Journal of Child Neurology

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).

The purpose of this review is to analyze the clinical applications of a remarkable series of advances made in molecular genetics, primarily with regard to Becker muscular dystrophy. A new classification is required to clarify such syndromes as Duchenne and Becker muscular dystrophy. Dystrophinopathies can be seen in patients with early onset and a severe course (Duchenne muscular dystrophy), patients with later onset and milder weakness (Becker muscular dystrophy), patients with myalgia and cramp syndrome, and patients with dilated cardiomyopathies. Dystrophin testing in muscle is the most sensitive test for identification of dystrophinopathy patients, although gene deletion studies can make the diagnosis in most cases. (J Child Neurol 1996;11:13-20).

We present 12 cases of males with myalgia and cramps and a normal muscle strength examination. All the patients had muscle dystrophin values consistent with Becker muscular dystrophy. Five of the patients had a normal electromyogram, and five had normal light microscopic muscle biopsy results. Of particular note, four of the 12 patients had normal serum creatine kinase levels, and four others had only mild elevations (less than twice the upper limit of normal). These patients establish an identifiable dystrophinopathy of adolescent boys and young men that can present with muscle pain and, in some cases, normal routine laboratory evaluations. (J Child Neurol 1996;11:21-24).

We studied a cohort of 73 children exposed to cocaine in utero to characterize the spectrum of neurologic and ophthalmologic abnormalities; 36 children with no documented in utero drug exposure were selected as a control group. Most referrals of cocaine-exposed children to the child neurologist were made in the 1st year of life (81%). Reasons for referral were hypertonia (29%), seizures (22%), developmental delay (11%), tremulousness (11%), and hypotonia (4%). The most common abnormal finding in the cocaine-exposed children was hypertonia/hyperreflexia (63%), which was rarely seen in the control group. In addition, hypertonia/hyperreflexia was underdiagnosed by referring physicians. Similarly, hypotonia was seen on neurologic examination of cocaine-exposed children more frequently than documented by referral (16% versus 4%). Hypotonia was rarely seen in the control group. Twelve (43%) of 28 cocaine-exposed children seen by a pediatric ophthalmologist had structural ophthalmologic abnormalities. Neurologic and ophthalmologic findings suggesting structural lesions of the nervous system must be considered in cocaine-exposed children. (J Child Neurol 1996;11:25-30).

Infantile spasms and the Lennox-Gastaut syndrome are considered to be age-specific pediatric epileptic syndromes and together constitute a significant percentage of medically resistant seizures in childhood. Twenty children, ages 4 to 28 months (median, 12 months), with medically refractory infantile spasms or the Lennox-Gastaut syndrome, were treated with the investigational benzodiazepine nitrazepam in an open-label study. Daily dosage of nitrazepam ranged from 0.5 to 3.5 mg/kg, with a median dosage of 1.5 mg/kg, divided into two doses per day. Side effects included pooling of oral secretions (12 children) and sedation (six children); however, no serious side effects were seen. Responses to nitrazepam were as follows: five complete responses (cessation of all seizures), seven partial responses (greater than 50% reduction of seizures), and eight with no response. Median duration of response was 9 months (range, 4 to 16 months) in children with infantile spasms and 14 months (range, 8 to 26 months) in children with the Lennox-Gastaut syndrome. Nitrazepam is an effective anticonvulsant in this small cohort of children with medically refractory infantile spasms and the Lennox-Gastaut syndrome, resulting in a 25% response rate and only modest side effects. (J Child Neurol 1996;11:31-34).

A new combination therapy, high-dose pyridoxal phosphate (40 to 50 mg/kg daily) and low-dose corticotropin (0.01 mg [0.4 IU]/kg daily), was tried in 28 children with infantile spasms. Monotherapy with pyridoxal phosphate provided excellent seizure control in three (11%) of the 28 subjects. Corticotropin was subsequently added to the regimen of the remaining 25 patients. At 1 month after discontinuing corticotropin, 21 (84%) of the 25 patients experienced no seizures, and 22 (88%) of the 25 showed improvement in their electroencephalographic findings. The mean interval until achievement of seizure control was 4.1 days after the initiation of corticotropin. The outcome in the 21 patients has been followed for a mean period of 34.9 months (range, 2 to 81 months). Of these 21 patients, six (29%) have had relapses of infantile spasms, and 10 (48%) have experienced normal development. Transient increases in liver enzymes occurred in 14 (50%) of the 28 patients, but none of the patients developed more serious side effects. The investigators conclude that combination therapy with high-dose pyridoxal phosphate and low-dose corticotropin is a promising new therapy. (J Child Neurol 1996;11:35-40).

