bluuebunny/crossref_metadata_2025 huggingface dataset:
Landau-Kleffner Syndrome With Continuous Spikes and Waves During Slow-Wave Sleep
Authors: Rintahaka Pertti J. , Chugani Harry T. , Sankar Raman
Published: December 2008

The Landau-Kleffner syndrome is sometimes associated with continuous spike-waves during slow-wave sleep. The clinical significance of this association is unclear. In order to investigate differences in glucose metabolic patterns between awake and sleep states in two children with Landau-Kleffner syndrome and continuous spike-waves during slow-wave sleep, fluorodeoxyglucose positron-emission tomographic (PET) studies were performed in each state. In the first patient, the awake interictal PET study revealed moderate hypometabolism in the thalamus and frontal and temporal cortex and mild hypometabolism in the parietal and anterior cingulate cortex bilaterally. Occipital cortex was severely hypometabolic bilaterally. In a repeat PET study performed during sleep in which continuous spike-waves during slow-wave sleep were present, the only difference noted compared to the awake study was a marked bilateral increase in temporal cortex metabolism. The awake interictal PET in the second child was normal, except for mildly increased relative glucose metabolism in the left inferior temporal cortex. The sleep PET study with continuous spike-waves during slow-wave sleep in this child showed hypermetabolism in both temporal lobes; however, this was more pronounced, with a wider distribution in the left temporal cortex. In normal subjects, PET studies performed during awake and sleep states have not revealed such differences. Whether the temporal lobes are involved in the generation of continuous spike-waves during slow-wave sleep remains to be confirmed in a larger group of patients. The first child was treated surgically with multiple subpial transection, following which continuous spike-waves during slow-wave sleep disappeared and language function improved. The second child has had no recovery of speech, although she is seizure free, has discontinued anticonvulsants, and no longer shows continuous spike-waves during slow-wave sleep on the electroencephalogram. The role of PET in selecting suitable candidates for surgery in Landau-Kleffner syndrome requires further study. (J Child Neurol 1995; 10: 127-133).
Neurobehavioral and Neurologic Outcome in Long-Term Survivors of Posterior Fossa Brain Tumors: Role of Age and Perioperative Factors
Authors: Chapman Catherine A. , Waber Deborah P. , Bernstein Jane H. , Pomeroy Scott L. , LaVally Beverly , Sallan Stephen E. , Tarbell Nancy
Published: December 2008

We evaluated the neuropsychological and neurologic outcome of 15 long-term survivors of posterior fossa tumors who were treated between 1970 and 1984 with cranial irradiation (n = 15) and surgery (n = 14). The interval between diagnosis and evaluation ranged from 4 to 20 years (median = 10 years). Earlier age at diagnosis (< 6 years) was associated with an increased incidence of severe neurologic and neuropsychological sequelae. Hydrocephalus, obtundation, and tumor extension outside the vermis also were more prevalent in the younger group. Poor neurobehavioral outcomes in young children with posterior fossa tumors may be related to more aggressive tumor growth or complications of the initial therapy and not solely due to toxicity from craniospinal irradiation. (J Child Neurol 1995;10:209-212).
Opsoclonus Myoclonus Syndrome Secondary to Epstein-Barr Virus Infection
Authors: Sheth Raj D. , Horwitz Samuel J. , Aronoff Stephen , Gingold Monique , Bodensteiner John B.
Published: December 2008

We report the first two children to have the "opsoclonus myoclonus syndrome" after a serologically confirmed acute Epstein-Barr virus infection. Although opsoclonus was absent in one patient, both patients had all other features typical of this syndrome. Patients without opsoclonus have been described as having an isolated postinfectious myoclonus syndrome but probably lie within the spectrum of opsoclonus myoclonus syndrome. The prognosis for the opsoclonus myoclonus syndrome in children with Epstein-Barr virus infection and without evidence for a neuroblastoma appears to be better than in those patients where a cause cannot be identified. (J Child Neurol 1995;10:297-299).
Neuroreality I. Dedicated Demolition of the Decade of the Brain: The Genuine Threat to Neurologic Research From the Animal Radical Right
Authors: Landau W.M. , Daube J.R. , Aminoff M.J. , Brey R.L. , Brooks B.R. , Deuel R.K. , Galaburda A.M. , Porter J.A. , Rosenbaum R.B. , Whitham R.H. , Wiggs J.W.
Published: December 2008

In this era of budgetary constraints, the biggest threat to continuing biomedical research is often seen as governmental funding cutbacks. However, a much larger threat looms—the antiscientific programs of the various so-called animal rights groups. Unless clinicians and scientists mount a concerted defense of scientific investigation, the repressive antiscience movement will win out and thrust us into a Dark Ages scenario, with only a few gallant enough to maintain scientific thought until another Enlightenment. During World War II, the German clergyman Martin Niemoeller lamented the general apathy that allowed a small group of dedicated ideologues (the Nazi hierarchy) to terrorize the Germans: "In Germany they came first for the Communists, and I didn't speak up because I wasn't a Communist. Then they came for the Jews, and I didn't speak up because I wasn't a Jew. Then they came for the trade unionists, and I didn't speak up because I wasn't a trade unionist. Then they came for the Catholics, and I didn't speak up because I was a Protestant. Then they came for me, and by that time no one was left to speak up." Not dissimilarly, the apathy of clinicians and biomedical scientists has permitted the radical animal rights movement to terrorize researchers and undermine our research freedom. In a call to action, the American Academy of Neurology has developed a statement (in association with the Foundation for Biomedical Research and other groups) on the threat to neurology research. This information was originally published in Neurology (1995;45: 609-610). In order to increase the dissemination of this important warning to clinicians and scientists everywhere, the Journal of Child Neurology in cooperation with the American Academy of Neurology is reprinting that material in this issue.
Topical Review: Clinical Aspects of Hereditary Ataxias
Authors: Subramony S.H.
Published: December 2008

