Steroid-responsive neurologic relapses in a child with a proteolipid protein-1 mutation.

A 10-year-old boy developed corticosteroid-responsive relapsing neurologic signs, including nystagmus and ataxia. MRI revealed multifocal T2 white matter hyperintensities; several were gadolinium-enhancing. CSF contained oligoclonal bands. Although the patient met criteria for multiple sclerosis (MS), the proteolipid protein-1 gene (PLP1) contained a mutation in exon 3B (c.409C>T), predicting a tryptophan-for-arginine substitution. This case raises questions about the role of inflammation in PLP1-related disorders and, conversely, PLP1 mutations in MS.

Reliability and validity of a DSM-IV based ADHD screener.

The Diagnostic Rating Scale (DRS) was completed by the parents and teachers of 82 children referred for clinical evaluations, 73 referred children seen twice, and 218 non-referred children from the community. The DRS, which uses a categorical rather than a dimensional rating approach, was 70% to 90% sensitive to diagnoses of Attention Deficit/Hyperactivity Disorder (ADHD) made by blind clinical teams. In research and clinical applications, the DRS could improve screening efficiency, especially in situations where it would be desirable to exclude all children who might have ADHD or identify all children with Hyperactive-Impulsive symptoms. Because of its objectivity and consistency with the Diagnostic and Statistical Manual (DSM)-IV criteria, the DRS could facilitate comparison of participant samples across studies.

Neurobehavioral profiles of children with neurofibromatosis 1 referred for learning disabilities are sex-specific.

We compared neurobehavioral profiles of 10 children with neurofibromatosis 1 (NF-1) referred for evaluation of learning disabilities (NF/LD) to those to learning disabled children without known genetic disease (LD), matched for age, sex, and estimated IQ. It was hypothesized that the NF/LD children would exhibit a neurobehavioral profile diagnostic of compromise of frontal/subcortical brain systems while those of the case controls would be heterogeneous. Records from a clinical data base were reviewed retrospectively for the neurological and neuropsychological components of an interdisciplinary learning disabilities evaluation. Neurological abnormalities were more frequent in the NF/LD group, involving gross and fine motor coordination, praxis, and megencephaly. As predicted, clinical neuropsychological diagnostic ratings and composite neurobehavioral observation scores were consistent with compromise of frontal systems in the NF/LD group. An unanticipated finding was that outcomes in the NF/LD group were sex dependent: Megencephaly was observed in females only; and the frontal/subcortical neurobehavioral profile was more consistently observed in females. Females with NF-1 with megencephaly may be at increased risk for a neurobehavioral syndrome contributing to LD that is consistent with compromise of frontal/subcortical brain systems.

Cerebral edema in acute hepatic failure: clinicopathologic correlation.

A child developed acute fulminant viral hepatitis and cerebral edema confirmed on postmortem examination. Clinical evidence of herniation, effacement of cortical sulci on computed tomography, and elevated cerebrospinal fluid pressure preceded complicating terminal events, demonstrated that cerebral edema was associated with acute hepatic failure, rather than complicating factors, and led to the patient's death. The mechanism is unknown.

Regional cerebral perfusion in Landau-Kleffner syndrome and related childhood aphasias.

Assessment of cerebral perfusion may elucidate pathogenesis of Landau-Kleffner syndrome (LKS). We obtained 99mTc-HMPAO SPECT studies in five children with LKS and in three children with syndromes of verbal-auditory agnosia. In LKS, perfusion showed temporoparietal asymmetry (9.56% +/- 3.44%) (n = 4) or bilateral parietal abnormality (n = 1). SPECT in non-LKS patients was normal (n = 1), showed (n = 1) totihemispheral hypoperfusion accompanying structural abnormality or (n = 1) a pattern resembling but distinct from LKS. Seizures in LKS patients had never occurred (n = 1), were controlled satisfactorily (n = 2), or poorly (n = 2). Maximum EEG abnormality was left centrotemoral-occipital (n = 1), left frontocentral (n = 1), bitemporal/left central (n = 1), and left central/parasagittal (n = 1). Asymmetric temporoparietal perfusion appears characteristic of LKS, differing from findings in other childhood linguistic disturbances. This abnormality occurs across a spectrum of seizure expression, diverging from the distribution of EEG abnormalities. The SPECT abnormalities parallel PET-defined LKS metabolic abnormalities, and may indicate central pathogenetic features of the disorder.

Juvenile fire setting and the photoparoxysmal response.

We report on 3 boys with fire setting, photoparoxysmal responses to intermittent photic stimulation, and temporal lobe electroencephalographic abnormalities. Fire setting resolved and behavior improved with administration of anticonvulsants.

