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We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls (P = 0.0009, OR = 7.2) and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls (P = 0.028, OR = 2.5). Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents (P = 0.037, OR = 6). Probands were more likely to carry an additional large copy-number variant when compared to matched controls (10 of 42 cases, P = 5.7 × 10 5, OR = 6.6). The clinical features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved.

The ketogenic diet (KD) is an established, effective nonpharmacologic treatment for intractable childhood epilepsy. The KD is provided differently throughout the world, with occasionally significant variations in its administration. There exists a need for more standardized protocols and management recommendations for clinical and research use. In December 2006, The Charlie Foundation commissioned a panel comprised of 26 pediatric epileptologists and dietitians from nine countries with particular expertise using the KD. This group was created in order to create a consensus statement regarding the clinical management of the KD. Subsequently endorsed by the Practice Committee of the Child Neurology Society, this resultant manuscript addresses issues such as patient selection, pre-KD counseling and evaluation, specific dietary therapy selection, implementation, supplementation, follow-up management, adverse event monitoring, and eventual KD discontinuation. This paper highlights recommendations based on best evidence, including areas of agreement and controversy, unanswered questions, and future research.

Proximal muscle weakness, often indicative of a myopathy, has a broad differential diagnosis in children. We present a case of an adolescent boy with proximal weakness and a mildly elevated creatine kinase. He was found to have spinal muscular atrophy type III rather than a myopathy.

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.

A family is presented with hyperexplexia, a rare autosomal dominant neurological disorder. Affected individuals manifest flexor hypertonia and hypokinesia during infancy. Later and throughout life, the condition is characterized by exaggerated involuntary myoclonic startle reactions, which on occasion result in falling. There are also marked nocturnal myoclonic jerks. Many family members have had congenital hip dislocations and inguinal hernias. Pre- and postnatal hypertonia is proposed as the cause for these problems. The nature and location of central nervous system dysfunction in hyperexplexia was investigated using electroencephalographic and brainstem-evoked response techniques. A dysfunction of cortical inhibition of the brainstem-mediated startle response is discussed as a possible pathogenic mechanism. Accurate diagnosis of this disorder is important in order to provide appropriate counseling and to initiate effective treatment.

Summary Purpose: To determine if the clinical characteristics of nonepileptic seizures (NES) are different in children younger than 13 years age as compared to adolescents. Methods: Retrospective review of medical records and video-EEGs (VEEG) of all patients with NES confirmed on VEEG monitoring was performed. Results: Sixty-eight (3.5%) of 1,967 patients monitored with VEEG had a clinical diagnosis of NES. Fifty-nine of 68 patients had their habitual event recorded. Mean age at the time of the VEEG diagnosis was 13 years 4 months. Twenty-two patients were less than 13 years (group A) and 37 were 13 years and older (group B). The male to female ratio was equal in group A, with female predominance seen in group B. NES commonly manifested as subtle motor activity in group A (p < 0.01) and prominent motor activity in group B (p < 0.001). Difficulties at school, family discord, and interpersonal conflicts, were frequent stressors in both groups. Sexual abuse was the least frequent. Depression was more common in group B; cognitive dysfunction (p < 0.001) and epilepsy (p < 0.01) were more common in group A. Conclusions: Differences in clinical semiology and predisposing factors may help identify young children and adolescents who might be at risk for the development of NES.

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 χ2 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.

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 47 042 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.

We report a case of a 14-year-old boy with a dysembryoplastic neuroepithelial tumor and mental retardation with intractable seizures, which were demonstrated to be predominantly tonic seizures by video-electroencephalography (EEG). He did not have any electrographic evidence of Lennox-Gastaut syndrome. Head magnetic resonance imaging (MRI) revealed a right parietal dysembryoplastic neuroepithelial tumor. He has been seizure free since surgical removal of the tumor. Clinicians need to be aware that tonic seizures can be associated with an underlying focal pathology that might be treatable. (J Child Neurol 2006;21: 813—816; DOI 10.2310/7010.2006.00186).