The hereditary ataxias are a group of complex genetic disorders the understanding of which is undergoing a revolution because of advances in molecular genetics. Within the last few years, at least seven different gene loci have been found to be responsible for these syndromes, and the search is on for additional loci that undoubtedly exist. This review summarizes the clinical features of the various hereditary ataxias with known gene loci, as well as others that are now defined on a clinical basis. It also deals with some of the imaging and neuropharmacologic advances that have been made in this group of disorders. (J Child Neurol 1995;10:353-362).
Demyelinating Peripheral Neuropathy in Merosin-Deficient Congenital Muscular Dystrophy
Authors: Shorer Zamir , Philpot Joanne , Muntoni Francesco , Sewry Caroline , Dubowitz Victor
Published: December 2008

It has recently been shown that merosin, a laminin variant, is deficient in a proportion of patients with congenital muscular dystrophy. Merosin is a heterotrimer composed of the α2, β1, and γ1 subunits, and further studies have shown that it is the α2 subunit that is deficient in these patients. Because the α2 subunit is also expressed in S-merosin, found in Schwann cells, we have investigated whether peripheral nerve function is also affected in these patients. Motor nerve conduction velocities and sensory distal latencies were examined in 25 cases of congenital muscular dystrophy and the results correlated with the merosin expression in their muscle biopsies. All but two of the 10 merosin-deficient cases had reduced motor nerve conduction, whereas all the merosin-positive cases had normal results. Analysis of the biopsies of these two cases showed that they produced merosin in reduced amounts, in contrast to all other merosin-deficient patients that produced no or only traces of merosin. Sensory nerve studies showed no difference between the two groups. These results indicate that a peripheral demyelinating neuropathy is a feature of merosin-deficient congenital muscular dystrophy. The fact that the α2 subunit is also expressed in Schwann cells supports the idea that the α2 gene, located on chromosome 6, is the candidate gene for merosin-deficient congenital muscular dystrophy. (J Child Neurol 1995;10:472-475).
Topical Review: Childhood Guillain-Barré Syndrome: Clinical Presentation, Diagnosis, and Therapy
Authors: Jones H. Royden
Published: December 2008

A rapidly progressive, generally symmetric, ascending flaccid paraparesis or quadriparesis that develops in an infant or child constitutes an uncommon but important pediatric neurologic emergency that requires immediate evaluation and treatment. The differential diagnosis primarily includes acute neuropathies, most commonly the childhood Guillain-Barré syndrome and, rarely, acute transverse myelitis or infantile poliomyelitis. A clinical distinction may be difficult in the younger child in whom detailed sensory examination is not possible. Although most children with Guillain-Barré syndrome usually have a benign and relatively limited clinical illness, some become severely ill, requiring intubation and careful intensive monitoring. To date, no well-controlled multi-institutional studies of treatment with either plasmapheresis or intravenously administered immunoglobulin have been developed in children despite the success of these modalities in adults. A review of the data available using these therapies is included in this study. (J Child Neurol 1996;11:4-12).
Etiologic Classification of Infantile Spasms in 140 Cases: Role of Positron Emission Tomography
Authors: Chugani Harry T. , Conti Jon R.
Published: December 2008

The classification of infantile spasms into symptomatic, cryptogenic, and idiopathic subgroups depends on clinical examination and available diagnostic technology. Positron emission tomography (PET) of glucose utilization is a powerful tool in detecting brain malformations (particularly cortical dysplasia) in infants with spasms. We analyzed etiologic data from 140 such infants, 78 girls and 62 boys, ages 2 months to 4 years 10 months (mean, 17 months). All had been evaluated extensively in one of two major medical centers. It should be emphasized that our referral population is biased toward infants with intractable spasms who fail to show a structural lesion. Seven patients had neurocutaneous syndromes, two had chromosomal abnormalities, two had inborn errors of metabolism, and one each had craniosynostosis or Menkes syndrome. Computed tomography and/or magnetic resonance imaging detected lesions in another 29 infants (20.7%) who did not have a specific disease or syndrome. Without the benefit of PET, the total number of symptomatic cases was 42 (30.0%). One infant, classified as idiopathic, had normal development and PET. In 97 cryptogenic cases, PET uncovered unifocal abnormalities in 30 and multifocal abnormalities in 62. Diffuse PET abnormalities, which did not provide specific etiologic information, were seen in three infants. Another two infants had normal PET scans. Thus, with the benefit of PET, the number of symptomatic cases rose dramatically from 42 (30.0%) to 134 (95.7%). The majority of unifocal and multifocal abnormalities on PET are believed to represent dysplastic lesions. (J Child Neurol 1996;11:44-48).
Neurologic Abnormalities in Infantile Autism
Authors: Haas Richard H. , Townsend Jeanne , Courchesne Eric , Lincoln Alan J. , Schreibman Laura , Yeung-Courchesne Rachel
Published: December 2008

