factors were assessed at the univariate level using the Pearson chi(2) and Fisher exact test and at the multivariate level using logistic regression analysis. Seventy-six of 111 children with perinatal stroke (68%) had cerebral palsy, most commonly hemiplegic (66/76; 87%). Multivariate analysis of the entire cohort showed both delayed presentation (OR,9.96; 95% CI, 3.10-32.02) and male sex (OR, 2.55; 95% CI, 1.03-6.32) were associated with cerebral palsy. In subgroup multivariate analyses: in children with neonatal presentation, bilateral infarcts were associated with triplegia or quadriplegia (OR, 5.33; 95% CI, 1.28-22.27); in children with unilateral middle cerebral artery infarcts, delayed presentation (OR, 10.60; 95% CI, 2.28-72.92) and large-branch infarction (OR, 8.78; 95% CI, 2.18-43.67) were associated with cerebral palsy. These data will aid physicians in planning long-term rehabilitative care for children with perinatal stroke.

Very early arterial ischemic stroke in premature infants.

Early stroke in the premature infant has rarely been described. Presented here are the cases of 23 infants, born between 23 and 35 weeks gestational age, with focal arterial ischemic stroke occurring before 44 weeks gestational age. Ten (43%) were male. Five children (22%) were half of a twin pair; no co-twin died. The most commonly affected territory was the middle cerebral artery territory. Three children with extreme prematurity (< or =26 weeks) had cerebellar infarcts. Twelve children had unilateral or bilateral intraventricular hemorrhages (grade 3 or higher in 8 of the 12). Twelve children had white matter injury: periventricular leukomalacia, hypoxic-ischemic encephalopathy, or both. Most children had multiple comorbidities, and the median neonatal intensive care unit stay was 63 days (range, 14-365). One child died in the neonatal intensive care unit (age 123 days). All 22 survivors were left with disabilities. Seventeen (77%) had cerebral palsy, 10 (45%) had epilepsy, and 17 (77%) had cognitive impairment. Arterial ischemic stroke appears to add to the neurologic disabilities commonly associated with prematurity.

Neuropsychologic outcomes in a case series of twins discordant for perinatal stroke.

Perinatal stroke may affect cognitive development, but few studies have addressed the details of cognitive function after perinatal stroke. The present study was designed to compare the neuropsychologic features of five sets of twins discordant for perinatal stroke. All of the affected children had unilateral middle cerebral artery infarction (two left, three right); four of the five infarcts were large-branch, affecting the entire M1 territory. Three of the five affected children had comorbid epilepsy. Measures of intelligence, memory, language, attention, executive function, visual-motor integration, and fine motor skills were administered to children at a median age of 5 years (range, 5-8 years). Relative to their unaffected co-twins, the twins with perinatal stroke exhibited lower levels of full scale (p=0.005), verbal (p=0.006), and nonverbal (p=0.005) intelligence. Children with perinatal stroke also showed significant deficits on tests of verbal memory (p=0.041), receptive language (p=0.011), verbal fluency (p=0.019), and visual attention (p=0.011), compared with their unaffected co-twins. Twin gestation may be a risk factor for poor cognitive outcome after perinatal stroke. Large infarct size and comorbid epilepsy may have contributed to some of the poor cognitive outcomes in this cohort.

Perinatal stroke and the risk of developing childhood epilepsy.

OBJECTIVES: To describe the prevalence of epilepsy after 6 months of age in children with perinatal stroke and examine whether perinatal data predict epilepsy onset and resolution. STUDY DESIGN: A retrospective review of 64 children with perinatal stroke. In children with at least 6 months of follow-up data, Kaplan-Meier curves, univariate log-rank tests, and Cox proportional hazards models were used to examine predictors of time to development of seizures, and time to resolution of seizures in children with epilepsy. The association of risk factors with the presence of epilepsy at any time after 6 months of age was examined using Fisher's exact test. RESULTS: Forty-one of the 61 children with at least 6 months of follow-up data (67%) had epilepsy between 6 months of age and last follow-up, but in 13 of 41, seizures eventually resolved and anticonvulsants were discontinued. Infarct on prenatal ultrasonography (P = .0065) and family history of epilepsy (P = .0093) were significantly associated with time to development of seizures after 6 months of age in the univariate analysis. No assessed variables were associated with time to resolution of epilepsy or with the presence of epilepsy after 6 months of age. CONCLUSIONS: Childhood epilepsy is frequent after perinatal stroke. Evidence of infarction on prenatal ultrasonography and a family history of epilepsy predict earlier onset of active seizures.

