Search

We report on a 4-1/2 year old girl with apparent CHARGE association who had a de novo inverted duplication (14)(q22-->24.3), iris colobomas, ventricular septal defect, soft tissue choanal atresia, intellectual impairment, growth retardation, sensorineural deafness, apparently low set ears, and upslanting palpebral fissures. Family history was unremarkable and parental chromosomes were normal. Similarities between this and previously reported cases of 14q duplication suggest that a locus for a gene or genes causing some of the anomalies of CHARGE association may reside in the region 14q22 to 24.3.

Objectives: To document the clinical and neurodevelopmental profiles of a cohort of patients with neonatal-onset propionic acidemia and to determine the efficacy of current therapy with respect to outcome., Method: The clinical, neurologic, and developmental status of six patients was prospectively evaluated during a 15-month period. Previous clinical and biochemical data were ascertained from hospital records to determine longitudinal nutritional status, number of episodes of hyperammonemia with ketoacidosis, and developmental performance with respect to age., Results: No deaths resulted from propionic acidemia since the identification of the oldest patient in the series in 1980. Therapeutic intervention (e.g., gastrostomy tube feeding) resulted in improved nutritional status and possibly contributed to improved survival. All children had hypotonia, resulting in a significant effect on motor development; however, focal neurologic deficits and evidence of movement or seizure disorder were absent. Mild cortical atrophy was evident on cranial magnetic resonance imaging in four patients. All children, including two patients with no significant episodes of hyperammonemia and normal growth since the neonatal period, had a mild to moderate degree of intellectual impairment., Conclusions: The results of our study suggest that current therapy for neonatal-onset propionic acidemia is associated with improved survival and nutritional status, and an absence of focal neurologic deficits. However, hypotonia and cognitive delay were still present, even in children with "optimal" metabolic control. Additional therapeutic advances are required to improve the developmental and cognitive outcome.

The authors evaluated 51 consecutive children with NF1 (aged eight to 16 years) to determine the frequency of intelectual impairment and learning disability due to NF1 alone, the profile of learning disabilities and the effect of clinical variables. 40 children completed the full assessment protocol. There was no support for a profile of predominantly visuoperceptual deficits in the NF1 population. There was no discrepancy between verbal and performance IQ, and the deficits in function were wide ranging. Clinical variables such as age, sex, socio-economic status, disease severity, macrocephaly and family history of NF1 were not associated with cognitive deficits. These results emphasise the need for developmental evaluation to be included in the routine assessment of children with NF1.

Haemostatis has not previously been studied in patients with neurofibromatosis 1 (NF-1), despite case reports of an association with von Willebrand disease and reported excessive bleeding in those undergoing surgery for neurofibromas. Platelets from NF-1 patients (n = 28) were tested for aggregation and ATP release with agonists including ADP, arachidonic acid, thrombin and collagen. Mepacrine staining of platelets and three different assays for von Willebrand factor (VWF) were also performed. In response to collagen as the platelet agonist, tested at both 2 and 1 micrograms/ml, NF-1 patients had an attenuated rate of aggregation (P < 0.007), aggregation lag phase (P < 0.005) and ATP release (P < 0.045), as well as requiring higher collagen concentrations to attain threshold aggregation response (P = 0.041). Normal platelets resuspended in selected NF-1 plasma exhibited significantly reduced platelet aggregation and release compared to controls, which was not corrected by mixing 1:1 with normal plasma. Collagen binding activity was reduced in NF-1 patients compared with controls (127% v 161%, P = 0.05). As a group, patients with NF-1 display defective platelet function characterized by in vitro evidence of impaired responsiveness to collagen. It is suggested that a plasma factor, present in a significant proportion of NF-1 patients, may interfere with the ability of collagen to interact with other proteins such as von Willebrand factor and the platelet collagen receptor.

Idiopathic hypothalamic dysfunction is a rare but well-defined entity in childhood characterized by adipsia-hypernatremia, obesity, poor thermoregulation, and disturbance of pituitary function. Two cases of idiopathic hypothalamic dysfunction are described. There are 10 previously reported cases in the literature, and the clinical features are compared. The present cases are unique in that the patients also had bilaterally dilated unresponsive pupils. In the first case, there was no demonstrable pathology at autopsy; in the second case, lymphocytic infiltration of the hypothalamus and midbrain associated with neuronal loss was present at autopsy. Possible etiologies are discussed.

