Aplastic anemia following therapy for absence seizures with ethosuximide.

We describe a case of aplastic anemia in an 8-year-old girl which was diagnosed 8 months after initiation of ethosuximide as treatment for absence seizures. Blood counts had been previously monitored and were normal. The patient successfully underwent allogeneic bone marrow transplantation. Only 8 cases of ethosuximide-associated aplastic anemia have been reported, and in only one of these reports, was ethosuximide used as a single antiepileptic agent. This rare, but potentially fatal complication of ethosuximide raises the question of whether routine monitoring of blood counts during ethosuximide therapy is useful and should be undertaken.

The persistent vegetative state in children: report of the Child Neurology Society Ethics Committee.

Increasing concern about children in a persistent vegetative state (PVS) prompted a survey of members of the Child Neurology Society regarding aspects of the diagnosis and management of this disorder. Major findings of those responding to this survey (26% response rate) were as follows: (1) 93% believed that a diagnosis of PVS can be made in children, but only 16% believed that this applied to infants younger than 2 months and 70% in the 2-month to 2-year group; (2) a period of 3 to 6 months was believed to be the minimum observation period required before a diagnosis of PVS could be made; (3) 86% believed that the age of the patient would affect the duration of time needed to make the diagnosis of PVS; (4) 78% thought a diagnosis of PVS could be made in children with severe congenital brain malformations; (5) 75% believed that neurodiagnostic studies would be of value and supportive of the clinical diagnosis of PVS; (6) members' opinions as to the average life expectancy (in years) for the following age groups after the patients were considered vegetative were: newborn to 2 months, 4.1; 2 months to 2 years, 5.5; 2 to 7 years, 7.3; and more than 7 years, 7.4; (7) 20% believed that infants and children in a PVS experience pain and suffering; and (8) 75% "never" withhold fluid and nutrition from infants and children in a PVS and 28% "always" give medication for pain and suffering.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated CSF beta-endorphin immunoreactivity in Rett's syndrome: report of 158 cases and comparison with leukemic children.

Because some symptoms of Rett's syndrome are suggestive of excessive endogenous opioid activity, we measured the levels of beta-endorphin-like immunoreactivity in lumbar CSF from 158 affected female patients and from 13 female controls. The mean (+/- SE) control level of beta-endorphin immunoreactivity in CSF was 35.3 +/- 2.8 pg/ml (range, 23 to 48 pg/ml), whereas those with Rett's syndrome had a mean level of 95.3 +/- 3.6 pg/ml (range, 31 to 293 pg/ml). The levels of beta-endorphin immunoreactivity in initial CSF samples exceeded the control range in 90% of the patients with Rett's syndrome. The mean beta-endorphin immunoreactivity was also elevated in CSF from leukemic children (119.2 +/- 16.9 pg/ml; range, 40 to 159 pg/ml), relative to the control group. These results are consistent with the hypothesis that some symptoms of Rett's syndrome may be associated with excessive endogenous opioid levels in the CNS.

Brain lesions in chronic granulomatous disease.

In chronic granulomatous disease (CGD) enzyme-deficient neutrophils and mononuclear cells lack the respiratory burst required for biocidal activity. Recurrent infections lead to granulomas in various organs but brain lesions are rare. In the present case, a 23-year-old male with numerous infections since early childhood died of overwhelming pulmonary aspergillosis. He first began to experience neurological deficits at the age of 17. Computerized tomography and magnetic resonance imaging revealed fleeting white matter lesions that were interpreted as multiple sclerosis (MS). At post mortem, three types of brain lesions were found: (1) Pigmented macrophages in perivascular spaces and the leptomeninges similar to those reported previously. They contained fine, golden-brown, lipofuscin-like material whose chemical composition included a sulfur peak by X-ray analysis. (2) Focal, well-demarcated, "burnt out" white matter lesions with loss of both myelin and axons and intense sclerosis. (3) Diffuse areas of mild pallor in the centrum ovale which spared the U fibers. The pigmented macrophages are characteristic of those seen in the periphery in CGD. The origin of the discrete, destructive white matter lesions is unclear. They may have resulted from: (i) earlier activity by CGD macrophages; (ii) previous infections due to sepsis or embolism; or (iii) possibly post-infectious encephalomyelitis. The more diffuse, mild, white matter lesions are attributed to edema. Evidence for MS, progressive multifocal leukoencephalopathy, or human immunodeficiency virus encephalitis was lacking. This case is presented to alert us to look more carefully for brain lesions in CGD, characterize them and to help determine their cause.

