Henry G. Dunn

Dandy‐Walker Syndrome: Analysis of 21 Cases

During the years 1950 to 1978, a total of 21 cases of Dandy‐Walker syndrome were seen at the Vancouver General Hospital. Apart from hydrocephalus, the associated brain anomalies included agenesis of the corpus callosum in four cases, occipital meningocele in two and aqueductal stenosis in one patient. Systemic malformations were present in four patients and included two cases of cleft palate, one of polycystic kidneys and one of congenital rubella syndrome. The over‐all mortality was 48 per cent, but has declined since 1965. Of the 12 cases treated surgically, only four have died. The number of shunt revisions was high (about two per patient). Of the 11 survivors, three have normal intelligence, four show mild mental retardation, and four are moderately to severely retarded. The differential diagnosis, clinical course and surgical therapy are discussed. It is recommended that double shunting of a lateral ventricle and of the enlarged fourth ventricle should be the primary procedure in cases associated with aqueductal stenosis or occlusion, and should be the secondary procedure in patients who exhibit recurrence of increased pressure in the posterior fossa after simple shunting of a lateral ventricle.

Cerebrospinal fluid values for monoamine metabolites, γ-aminobutyric acid, and other amino compounds in Rett syndrome

We measured concentrations of 3-methoxy-4-hydroxy-phenylglycol, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid--the metabolites of noradrenaline, dopamine, and serotonin used as central neurotransmitters--in the cerebrospinal fluid (CSF) specimens of five girls with Rett syndrome. These patients met the clinical criteria for both inclusion and exclusion of the diagnosis of Rett syndrome. In contrast to previous reports, cerebral monoamine metabolites were present in normal concentrations in CSF. In addition, concentrations of gamma-aminobutyric acid and of a large number of other amino acids and related compounds were normal in the CSF of patients with the syndrome. We doubt that an underlying biochemical cause for this disorder has yet been discovered.

Heredofamilial Brachial Plexus Neuropathy (Hereditary Neuralgic Amyotrophy with Brachial Predilection) in Childhood

Three families with a total of at least 12 members affected by heredo‐familial brachial plexus neuropathy (hereditary neuralgic amyotrophy) are described, and three affected boys (age‐range 4 to 7 years 10 months) are reported in detail. All three children had recurrent episodes of pain in the shoulders and arms, followed by weakness and wasting of affected muscles. Subsequently there was gradual recovery. All three had close‐set eyes, and affected relatives usually had a similar physiognomy. Case 1 had had an inappropriately low birthweight, and his affected mother was significantly small (154cm). The other two boys were of borderline low‐normal stature. Case 2 required plication of his left hemi‐diaphragm at the early age of seven weeks, probably because of left phrenic paralysis. He also had a cleft palate. In all three families the condition appeared to be inherited through an autosomal dominant gene.

THE PRADER‐LABHART‐WILLI SYNDROME: REVIEW OF THE LITERATURE AND REPORT OF NINE CASES

In 1956 Prader and his associates described a syndrome of obesity, small stature, acromicria and oligophrenia, regularly preceded by an amyo‐tonic state in the newborn period. The males also had a hypoplastic flat scrotum, inguinal or abdominal retention of testes and delayed puberty. A tendency to the development of diabetes mel‐litus in the teenage years was also noted, and the diabetes was of the type normally encountered with onset at maturity rather than in childhood.

Nerve Conduction Studies in Children with Friedreich's Ataxia and Ataxia‐telangiectasia

Nerve conduction was studied in nine patients with Friedreichs ataxia aged between 2 1/2 and 21 1/2 years. The younger children exhibited only progressive ataxia, depressed tendon reflexes and minimal peripheral sensory loss, whereas the older patients exhibited the more complete clinical picture with skeletal deformities, cardiomyopathy and extensor plantar responses. In all cases, electrodiagnostic studies showed normal or slightly low conduction velocity in the motor fibres of the median and lateral popliteal nerves, contrasting with marked reduction or absence of sensory action potentials in median nerves. Sensory action potentials in ulnar nerves and ascending nerve action potentials in lateral popliteal nerves were found to be similarly depressed when tested.

Acute CASi BIPOK? Encephalopathy and Status Epilepticus Associated with Human Herpes Virus 6 Infection

A previously healthy 22‐month‐old boy presented in status epilepticus with high fever. He was comatose, with upper respiratory‐tract infection. The seizures responded to anticonvulsant therapy. The boys temperature returned to normal within 24 hours and he recovered slowly from his encephalopathy. On the third hospital day, he exhibited the characteristic rash of roseola infantum. Acute infection with human herpes virus 6 (HHV‐6) was established serologically by enzyme immunoassay. HHV‐6 DNA was not detected by polymerase chain reaction in CSF or serum at the onset of illness, but was found three months later in the childs saliva. The pathogenesis of the patients encephalopathy is discussed. It is concluded that HHV‐6 infection should be considered in infants and young children with febrile status epilepticus.