Background: Maternal prothrombotic disorders may contribute to stroke in the fetus before and during birth. Many of the mothers of children with perinatal stroke have no previous history of pathologic thrombosis. Objective: To determine if finding the Factor V Leiden mutation, prothrombin 20210 G-A gene defect, or methylene tetrahydrofolate reductase C677T mutation in an asymptomatic mother of a child with perinatal stroke would affect that mother9s ability to obtain health insurance. Methods: 1) The authors reviewed the literature on genetic prothrombotic risk factors and health insurance. 2) The authors surveyed the 17 largest insurance carriers in Indiana to find if diagnosing genetic prothrombotic risk factors in asymptomatic mothers of children with perinatal stroke would affect the mothers9 health insurance status. Results: Three articles on genetic prothrombotic risk factors and insurance were identified. Twelve of 17 insurance companies responded to our survey; three had policies on genetic testing. Most companies refused to provide clear, useful information on their policies regarding these risk factors. Conclusions: The authors are currently unable to counsel their patients9 families on the long-term insurance implications of screening for genetic prothrombotic risk factors. The insurance implications of diagnosing healthy women with genetic prothrombotic risk factors need further study.

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. ( J Child Neurol 2005;20:620—624).

We report a case of a 5-year-old boy with intractable partial seizures who developed a transient hemiparesis, worsening of the electroencephalogram (EEG) and a change in his seizure pattern with increased seizure frequency after receiving topiramate (TPM). Symptoms resolved within a month after TPM was discontinued. Clinicians need to be aware that TPM use may occasionally be associated with focal motor weakness and exacerbation of seizures.

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.

Majority of children has head size that is appropriate for age and gender. But a few have either too small or too large head at birth or may be of postnatal acceleration. Abnormality of head circumferences is determined by brain size, including any malformations and space occupying lesions, cerebrospinal fluid (CSF) and blood volume, presence of subdural fluid and thickness of skull bones and overlying tissue scalp. Macrocephaly is used when the head size exceeds the mean by more than two standard deviotions of age and gender. Macrocephaly is seen in association with several cranioskeletal displastic conditions.

The vasculitides are a heterogeneous group of disorders. Vasculitides secondary to infectious diseases are more common than those attributable to noninfectious causes, especially in developing countries. Cerebral vasculitides might be a primary disorder or complicate a systemic disease. We review the clinical presentation, pathology, and treatment of noninfectious vasculitides in children. Henoch-Schonlein purpura and Kawasaki disease are two of the most common vasculitic disorders in children. Noninfectious cerebral vasculitis is a rare cause of stroke in childhood. Mimics of vasculitis (look-alikes) should be considered whenever cerebral vasculitis is suspected.

We undertook this study to investigate the relationship between white-matter abnormalities (seen on brain magnetic resonance imaging [MRI]) and muscle tone and muscle stretch reflexes on clinical examination. We identified all patients less than 5 years of age who had undergone cranial MRI studies at Riley Hospital for Children between June 30, 1999, and July 1, 2000, whose scans were read as showing white-matter abnormalities. We measured two ratios and the thickness of the corpus callosum as indicators of the quantity of cerebral white matter. The ratios were R1, the ratio of the thickness of the white matter at the level just above the body of the lateral ventricle compared with the width of the hemisphere, and R2, the ratio of the thickness of the white matter to the width of the hemisphere at the level of the trigone of the lateral ventricle. The thickness of the corpus callosum was measured at the junction of the anterior two thirds and the posterior third. We also evaluated the signal intensity of the cerebral white matter by reviewing the fluid-attenuated inversion-recovery images and grading the signal as normal to severely abnormal depending on the degree and extent of high signal intensity seen (0 = normal to 4+). Thirty-eight children less than 5 years of age who underwent MRI scans between June and August 2000 and who were found to have normal tone prospectively and normal MRI scan on review served as a control group. We identified 215 patients who had white-matter abnormalities; of these, only 142 (66%) had documented tone assessments in their medical record. Our study group was divided into three groups: increased ( n = 35), decreased ( n = 53), and normal tone ( n = 54). All three measurements of white matter in each of the three study groups were significantly below values for control children. The children with white-matter abnormalities and decreased tone had significantly less signal intensity abnormality than the other study groups. Children with white-matter abnormalities and increased tone had a greater frequency of increased reflexes and tended to have more signal abnormalities than the other groups. The group of children with white-matter abnormalities and normal tone had the least amount of cerebral white-matter deficiency of the three study groups. In patients with strikingly decreased quantities of cerebral white matter, those with normal signal-intensity white matter are likely to be hypotonic with normal reflexes and those with increased signal intensity in the white matter are likely to be spastic. ( J Child Neurol 2001;16:668-672).