Neuroanatomic, pathologic, and neurobehavioral studies point to a cerebellar and parietal abnormality in autism. We used a standardized protocol to examine neurologic function in 28 pediatric autistic subjects and 24 pediatric normal healthy volunteer controls. As a group, the autistic subjects had quantitative measures from magnetic resonance imaging suggesting hypoplasia or hyperplasia of the cerebellar vermis, as well as measurements of posterior corpus callosum suggesting abnormalities of posterior cortex. In groups of tests that reflect cerebellar and parietal function, the neurologic abnormalities detectable by clinical examination were significantly greater for autistic subjects than for normal controls. These studies confirm that the structural and behavioral deficit in autism does lead to abnormalities that can be detected on the clinical neurologic examination. (J Child Neurol 1996; 11:84-92).
Blink Reflex in Cerebral Palsy: Evaluation of Late Components in Patients With Normal Auditory Brainstem Responses
Authors: Inagaki Masumi , Kaga Makiko , Maegaki Yoshihiro , Kinoshita Hirotoshi , Hirano Satoru
Published: December 2008

The electrically elicited blink reflex was examined and evaluated quantitatively in 60 controls and seven patients with cerebral palsy due to perinatal asphyxia who exhibited normal auditory brainstem responses. In the controls, the early component (R1) latency changed slightly from infancy to adulthood, and the late component (R2 and R2') latencies decreased to adult values by 4 to 6 years of age. The electromyographic activity of R2 and R2' increased later and became mature in the young adolescent period. Prolonged R2 latency and decreased R2 amplitude were observed more frequently than R1 abnormalities in the patients. The electromyographic activity of R2 in the patients was lower than that in control subjects more than 13 years old. Almost all patients showed bilateral cerebral atrophy and dilated lateral ventricles, but only one patient exhibited distinct pontine atrophy on cranial computed tomographic scan. These electrophysiologic abnormalities suggest that decreased excitability of intemeurons of the reflex arc was present in the patients, particularly in older ones. The blink reflex test seems to be more sensitive than the auditory brainstem response for detecting brainstem dysfunction in patients with cerebral palsy due to neonatal asphyxia. (J Child Neurol 1996;11:205-209).
Leukoencephalopathy, Megalencephaly, and Mild Clinical Course. A Recently Individualized Familial Leukodystrophy. Report on Five New Cases
Authors: Goutières Françoise , Boulloche Jacques , Bourgeois Marie , Aicardi Jean
Published: December 2008

Five children presented in the first months of life with progressive megalencephaly and leukodystrophy characterized by diffuse swelling of the white matter, cystic cavitations in frontal and temporal lobes, and a slow progressive course contrasting with the intensity of the leukodystrophic process. Four had epilepsy. Two were brothers and three had consanguineous parents. No metabolic defect was detected. The clinical and magnetic resonance imaging features are similar to those of patients previously reported. These five new cases add arguments to delineate a new type of leukodystrophy with megalencephaly in infancy and autosomal recessive inheritance. (J Child Neurol 1996;11:439-444).
Preoperative Clinical, EEG, and Imaging Findings Do Not Predict Seizure Outcome Following Temporal Lobectomy in Childhood
Authors: Goldstein Rita , Harvey A. Simon , Duchowny Michael , Jayakar Prasanna , Altman Nolan , Resnick Trevor , Levin Bonnie , Dean Patricia , Alvarez Luis
Published: December 2008

Although certain clinical, electroencephalographic (EEG), magnetic resonance imaging (MRI), and pathologic findings in adults with intractable temporal lobe epilepsy predict seizure outcome following temporal lobectomy, predictors of seizure outcome have not been studied systematically in pediatric temporal lobectomy series. We retrospectively analyzed preoperative clinical, EEG, and neuroimaging findings with reference to seizure outcome (seizure free or non-seizure free) in 33 children (mean age, 9.3 years) who underwent tailored temporal lobe resections for intractable temporal lobe epilepsy. Trends were apparent with (1) younger age at seizure onset, younger age at surgery, shorter duration of epilepsy, localized unilateral temporal lesions on MRI, and right-sided surgery more frequently associated with a seizure-free outcome, and (2) significant prior history, daily preoperative seizures, generalized motor seizures, mental retardation, and localized unilateral temporal epileptiform EEG activity more frequently associated with a non-seizure-free outcome. However, none of these findings, alone or in combination, correlated with postoperative seizure status at a statistically significant level. Submitting the four variables generally considered to be most predictive of favorable outcome (ie, normal intelligence, unilateral ictal and interictal EEG discharges, and focal temporal MRI lesion) to a multiple-cutoff procedure did not predict seizure freedom. Our data indicate that predictors of outcome of temporal lobectomy in adults may not apply in children, perhaps due to inherent neurobiologic differences in the etiology and expression of temporal lobe epilepsy, and should therefore not be used as sole determinants of surgical candidacy in children. (J Child Neurol 1996;11:445-450).
Infantile Intranuclear Rod Myopathy
Authors: Goebel Hans H. , Piirsoo Anders , Warlo Irene , Schofer Otto , Kehr Stephan , Gaude Michael
Published: December 2008

