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Epidural cerebrospinal fluid (CSF) collections after lumbar puncture are a rare and underdiagnosed entity in the pediatric population. Physicians should maintain vigilance about warning signs of severe progressive back pain extending beyond the puncture site and new neurological symptoms after lumbar puncture. Extensive symptomatic epidural collections, which may be dorsal and compromise the thecal sac, can be secondary to CSF leakage. Early diagnosis with spinal magnetic resonance imaging and prompt treatment is vital in reducing morbidity and mortality. These collections typically resolve with conservative management and no serious sequelae. We report a rare case of spinal epidural collection following a lumbar puncture in a patient with idiopathic intracranial hypertension that was successfully treated with a blood patch and surgical decompression in the setting of significant neurological deterioration.

Prospective memory, the ability to remember to perform an intended act in the future, is a complex process that involves several stages and cognitive domains. This study sought to investigate prospective memory functioning in children with idiopathic epilepsy using tasks from the Rivermead Behavioral Memory Test for Children (RBMT-C) and the Memory for Intentions Screening Test for Youth (MISTY). Performances on prospective memory task characteristics of the MISTY (i.e., cue-type, length of time delay, and response type) were also compared between and across participant groups. Healthy children (N = 26) were found to have higher overall IQ and verbal IQ scores when compared to children with epilepsy (N = 19). Group differences in prospective memory functioning were found in subtests of the RBMT-C but not on the MISTY. Lastly, while there was no significant interaction effect between the groups and MISTY task characteristics, main effects were found across participant groups; all participants performed better on event-based tasks when compared to time-based tasks and on two-minute when compared to 10-minute time delays. Overall, findings suggest potential differences in cognitive functioning, particularly in IQ and prospective memory, in children with idiopathic epilepsy, though due to differences in findings across prospective memory tasks, further research is warranted to more definitively ascertain the extent, if any, of prospective memory deficits in children with epilepsy.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Individuals rely on the perception of pain to avoid injury, to signal disease, and to warn about tissue inflammation and damage. However, the inheritance of inappropriate, extreme, or inadequate pain production is a source of significant human suffering. Substantial progress has been made in our understanding of the genetics and pathophysiology of pain through the study of individuals and families with several specific inherited pain syndromes. These studies have led to the discovery of a number of gene mutations associated with specific ion channel disturbances that produce familial inherited pain sensitivity and insensitivity syndromes. The sodium channel has been identified as the primary determinant of most of these syndromes. This article focuses on the inherited pain syndromes and their corresponding ion channel mutations. There is hope that through continued research into these ion channels and pain syndromes, targeted drug therapy would be fruitful and beneficial to those afflicted.

Tuberous sclerosis complex is an autosomal-dominant, neurocutaneous, multisystem disorder characterized by cellular hyperplasia and tissue dysplasia. The genetic cause is mutations in the TSC1 gene, found on chromosome 9q34, and TSC2 gene, found on chromosome 16p13. The clinical phenotypes resulting from mutations in either of the 2 genes are variable in each individual. Herein, advances in the understanding of molecular mechanisms in tuberous sclerosis complex are reviewed, and current guidelines for diagnosis, treatment, follow-up, and management are summarized.

These are commentaries of a Cochrane review, published in this issue of EBCH, first published as: Zehetner AA, Orr N, Buckmaster A, Williams K, Wheeler DM. Iron supplementation for breath-holding attacks in children. Cochrane Database of Systematic Reviews 2010, Issue 5. Art. No.: CD008132. DOI: 10.1002/14651858.CD008132.pub2. Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration

The epidemiology of lesions identified by magnetic resonance imaging (MRI), along with the use of pre-surgical evaluations and surgery in childhood-onset epilepsy patients has not previously been described. In a prospectively identified community-based cohort of children enrolled from 1993 to 1997, we examined (i) the frequency of lesions identified by MRI; (ii) clinical factors associated with 'positive' MRI scans; and (iii) the utilization of comprehensive epilepsy evaluations and neurosurgery. Of the original cohort of 613 children, 518 (85%) had usable MRI scans. Eighty-two (16%) had MRI abnormalities potentially relevant to epilepsy ('positive' scans). Idiopathic epilepsy syndromes were identified in 162 (31%) of whom 3% had positive scans. The remainder had non-idiopathic epilepsy syndromes of which 22% had positive MRI findings. Multiple logistic regression analysis identified non-idiopathic epilepsy and abnormal motor-sensory (neurological) examinations as predictors of a positive MRI scan. Of the non-idiopathic patients with normal neurological exams and who were not pharmacoresistant, 10% had positive MRI scans, including four patients with gliomas. Evaluations at comprehensive epilepsy centres occurred in 54 pharmacoresistant cases. To date 5% of the imaged cohort or 8% of non-idiopathic epilepsy patients have undergone surgical procedures (including vagal nerve stimulator implantation) to treat their epilepsy (n = 22) or for tumours (n = 6) without being drug resistant. Applying our findings to the general population of children in the USA, we estimate that there will be 127/1 000 000 new cases per year of pharmacoresistant epilepsy, and 52/1 000 000 childhood-onset epilepsy patients undergoing epilepsy evaluations. In addition, approximately 27/1 000 000 will have an epilepsy-related surgical procedure. These findings support recommendations for the use of MRI in evaluating newly diagnosed paediatric epilepsy patients, especially with non-idiopathic syndromes, and provide estimates on the utilization of comprehensive evaluations and surgery.