Pre-eruptive varicella encephalitis and cerebellar ataxia.

Varicella-related neurologic symptoms usually appear during or following the exanthem. Pre-eruptive neurologic manifestations are extremely rare. We report a 6-year-old boy who developed encephalitis, characterized by drowsiness and left-sided hyperactive deep tendon reflexes and cerebellar ataxia, both of which antedated the exanthem by 16 days. The diagnostic and public health implications are discussed.

Late effects of central nervous system treatment of acute lymphoblastic leukemia in childhood are sex-dependent.

The authors measured the cognitive function and physical growth of 51 children who had been treated for acute lymphoblastic leukemia with chemotherapy, cranial irradiation and intrathecal methotrexate, and who had remained disease-free for five to 12 years. A comparison group of 15 children treated for Wilms' tumor was also studied. Cognitive impairment and growth retardation were greater among the leukemia group. Of potentially greater significance, however, was the finding that female sex was the pre-eminent risk factor for central nervous system toxicity resulting from treatment. Cognitive impairment, short stature and excessive weight were all more prevalent among females than males. Approximately half the children were microcephalic, but there was no sex difference. Age at evaluation and diagnosis, as well as socio-economic status, were differentially related to outcomes for the two sexes. The authors believe the sex differences were indicative of a fundamental interaction between postnatal neural development and other biological processes.

Sex differences in cognitive processing in children treated with CNS prophylaxis for acute lymphoblastic leukemia.

Evaluated cognitive processing in 51 children (27 female, 24 male) who had been treated for acute lymphoblastic leukemia (ALL) with CNS prophylaxis (cranial radiation in combination with intrathecal chemotherapy) and were continuously disease-free for 5 to 12 years. The control group comprised 15 children treated for Wilm's tumor. Functions assessed included visuoperceptual skills, generation of organizational strategies, sensitivity to organizational structure, and attention. The ALL group showed performance deficits relative to the solid tumor controls in appreciating the organization inherent in complex visuospatial material and alertness, with females more severely affected than males. Sex differences favoring males on IQ and academic achievement were related to these cognitive processes.

Nondextrality and autoimmune disorders among relatives of language-disabled boys.

The incidences of autoimmune diseases, nonrighthandedness, and premature graying of the hair have been said to be increased among the relatives of dyslexic persons. I undertook a prospective evaluation of the relatives of 100 language-disabled boys seen in a tertiary hospital learning disabilities clinic. I established the incidence of these characteristics and compared the results with those obtained from the relatives of 100 boys referred to a neurology clinic for evaluation of seizures or muscle disease. The families of the language-disabled boys were divisible into two groups, one with an increased incidence of these characteristics and one with a decreased incidence as compared with the control group. This suggests a biological heterogeneity among these families, despite a similar phenotype among all the language-disabled probands.

Deep tendon reflexes in premature infants.

Ten classic deep tendon reflexes (DTRs) were evaluated in 62 premature infants of greater than 27 weeks post-conceptional age. The pectoralis major was the most readily elicitable reflex in all infants (100%), regardless of maturity. Achilles, patellar, biceps, thigh adductors, and brachioradialis reflexes also were obtained in at least 98% of babies of greater than 33 weeks gestation. Among these reflexes, less mature infants (less than 33 weeks gestation) had decreased elicitation rates for patellar and biceps reflexes and overall had diminished reflex intensity when compared to older infants (33-36 weeks gestation). By order of decreasing rate, finger flexors, jaw, crossed adductors, and triceps reflexes were less frequently elicited in both groups. Equal DTRs were obtained often in healthy and previously ill infants of less than 33 weeks gestation. Head position had no apparent affect on the ability to elicit reflexes. Theophylline therapy tended to intensify the Achilles reflex and the quiet, wakeful state appeared to be the most optimal state for the elicitation of DTRs.

Factors influencing the vitreous potassium concentration in the rat.

The vitreous of the intact eye of the rate was perfused with artificial medium to study factors that influence the vitreous potassium concentration. The vitreous potassium concentration in anesthetized rats was 5.07 mM. Perfusion with media containing higher or lower potassium concentrations led to passive diffusion of potassium out of or into the vitreous, respectively. Ouabain caused a release of potassium from the retina into the vitreous. Photic stimulation reduced the vitreous potassium concentration, presumably as a result of neuronal hyperpolarization. Glutamate raised and glycine lowered the vitreous potassium concentration, effects that also may be related to retinal depolarization and hyperpolarization, respectively.