A retrospective review of X-linked Charcot-Marie-Tooth disease in childhood.

OBJECTIVE: X-linked Charcot-Marie-Tooth disease (CMTX) is infrequently diagnosed in childhood, and its clinical and neurophysiologic features are not well-described. We reviewed clinical, neurophysiologic, and pathologic findings in 17 children with CMTX. METHODS: This was a retrospective review of children with CMTX from 2 tertiary pediatric hospitals. The diagnosis of CMTX was based on an identifiable connexin 32 mutation (CMTX1) or a consistent pedigree and neurophysiologic features in children without a connexin 32 mutation (CMTX-other). RESULTS: Six boys and 2 girls from 8 kindreds had CMTX1, and 8 boys and 1 girl from 5 kindreds had other forms of CMTX (CMTX-other). Fifteen children, including males and carrier females, were symptomatic from infancy or early childhood (younger than 5 years). In addition to the typical Charcot-Marie-Tooth disease clinical phenotype, some patients had delayed motor development, sensorineural hearing loss, tremor, pathologic fractures, or transient CNS disturbances. Eleven children underwent nerve conduction studies. Median nerve motor nerve conduction velocities were in the intermediate to normal range (30-54 m/s) in all children older than 2 years. Axon loss, reflected by low-amplitude compound muscle action potentials, was present in all patients. A pattern of X-linked dominant inheritance, with carrier females showing an abnormal neurologic or neurophysiologic examination, correlated with the presence of a connexin 32 mutation in all but 2 pedigrees. CONCLUSIONS: The clinical phenotype of CMTX is broader than previously reported. Onset in males and carrier females is most often in early childhood. Families with an X-linked dominant inheritance pattern are likely to have CMTX1.

Treatment of obstructive sleep apnea in achondroplasia: evaluation of sleep, breathing, and somatosensory-evoked potentials.

The occurrence of obstructive sleep apnea (OSA) is achondroplasia has been linked to brain stem compression. Overnight sleep studies (11 subjects) and somatosensory-evoked potentials (SEP's, 10 subjects) were recorded before and after conventional treatment of OSA in achondroplasia. The two groups were derived from 30 subjects who underwent diagnostic sleep studies and SEPs, including 15 females and 15 males with a median age 6.6 years (range 1.0-47.6) at the time of the first study. In 30 initial studies there was no correlation between severity of OSA and abnormalities on SEP evaluation. Treatment of 17 subjects included adenotonsillectomy (n = 3), weight loss (n = 1), and nasal-mask continuous positive airway pressure (CPAP) (n = 13). Sleep studies in 11 subjects after a delay of 8.8 +/- 2.8 months showed a reduction in respiratory disturbance index (RDI) from 38.4 +/- 6.9 to 6.5 +/- 1.8 events hr(-1) (p < 0.001) and movements/arousals fell from 10.4 +/- 2.2 to 4.8 +/- 0.2 hr(-1) (p < 0.04). Obstructive events were reduced from 33.7 +/- 6.9 to 2.4 +/- 1.0 hr(-1) (p < 0.001). Improvement of respiratory indices was associated with an increased proportion of slow-wave sleep from 25.2 +/- 4.0% to 32.3 +/- 2.4% (p = 0.01), and decrease in stage 1-2 sleep from 59.3 +/- 5.8% to 46.6 +/- 1.9% (p = 0.03). There was no increase in the percentage of REM sleep (15.2 to 21.2%). Repeat SEP studies in 10 subjects, after clinically effective treatment of OSA, showed improvement of SEP score of at least 1 grade, in 5 of 7 (71%) with initially abnormal values. We conclude that treatment of relieve upper airway obstruction improves OSA in achondroplasia, accompanied by changes in sleep structure and, in some cases, improved studies of neurological function.

ACTH treatment in intractable seizures of childhood.