We assessed residual cognitive deficits in young people with idiopathic and cryptogenic epilepsy. In the setting of an ongoing prospective study, we invited participants initially diagnosed and enrolled in the cohort 8-9 years earlier to undergo standardized neuropsychological assessment. Sibling controls were invited when available. We analyzed 143 pairs in which cases had idiopathic or cryptogenic epilepsy and both case and control had normal intelligence. Compared with that for siblings, the Full Scale IQ for cases was 3.3 points lower (P=0.01) mainly due to slower processing speed, which was 5.6 points lower (P=0.0004). Word reading (P=0.04) and spelling (P=0.01), but not other scores, were also lower in cases. Remission status and drug use did not influence findings. In young people of normal intelligence with idiopathic or cryptogenic childhood-onset epilepsy, substantial residual effects of epilepsy appear to be confined largely to slower processing speed.

Orbital pseudotumor, also known as idiopathic orbital inflammation, is a benign, idiopathic, noninfectious, and nonneoplastic clinical syndrome with an inflammatory mass within the orbit and no identifiable cause. This disease is rare in the pediatric population, especially in very young children. In this article, the authors describe a 2-year-old girl who was presented with right eye ptosis, near-complete ophthalmoplegia, decreased visual acuity, and pupillary changes. She recovered completely with high-dose steroid therapy. The authors review the literature and discuss the diagnostic implications and treatment strategies.

Summary Purpose: To determine the frequency and determinants of subnormal global cognitive function in a representative, community-based sample of children prospectively identified at the time of initial diagnosis of epilepsy. Methods: In children enrolled with newly diagnosed epilepsy and followed a median of 10.5 years, level of cognitive function (within normal, borderline, mild, moderate to severe mental retardation (MR), neurologically devastated, and impaired but not further classified (NFC)) was determined based upon neurologists' and school records, repeated parental interviews, and, in over half the participants, standardized neuropsychological testing. For multivariable analyses, subnormal cognitive function was designated as consistent with a full scale IQ < 80. Results: Global cognitive function was considered within normal, N = 451 (73.6%), borderline, N = 31 (5.1%), mild MR, N = 21 (3.4%), more severe MR, N = 45 (7.3%), devastated, N = 29 (4.7%), and impaired-NFC, N = 36 (5.9%). Age at onset

To correlate prognosis of hypoxic-ischemic white-matter injury with magnetic resonance imaging (MRI). In a retrospective review at an urban medical center, three adult and three pediatric patients with predominant white-matter involvement caused by hypoxic-ischemic injury were evaluated over a 15-month period. Five patients with MRI-defined hypoxic-ischemic leukoencephalopathy had a favorable outcome, and one with associated diffusion-weighted abnormality of deep gray structures died. The prognosis of hypoxic-ischemic leukoencephalopathy is more favorable than previously reported, and diffusion-weighted imaging abnormality of deep gray structures was associated with a poor outcome.

Tuberous sclerosis complex is an autosomal dominant multisystem disorder. Spontaneous mutations occur in up to 60% of patients with gene loci located on chromosomes 9q34 ( TSC1) and 16p13 ( TSC2). Diagnosis is established with the identification of various neurocutaneous markers and multiple organ system hamartomas. The variable expression of severity, the potential for cognitive dysfunction, and epilepsy compound the clinical picture. The intracranial abnormalities include the identification of migration and hamartomatous brain lesions, such as tubers, subependymal nodules, and subependymal giant cell astrocytomas. A number of other neuroimaging and morphometric abnormalities coexist, which can be identified with current neuroimaging techniques. This review examines the spectrum of brain abnormalities encountered in tuberous sclerosis complex and presents them as not merely a collection of lesions but more cohesively in the context of a global neuronal migration disorder. ( J Child Neurol 2004;19:650—657).

Selective insult to brain deep gray matter nuclei is uncommon, may be congenital or acquired, acute or chronic, and varied in etiology. Determining the etiology relies on history, clinical presentation, laboratory investigations, and lesion pattern on Neuroimaging.We review the differential diagnosis and clinical, laboratory and neuroimaging pattern of conditions that manifest with lesions of deep gray matter nuclei in the context of representative case studies.While presentations may vary in individual patients, the essentials of history, clinical examination, laboratory evaluation,and neuroimaging lesion pattern can be efficiently directed to differentiate the various etiologies of deep gray matter nuclei lesions. In this review we focus on the etiologic classification and diagnostic approach to acute and chronic conditions that manifest on neuroimaging with bilateral symmetric lesions of deep gray matter nuclei.

Objective: To determine whether the clinical features of neonatal seizures are of value in predicting outcome. Study design: Demographic features, clinical seizure types, etiologic factors, and laboratory findings of all 77 patients with seizures admitted to our neonatal intensive care unit over a consecutive 7-year period were extracted from the medical records. Results: Twenty-three (30%) died; 59% of the survivors had abnormal neurologic examinations, 40% were mentally retarded, 43% had cerebral palsy, and 21% were epileptic at mean follow-up of 3.5 years. Compared with patients with other seizure types, those with subtle and generalized tonic seizures had a significantly higher prevalence of epilepsy ( P =.04 and P =.01 respectively); mental retardation ( P =.02; P =.007), and cerebral palsy ( P =.03; P =.002). Subtle seizures were, in addition, more likely to be associated with abnormalities on the neurologic examination at follow-up ( P =.03). Similar outcome comparisons for those with focal and multifocal clonic, focal tonic, and multifocal myoclonic seizures revealed no significant differences. However, patients with ≥2 seizure types were significantly more likely to have epilepsy ( P =.02), mental retardation ( P =.001), cerebral palsy ( P =.001), and abnormal examinations ( P =.05). Conclusions: Clinical semiology is predictive of outcome in neonates with seizures and suggests the presence of unique pathophysiologic processes for different seizure types. (J Pediatr 2002;140:707-12)