Using a single-patient (n = 1) clinical trial, we studied a 7-year-old boy who presented with unsatisfactory progress in school and whose electroencephalogram had very active independent frontal spike discharges. He had not had clinical seizures. The patient was randomized to receive valproic acid, 125 mg twice daily, (four periods) or matching placebo (four periods) over 8 weeks. Primary endpoints were the Wechsler Intelligence Scale for Children-Revised Coding subtest and a handwriting sample. Behavior was monitored using teacher's and parent's Conners questionnaires. His score on the Wechsler Intelligence Scale for Children-Revised Coding subtest was significantly improved while he was taking valproic acid (P = .03). His electroencephalogram improved from a pretreatment recording of 28 spike discharges per minute to a normal recording while on valproic acid. We conclude that in this patient, valproic acid had a cognitive enhancing effect, probably by reducing epileptiform discharges. (J Child Neurol 1996;11:41-43).

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).

We have studied the neurodevelopmental outcome of 104 consecutive unselected children who underwent open-heart surgery from 1987 through 1989. Survivors had formal neurologic and psychometric examinations after 2 years of age. Mean IQ was 90, and 78% had scores above 70. Cerebral palsy occurred in 22%. Deep hypothermia for longer than 45 minutes was associated with IQ less than 85 (P < .001) and later cerebral palsy (P = .02). Those less than 1 month old at operation had a median IQ of 96, and 25% had cerebral palsy. Median IQ for survivors of hypoplastic left heart syndrome was 66, only one had an IQ above 70, and 57% had cerebral palsy. Median IQ for transposition of great arteries was 109, only one was less than 85, and all had normal neurologic examinations. Those between 1 and 6 months of age at operation had a median IQ of 93, with 64% above 85, and 5% had cerebral palsy. Those older than 6 months had a median IQ of 99, with 70% above 85, and 13% had cerebral palsy. For infants less than 1 month old at operation, a strong association existed between outcome, type of lesion, and duration of deep hypothermia (P < .01), although not in all cases. In those older than 1 month at operation, no association existed between outcome and any study variable. Although the majority of children have an uneventful outcome after open-heart surgery, a significant morbidity exists. This is related to several factors, including type of lesion and duration of hypothermia, particularly in neonates; preoperative congenital and acquired lesions; and possible perioperative cerebrovascular events. (J Child Neurol 1996;11:49-53).

An 8-year-old girl and her 4-year-old sister presented with psychomotor retardation during the 1st year of life. This was fol lowed by spasticity, seizures, and in the older patient, progressive loss of faculties and death. Computed tomographic and magnetic resonance imaging scans demonstrated progressive cerebral atrophy in both patients. Postmortem examination in the older sibling showed diffuse atrophy of the supragranular layers of the cerebral cortex, atrophy and gliosis of the white matter, and accumulation of numerous amylaceous (polyglucosan) bodies within the cytoplasm of cell processes. The inclusions were closely associated with atrophy of the parenchyma. The findings suggest that this disorder is different from other childhood diseases in which amylaceous bodies accumulate within the brain. (J Child Neurol 1996;11:58-62).

Twenty-four children with Williams syndrome underwent systematic neurologic evaluations. Abnormalities of mental status, motor coordination, tone, and gait were most prevalent. Tone abnormalities varied as a function of age, with younger children frequently exhibiting decreased tone and older subjects almost exclusively having increased tone. The gait and coordination abnormalities persisted among older subjects, indicating that they were not simply maturational problems. Physicians caring for such youngsters need to be aware that a variety of neurologic abnormalities are common in Williams syndrome and may change or progress over time. Neurologic examinations that reveal findings beyond the typical pattern that we report may raise suspicion for added neurologic insult and warrant further investigation. (J Child Neurol 1995;10:63-65).

We conducted a representative survey to obtain current information about attitudes of pediatricians, child neurologists, and pediatric surgeons in Hungary regarding Down syndrome. The findings are compared to those of a similar study from Canada. In the treatment of mentally handicapped newborns, none of the Hungarian doctors would choose active euthanasia; only a few percent would perform passive euthanasia. Hungarian doctors give priority to the hospital-based ethical committee in the decision-making process regarding the treatment versus nontreatment of a newborn with major congenital anomalies. In contrast to the Canadians, only a few doctors would discuss this question with parents and nurses. Most Hungarian physicians are not aware of legal regulations in this field. These attitudes can be explained by religious and cultural traditions different from the Canadian and Western European standards. The Hungarian medical community, like other Eastern European countries, is much more authoritative than the Canadian system. Furthermore, the appropriate legal regulations are not yet properly codified. (J Child Neurol 1996;11:66-70).