CNS aquaporin-4 autoimmunity in children.

BACKGROUND: In adult patients, autoantibodies targeting the water channel aquaporin-4 (AQP4) are a biomarker for a spectrum of CNS inflammatory demyelinating disorders with predilection for optic nerves and spinal cord (neuromyelitis optica [NMO]). Here we describe the neurologic, serologic, and radiographic findings associated with CNS AQP4 autoimmunity in childhood. METHODS: A total of 88 consecutive seropositive children were identified through service evaluation for NMO-IgG. Sera of 75 were tested for coexisting autoantibodies. Clinical information was available for 58. RESULTS: Forty-two patients (73%) were non-Caucasian, and 20 (34%) had African ethnicity. Median age at symptom onset was 12 years (range 4-18). Fifty-seven (98%) had attacks of either optic neuritis (n = 48; 83%) or transverse myelitis (n = 45; 78%), or both. Twenty-six (45%) had episodic cerebral symptoms (encephalopathy, ophthalmoparesis, ataxia, seizures, intractable vomiting, or hiccups). Thirty-eight (68%) had brain MRI abnormalities, predominantly involving periventricular areas (in descending order of frequency): the medulla, supratentorial and infratentorial white matter, midbrain, cerebellum, thalamus, and hypothalamus. Additional autoantibodies were detected in 57 of 75 patients (76%), and 16 of 38 (42%) had a coexisting autoimmune disorder recorded (systemic lupus erythematosus, Sjögren syndrome, juvenile rheumatoid arthritis, Graves disease). Attacks were recurrent in 54 patients (93%; median follow-up, 12 months). Forty-three of 48 patients (90%) had residual disability: 26 (54%) visual impairment and 21 (44%) motor deficits (median Expanded Disability Status Scale 4.0 at 12 months). CONCLUSIONS: Aquaporin-4 autoimmunity is a distinctive recurrent and widespread inflammatory CNS disease in children.

Contrasting effects of IFNbeta and IVIG in children with central and peripheral demyelination.

Reported are three children with MS who responded dramatically to interferon-beta (IFNbeta) therapy. While on immunomodulatory therapy, they developed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) that responded to IV immunoglobulin (IVIG) administration. These cases emphasize two interesting observations: 1) IFNbeta treatment did not prevent development of CIDP; 2) CIDP in the context of MS responded to IVIG, even though IVIG had no therapeutic effect on the central demyelinating disease.

Newborn hearing screening in Hawaii.

Hawaii has been a pioneer and national leader in implementing universal newborn hearing screening. In fact, Hawaii is one of only two states (Rhode Island is the other) which have a statewide newborn hearing screening program in which 95% or more of all newborns are screened. Hawaii is the best example of a truly integrated system of services to provide effective intervention for all infants and toddlers who are identified as having a hearing loss. The success of the newborn hearing screening program is measurable in two ways: 1) all available information indicates that not a single infant with hearing loss has been missed by the screening process and not a single infant has been misdiagnosed as having a hearing loss; and 2) many of the children identified with hearing loss by the newborn hearing screening program have transitioned out of the early intervention program with age-appropriate developmental and communication skills. The success of Hawaii's program is a tribute to the enthusiastic support and collaboration of legislators, pediatricians, hospital staff, and DOH personnel.

The electrophysiologic profile of Dejerine-Sottas disease (HMSN III).

Electrophysiologic studies in 11 patients with Dejerine-Sottas disease (hereditary motor and sensory neuropathy type III, HMSN III) showed median and ulnar motor nerve conduction velocities less than 6 m/sec in all but 1 patient. Marked temporal dispersion without conduction block was present in all patients. Uniform slowing in adjacent motor nerves was consistent with other studies of inherited neuropathies, although marked temporal dispersion may make HMSN III more difficult to distinguish from acquired neuropathies than other hereditary conditions. The electrophysiologic features of HMSN III patients were significantly different from a series of patients with other hereditary neuropathies chosen because of very slow nerve conduction velocity.

Nerve conduction studies in infants and children.

The electrophysiologic evaluation of peripheral nerves may provide critically important information, both with respect to diagnosis and prognosis, in the child with a suspected neuromuscular disorder. However, special attention to various technical considerations is necessary to avoid misleading results. Utilizing these techniques, both hereditary and acquired neuropathies may be identified and characterized. The latter has become especially important in view of recent advances in the treatment of acquired demyelinating neuropathies.

Chronic idiopathic anhidrosis.

We describe the cases of eight patients with chronic idiopathic anhidrosis. These patients were heat intolerant and became hot, flushed, dizzy, dyspneic, and weak but did not sweat when the ambient temperature was high or when they exercised. Four patients had preganglionic sudomotor lesions and in the remaining 4 the lesion appeared to be postganglionic. The patients did not have orthostatic hypotension, other evidence of generalized autonomic failure, or symptomatic somatic neuropathy. One patient regained thermoregulatory sweat function and no patient's condition progressed to generalized autonomic failure. Chronic idiopathic anhidrosis appears to be distinctly different from other autonomic neuropathies that tend to carry much poorer prognoses.

Tuberous sclerosis, early onset of seizures, and mental subnormality: study of discordant homozygous twins.

In two sets of male homozygous twins with tuberous sclerosis, one twin in each set suffered frequent generalized seizures from early life, and the second either had no seizures or had only short-lived seizures. One twin of each pair is of normal intelligence, and the other is mentally subnormal. We propose that generalized seizures occurring in early life are an important mechanism in an apparently progressive dementing process in some infants and children with tuberous sclerosis. If our assumption is correct, an early attempt to control generalized seizures in these patients is indicated even in the presence of the cortical, subcortical, and subependymal pathologic changes characteristic of cerebral tuberous sclerosis.