Two cousins with neonatal stroke, PAI-1 4G variant and MTHFR A1298C mutation.

The authors describe 2 female cousins with neonatal stroke. One was heterozygous for the plasminogen activator inhibitor-1 4G variant and compound heterozygous for the A1298C and C677T methylenetetrahydrofolate reductase mutations. Her cousin was homozygous for the plasminogen activator inhibitor-1 4G variant and heterozygous for the methylenetetrahydrofolate reductase A1298C and factor V Leiden mutations.

Accuracy of ICD-9 codes for identifying children with cerebral sinovenous thrombosis.

Childhood sinovenous thrombosis is rare, making it difficult to study; International Classification of Diseases, ninth revision (ICD-9), code searches across multiple hospitals would permit the identification of large numbers of children with sinovenous thrombosis. However, the accuracy of these codes for identifying childhood sinovenous thrombosis has not been established. We performed a retrospective search of admissions records for Riley Hospital for Children in Indianapolis, Indiana, from January 1999 to June 2005 using ICD-9 codes 325 (cerebral sinovenous thrombosis, excluding nonpyogenic cases and cases associated with pregnancy and the puerperium), 437.6 (cerebral venous thrombosis of nonpyogenic origin), and 671.5 (cerebral venous thrombosis in pregnancy or the puerperium) in any position. During this period, there were 47042 admissions. ICD-9 code 325 identified 61 admissions on 56 children. Only 13% were of pyogenic origin. Fifty-two (92.9%) had "possible, probable, or definite" sinovenous thrombosis, but only 76.9% of those had "probable or definite" sinovenous thrombosis. Uncertainty in diagnoses stemmed from limitations in imaging and disagreement over interpretation of imaging studies. ICD-9 code 325 in the primary position identified 7 children; all had possible (n = 1), probable (n = 1), or definite (n = 5) sinovenous thrombosis. ICD-9 code 437.6 identified a single admission on a single case of probable cerebral venous thrombosis; it was unclear whether this case was "nonpyogenic." ICD-9 code 671.5 did not identify any children. ICD-9 code 325 is useful for identifying children likely to have sinovenous thrombosis, but it is not useful for differentiating pyogenic and nonpyogenic cases, and uncertainty in clinical diagnosis makes it difficult to gauge the true accuracy. Furthermore, it is important to search for the code in any position as limiting searches to the primary position misses most cases.

Epilepsy in children with delayed presentation of perinatal stroke.