Background. Severe breath-holding spells (BHS) in children consist of a stereotypical sequence of provocation to cry, noiseless expiration, color change, and loss of consciousness. Parenting a child who exhibits BHS is likely more stressful than parenting a healthy child, owing to this additional medical concern. It is also likely more stressful than parenting a child with a convulsive seizure disorder (SD), because it is often not recognized or misdiagnosed as behavioral rather than medical. Mothers of children with BHS were hypothesized to suffer significantly greater stress than mothers of children with SD or mothers of children without any significant medical conditions. Objectives. To examine maternal stress in parenting a child who exhibits BHS, and to identify the specific areas of stress impact, compared with mothers of children with a convulsive SD and mothers of control children. Methods. The Parenting Stress Index and questions regarding how mothers coped were individually administered to 34 mothers of children with BHS, 16 mothers of children with SD, and 16 mothers of children with no medical conditions (controls). Results. Mothers of children with BHS or SD experience more overall stress and disruption in their attachment or understanding of their child, compared with control mothers. These groups of mothers (BHS and SD) also perceived their child as more distractible/hyperactive, less adaptive, and more demanding than did control mothers. However, mothers of the BHS group alone showed significant disruption in their sense of competence as a parent, maintaining self-identity, and receiving positive reinforcement from their child. Mothers of children with SD showed a similar trend, but it was not significant. These findings were not related to maternal health or feelings of depression/isolation, insufficient spousal support, child's mood, or other life stresses. Conclusion. Parenting a child with BHS or SD impacts a greater degree of life stress on mothers of these children than does parenting control children, although the stress is greater for the BHS group than for the SD group.

An analysis of patients followed with a diagnosis of neurofibromatosis-1 and headache was conducted. Characterization of headache type was done after chart review of 81 patients with neurofibromatosis-1 and headache. Consent was obtained for subsequent telephone interviews using a standardized questionnaire concerning the onset, characteristics, timing, triggers, and associated symptoms of the patients' headaches. Data was summarized and tabulated. Of 132 patients with neurofibromatosis-1, 81 were identified with any headache by screening history. Recurrent headaches were present in 77% of patients and in 47% of our neurofibromatosis-1 clinic population. Fifty-three of 81 patients were accessible for and agreeable to telephone interview. There were 23 male patients and 30 female patients aged 56/12 to 496/12 years, with a mean age of 20.9 years. Eighty-one percent reported having experienced recurrent headaches within the year. The majority reported onset of headache prior to the age of 10 years. Headache characteristics included the following: frequency of monthly or less, frontotemporal location, pulsating or pressing quality, and moderate severity (pain scale 4 to 5 out of 10). Headaches interfered with daily activities, had weekend occurrence, and had a duration less than 2 hours. Common headache triggers included stress, "change in weather," menstruation, fatigue, and certain foods. A high percentage of patients reported associated symptoms of nausea with or without vomiting (37%), phonophobia, photophobia, pallor, and visual scotoma. We classified 34% of the patients as having migraine (25% with aura, 9% without aura), 45% with nonmigrainous headache only, and 15% with mixed headache types (either intermittently), and 7.5% with other head pains. We conclude that patients with neurofibromatosis-1 are at greater risk for headaches than the general population. While the prevalence of both migraine and nonmigraine headache is somewhat greater than in the general population, the proportion of tension-type headache, especially in young children, is greater than expected. ( J Child Neurol 2000;15:235-238).

The clinical and neurophysiologic findings of two children presenting with focal weakness and atrophy in unusual nerve distributions and no apparent antecedent injuries are reported. Patient 1 presented with a droopy left shoulder that was initially attributed to scoliosis. Patient 2 presented with right biceps brachii atrophy that was first brought to his parent's attention during a routine physical examination. In addition to documenting focal spinal accessory and musculocutaneous mononeuropathies as the cause of weakness in Patients 1 and 2, respectively, nerve conduction studies also revealed evidence of superimposed diffuse demyelinating polyneuropathy in both children. The latter findings suggested the diagnosis of hereditary neuropathy with liability to pressure palsies and led to definitive DNA diagnoses.

A 3-day-old infant presented with anorexia, irritability, hypotonia, and seizures. Blood ammonia was 2115 pmol/L and amino and organic acid analyses were consistent with ornithine transcarbamylase deficiency. Liver biopsy confirmed only 1% enzyme activity. The patient was treated with hemodialysis. An electroencephalogram (EEG) revealed multifocal independent spike-and-sharp-wave discharges. After initial stabilization he was placed on a low-protein diet with citrulline and phenylbutyrate. Conjugating agents (arginine, sodium benzoate, and sodium phenylacetate) have been added during periods of metabolic decompensation. Although developmentally delayed, the patient has shown signs of clinical improvement and EEG activity has likewise improved with only mild background slowing and no evidence of epileptogenic activity at 4 years of age. A second infant presented at 3 days of age with a similar history, blood ammonia of 1382 μmol/L, and metabolic studies indicative of ornithine transcarbamylase deficiency. EEG showed multifocal independent ictal and interictal discharges. Electrographic abnormalities persisted despite lowering of blood ammonia with hemodialysis and conjugating agents. The patient continued to decline clinically and died on the 7th hospital day. EEG changes parallel the clinical course of ornithine transcarbamylase deficiency and may serve as an objective marker of the effectiveness of therapeutic interventions. (J Child Neurol 1999;14:533-536).