The authors report the long-term prospective follow-up of two unrelated females with congenital hypomyelinating neuropathy (CHN) and review previously reported cases. The authors' first patient presented with neonatal hypotonia and extremely slow nerve conduction velocities. Sural nerve biopsy revealed profound hypomyelination, without inflammation or evidence of myelin breakdown. She is now 9 years of age, and her motor function has continued to improve. Follow-up nerve-conduction velocities are unchanged. The authors' second patient presented at 5 months with hypotonia. Nerve-conduction velocities were extremely slow, and sural nerve biopsy revealed severe hypomyelination, with no inflammation or evidence of myelin breakdown. She is now 5 years of age and has also demonstrated improved motor function. Repeated nerve-conduction velocities are unchanged. Both patients have normal cognitive development. Molecular genetic analysis in Patient 2 disclosed a point mutation in the myelin protein zero gene; this same point mutation has been reported in three other patients diagnosed with Dejerine-Sottas syndrome (DSS) but has never been reported in a patient with CHN. Although CHN is a distinct clinical entity, it may share similar genetic features with DSS.

Spontaneous spinal epidural hematoma is rare in children. It is usually confined to the dorsal epidural space. Ventral spontaneous spinal epidural hematoma (SSEH) is rarer, with only two previous reports. The authors present three children, two with dorsal and one with ventral spinal epidural hematoma, and review the literature. No etiology of the hematoma was found in the authors' patients and there was no history of trauma. A review of 24 patients of children younger than 18 years of age reported in the literature and the authors' three patients revealed that the cervicothoracic region was the most common site of SSEH, the mode of onset was frequently subacute, and there was no male preponderance as has been reported in adults. We found that the initial symptoms were often nonspecific, leading to a delay in diagnosis, especially in younger children. Follow-up data revealed that 15 of the 27 patients recovered completely, 11 had residual neurologic deficits, and one patient died. Irritability and neck pain with restricted movements of the cervical spine in an afebrile child may be early signs of SSEH and often precede onset of neurologic deficits by several hours to days. These signs should alert the clinician to consider spinal epidural hematoma and the need for urgent magnetic resonance imaging (MRI) of the spine for early diagnosis and treatment to minimize morbidity.

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.

Specific strategies for primary and secondary stroke prevention in children and young adults can only be recommended once the causes of stroke in these age groups are well described. ICD-9 codes were used to identify children aged 1 to 18 years with acute ischemic stroke. Young adults aged > 18 to 45 years were identified from the Indiana University and Northwestern University Young Adults Stroke Registries. Validated criteria were used to subtype ischemic stroke as atherothrombotic (AT), cardioembolic (CE), small-vessel (SV), other determined cause, or unknown cause. Ninety-two children and 116 young adults were identified. Stroke subtypes in children/young adults (percentages) were as follows: AT 0/16 (p < 0.001), CE 15/14 (p = 1.0), SV 0/3 (p = 0.26), other 49/44 (p = 0.40), and unknown 36/23 (p = 0.04). Children had more prothrombotic causes (25% versus 14%, p = 0.03), and young adults had more dissections (3% versus 15%, p = 0.005). Children aged 15 to 18 years had causes of ischemic stroke more similar to those in young adults. The cause of ischemic stroke is less often identified in children than it is in young adults. Children have more prothrombotic causes of stroke, and adults have more atherothrombotic causes and dissections. Lacunar strokes are rare in both children and young adults. The age of 15 years should be used to separate childhood from young-adult ischemic stroke.

Clinical and radiologic findings in a child with acute motor axonal neuropathy are reported. A 16-year-old boy with mild cerebral palsy presented 1 week after an upper respiratory tract infection with low back pain, ascending weakness, and areflexia. Cerebrospinal fluid (CSF) examination revealed albuminocytological dissociation. Serial electromyograms (EMGs) with nerve conduction velocity (NCV) studies revealed findings of motor axonal neuropathy. Spine MRI revealed enhancement of the cauda equina. Acute motor axonal neuropathy (AMAN) may be an underrecognized cause of acute flaccid paralysis, and to our knowledge no pediatric cases have been reported in the United States. MRI findings have not been reported previously.

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 mile-stones 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. ( J Child Neurol 2005;20:444—446).

Spontaneous spinal epidural hematoma (SSEH), is a rare and potentially fatal condition that responds favorably to early surgical intervention and should be considered in the differential diagnosis of spinal cord compression. There are few reported cases in children. We present a case of spontaneous spinal epidural hematoma in an 18-month-old child and review the literature.