A subgroup of children with perinatal stroke do not present clinically until after the perinatal period. Detailed epilepsy outcomes in these children have not been well studied. A retrospective cohort study of 45 children with delayed presentation of perinatal stroke identified by review of pediatric stroke clinic records, physician referral, and International Classification of Diseases, Ninth edition, code searches of hospital records, was performed at a tertiary pediatric hospital in Indianapolis, Indiana. A modified version of the Engel scale was used to grade epilepsy outcomes. The chi(2) test, Fisher's exact test, and relative risks were calculated to examine the association of epilepsy at time of last follow-up with initial presentation with seizures, infantile spasms, radiographic findings, and initial abnormal electroencephalogram (EEG). These tests were also used to examine the association of epilepsy with cognitive or motor disability and the association of initial abnormal EEG with motor disability. Patients presented with hemiparesis (40; 89%), seizures (4; 9%), or headaches (1; 2%). All had unilateral infarcts on cranial imaging. Four children (9%) had infantile spasms, 2 at presentation and 2 later. Nineteen children received at least 1 EEG for suspicious spells or frank seizures; initial EEG was abnormal in 16 patients (84%). At last follow-up, 17 patients (38%) had epilepsy, which was severe in 4 (24% of those with epilepsy). Initial presentation with seizures (relative risk = 3.2; 95% confidence interval, 2.0-4.9) and infantile spasms (relative risk = 3.2; confidence interval, 2.0-4.9) were associated with epilepsy at last follow-up. Infantile spasms were also associated with moderate-to-severe epilepsy at last follow-up (relative risk = 10.3; confidence interval, 1.9-54.4). Epilepsy at last follow-up was associated with cognitive disability (P = .05). Initial abnormal EEG was not associated with cerebral palsy (P = .30). Epilepsy is frequent in children with delayed presentation of perinatal stroke and is associated with initial presentation with seizures and infantile spasms at any point in time. Cognitive disability often accompanies epilepsy in these children.

Age-related variation in presenting signs of childhood arterial ischemic stroke.

The objective of this study was to determine whether there are age-related variations in the clinical presentation of cerebral arterial ischemic stroke in children after the perinatal period. We performed a retrospective record review of 76 children with cerebral arterial ischemic stroke occurring between 44 weeks of conceptional age and age 19 years. These children were seen by our pediatric stroke group between September 1, 1989 and August 1, 2005. We examined the following clinical presentations: epileptic seizures, focal weakness, and altered mental status. We compared the frequency of each presentation in children with arterial ischemic stroke up to and after age 1 year. Children aged <1 year were significantly more likely than older children to present with epileptic seizures (45.5% vs 10.8%, P = 0.01) and altered mental status (36.4% vs 7.7%, P = 0.02), and there was a trend for them to be less likely than older children to present with focal weakness (45.5% vs 76.9%, P = 0.06). Children aged <1 year with cerebral arterial ischemic stroke were more likely to present with epileptic seizures and altered mental status than children aged >or=1 year, and may be less likely to present with focal weakness. These findings may aid in the recognition of stroke in young children.

Association of cerebral palsy with other disabilities in children with perinatal arterial ischemic stroke.

The association of cerebral palsy with other disabilities in children with perinatal stroke has not been well-studied. We examined this association in 111 children with perinatal stroke: 67 with neonatal presentation, and 44 with delayed presentation. Seventy-six children (68%) had cerebral palsy, which was hemiplegic in 66 and tri- or quadriplegic in 10. Fifty-five (72%) children with cerebral palsy had at least one other disability: 45 (59%) had a cognitive/speech impairment (moderate-severe in 20), and 36 (47%) had epilepsy (moderate-severe in 11). In children with neonatal presentation, cerebral palsy was associated with epilepsy (P = 0.0076) and cognitive impairment (P = 0.0001). These associations could not be tested in children with delayed presentation because almost all children in this group had cerebral palsy. In another analysis with multivariate logistic regression for children with cerebral palsy, children who had both neonatal presentation and history of cesarean-section delivery were more likely to have epilepsy (P = 0.001). Children with cerebral palsy after perinatal stroke who had neonatal presentation were more likely to have severe cognitive impairment (odds ratio, 7.78; 95% confidence interval, 1.80-47.32) or severe epilepsy (odds ratio, 6.64; 95% confidence interval, 1.21-69.21) than children with delayed presentation. Children with cerebral palsy after perinatal stroke are likely to have an additional disability; those with neonatal presentation are more likely to have a severe disability.

Cerebral sinovenous thrombosis in the neonate.