At the recent Tuberous Sclerosis Consensus Conference, a subcommittee proposed recommendations to guide the rational use of diagnostic studies in patients with tuberous sclerosis complex. Recommendations were made for diagnostic evaluation at the time of diagnosis, when testing helps both to establish the diagnosis and to identify potential complications. Additional guidelines were proposed for the ongoing surveillance of established patients to detect later complications of tuberous sclerosis complex. In the absence of comprehensive population studies to govern the use of diagnostic studies in individuals with tuberous sclerosis complex, the panel developed guidelines based on the disorder's natural history, concentrating on complications that are common, clinically significant, and more easily managed when found early. Finally, the group made suggestions for the use of diagnostic tests to identify family members who have tuberous sclerosis complex. Although these recommendations should standardize and improve our use of diagnostic studies in individuals with tuberous sclerosis complex, the clinical approach in a given patient must remain flexible enough to meet the needs of individual patients and families. (J Child Neurol 1999;14:401-407).

Guillain-Barre syndrome (GBS) is an acute inflammatory demyelinating polyradiculoneuropathy manifested by progressive flaccid paralysis.1,2 With the eradication of poliomyelitis, GBS has become the most common cause of acute motor paralysis in children. The etiology and pathophysiology of GBS has a postulated immune-mediated mechanism.3,4 In classical GBS there is destruction of peripheral nerve myelin sheath, which results in the hallmark symptomatology. There are also less frequently encountered axonal variants, those with and without sensory involvement and an ataxia-ophthalmologic syndrome with no weakness (Miller-Fisher syndrome). These other axonal variants have a more clearly understood immunologic basis that involves antibody attack on a variety of target glycolipid antigens on nerve terminals and axons.4 Classic demyelinating GBS syndrome has a less well-defined pathogenesis. The disorder typically begins after recovery from a preceding illness or vaccination. Distal paresthesias evolve into a symmetrically progressive ascending distal and proximal weakness of the limbs. There are diminished or absent tendon stretch reflexes, often in association with facial weakness and limb and back pain.1,2 After several days the cerebrospinal fluid (CSF) demonstrates an elevation in protein without significant pleocytosis (albuminocytological dissociation). Weakness may continue to progress rapidly with need of ventilatory support, often with associated autonomic dysfunction. It has generally been perceived that the clinical course in children may be somewhat milder, with greater likelihood of recovery in comparison to adults.1 Immune-mediated mechanisms involving both cellular and humoral responses in GBS have been postulated. Microscopic studies have demonstrated both lymphocyte and macrophage infiltration into nerve fibers.3,4 Experimental allergic neuritis can mimic the symptoms of GBS in rodents and rabbits after immunization with peripheral nerve extracts.5,6 Despite failure to exacerbate mild experimental allergic neuritis in rodents with the transfer of sera from patients … Reprint requests to (F.J.D.), Department of Pediatrics, Connecticut Children’s Medical Center, 282 Washington St, Suite 2A, Hartford, CT 06106. E-mail: fdimari{at}ccmckids.org

SMART syndrome (stroke-like migraine attacks after radiation therapy) is a rare condition that involves complex migraines with focal neurologic findings in patients following cranial irradiation for central nervous system malignancies. Little is known about the mechanisms behind the disorder, making successful treatment challenging. We report 2 new cases of SMART syndrome in pediatric patients as well as review all documented cases of the syndrome. Each of our 2 pediatric patients suffered multiple episodes. Attacks were characterized by severe headache, visual disturbance, aphasia, and weakness. Recovery occurred over several days to weeks. The data from all documented reports of SMART syndrome indicate a greater prevalence for male gender. An age-dependent pattern of onset was also observed, with a greater variability of syndrome onset in patients who received cranial irradiation at a younger age. SMART appears to be a reversible, recurrent long-term complication of radiation therapy with possible age- and gender-related influences.

Hemorrhage complicating acute carbon monoxide poisoning is usually confined to the basal ganglia. The authors report three people with acute carbon monoxide poisoning manifesting selective or prominent white matter involvement complicated by hemorrhagic infarction on CT and MRI in one and by subcortical T2*-weighted MRI abnormality in all three.

Article abstract-Rationale and objectives: We undertook an MRI brain morphometric analysis to investigate the relationships between brain and skull base growth and clinical function in patients with achondroplasia as compared to normal controls. Methods: Patients selected for evaluation included pediatric patients who underwent T1 and T2 or dual-echo, proton-density axial T1- and T2-weighted and T1 sagittal brain MRI during 1988 to 1992. Study subjects (n = 11) were diagnosed with achondroplasia by clinical and radiologic criteria and compared to an age- and gender-matched control group (n = 25). Twenty-four predetermined ventricular and brain parenchymal dimensions and area calculations were evaluated. Data were analyzed using two-tailed t tests, chi-squared analysis, ANOVA, and ANCOVA, adjusting for age and sex. Correlational analyses with respect to subject type and age were done separately. Results: There were 36 patients (11 subjects with 15 MRI examinations, mean age 2.3 years, and 25 controls with 26 MRI examinations, mean age 3.0 years). Significant differences existed for 11/17 measures. Achondroplasts had a significantly larger bifrontal width (p < 0.0001), bicaudate width (p < 0.0001), frontal horn diagonal length (p < 0.05), biatrial width (p < 0.0001), biparietal diameter (p < 0.05), and iter to incisural line distance (p < 0.0001). Achondroplasts had significantly smaller frontal lobe depths (p < 0.01), optic tract angles (p < 0.0001), foramen magnum diameters (p < 0.0001), and sinojugular transition zones (p < 0.05). There were no differences in brainstem heights or fourth ventricular widths between achondroplasts and controls. Furthermore, with respect to age, frontal lobe depth was smaller when compared to controls and the descending sigmoid sinus area became increasingly larger. Conclusions: Achondroplastic subjects experience dynamic changes in brain morphometry resulting in a rostral displacement of the brainstem with gradual compression of the frontal lobes due to enlargement of the supratentorial ventricular spaces commensurate with an increase in venous sinus distension.NEUROLOGY 1995;45: 519-524