Acute Hemiplegia in Kawasaki Disease and Infantile Polyarteritis Nodosa

Although aseptic meningitis, lethargy and irritability occur frequently in Kawasaki disease and infantile polyarteritis nodosa, other neurological manifestations are rare. The authors report one case of Kawasaki disease and one of infantile polyarteritis nodosa, both associated with acute hemiplegia. Both patients had received courses of oral corticosteroids for their underlying disease prior to the onset of the hemiplegia. Pathological studies, as well as the four previously reported cases, are reviewed.

Importance of Rett syndrome in child neurology.

The syndrome of brain atrophy in girls described by Andreas Rett in 1966 [Rett, Wien Klin Wochenschr, 1966;116:723-726] was brought to the attention of the English-speaking world by Hagberg et al. in 1983 [Hagberg et al., Ann Neurol, 1983;14:471-479]. Four clinical stages after the age of 6 months were described in classical cases of Rett syndrome (RS), namely early onset stagnation at 6 months to 1(1/2) years, the rapid destructive stage at 1-3 years, the pseudo-stationary stage from pre-school to school years, and the late motor deterioration stage at 15-30 or more years. The rapid destructive stage causes profound dementia with loss of speech and hand skills, stereotypic movements, ataxia, apraxia, irregular breathing with hyperventilation while awake, and frequently seizures. Most cases are isolated in their families, apart from identical twins. However, linkage studies in rare familial cases suggested a critical region at Xq28. In 1999 American investigators found several mutations in the X-linked gene MECP2 encoding Methyl-CpG-binding protein 2 in a proportion of Rett patients. The protein MeCP2 can bind methylated DNA and when mutated may interfere with transcriptional silencing of other genes and result in abnormal chromatin assembly. Many different mutations of the protein are being studied in humans and in mice. Neuropathological studies have shown decreased brain growth and decreased size of individual neurons, with thinned dendrites in some cortical layers, and abnormalities in substantia nigra, suggestive of deficient synaptogenic development, probably starting before birth. Electrophysiology demonstrates progressively abnormal electroencephalograms (EEG) in the first three stages of the syndrome, with some subsequent improvement and occurrence of pseudoseizures. Neurometabolic factors are discussed in detail, particularly reduced levels of dopamine, serotonin, noradrenaline and choline acetyltransferase (ChAT) in brain, also estimation of nerve growth factors, endorphin, substance P, glutamate and other amino acids and their receptor levels. Autonomic dysfunction is described, particularly reduced vagal and overactive sympathetic activity. Neuro-imaging may be required for further investigation, as shown in the differential diagnosis.

Congenital rubella syndrome associated with calcific epiphyseal stippling and peroxisomal dysfunction

An infant girl had the clinical and immunologic findings of congenital rubella syndrome but also had arthrogryposis multiplex and calcific epiphyseal stippling. Spastic quadriparesis developed, and both physical and behavioral development were slow. Increased spasticity of the legs at 5 1/2 years was related not to progressive rubella encephalomyelopathy but to spinal cord compression by abnormal cartilaginous tissue. The presence of a peroxisomal disorder was demonstrated by a greatly increased level of phytanic acid and slightly increased levels of hexacosanoate in serum and by reduced activity of peroxisomal dihydroxyacetone phosphate acyltransferase and a slightly increased ratio of cytosolic to peroxisomal catalase activity in cultured fibroblasts. A reduction in the number and size of peroxisomes was demonstrated in cultured fibroblasts, and a needle biopsy specimen of the liver also showed the peroxisomes to have a smaller diameter than usual. We recommend that any child with epiphyseal stippling be assessed for peroxisomal disease and that the potential for spinal cord compression by dysplastic bone or cartilage be recognized. The association of peroxisomal dysfunction with congenital rubella has not been described previously. The interaction between rubella virus infection and peroxisomal function may need further investigation.

Krabbe's leukodystrophy without globoid cells

Krabbes infantile cerebral sclerosis with a prolonged course was present in a boy who became increasingly hypertonic during infancy and had an increased protein level in the spinal fluid. At 4 years he showed significant growth failure, profound mental retardation, spastic quadriplegia, bilateral optic atrophy, and depressed tendon reflexes. Conduction velocity in motor fibers of the median nerve had become progressively impaired. Autopsy at 5 years 10 months showed severe leukodystrophy with demyelination and gliosis. No stored breakdown products or globoid cells were seen in the brain. Galactosyl ceramide beta-galactosidase was virtually absent, and hardly any myelin was demonstrable on chemical and electron microscopic studies. The presence of globoid cells may not be essential for the pathologic diagnosis of Krabbes leukodystrophy in the presence of appropriate enzyme deficiency.