This report concerns three unrelated floppy infants, two girls and one boy, each biopsied at the age of 1 month. They were hypotonic since birth and required artificial ventilation. The two girls died at the ages of 4 and 3½ months, respectively, the boy is still alive at the age of 2 years, but requires assisted ventilation. Each of the three infants showed, by muscle biopsy, abundant intranuclear rods, the boy and one girl also had sarcoplasmic rods, which were not present in the other girl's muscle. Absence of sarcoplasmic rods, but the presence of intranuclear rods could also be documented in her autopsied muscle. Using an antibody against α-actinin, immunoelectron microscopy showed reaction of the sarcoplasmic and intranuclear rods demonstrating their Z-band origin. To our knowledge, this is the first report on rod myopathy with intranuclear rods only and of an immunoelectron microscopic demonstration of α-actinin in intranuclear rods. The presence of intranuclear rods in infants with nemaline myopathy also appears to indicate a grave prognosis of their rod myopathy. (J Child Neurol 1997; 12:22-30).
Clinical Role of Positron Emission Tomography in Children With Tuberous Sclerosis Complex
Authors: Rintahaka Pertti J. , Chugani Harry T.
Published: December 2008

We evaluated the clinical role of positron emission tomography (PET) in 23 children with tuberous sclerosis complex. Mean age of the children when first scanned was 3.3 years. Mean age when seizures began was 8.7 months. All, except three, were at least mildly developmentally delayed. PET images were visually analyzed and compared to computed tomography (CT), magnetic resonance imaging (MRI), and the electroencephalogram (EEG). In two infants, interictal PET study was normal. One of the studies was performed with a low resolution early generation scanner at age 7 months; the other infant was 2 days old. Twenty-one of the 23 children had focal or multifocal cortical hypometabolism. Some hypometabolic cortical regions on PET did not show corresponding abnormalities on CT and MRI, and may be due to epileptogenic mechanisms or small tubers. PET provides additional localizing information to CT and MRI in patients with tuberous sclerosis complex. However, because of the normally low cerebral glucose metabolism in infancy, PET may give false negative findings if performed prior to about 1 year of age. The usefulness of glucose metabolism PET in most patients with tuberous sclerosis complex is limited. However, if the EEG, CT, and MRI abnormalities are unifocal or unilateral, and surgery is being contemplated, more detailed evaluation with PET may help to determine if contralateral tubers are present and evaluate the functional integrity of the brain as a whole. (J Child Neurol 1997;12:42-52).
Topical Review: Gene Therapy for Neurologic Disease: Benchtop Discoveries to Bedside Applications. 2. The Bedside
Authors: Maria Bernard L. , Medina Carlos D. , Hoang Karin B.N. , Ian Phillips M.
Published: December 2008

Important advances in basic research have made it possible to examine the safety, toxicity, and efficacy of gene therapy in humans for over 5 years. The development of sophisticated gene delivery systems has resulted in approval by the Recombinant DNA Advisory Committee (RAC) of 125 gene therapy or gene marking studies. One of the primary applications of current retroviral-mediated gene insertion technology has been for malignant brain tumors. Studies are therefore underway to examine the efficacy of "suicide" gene therapy in children with recurrent brain tumors and adults with newly diagnosed or recurrent gliomas. Since a high proportion of genetic disorders produce neurologic dysfunction, gene therapy is likely to impact the management of neurologic disease in the foreseeable future. Patients with human immunodeficiency virus (HIV), Gaucher's disease, and Hunter syndrome are now enrolled in gene therapy trials. It will be challenging for the child neurologist to stay abreast of rapid developments in the field of gene therapy. By participating in the design and implementation of clinical trials in gene therapy, the neurologist may reduce the intense toll that several neurologic diseases take on children and their families. ( J Child Neurol 1997;12:77-84).
Urodynamic and Neurophysiologic Evaluation of Patients With Diastematomyelia
Authors: Kothari Milind J. , Bauer Stuart B.
Published: December 2008

Diastematomyelia is a form of an occult dysraphism, which can present with lower urinary tract dysfunction. We present the findings in 21 patients with diastematomyelia evaluated at the Children's Hospital in Boston. Seventy-six percent of the patients were female. Eighty-six per cent had a cutaneous lesion present overlying the spine. Urodynamic and electrophysiologic studies showed abnormalities in 17 (81%) of 21 patients, of whom 13 (62%) had upper motor neuron dysfunction. Seventeen patients underwent corrective spinal surgery and none of the patients deteriorated on a follow-up urodynamic and electrophysiologic study. We recommend that patients with cutaneous, midline lower back lesions with or without lower urinary tract dysfunction be evaluated with a urodynamic and electrophysiologic study to characterize the extent of neurologic and urologic dysfunction. ( J Child Neurol 1997; 12:97-100).
Right Hemisphere Dysfunction in Subjects With Attention-Deficit Disorder With and Without Hyperactivity
Authors: García-Sánchez Carmen , Estévez-González Armando , Suárez-Romero Emilia , Junqué Carme
Published: December 2008