We prospectively acquired clinical data regarding the presentation, evaluation, and developmental progress of all patients identified with dissociated motor maturation to define their clinical outcomes. Children ( N = 8) referred for evaluation of suspected cerebral palsy because of delayed sitting or walking and identified to have dissociated motor maturation were followed with serial clinical examination. All displayed the characteristic “sitting on air” posture while held in vertical suspension and had otherwise normal developmental assessments. This posture is composed of the hips held in flexion and abduction with the knees extended and feet plantar or dorsiflexed. Three children were initially evaluated at 10 months of age owing to absence of sitting and five other children were evaluated at a mean of 14 months (range 12—19 months) owing to inability to stand. Follow-up evaluations were conducted over a mean of 10.5 months (range 5—34 months). Five children were born prematurely at 34 to 36 weeks gestation. Denver Developmental Screening Test and general and neurologic examinations were normal except to note hypotonia in six children and the “sitting on air” posture in all of the children. Four children have older siblings or parents who “walked late” (after 15 months). On average, the children attained sitting by 8 months (range 7—10 months). One child did not crawl prior to independent walking, two children scooted rather than crawled, and five children crawled at an average of 13.5 months (range 10—16 months). All children cruised by a mean of 18 months (range 16—21.5 months) and attained independent walking by 20.1 months (range 18—23.5 months). Neuroimaging and serum creatine kinase enzyme testing were normal in two children who were tested. These eight children conform to the syndrome of dissociated motor maturation. The “sitting on air” posture serves as a diagnostic sign and anticipated excellent prognosis, but follow-up is required to ensure a normal outcome. ( J Child Neurol 2003;18:391—393).

Academic health centers (AHCs) have traditionally been a vibrant locale for cutting-edge medical research, androgogic education and innovative clinical care for the most vexing diseases. While these pursuits have coexisted and flourished, the realities of the health-care business environment have demanded reformatting and emulation of a corporate organizational model. This evolution has impacted the core identities of the AHC and challenged individual medical-educators, clinician-scientists and basic science investigators to persist and succeed in this milieu. The AHC has a unique capacity to muster the innate learning drive of these individuals into an organizational mission as it balances the pressures exerted from both the internal and external environments. The AHC as an organization can be viewed as an experimental condition with modifiable variables to which its professionals can react, adapt to, and transform. Organizational learning and change implementation is in essence an experiment in human behavior modification. While all individuals are subject to change, merely assembling them in a single locale determines neither a predictable homogeneous outcome nor the success of their endeavor. This article highlights some of these propositions and offers a philosophical approach to advance the AHC as an organization through the creativity and innovation of its professional ranks.

Context We have previously shown that serum VEGF-D is elevated at baseline, correlates with kidney angiomyolipoma size at baseline and 12 months, and decreases with sirolimus treatment in adults with tuberous sclerosis complex (TSC). To further investigate the utility of serum VEGF-D for longer term monitoring of TSC kidney disease, we present VEGF-D level results with 24 month follow-up. Objective To compare 24 month VEGF-D levels in two subgroups of sirolimus treated patients (OFF SIROLIMUS AFTER 12 MONTHS or ON SIROLIMUS AFTER 12 MONTHS). Design and Intervention(s) Serum VEGF-D was measured in samples collected from subjects enrolled in a phase 2 multicenter trial evaluating sirolimus for the treatment of kidney angiomyolipomas associated with TSC or TSC/LAM. All participants were treated with sirolimus from 0–12 months. During months 12–24, sirolimus was discontinued in one subgroup. The other subgroup was treated with additional sirolimus. Setting Adult TSC participants were recruited from six clinical sites in the United States (comprehensive TSC clinics, 5; urology clinic, 1). Patients There were 28 TSC patients who completed all 24 months of the study and serum samples were available at 24 months from 18/28 patients. Main Outcome Measure(s) We compared the percent change in VEGF-D levels (baseline to 24 months) in patients from the two treatment subgroups. Results At 24 months, VEGF-D levels decreased by 67% compared with baseline (to 787±426 pg/ml) in the ON SIROLIMUS AFTER 12 MONTHS group versus a 13% decrease (to 2971±4014 pg/ml) in the OFF SIROLIMUS AFTER 12 MONTHS group (p = 0.013, Mann-Whitney test). A similar trend was observed in kidney angiomyolipoma size but not in pulmonary function tests. Conclusions Serum VEGF-D may be useful for monitoring response to treatment with sirolimus and kidney angiomyolipoma size in patients with TSC, but confirmation is needed. Trial Registration Clinical trials.gov NCT00126672.