BACKGROUND: There are few studies on neonatal cerebral sinovenous thrombosis (SVT). OBJECTIVES: To describe the presentations, treatments, and outcomes of neonatal SVT and to assess infarction as a predictor of outcome. DESIGN: Retrospective chart study. SETTING: A tertiary pediatric hospital in Indianapolis, Ind. Patients Forty-two children with neonatal SVT identified using International Classification of Diseases, Ninth Revision code searches from 1986 through June 2005 and review of neurology clinic records. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Cognitive impairment, motor impairment, and epilepsy at last clinic visit. RESULTS: Gestational or delivery complications or risk factors and comorbid conditions such as dehydration, sepsis, and cardiac defects were common (gestational/delivery factors in 82% [31 of 38 with available maternal data]; comorbid conditions in 62% [26 of the 42]). Twenty-four (57%) presented with seizures. Twenty-five (60%) had infarcts, which were hemorrhagic in 22. Only 27 (64%) of 42 received prothrombotic evaluations; none had persistent deficiencies of protein C, protein S, or antithrombin III. Three (7%) received heparin sodium. All other children received only supportive care. One child died. Outcome data were available for 29 (71%) of the 41 survivors; of these, 23 (79%) had impairment(s). Two were known to be in early intervention, and no further information was available. Of the remaining 27, 16 (59%) had cognitive impairment, 18 (67%) had cerebral palsy, and 11 (41%) had epilepsy. Infarction was associated with the presence of later impairment (P = .03). CONCLUSIONS: The presentation of neonatal SVT is often nonspecific, the diagnosis can be difficult to make, treatment beyond supportive care is rarely used, and outcomes can be severe. Further work is needed to develop standardized guidelines for the evaluation and treatment of neonatal SVT.

Perinatal stroke in twins without co-twin demise.

Perinatal stroke in twins without co-twin demise has not been well-described. In this study, the International Classification of Diseases- 9th edition code searches and medical record review were used to identify all children with arterial ischemic stroke examined in a pediatric stroke clinic over a 2-year period. Four of the 35 children (11.4%) with perinatal arterial ischemic stroke were twins; none had co-twin demise. No co-twin had any clinical evidence of perinatal stroke. The most common findings on prothrombotic evaluation were elevated antiphospholipid antibodies (2), elevated lipoprotein a (2), and elevated Factor VIIIc (2). Twin gestation without co-twin demise may be a risk factor for perinatal stroke, and might help explain the higher incidence of cerebral palsy in twins.

Outcomes of children with infantile spasms after perinatal stroke.

The object of this study was to describe the outcomes of children with infantile spasms resulting from perinatal stroke. We used International Classification of Diseases, Ninth Revision (ICD-9) searches of billing records to identify 110 children with infantile spasms examined at our hospital from 1998 through 2005. Five of the 99 with symptomatic spasms (5%) had perinatal stroke. An additional five children with spasms caused by perinatal stroke were identified from pediatric stroke clinic records. Seven of the 10 children with spasms due to perinatal stroke presented with stroke as neonates. Three initially appeared healthy but were diagnosed with "presumed perinatal stroke" after radiographic imaging for their spasms evaluation. Median age at last follow-up was 6.3 years: 9 (90%) had epilepsy, 8 (80%) manifested cognitive impairment, and all (100%) had cerebral palsy. The three children who had delayed presentation of "presumed perinatal stroke" had better epilepsy and cognitive outcomes than the seven with neonatal presentation (P = 0.03). Perinatal stroke accounts for 5% of symptomatic spasms and results in high rates of chronic disability similar to those observed with other types of symptomatic spasms. However, a subgroup of children with spasms caused by delayed presentation of "presumed perinatal stroke" appears to have better epilepsy and cognitive outcomes.

A 9-year-old boy with a history of large perinatal stroke, infantile spasms, and high academic achievement.

The prognosis for intellectual development in children with symptomatic infantile spasms is usually poor. We report a 9-year-old boy with a history of a large, presumed perinatal, left middle cerebral artery infarct discovered when he developed infantile spasms at 6 months of age. The infantile spasms responded to treatment with adrenocorticotropic hormone. He attained cognitive milestones at normal times, requiring only speech therapy for dysarthric speech. At 9 years of age, he has seizures and a severe right hemiparesis but is an articulate honor roll student in advanced English classes. The development of infantile spasms after large-branch middle cerebral artery stroke does not always predict future mental retardation.