The attention-deficit disorder, with and without hyperactivity, is associated with defective attention, response inhibition and, in attention-deficit disorder with hyperactivity, with motor restlessness. In adults, inattention, defective response inhibition, and impersistence are more commonly seen in right hemisphere lesions. In the present study, we investigate possible right hemisphere dysfunctions in attention-deficit disorder with hyperactivity and attention-deficit disorder without hyperactivity. The right hemisphere performance of 60 teenagers, 16 having attention-deficit disorder with hyperactivity, 9 having attention-deficit disorder without hyperactivity, and 35 controls, selected clinically (DSM-III) and experimentally (through Continuous Performance Test and Paced Auditory Addition Task), with normal IQ was assessed using a wide-ranging battery of visuospatial, visuoperceptive, and visuoconstructive functions (Benton's Line Orientation, Benton's Visual Retention, Raven's Progressive Matrices, Wechsler Adult Intelligence Scale [WAIS] Block-Design, Rey's Complex Figure). Teenagers with attention-deficit disorder with and without hyperactivity performed significantly worse than controls. Greater differences were found between subjects with attention-deficit disorder without hyperactivity and control than between subjects with attention-deficit disorder with hyperactivity and control subjects. Our results seem to be consistent with right-hemisphere dysfunction, especially in subjects with attention-deficit disorder without hyperactivity. Additionally, WAIS Block-Design and Benton's Line Orientation are the visuospatial tests with the highest discriminant power to differentiate between controls, subjects with attention-deficit disorder without hyperactivity, and subjects with attention-deficit disorder with hyperactivity. ( J Child Neurol 1997;12:107-115).
Magnetic Resonance Imaging in the Congenital Adrenal Hyperplasia Population: Increased Frequency of White-Matter Abnormalities and Temporal Lobe Atrophy
Authors: Nass Ruth , Heier Linda , Moshang Thomas , Oberfield Sharon , George Ajax , New Maria I. , Speiser Phyllis W.
Published: December 2008

Congenital adrenal hyperplasia results from an adrenal enzyme deficiency, that causes an underproduction of glucocorticoids and sometimes mineralocorticoids and a resultant overproduction of androgens, until treatment with replacement glucocorticoids is instituted. The goal of this study was to determine the frequency and etiology of white-matter changes and temporal lobe atrophy demonstrable on magnetic resonance imaging (MRI) in a group of children and young adults with congenital adrenal hyperplasia. About one third of the patients evidenced white-matter abnormalities or temporal lobe atrophy. All patients, except one with a known stroke, had normal neurologic examinations. Exposure to excess exogenous glucocorticoids in the process of being treated for congenital adrenal hyperplasia is the most theoretically appealing explanation for these MRI findings. However, the relationship of MRI findings to treatment status (over- versus under-suppressed) does not run in clear parallel. (J Child Neurol 1997;12:181-186).
Nerve Growth Factor Levels in Cerebrospinal Fluid From Patients With Neurologic Disorders
Authors: Suzaki Ichiro , Hara Toshiro , Maegaki Yoshihiro , Narai Sakae , Takeshita Kenzo
Published: December 2008

Nerve growth factor levels were measured in the cerebrospinal fluid from 73 patients with neurologic disorders and non-neurologic acute illnesses by a two-site enzyme immunoassay. Elevated nerve growth factor levels in cerebrospinal fluid were demonstrated in 2 of 7 patients with bacterial meningitis, 7 of 14 patients with viral meningitis or encephalitis, and 1 with multiple sclerosis. Follow-up examinations of the 3 patients (1 with bacterial meningitis, 1 with viral meningitis, and 1 with multiple sclerosis) at convalescent stage showed diminished nerve growth factor levels in cerebrospinal fluid. None of the other patients showed elevation of nerve growth factor levels in cerebrospinal fluid. Nerve growth factor levels in cerebrospinal fluid were not correlated with cell numbers in patients with meningitis or encephalitis. No relationship was observed between nerve growth factor levels and outcome in patients with viral meningitis or encephalitis and bacterial meningitis. Nerve growth factor in cerebrospinal fluid may play a role in neuronal recovery or function as an immunomodulator in children with inflammatory and immune-mediated neurologic disorders. (J Child Neurol 1997; 12:205-207).
β-Galactosidase Gene Mutations in Patients With Slowly Progressive GM1 Gangliosidosis
Authors: Kaye Edward M. , Shalish Christo , Livermore James , Taylor Harold A. , Stevenson Roger E. , Breakefield Xandra O.
Published: December 2008

Three unrelated North American cases with slowly progressive forms of GM1 gangliosidosis were found to have two unique point mutations and a 9 bp insertion in the coding region of the gene encoding β-galactosidase. Case 1 was noted to have a 9 bp insertion {CAGAATTTT} on one allele between nucleotides 730 and 731 with no other mutations identified in the other allele. In case 2, two point mutations were found: a unique G→A transition at nucleotide 602 causing an Arg→His substitution in codon 201 (mutation R201H); and a previously identified G→T transition at nucleotide 1527 causing a Trp→Cys substitution in codon 509 (mutation W509C), which has been noted in adult and chronic forms of GM1 gangliosidosis. Case 3 had a unique point mutation (A→G transition at nucleotide 797) resulting in a Asn→Ser amino acid substitution in codon 266 (mutation N266S), with no other mutations found in the same or the other allele. Single-strand conformation polymorphism performed on over 100 controls did not demonstrate the presence of the point mutations R201H or N266S. Also, the mutant proteins coded by the two point mutations did not show enzymatic activity in the Cos-1 cell expression system confirming that these mutations are associated with low enzyme activity. ( J Child Neurol 1997;12:242—247).
Treatment of Children With Williams Syndrome With Methylphenidate
Authors: Bawden Harry N. , MacDonald G. Wayne , Shea Sarah
Published: December 2008