This investigation correlated incidence and degree of autonomic dysfunction with the degree of motor impairment in children hospitalized with Guillain-Barré syndrome. Motor weakness varies, as does the effect on autonomic function including heart rate, vasomotor stability, sweating, continence, and blood pressure. After Institutional Review Board approval, hospitalized patients with Guillain-Barré syndrome

Objective. Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder in which many cardinal features may have a neurologically based patho-physiology involving both the central and peripheral components of the autonomic nervous system. Autonomic nervous system function was studied noninvasively in a group of subjects with PWS and control subjects to determine whether autonomic nervous system dysfunction exists as part of the PWS. Design/setting. This cross-sectional study was performed in the neurophysiology laboratory at a tertiary care facility. Methods. Evaluation included anthropometric measurements and calculation of a body mass index (BMI). Simultaneous electrocardiography and serial recordings of pulse rate and systolic/diastolic mean arterial blood pressures during orthostatic maneuvers were taken. Pupillary response to the instillation of dilute pilocarpine and measurements of plasma norepinephrine at rest and after standing were also obtained. Results were analyzed using two-tailed t tests, Fisher exact test, analysis of variance, and analysis of covariance adjusting for age, gender, and BMI. Patients. There were 14 subjects with PWS (8 female, 6 male; aged 4 to 40 years, mean age 16 years) and 8 control subjects (4 female, 4 male; aged 5 to 37 years, mean age 19 years). Results. Abnormal findings were obtained only in subjects with PWS. Analysis of covariance adjusting for age, gender, and BMI revealed a trend for subjects with PWS to have lower resting diastolic blood pressure (P < .09) and significantly less change in diastolic blood pressure after standing (P < .02). Subjects with PWS had significantly greater BMI than did control subjects (P < .001), which correlated significantly with all pulse rate measurements where the greater the BMI the higher the pulse rate at rest (r = .25, P < .04) and the lower the pulse rate after arising from lying to standing at both 15 and 30 seconds (r = .17, P < .1; r = .55, P < .08 respectively). Pupillary constriction of 2 mm or more was seen in 7 of 14 subjects with PWS and in no control subjects (P < .004). The 30:15 R-R interval ratio was abnormal in 6 of 14 subjects with PWS and in no control subjects (P < .03). Conclusions. These results suggest that patients with PWS have a detectable underlying autonomic dysfunction characterized principally by diminished parasympathetic nervous system activity.

The neuromodulator adenosine is an endogenous sleep promoter, neuroprotector and anticonvulsant, and people with autism often suffer from sleep disruption and/or seizures. We hypothesized that increasing adenosine can decrease behavioral symptoms of autism spectrum disorders, and, based on published research, specific physiological stimuli are expected to increase brain adenosine. To test the relationship between adenosine and autism, we developed a customized parent-based questionnaire to assess child participation in activities expected to influence adenosine and quantify behavioral changes following these experiences. Parents were naive to study hypotheses and all conditions were pre-assigned. Results demonstrate significantly better behavior associated with events pre-established as predicted to increase rather than decrease or have no influence on adenosine. Understanding the physiological relationship between adenosine and autism could open new therapeutic strategies--potentially preventing seizures, improving sleep, and reducing social and behavioral dysfunction.

Syncope is a self-limited loss of consciousness produced by cerebral hypoperfusion/hypoxia. The objective of this study was to categorize the etiology and determine the frequency of concurrent epilepsy and whether laboratory testing is diagnostically useful. This was an institutional review board—approved retrospective chart review. Data were analyzed using descriptive statistics. There were 141 subjects (90 girls [63.8%]; mean age, 12.01 years). Of the syncope referrals, 86 of 123 (69.9%) had simple syncope, 35 of 123 (28.4%) had syncopal convulsions, and 2 of 123 (1.6%) had epilepsy alone. An electroencephalogram was performed in 64.7% (91/141) of the subjects but was diagnostic in 1 of 91 (1.4%) for epilepsy. Magnetic resonance imaging and/or computed tomography scans, electrocardiograms/Holter monitoring/stress testing, and blood tests were primarily normal or nondiagnostic, with 6 of 238 (2.5%) total tests contributing to the diagnosis. Primary neurocardiogenic syncope was identified in 78% (111/141) of all subjects (82% boys, 75% girls). Thirty-eight percent had syncopal convulsions, and 2.8% (4/141) had concurrent epilepsy. A detailed medical history was the most useful diagnostic tool.

Background Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2. Methods We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas. Results 36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1–2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline). Conclusions Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration treatment in adults and children with TSC. Trial Registration Clinicaltrials.gov NCT00126672

Möbius sequence consists of a congenital bilateral facial nerve palsy and external ophthalmoplegia often associated with malformations of the limbs and orofacial structures. The pathogenesis of the sequence is a subject of debate. However, a new hypothesis proposes that Möbius sequence results from an interruption of embryonic blood supply (subclavian artery supply disruption sequence). Here we present an infant with bilateral facial nerve palsy (VII), external ophthalmoplegia (IV, VI), paresis of cranial nerves V, IX, X, XI, and XII, absence of the pectoralis major muscle (Poland anomaly), terminal transverse limb defects, and absence of the right diaphragm. Also, he was found to have discrete foci of brainstem calcifications in the region of the dorsal respiratory group on both CT scan and the histologic sections with microscopic evidence of diffuse brainstem "injury." The anomalies and histopathology noted in this infant imply that vascular insufficiency prior to the sixth week of gestation involving the proximal sixth intersegmental artery may result in the manifestations presented in this report and lend further support for the existence of a subclavian artery supply disruption sequence.