To determine whether previously reported areas of increased T2 signal intensity on MRI examination in children with neurofibromatosis type 1 (NF 1) are associated with deficits in development and learning common in this population, we evaluated 51 children with NF 1 (aged 8 to 16 years). Forty children completed the full assessment protocol (MRI, medical, psychometric, speech therapy, and occupational therapy assessments). The mean Full Scale IQ scores for the entire study population showed a left shift compared with the normal population, and the distribution of IQ scores was bimodal, suggesting that there are two populations of patients with NF 1--those with and those without a variable degree of cognitive impairment. There was no association between lower IQ scores and any clinical variable. Areas of increased T2 signal intensity unidentified bright objects (UBO+) were present in 62.5% of the study population, and their presence was not related to clinical severity, sex, age, socioeconomic status, macrocephaly, or family history of NF 1. However, compared with children without areas of increased T2 signal intensity (UBO-), the UBO+ group had significantly lower mean values for IQ and language scores and significantly impaired visuomotor integration and coordination. Children with areas of increased T2 signal intensity were at a much higher risk for impaired academic achievement. Children without increased T2 signal on MRI (UBO-) did not significantly differ from the general population in any measure of ability or performance. Areas of increased T2 signal on MRI represent dysplastic glial proliferation and aberrant myelination in the developing brain and are associated with deficits in higher cognitive function.(ABSTRACT TRUNCATED AT 250 WORDS)

Optic gliomas occur in 15% of patients with neurofibromatosis type 1 (NF 1) and are a significant cause of morbidity. Of these tumors, 20-30% become symptomatic, usually before age 10 years. Previous studies have suggested that visual evoked potentials (VEPs) are a sensitive method for the detection of asymptomatic optic gliomas. Because routine neuroimaging of children with NF 1 is currently not recommended, the role of pattern-shift VEPs (PS VEPs) as a screening test for optic gliomas was evaluated. PS VEPs were performed on 10 children with NF 1 and optic gliomas and 20 children with NF 1 and normal visual pathways (as defined on MRI). PS VEPs had 90% sensitivity for detecting optic gliomas, with an increase in sensitivity to 100% when hemifield stimulation was used. The specificity of the test was 60%. Four of 20 children without optic gliomas had thickened optic nerves on computed tomography which represented dural ectasia with normal visual pathways on MRI; PS VEPs were normal in these patients. The efficacy of PS VEPs as a routine screen for optic gliomas is limited by the age at which children will cooperate with the test procedure and the high incidence of false-positive results; however, VEPs do provide a useful adjunct to routine clinical ophthalmologic assessment in the detection of optic gliomas in children with NF 1. Abnormal test results provide a stronger indication for neuroimaging. The early detection of optic gliomas allows for close monitoring of tumor progression and earlier intervention prior to significant visual loss.

Background: Hemiplegia is a rare manifestation of posterior cerebral artery occlusion. The acute clinical picture may be difficult to differentiate from occlusion of the middle cerebral artery. A mechanism for the hemiplegia has not been conclusively determined., Case Description: We describe a patient with hemiplegia secondary to posterior cerebral artery occlusion by an embolized fragment of a prosthetic valve. Computed tomographic scan showed the foreign body just distal to the origin of the posterior cerebral artery with infarction of its vascular territory. These findings were later confirmed at autopsy. There was no radiological or autopsy evidence of involvement of the other cerebral arteries or their territories., Conclusions: The patient provides further evidence that occlusion of the posterior cerebral artery just distal to its junction with the posterior communicating artery may produce contralateral hemiplegia without oculomotor nerve nucleus involvement.

Neurofibromatosis type 1 is a common multisystem disorder, best managed in a multidisciplinary clinic. In 1991, the first Australian neurofibromatosis clinic was established at the Children's Hospital, Camperdown, and the clinical characteristics of the first 150 families are reviewed. Two hundred individuals were assessed; there was an equal sex distribution, and 55% of cases were sporadic. Advanced paternal age appeared to predispose to new mutations in the neurofibromatosis gene. Café-au-lait spots and axillary freckling were important to the diagnosis of neurofibromatosis type 1 during childhood, and neurofibromas and Lisch nodules, although often not appearing until after puberty, were present in almost all patients over 30 years of age. Short stature (27%), macrocephaly (43%), scoliosis (20.5%), and learning disabilities (45%) were common associated features. The prevalence of disease complications was similar to the major US and European studies.

Intracranial dermoid cysts and acquired oculomotor nerve palsies are individually rare in childhood. This report describes a 4-year-old boy with acute oculomotor nerve palsy and pupillary sparing secondary to a dermoid within the lateral wall of the cavernous sinus. The clinical signs resolved after complete surgical excision of the tumor with no evidence of recurrence on computed tomography 1 year later. This is the first case report in childhood of a dermoid within the cavernous sinus and of an isolated oculomotor nerve palsy due to a dermoid cyst.

A case of brain-stem encephalitis with strong serologic evidence of acute Epstein-Barr virus infection is described. Recovery was rapid without treatment, but mild neurologic sequelae were seen at 6-month follow-up. Epstein-Barr virus infection in childhood may be asymptomatic and heterophil antibody negative. Encephalitis is an unusual but well-recognized complication of Epstein-Barr virus infection, but localized brain-stem involvement, to our knowledge, has not been previously described.