Children with Williams syndrome frequently present with symptoms of attention deficit hyperactivity disorder (ADHD), but there is little information that stimulant medication is useful in this population. A series of double-blind, placebo-controlled case studies was used to evaluate the cognitive and behavioral effects of methylphenidate on four children with Williams syndrome. Teachers and mothers completed behavioral rating scales and cognitive tests of attention, learning and memory, and academic productivity and accuracy in mathematics in each medication condition. Two of the children responded favorably in terms of decreased impulsivity, decreased irritability, and lower activity level as well as improved ability to pay attention. Methylphenidate is a useful adjunct in the treatment of some children with Williams syndrome. ( J Child Neurol 1997;12:248—252).
Optimizing the Indication of Vigabatrin in Children With Refractory Epilepsy
Authors: Lortie Anne , Chiron Catherine , Dumas Caroline , Mumford John P. , Dulac Olivier
Published: December 2008

This review was conducted to evaluate the long-term prognosis of children responding to vigabatrin by examining the incidence of increased seizure frequency, loss of efficacy, and appearance of new seizures in a cohort of 196 children (mean age, 68.2 months; range, 2 months to 19 years) with drug-resistant epilepsy, who had received vigabatrin as add-on treatment in clinical trials. The results indicate that an increase in seizure frequency was uncommon, occurring in only 10% of children with highly drug-resistant epilepsy and that it usually appears shortly after the initiation of treatment. It was clearly not dose-dependent and most often occurred in patients with nonprogressive myoclonic epilepsy. No specific seizure type was specially involved and usually the problem reversed on discontinuing vigabatrin. Loss of efficacy was also uncommon (12% of patients), and again no specific seizure type was found to be associated. Epilepsy syndrome does seem to be a better predictor of loss of efficacy because it occurred most often in symptomatic generalized epilepsies and cryptogenic infantile spasms. A total of 21 patients (11%) developed genuinely new types of seizures. Fifteen of these patients developed new partial seizures that had little impact on the patients' overall clinical improvement. The new partial seizures were better tolerated than the initial seizure type which in most cases had disappeared. Approximately 3% of patients experienced new generalized seizures that aggravated their initial condition. These occurred most often in patients with nonprogressive myoclonic epilepsy; therefore vigabatrin should be used with particular caution in such patients. ( J Child Neurol 1997;12:253-259).
Muscle Fatigue in Spinal Muscular Atrophy
Authors: Iannaccone Susan T. , White Michael , Browne Richard , Russman Barry , Buncher Ralph , Samaha Frederick J.
Published: December 2008

We previously reported that patients with spinal muscular atrophy do not lose muscle strength over time as measured quantitatively. However, we noted that many patients with spinal muscular atrophy suffer from what they called fatigue. We wondered if we could measure fatigue during a single maximal voluntary contraction, whether fatigue might increase with time, independent of muscle strength, and whether increasing fatigue might correlate with loss of function in some patients. We measured fatigue during a single maximal voluntary contraction in a cohort of patients having spinal muscular atrophy using quantitative strength testing. We included only patients with spinal muscular atrophy aged 5 years or older, so they could follow instructions regarding muscle contraction, and who were followed for at least 2 years. Seventy-six children with spinal muscular atrophy and 24 untrained individuals, aged 5 to 57 years (mean, 16.8 years), were studied. There was no discernible abnormal fatigue in patients with spinal muscular atrophy compared to untrained controls using our methodology. Thus, spinal muscular atrophy may not be associated with fatiguability. Moreover, spinal muscular atrophy does not appear to cause progressive muscle fatigue with age or loss of function. It is possible that fatigue was undetectable by our methods. An alternative explanation is that what patients describe as fatigue may be caused by factors outside the neuromuscular system. Such factors may include chronic respiratory insufficiency with hypoventilation and carbon dioxide retention as well as chronic malnutrition and negative nitrogen balance. ( J Child Neurol 1997;12:321-326).
Somatosensory Evoked Magnetic Fields From Primary Sensorimotor Cortex in Juvenile Neuronal Ceroid Lipofuscinosis
Authors: Lauronen Leena , Heikkilä Erika , Autti Taina , Sainio Kimmo , Huttunen Juha , Aronen Hannu J. , Korvenoja Antti , Ilmoniemi Risto J. , Santavuori Pirkko
Published: December 2008

The present study evaluated neurophysiologic function of the primary sensorimotor cortex in juvenile neuronal ceroid lipofuscinosis. A 122-channel magnetometer, which allowed studies of the somatosensory system in millimeter and millisecond precision, was used to record somatosensory evoked magnetic fields to median nerve stimulation from 10 patients and their matched control subjects. In both patients and controls, the somatosensory evoked magnetic fields from primary sensorimotor area typically consisted of N20m, P35m, and P60m deflections. In the patients, N20m was significantly delayed, whereas P35m peaked earlier than in the control subjects. The source strengths for N20m and P35m were greater in the patients than in the controls. Both deflections showed a significant positive correlation with the disease duration: the sources were stronger in the older patients than in the younger ones. P60m deflections were normal or reduced in the patients. The results indicated increased thalamocortical excitability in the sensorimotor cortex in juvenile neuronal ceroid lipofuscinosis. (J Child Neurol 1997;12:355-360).
Aspartylglucosaminuria: Radiologic Course of the Disease With Histopathologic Correlation
Authors: Autti Taina , Raininko Raili , Haltia Matti , Lauronen Leena , Vanhanen Sanna-Leena , Salonen Oili , Aronen Hannu J. , Wirtavuori Kari , Santavuori Pirkko
Published: December 2008