Between 1980 and 1989, 21 children suffering from intractable seizures other than infantile spasms were treated with intramuscular ACTH at the Children's Hospital Camperdown. Five patients had two courses of ACTH therapy, 24% of patients had a good response (group A), 56% responded transiently (group B) and 20% did not respond (group C). Group A had normal development and no neurological deficits prior to seizures. A favourable response was not observed in patients with partial seizures, 90% of the patients who responded had a recurrence of seizures. Mean time to recurrence was 9.0 +/- 7.3 months in group A and 1.6 +/- 2.0 months in group B. Hypokalaemia, hypertension and infection were found in 42.9%, 33.3% and 19.1% respectively. ACTH also had effects on concurrent anti-epileptic drug levels.

SEPs to median nerve stimulation: normative data for paediatrics.

Somatosensory evoked potentials (SEPs) provide neurologists with an assessment of the neuraxis from peripheral nerve to sensory cortex. Their value is particularly relevant in paediatric neurology as sensory clinical examination can be difficult in young infants and children. The clinical utility of SEPs, however, requires knowledge of the alterations in wave form which occur with growth and development. This study presents normative SEP data from 4 months-35 years. Different non-linear maturational months-35 years. Different non-linear maturational patterns were seen in spinal and central segments of the nervous system. The cervical components (N12, N13) changed little in latency until 2-3 years, the N20 decreased in latency until 2-3 years and P22 decreased in latency until 6-8 years, after which latencies increased until adulthood. The greatest latency changes occurred in N12 and N13, the least in N20. Wave form morphology and interpeak latencies also changed with age. Adult morphology was achieved early (from 1 year), but central conduction time (N13-N20) reached adult values only at 6-8 years. This study provides normative values of SEPs during maturation and a functional assessment of pathways known to myelinate and mature at varying rates.

Longitudinal multimodal evoked potential studies in abetalipoproteinaemia.

Recent studies have reported that in abetalipoproteinaemia patients high dose vitamin E therapy may arrest or improve the neurological syndrome. Five patients with abetalipoproteinaemia have been followed since 1982, when all were started on high dose vitamin E therapy. Auditory brainstem responses (ABR), visual evoked potentials (VEP), and sensory evoked potentials (SEP) were recorded every six to twelve months. The vitamin E levels stayed below normal range in all patients; the neurological status remained relatively stable in most of the patients over the four years. The ABRs were consistently normal in all patients over the period of study. The VEPs improved in one patient with introduction of vitamin E therapy, and remained stable in the others, one of whom always had abnormal VEPs. The cortical SEPs were abnormal in all but the least affected patient and fluctuated in the two patients who also demonstrated some deterioration in neurological status. These results suggest that serial assessments combining neurological and neurophysiological studies provide important information in the follow-up of patients with abetalipoproteinaemia and that the SEP is the evoked potential best suited for the detection of the neurological changes in this disorder.

Somatosensory evoked potentials: Part II. A review of the clinical applications in pediatric neurology.

Fundamental to the clinical application of somatosensory evoked potentials is an understanding of the neural generators, the changes in disease states, and the effects of growth and maturation; aspects relevant to pediatric somatosensory evoked potentials were discussed previously (Part I). The importance of establishing normative data across age- and size-matched controls in the pediatric population, however, cannot be overstated. The following review of the clinical applications of somatosensory evoked potentials in pediatric neurology is based on a review of the literature and on the experience gained from over 900 studies performed in our laboratory during the last 4 years.

Somatosensory evoked potentials: Part I. A review of neural generators and special considerations in pediatrics.

Despite the recognition of evoked potentials in the late nineteenth century and the recording of somatosensory evoked potentials (SEPs) in 1947, there still is much to be learned about the origin of the SEP and its applications, particularly in the field of pediatric neurology. We summarize relevant data from the literature concerning the neural sources and present the currently accepted generators of the various peripheral, subcortical, and cortical components. The importance of factors such as growth, maturation, and the effects of sedation and sleep are discussed. The clinical applications of SEPs in pediatric neurology will be presented in Part II.