The purpose of this study was to determine the locations and characterize the types of brain abnormalities noted on brain magnetic resonance imaging in patients with probable and definite neurofibromatosis type 1. Patients with definite neurofibromatosis type 1 (n = 17) were studied when clinically indicated, and patients with probable neurofibromatosis type 1 (n = 9) were studied to evaluate for asymptomatic optic pathway glioma. Of the 26 patients evaluated, 14 (53%) had high-intensity signal abnormalities and 11 (42%) had significant structural abnormalities. Subsequent clinical follow-up has confirmed conversion to a definite neurofibromatosis type 1 diagnosis in three of the four cases of probable neurofibromatosis type 1 who had high-intensity signal abnormalities. The most common locations of high-intensity signal lesions were in the globus pallidus of the basal ganglia and cerebellar white matter. Tortuous or thickened optic nerves and/or optic chiasm were seen in eight cases. Brain magnetic resonance imaging scans frequently reveal high-intensity signal lesions and structural abnormalities in selected patients with both probable and definite neurofibromatosis type 1. These findings may allow for a definitive diagnosis in clinically probable cases. (J Child Neurol 1993;8:32-39).

Evidence from multiple sources has highlighted the increased burden of cognitive, behavioral, and psychiatric disorders in childhood-onset epilepsy. Some of this increased morbidity, however, is attributable to underlying structural and metabolic insults. We assessed whether cognitive/behavioral/psychiatric disorders were associated with epilepsy of unknown or presumed genetic cause in young people with epilepsy (cases) compared to sibling controls. Our analyses included 217 cases who were enrolled in the Connecticut Study of Epilepsy between 1993 and 1997 and 217 sibling controls. Information was collected from a parent interview conducted 8-9 years after the case was diagnosed with epilepsy. Compared to controls, parents were more likely to report that their case children were slow learners (OR=4.6, p

One hundred eight out of 256 (42%) surveys were completed by registered school nurses (SNs) working in the Connecticut public school system. Of the 108 respondents, 99% were RNs and 1% were LPNs. Each SN spent an average of 19 working days a month at school, in elementary (71 %) and/or preschool (40%) settings. Professional experience and educational backgrounds were variable. Over 40% had never received formal instruction regarding childhood headache (CH), and an additional 32% had received less than two hours. School nurses ranked CH behind minor trauma, GI upset, and URI as the fourth of the 13 most common clinical problems encountered at school. An average of 35 children with headaches were seen each month. A brief description of, and inquiry about, other systemic symptoms were nearly always made. Only 62% of the SNs usually asked a child about neurological symptoms. A child's temperature and pulse were measured routinely by 84% of SNs, whereas blood pressure and neurological assessment were obtained routinely only in approximately 12%. Treatment varied; nonetheless, 31 % routinely allowed the child to rest or sleep as part of their management plan. Analgesic was administered routinely only by 10%. Approximately one third generally discussed a disposition plan with the child's parents, whereas only 3% usually spoke with the child's physician. Although 51 % of the respondents felt they were "constrained by school policy" in their management of CH, half of these individuals (71 % of all respondents) did not want more latitude. It is concluded from this survey that despite limited formal instruction about CH, SNs dealt with CH in a reasonable manner.

Tumefactive demyelinating lesions are a known but uncommon complication of multiple sclerosis, a disease rarely reported in children. This is the case of a 16-year-old African American patient with multiple sclerosis, who developed 2 tumefactive demyelinating lesions. Review of the literature and our own experience helped formulate an algorithm for therapeutic options during an acute attack.

A 12-year-old male developed progressive proximal upper extremity weakness over a 3- to 4-year period. The clinical findings of proximal upper extremity weakness and atrophy, prominent scapular winging, and no sensory deficits or upper motor neuron signs suggested a neuromuscular disorder. Electromyography was consistent with a chronic denervating disorder involving the upper cervical anterior horn cells or their axons. A cervical magnetic resonance image revealed a large intramedullary mass extending from the inferior aspect of the fourth ventricle down to the level of T2. A biopsy of the lesion was consistent with a low-grade astrocytoma.

Acute changes in mental status (AMS) develop in children with cancer from a multitude of cancer- and treatment-related complications. To determine the incidence, etiology, and outcome of children with cancer who had AMS, the medical records of all children under 18 years of age with systemic cancer (excluding primary central nervous system tumors) who had AMS in our institution during the years 1981 through 1987 were reviewed. AMS developed in 89 of 815 children at risk (11%). The AMS was caused by seizures in 53 (60%), an encephalopathy in 24 (27%), and a stroke syndrome in 12 (13%). AMS occurred in 42 of 305 (14%) with leukemia, 16 of 139 (12%) with lymphoma, 14 of 136 (10%) with sarcoma, 10 of 104 (9%) with neuroblastoma, and 7 of 104 (5%) with other malignancies. Children with acute lymphocytic leukemia were more prone to having seizures (61%), while children with nonacute lymphocytic leukemia were almost equally likely to have encephalopathies, strokes, or seizures. Children with lymphoma were admitted for treatment most often with an encephalopathy (44%). Etiologies for AMS were evaluated vigorously, and one or more etiologies were identified in 80 of 89 (89%) patients. Dependent on the type of tumor, the anticancer treatment used and, timing during the course of illness AMS occurred, specific diagnoses were more likely. Neurologic morbidity and mortality were dependent on the cause of AMS. Children with seizures that were initially difficult to control were more likely to require long-term anticonvulsant therapy.