During the 4-year period, 1982-1986, 18 patients presented to the Children's Hospital, Camperdown, Sydney, with the following features: (1) Recurrent "absences" clinically indistinguishable from childhood absence epilepsy, (2) Normal clinical examination, (3) Electroencephalogram (EEG) demonstrating normal waking background and sleep activity. On hyperventilation, "absences" occurred, characterized on EEG by a marked build-up of paroxysmal slow-wave activity unassociated with evidence of epileptic activity. We designate these attacks "pseudoseizures caused by hyperventilation resembling absence epilepsy." Individual cases demonstrated a variety of other symptoms consistent with the hyperventilation syndrome. There was an identifiable environmental stress in 13 of the 18 cases. Follow-up of 13 patients after a mean period of 20 months revealed that only two children continued to have occasional absences, associated with a clear history of breathing up when upset. Treatment did not influence outcome. On repeat hyperventilation with EEG and respiratory monitoring, five of the 13 had pseudoseizures. There was no indication that susceptibility to these episodes was associated with an abnormal CO2 response. It is postulated that the occurrence of pseudoseizures is related to cerebrovascular immaturity and an excessive vasoconstrictor response to a given level of CO2.

Job analysis data are helpful in solving a wide range of rehabilitation and ergonomic problems. The ergonomic job analysis procedure for the disabled is based on a universal procedure, called AET (Arbeitswissenschaftliches Erhebungsverfahren zur Tätigkeitsanalyse). To this basic procedure a supplement for the analysis of jobs for the disabled has been developed. The idea of supplementing a basic job analysis procedure for special purposes enables us not only to compare (cluster analysis) basic data of a wide range of jobs but also to analyse groups of jobs in more detail. This paper describes structure and contents of the supplement for the disabled. Examples for application are given.

The aim of this study was to test the hypothesis that thalidomide acts upon the embryonic peripheral nervous system rather than upon mesenchyme. Pregnant rabbits were given oral thalidomide (150 mg/kg/day) on Days 7-11 of gestation. Fetuses were removed at laparotomy, under anaesthesia, on Day 29 of gestation. Seven fetuses with partial or total absence of the tibia, five treated fetuses without deformities, and four untreated controls were photographed, radiographed, killed and fixed for histological examination. Sciatic nerves were dissected and transverse sections were taken from an identical site. Total fascicular area, myelinated fibre number, fibre density and diameter distribution were obtained. There was a significant reduction in total fascicular area, and in the number of large diameter fibres in all treated animals. There was a significant depletion of total fibre numbers in deformed fetuses compared with controls. These findings are similar to the quantitative changes described in human adult subjects with thalidomide polyneuropathy, and are consistent with primary axonal degeneration in both instances. It is concluded that thalidomide acts upon embryonic nerves rather than on mesenchyme, and that dysmelic deformities of the limbs are secondary to toxic embryonic neuropathy. It is suggested that skeletal defects result when irreversible damage to the nerves reduces the transverse fascicular area below a critical minimum threshold.

During the 1970s, there was an epidemic of neonatal convulsions occurring in apparently normal babies during the fourth and fifth days of life. This syndrome was noted in France as well as in Australia. A study was undertaken to review the King George V Hospital (KGV) experience with these 'fifth day fitters'. All cases of neonatal convulsions at KGV during the years 1972-85 were reviewed. A total of 94 cases of fifth day fits occurred during this period, accounting for 57% of all neonatal convulsions occurring during 1972-79. The fits occurred in healthy term infants after an uncomplicated pregnancy. They appeared on the fourth and fifth days of life. The seizures lasted an average of 24 h, were refractory to drug therapy and, despite extensive investigation, no cause was found. The infants were assessed as normal at the time of discharge from hospital. Follow-up of these infants was incomplete. However, from the data available, it cannot be assumed to be a benign entity. The 'fifth day fit' syndrome reached epidemic proportions at a number of maternity units during the 1970s. At KGV, no case has been observed since 1982.

It has been suggested that complexes of multiple congenital malformations, involving limbs and viscera, may be caused by embryonic neural crest injury. Structures supplied by the sensory and autonomic nerves derived from the injured zone of crest would suffer defective development through presumed impairment of neurotrophic influence. Our study aimed to examine this concept by a retrospective analysis of autopsy findings in 27 babies who died of multiple congenital malformations associated with longitudinal limb defects. Sclerotome maps of the segmental sensory innervation of the skeleton were used to analyse the limb defects in terms of their nerve supply. From a review of the literature, the approximate segmental contribution of neural crest to the autonomic innervation of internal organs was ascertained, and thus "viscerotome" diagrams were constructed. Application of sclerotomes and viscerotomes to the data derived from the autopsy reports showed a neuroanatomic correlation in 89% of cases. Interpretation of multiple malformation syndromes is proposed on the basis of neurotomes, or embryonic developmental fields with common regional innervation.