Clinical features of thalamic strokes have not been well delineated in children. Six children with ischemic thalamic infarcts (3 M, 3 F; age range: 21 months to 14 1/2 years) are reported. Three patients had infarction in the thalamoperforate artery territory and all had a decreased level of consciousness and hemiparesis; two of them also had associated ocular motility abnormalities. One patient with left thalamotuberal artery stroke presented with aphasia. Two patients with thalamogeniculate artery infarcts had hemiparesis and involvement of the posterior cerebral artery. Etiologic factors in our patients were: infectious vasculitis, congenital heart disease, migraine, and unknown in 1 patient each and trauma in 2 patients. Follow-up information was available for 5, 4 of whom recovered completely. One patient was left with a neurologic deficit. We conclude that the prognosis of ischemic thalamic strokes in children is relatively good.

Fifteen children with periodic lateralized epileptiform discharges are reported and clinical and radiologic features and outcome are presented. Both structural cerebral lesions and metabolic factors were associated with periodic lateralized epileptiform discharges. Although all patients had seizures, 8 had status epilepticus. Seven patients survived and 8 patients died. Six of the 7 survivors had residual seizures. Periodic lateralized epileptiform discharges in children are associated with acute encephalopathies and there is a high incidence of subsequent epilepsy.

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.

We report a 3-year-old boy with bathing epilepsy clinically manifesting as complex partial seizures precipitated by immersion in warm water during bathing and showering. Two seizures were recorded on video. During one, a simultaneous ictal EEG recording revealed an ictal pattern over the left hemisphere. Warm water was demonstrated to be the specific precipitating stimulus; hot dry towels and cold water did not provoke seizures or EEG abnormalities.

The neurologic complications of 24 children, ages 5 months to 18 years, following orthotopic liver transplantation at the Indiana University hospitals are reported. Biliary atresia (14 patients) was the most common cause for orthotopic liver transplantation. Three children died. Seventeen children (70%) had no neurologic deficit on follow-up 6 months or longer after transplantation. Eleven children (46%), including 4 of 16 patients (25%) who had received OKT3, had neurologic complications. Seven children (29%) had newonset seizures; 4 of these patients had status epilepticus. Two children had intracranial hemorrhage. Seizures occurred later in children than in adults following orthotopic liver transplantation and were not associated with poor prognosis. Longer term follow-up is indicated to assess subtle, cognitive deficits following liver transplantation in children.

In a prospective study of the growth and neuropsychologic function of hemophilic subjects, 333 boys, median age of 12.3 years, had baseline neurologic examinations. The study population included 207 individuals (62%) who were seropositive for human immunodeficiency virus type 1 (HIV-1). Overall results indicated that 11% had abnormalities of cranial nerve function, 17% had abnormal deep tendon reflexes, 23% had abnormal strength, 25% had abnormal coordination, and 31% had abnormal tone, bulk, or range of motion. By contrast, 2% or fewer displayed abnormal movements or had abnormal pain or vibratory sensation, or altered mental status. Abnormalities were more common in older hemophilic subjects (eg, 67 [38%] of 177 subjects ≥12 years of age had abnormal tone, bulk, or range of motion vs 36 [23%] of 156 subjects < 12 years of age). When compared with regard to HIV-1 status, HIV-seronegative and HIV-seropositive subjects did not differ with regard to head circumference or the frequency of abnormalities of cranial nerve function, sensation, muscle strength, or coordination. However, deep tendon reflexes and tone, bulk, or range of motion were more frequently abnormal in HIV-1-seropositive individuals. More HIV-1-positive subjects had at least one increased deep tendon reflex (13/207 [6.3%] vs 1/126 [0.8%] in seronegatives) and more had non-hemophilia-related decreases in muscle bulk (7/207 [3.4%] vs 0/126 in seronegatives). These results indicate that hemophilia causes substantial neurologic dysfunction and that certain findings, such as changes in muscle-stretch reflexes or muscle bulk, may also reflect the neurologic consequences of HIV infection.