Twelve living patients (aged 19 months to 32 years) with aspartylglucosaminuria were examined by magnetic resonance imaging (MRI), and the magnetic resonance (MR) images of 16 healthy volunteers (aged 4 to 32 years) were used as controls. One patient was examined twice. Postmortem MRI and histopathologic analysis were done on the brains of four additional adult patients. Signal intensities determined quantitatively on T2-weighted images differed significantly between patients and controls, being higher from the white matter (P < .0002) and lower from the thalami (P < .03) in the patients. The generally increased signal intensity of the white matter was most obvious in the young patients, with many focal areas of very high signal intensity in the subcortical white matter. The subcortical white matter showed a somewhat increased signal intensity even at the age of 32 years. In two of the four postmortem MR images, the distinction between the gray and white matter was still poor. At histopathologic analysis, the basic cortical cytoarchitecture was generally preserved but most neurons contained vacuoles, which were also found in the neurons of the deep gray matter. In two of the four autopsy cases the white matter showed diffuse pallor of myelin staining and some gliosis. Thus aspartylglucosaminuria is primarily a gray-matter disease also affecting white matter by delaying myelination. (J Child Neurol 1997;12:369-375).
"Joubert Syndrome" Revisited: Key Ocular Motor Signs With Magnetic Resonance Imaging Correlation
Authors: Maria Bernard L. , Hoang Karin B.N. , Tusa Ronald J. , Mancuso Anthony A. , Hamed Latif M. , Quisling Ronald G. , Hove Martin T. , Fennell Eileen B. , Booth-Jones Margaret , Ringdahl Deborah M. , Yachnis Anthony T. , Creel Gwen , Frerking Beth
Published: December 2008

Joubert syndrome is characterized by episodic hyperpnea and apnea, developmental delay, hypotonia, truncal ataxia, ophthalmologic abnormalities, and vermian dysgenesis. We studied 15 patients with the diagnosis of Joubert syndrome to (1) more fully define the syndrome's clinical features, and (2) correlate the clinical features with magnetic resonance imaging (MRI) findings. Eight of 15 patients had a history of episodic hyperpnea and apnea. All patients had developmental delay and hypotonia. Of the 13 patients receiving detailed neuro-ophthalmologic evaluations, three had optic nerve dysplasia, pendular nystagmus, and gaze-holding nystagmus. All 13 patients had a normal vestibulo-ocular reflex based on head thrust, but had absent to poor ability to cancel the vestibulo-ocular reflex horizontally and vertically. Twelve of 13 patients had impaired smooth pursuit. Twelve of 13 patients had defects in initiation of saccades and quick phases. Two of the most consistent radiologic features were absent or hypoplastic posterior cerebellar vermis, and deformed midbrain and pontomesencephalic junction, which based on ocular motor physiology correlate with the vestibulo-ocular reflex cancellation/pursuit defect and saccade initiation defect, respectively As a result of midbrain, vermian, and superior cerebellar peduncle abnormalities, axial neuroimaging showed a unique "molar tooth" appearance of these structures. These results indicate that Joubert syndrome results from maldevelopment of the midbrain and cerebellar vermis, producing a pathognomonic sign on MRI. (J Child Neurol 1997;12:423-430).
Neuromotor Functioning in Children With Tourette Syndrome With and Without Attention Deficit Hyperactivity Disorder
Authors: Schuerholz Linda J. , Cutting Laurie , Mazzocco Michele M. M. , Singer Harvey S. , Denckla Martha B.
Published: December 2008

Neuromotor function was assessed in 94 children of normal intelligence with Tourette syndrome, Tourette syndrome and attention-deficit hyperactivity disorder (ADHD), or ADHD only, using the Physical and Neurological Examination of Subtle Signs (PANESS). Time to complete six motor movements was analyzed separately by side (left and right) and complexity (simple and patterned). All groups performed faster on their preferred, dominant side. Although all groups took longer to complete patterned versus simple movements, the group with ADHD had a larger discrepancy for complexity than the other two groups. The speed for simple and patterned tasks was at or faster than age expectations for 54% of tasks in the group with Tourette syndrome but only 15% of tasks in the other two groups. More children in the group with Tourette syndrome (76%) than the groups with Tourette syndrome with ADHD (54%) or ADHD only (65%) performed movements within normal time limits for age. Findings suggest that Tourette syndrome is not associated with motor slowing. (J Child Neurol 1997; 12:438-442).
Use of the Modified Mini-Mental State Examination With Children
Authors: Besson Penny S. , Labbé Elise E.
Published: December 2008

The validity and reliability of the modified version of the Mini-Mental State Examination with children was examined. The Modified Mini-Mental State Examination was administered to 99 children between 4 and 12 years of age (45 males and 54 females) to assess expected scores for nonclinical children and with a clinical sample. Concurrent validity was assessed through correlations of Modified Mini-Mental State Examination scores with Wechsler Intelligence scores and Child Behavior Checklist scores. The Modified Mini-Mental State Examination was administered to 26 children on two occasions to determine test-retest reliability Means and standard deviations of scores are reported by age and grade level. Test-retest reliability coefficients were positively significant. For the nonclinical sample, Modified Mini-Mental State Examination scores were significantly and positively correlated with Verbal IQ and Child Behavior Checklist scores. Modified Mini-Mental State Examination scores were significantly correlated with Verbal IQ scores in the total and clinical samples. (J Child Neurol 1997;12:455-460).
Positron Emission Tomography in Children With Neurofibromatosis-1
Authors: Kaplan Allen M. , Chen Kewei , Lawson Michael A. , Wodrich David L. , Bonstelle Charles T. , Reiman Eric M.
Published: December 2008