In this study we investigated centrally mediated parasympathetic regulation of modulated cardiac vagal tone among children with severe cyanotic and pallid breath-holding spells by examining respiratory sinus arrhythmia. Respiratory sinus arrhythmia was evaluated in 41 children; 17 subjects with cyanotic breath-holding spells (6 boys, 11 girls; mean age 37.1 months), 7 subjects with pallid breath-holding spells (2 boys, 5 girls; mean age 33.0 months), and 17 controls (8 boys, 9 girls; mean age 41.2 months). Subjects had recurrent (more than 3) severe breath-holding spells. Each subject's electrocardiogram was recorded in a quiet room and digitized by an 80386 personal computer during five 1-minute periods. R-R intervals within each 1-minute period were converted to heart rate in 120 successive 0.5-second intervals. The resultant heart rate time series was converted to its underlying frequency composition by a fast Fourier transform and averaged across minutes. Respiratory sinus arrhythmia was defined as the variability in the time series over a frequency range (0.096 Hz to 0.48 Hz) corresponding to a range of respiratory rates from 6 to 30 breaths per minute. ANCOVA adjusting for age and sex was conducted with the subject group as the independent measure. There were no significant differences between subjects with cyanotic breath-holding spells and controls. Pallid breath-holding spell subjects had a marked difference in respiratory sinus arrhythmia from either controls or subjects with cyanotic breath-holding spells, demonstrating less variability in respiratory sinus arrhythmia (P < .042) This study supports the hypothesis that there exists autonomic dysregulation in pallid breath-holding spells, caused by a primary central parasympathetic disturbance distinct from the dysregulation found in cyanotic breath-holding spells. (J Child Neurol 1998;13:440-442).

The paroxysmal nonepileptic events of childhood are a group of disorders, syndromes, and phenomena that mimic true epileptic seizures. Clinical experience and a clear description of the event in question will usually lead to a correct categorization. They span in age from neonate to young adult and are apt to be the most common diagnostic challenges clinicians face regularly. The key to diagnosis is a detailed history and careful observation. Despite the large number of discrete entities enumerated herein, common principles in clinical approach are successful and described. Each entity can pose a significant clinical challenge in identification, etiologic pathophysiology, genetics, and management. A simple division is offered here separating those episodes that are associated with an altered mental status or occurring during sleep and those without an altered mental status or occurring while awake.

The most common seizures experienced by young children are febrile seizures,1,2 which affect up to 4% to 5% of children ≤5 years old in the United States and Europe.1,2 In other portions of the world, the frequency may exceed 10% to 15%.2 Febrile seizures are defined as seizures associated with a febrile illness in the absence of central nervous system infection or acute electrolyte imbalance in children >1 month of age without previous afebrile seizures.3 These seizures have been defined further as simple or complex: simple febrile seizures are generalized seizures that last 15 minutes) and/or occur in a series over 24 hours.3,4 The associated morbidity and mortality from febrile seizures is extremely low, with no associated adverse cognitive outcomes even when the seizures are prolonged.1,5,6 Risk factors predicting first febrile seizure, recurrent febrile seizures, and subsequent epilepsy have been well enumerated1 (see Table 1). View this table: TABLE 1 Risk Factors for Patients Associated With Febrile Seizures Although there has existed ample investigation and data concerning initial management, treatment approaches, and outcomes in children with simple febrile seizures, there has been somewhat less well-developed data concerning complex febrile seizures. This is particularly true in regards to neuroimaging in the context of complex febrile seizures in an emergency-department setting. In this … Address correspondence to Francis J. DiMario, Jr, MD, Department of Pediatrics, Connecticut Children's Medical Center, 282 Washington St, Suite 2A, Hartford, CT 06106. E-mail: fdimari{at}ccmckids.org

We report two children with transient myasthenia gravis preceded by viral illnesses. The first is a 5-year-old boy who developed oculobulbar weakness 2 weeks following a varicella-zoster infection. The second is a 4-year-old boy who developed facial diplegia and dysarthria several weeks following a viral pharyngitis. Myasthenia gravis was diagnosed based on the substantial decremental changes on 3 Hz repetitive motor nerve stimulation studies for the first child and on the positive edrophonium test and complete improvement in symptoms during pyridostigmine therapy for both children. In both cases, the symptoms gradually resolved and have not recurred following discontinuation of pyridostigmine. Molecular mimicry between the acetylcholine receptor and viral proteins might provide the nidus for the immune response in this variant of myasthenia gravis. ( J Child Neurol 2005;20:441—444.)

The article by Laptook et al1 in the March issue of Pediatrics examined clinical follow-up assessments at 18 to 22 months’ corrected age of an extremely low birth weight (ELBW) infant cohort cared for in the Neonatal Research Network Centers within the years 1995–1999. From the study cohort of 1749 infants, 84% (1473 infants) returned for follow-up assessments. The authors found that nearly 30% of those infants with a normal, early, and late head ultrasound (HUS) (performed at a mean age of 6 and 47 days, respectively) were found later to have either cerebral palsy (CP) (9.4%) and/or a low (

In this issue, Gilbert et al1 have provided some new insights into the utility of sleep deprivation before recording of electroencephalograms (EEGs), to increase the likelihood of identification of interictal epileptiform discharges. A design flaw, which makes the results less universally applicable, is that the subjects and referring physicians both represented heterogeneous groups. The subjects included children who were known epileptics, patients with initial seizures, children with and without antiepileptic drug treatment, and children with a variety of other presenting complaints. The referring physicians were specialists and generalists treating differing populations. Nevertheless, by comparing 2 time periods during which subjects underwent EEG recording with a standard sleep deprivation protocol or a non–sleep-deprivation protocol, the authors were able to establish a large enough sample size to provide some important results. Of the 820 eligible subjects who underwent EEG recordings during …