Increasing concern about children in a persistent vegetative state (PVS) prompted a survey of members of the Child Neurology Society regarding aspects of the diagnosis and management of this disorder. Major findings of those responding to this survey (26% response rate) were as follows: (1) 93% believed that a diagnosis of PVS can be made in children, but only 16% believed that this applied to infants younger than 2 months and 70% in the 2-month to 2-year group; (2) a period of 3 to 6 months was believed to be the minimum observation period required before a diagnosis of PVS could be made; (3) 86% believed that the age of the patient would affect the duration of time needed to make the diagnosis of PVS; (4) 78% thought a diagnosis of PVS could be made in children with severe congenital brain malformations; (5) 75% believed that neurodiagnostic studies would be of value and supportive of the clinical diagnosis of PVS; (6) members' opinions as to the average life expectancy (in years) for the following age groups after the patients were considered vegetative were: newborn to 2 months, 4.1; 2 months to 2 years, 5.5; 2 to 7 years, 7.3; and more than 7 years, 7.4; (7) 20% believed that infants and children in a PVS experience pain and suffering; and (8) 75% "never" withhold fluid and nutrition from infants and children in a PVS and 28% "always" give medication for pain and suffering.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose transporter type 1 (GLUT1) deficiency syndrome is a rare, treatable cause of developmental delay and seizures. It must be considered in the differential diagnosis of infants with intractable seizures. The finding of a low glucose level in the cerebrospinal fluid with normal level in the blood in the absence of pleocytosis or other cerebrospinal fluid abnormalities identifies the condition. Genetic analysis for confirmation is available. Treatment with antiepileptic medications often is unsuccessful, and the ketogenic diet is the favored treatment for seizure control. Early identification and initiation of treatment may prevent or lessen the severity of developmental delay.

A 3-year-old boy with ulcerative colitis and developmental delay presented with a 3-week history of headaches, emesis, and dehydration. His neurologic examination was nonfocal, but MR venogram revealed cerebral sinovenous thrombosis (figure). He was rehydrated and discharged on enoxaparin. Three months later he starting having difficulty reaching for objects and was running into walls. Repeat MRI and MR venogram demonstrated residual thrombosis and interval development of papilledema …

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 χ2 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.

The association of cerebral palsy with other disability 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%) of the children with cerebral palsy had at least one other disability: 45 (59%) had cognitive/speech impairment which was moderate-severe in 20, and 36 (47%) had epilepsy which was moderate-severe in 11. In children with neonatal presentation, cerebral palsy was associated with epilepsy (0.0076) and cognitive impairment (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 a 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 (OR 7.78; 95% CI 1.80–47.32) or severe epilepsy (OR 6.64; 95% CI 1.21–69.21) than children with delayed presentation. Children with cerebral palsy after perinatal stroke are likely to have additional disability; those with neonatal presentation are more likely to have severe disability. These findings will help pediatricians in planning long-term rehabilitative care.

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.

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 aged1 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 aged1 year with cerebral arterial ischemic stroke were more likely to present with epileptic seizures and altered mental status than children agedor=1 year, and may be less likely to present with focal weakness. These findings may aid in the recognition of stroke in young children.

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.

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.

Objective To evaluate family history of early pathological thrombosis as a screen for genetic prothrombotic risk factors in children with stroke. Study design A 5-year retrospective review of standardized pediatric stroke clinic evaluations of children with arterial ischemic stroke (AIS) or sinovenous thrombosis (SVT). A family history of early pathological thrombosis was defined as stroke, heart attack, or deep venous thrombosis before 50 years of age or multiple miscarriages in the parents or grandparents of the patient. We evaluated the association between family history and the presence of the Factor V Leiden mutation (FVL) and/or Prothrombin G20210A mutation (PTG) in these children. Results The study included 68 children. Thirteen (19.1%) had a positive family history of early pathological thrombosis, nine (13.2%) were heterozygous for FVL, and one (1.5%) was heterozygous for PTG. Family history was not associated with the presence of FVL (p = .36) or FVL combined with PTG (p = .40). For FVL, family history had a positive predictive value of 23.1% and a negative predictive value of 89.1%. Conclusion A family history of early thrombosis is not associated with the presence of FVL or PTG in children with stroke. We recommend that all children with stroke receive a prothrombotic workup regardless of family history.

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.

Mesial temporal sclerosis (MTS) has been linked to prolonged febrile seizures. The sequence of changes in the temporal lobe/hippocampus following prolonged febrile seizures and status epilepticus is beginning to be elucidated. We obtained repeated magnetic resonance imaging (MRI) volumetric analysis of the hippocampi in a 23-month-old boy after a prolonged focal febrile seizure. Three days after a prolonged left focal febrile seizure, brain MRI showed increased T2 weighted signal and increased volume (swelling) of the right hippocampus. Repeat MRI 2 months later demonstrated sclerosis of the right hippocampus. Review of the literature shows four other children with prolonged focal seizures associated with the MRI sequence of temporal lobe swelling followed by sclerosis. All had left focal seizures followed by right MTS. Our patient demonstrates a shorter interval for the radiologic development of hippocampal sclerosis compared to other reports.

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.