Neurofibromatosis-1 is an autosomal dominant genetic disorder commonly associated with neuropsychological complications. Focal areas of high signal intensity on magnetic resonance imaging (MRI) scans occur commonly but have shown inconsistent correlation with neuropsychological problems. Positron emission tomography (PET) scans utilizing [18F]fluoro-2-deoxy-D-glucose and MRI studies were performed on 10 children with neurofibromatosis-1 and multiple focal areas of high signal intensity to evaluate the regional cerebral metabolic rate for glucose of these lesions and other central nervous system structures. Co-registered PET and MRI studies confirmed reduced glucose metabolism of large focal areas of high signal intensity. Visual inspection and semiquantitative analysis of PET images demonstrated thalamic hypometabolism and varying degrees of cortical inhomogeneity in all cases of neurofibromatosis-1 compared to normal controls. Although a primary defect of the thalamus or cerebral cortex has not been defined, the metabolic abnormalities of this study suggest a potential relationship between these structures and the neuropsychological dysfunctions noted in neurofibromatosis-1. (J Child Neurol 1997; 12:499-506).
Cavum Septi Pellucidi and Cavum Vergae in Normal and Developmentally Delayed Populations
Authors: Bodensteiner John B. , Schaefer G. Bradley , Craft Jennifer M.
Published: December 2008

Recent studies have shown that the persistence of the cavum septi pellucidi beyond the neonatal period is a marker of cerebral dysgenesis. It has been suggested that the finding of a persistent cavum vergae is also a marker of disturbed brain development. In order to investigate this hypothesis we reviewed 161 brain magnetic resonance imaging scans from normal individuals for the presence of cavum septi pellucidi or cavum vergae, or both. In the 34 prospectively obtained normal adults, there were no individuals with either a cavum septi pellucidi or cavum vergae. In the "defined" normal subjects 3 of 127 individuals (2.4%) had a cavum septi pellucidi whereas a cavum vergae was noted in 26 of 127 (20.5%). We next reviewed the neuroimaging studies of 249 children and adults evaluated for mental retardation or developmental delay. A cavum septi pellucidi was found in 38 of 249 (15.3%) and a cavum vergae in 48 of 249 (19.3%) of these patients. A cavum septi pellucidi and cavum vergae were found together in 19 of 249 (7.6%). We interpret these data as showing that the cavum septi pellucidi is rarely seen in normal individuals although the cavum vergae is seen with the same frequency in normal and retarded populations. Thus we conclude that the cavum septi pellucidi serves as a significant marker of cerebral dysfunction manifested by neurodevelopmental abnormalities while the cavum vergae alone does not identify individuals at risk for cognitive delays. ( J Child Neurol 1998;13:120-121).
Molecular Basis of Genetic Heterogeneity: Role of the Clinical Neurologist
Authors: Rowland Lewis P.
Published: December 2008

Advances in molecular genetics have disclosed many different explanations for allelic heterogeneity, how different clinical syndromes arise from mutations in the same gene. The converse, how similar clinical syndromes arise from mutations of different genes on different chromosomes is called locus heterogeneity. Both, however, give rise to some disease-defining mutations, as in childhood spinal muscular atrophy or Duchenne muscular dystrophy. Nevertheless, new problems have been created, including what might be called "diagnosis by the number," diverse syndromes from mutations in the same gene without current explanation, or siblings with different clinical syndromes. These discoveries have transformed the clinical neurology of heritable diseases. They also provide clinicians with new responsibilities and opportunities in defining clinical syndromes and influencing the evolution of our clinical language. ( J Child Neurol 1998;13:122-132).
Learning Disabilities With and Without Attention-Deficit Hyperactivity Disorder: Parents' and Teachers' Perspectives
Authors: Tirosh Emanuel , Berger Joseph , Cohen-Ophir Michal , Davidovitch Michael , Cohen Ayala
Published: December 2008

Our objective was to delineate the educational and behavioral differences between learning disabled children with and without attention-deficit hyperactivity disorder (ADHD). A restrospective (TROHOC) multimeasure comparative design was employed. Parents' and teachers' questionnaires (ANSER system) pertaining to attention-activity, associated behaviors, and scholastic achievements were compared. Parents' questionnaires failed to distinguish between the two groups. Teachers' questionnaires were significantly more sensitive. Significant correlations between educational achievements and attention-activity and associated behaviors scores among children with learning disabilities were evident, no such correlations were found in the group with learning disability with ADHD. The factor analysis identified different educational and behavioral aggregates with language related difficulties and externalizing behaviors more typically aggregated in the learning disabled group with ADHD and recall deficit and internalizing/neurotic behaviors in the group with learning disability only. ADHD appears to be an associated comorbidity and not necessarily a specific learning deficit. However, children with learning disability with ADHD possibly have a different underlying neurocognitive pattern than their peers with learning disabilities only. (J Child Neurol 1998;13:270-276).