A 10-year-old girl with coexistent moyamoya disease and Graves' disease.

There are rare reports of young women with moyamoya disease associated with Graves' disease; we are unaware of any previous reports of this association in prepubescent girls. We report a 10-year-old girl who presented with multiple bilateral strokes. Cerebral angiography demonstrated moderate to severe stenosis of her bilateral distal internal carotid arteries and proximal anterior and middle cerebral arteries, which was greater on the right. Thyroid function tests demonstrated suppressed thyroid-stimulating hormone and elevated thyroid hormone levels. Serum antiphospholipid antibody screen demonstrated mild elevations of antiocardiolipin IgG. Possible mechanisms predisposing individuals to concurrent moyamoya and Graves' disease are discussed.

Arterial strokes in children.

Pediatric stroke has received special attention in the recent literature. It is now recognized as an important cause of mortality and morbidity in pediatric population. Varied and poorly specific symptomatology as well as overlapping risk factors makes the diagnosis of stroke in childhood challenging. Therapy remains controversial. The use of anticoagulation and thrombolysis in the management of acute stroke in children has not been systematically studied. In this article, we discuss the natural history, investigation, and treatment of pediatric arterial hemorrhagic and ischemic strokes.

Cerebral venous thrombosis and venous malformations in children.

Venous strokes are not as common as arterial strokes in the pediatric population, but may be associated with significant mortality and morbidity. Cerebral vein thrombosis and venous sinus thrombosis are responsible for most venous strokes. Vein of Galen malformation is a rare but important cause of mortality in neonates and infants. Awareness of these potential causes of stroke in the pediatric population, early diagnosis, and appropriate therapeutic strategies are paramount to reduce mortality and improve neurologic outcome.

Dysphagia in children: an overview.

Swallowing is a vital body function. It is important in maintaining optimal nutritional status. Dysphagia is any disturbance in swallowing. Dysphagia in children most commonly presents as feeding or respiratory difficulty. Dysphagia may be for solid foods or liquids or both. A careful history and examination are important in determining the etiology. Both, neurologic or non-neurologic conditions may cause dysphagia in children. Evaluation is often multidisciplinary in nature. A definitive diagnosis is possible in most cases and facilitates management and prognosis.

Thyrotropin-releasing hormone in the treatment of intractable epilepsy.

Intractable seizures remain a significant therapeutic challenge despite current advances in the treatment of epilepsy. Thyrotropin-releasing hormone, the first neuroendocrine releasing factor to be isolated and fully characterized, was also the first releasing factor investigated as a possible neurotransmitter/neuromodulator outside the hypothalamus. Basic and clinical research has revealed a distinct neuroanatomic distribution and a neurochemical role for thyrotropin-releasing hormone in seizure modulation. Thyrotropin-releasing hormone and selected analogs were reported to have antiepileptic effects in several animal seizure paradigms, including kindling and electroconvulsive shock. Clinically, thyrotropin-releasing hormone treatment has been reported to be efficacious in such intractable epilepsies as infantile spasms, Lennox-Gastaut syndrome, myoclonic seizures, and other generalized and refractory partial seizures. Herein, we review evidence that suggests that thyrotropin-releasing hormone and selected thyrotropin-releasing hormone analogs may represent a new class of novel antiepileptic drugs, namely, antiepileptic neuropeptides and provide insights into potential new treatments for the intractable epilepsies.

Measuring gross motor recovery in young children with early brain injury.

Motor outcome measures may be used in both research and clinical practice. Although many motor outcome measures exist, only a small subset are suitable for use in children, and an even smaller subset is suitable for use in children under the age of 5 years who are undergoing rapid motor development. In this article, the issues involved in choosing an outcome measure are reviewed, and four of the most common gross motor outcomes measures used in young children are discussed.