Naltrexone therapy of apnea in children with elevated cerebrospinal fluid beta-endorphin.

Previous studies have indicated increased immunoreactivity of the endogenous opioid peptide beta-endorphin in the cerebrospinal fluid (CSF) of infants under 2 years of age with apnea. To assess the role of endogenous opioids in the pathogenesis of apnea in children, the effect of oral treatment with the opioid antagonist naltrexone was studied in apneic infants, as well as in older apneic children, with demonstrated increases in CSF immunoreactive beta-endorphin (i-BE). In the 8 apneic infants with elevated i-BE in lumbar CSF (range, 55-155 pg/ml; normal, 17-52 pg/ml), no further apnea occurred during naltrexone therapy (1 mg/kg/day, by mouth). Five children (2-8 years old) with apnea of unknown cause had elevated CSF i-BE (range, 74-276 pg/ml) compared to 6 age-matched nonapneic children (range, 15-48 pg/ml). No apneic events occurred during naltrexone therapy, except in 1 child during stressful events, but apnea recurred in some patients after attempts to discontinue naltrexone treatment. Adverse effects of naltrexone included complaints of headaches in 2 children and symptoms of a narcotic withdrawal syndrome during the first 3 days of treatment in 1 child. Three children with Leigh's syndrome had elevated CSF i-BE (range, 104-291 pg/ml) and their apnea also responded to naltrexone. We conclude that elevated endogenous opioids contribute to the pathogenesis of apnea in children and may even result in physical dependence.

Cerebrospinal fluid studies in the Rett syndrome: biogenic amines and beta-endorphins.

The etiology of the Rett syndrome (RS) is unknown. Reduced function of biogenic amines has been described. Symptoms of central apnea, hyperventilation, hypothermia, peripheral analgesia, muscle rigidity, myoclonic jerks, hand stereotypy and seizures occur in RS and have been suggested as a result of elevated central beta-endorphins. It was hypothesized that a dysfunctional modulation of endogenous opiate systems and biogenic amines may be present. Cerebrospinal fluid (CSF) from 12 girls with RS was studied for beta-endorphin immunoreactivity, and biogenic amines. Lactates and pyruvate levels were measured. Eleven of the 12 girls had elevated beta-endorphin immunoreactivity in CSF, 4 girls had reduced biogenic amines and 6 girls had elevated pyruvate and lactate levels. Whether the elevated beta-endorphin immunoreactivity is a primary disorder or is a result of secondary feedback mechanisms is unknown. Naltrexone, an antiopioid drug, may reduce symptoms.

Possible hyperendorphinergic pathophysiology of the Rett syndrome.

The Rett syndrome is a postnatal developmental and neurological disorder seen only in girls. Many of the symptoms of this disorder, such as microcephaly, stereotypy, respiratory disturbances and seizures, are analogous to the effects of the administration of beta-endorphin or other opioids in animals. Preliminary reports of elevated beta-endorphin-like immunoreactivity in the cerebrospinal fluid of girls with the Rett syndrome, as well as improvement in some of their symptoms during the administration of the opioid antagonist naltrexone, are suggestive of endorphinergic hyperactivity. Thus, the pathophysiology of the Rett syndrome might involve excessive stimulation of opioid receptors in the central nervous system by beta-endorphin or other endogenous opioids.

Increased cerebrospinal fluid beta-endorphin immunoreactivity in infants with apnea and in siblings of victims of sudden infant death syndrome.

To gain further insight into the possible role of endogenous opioid peptides in the respiratory difficulties associated with the apnea of infancy and other disorders possibly related to apnea, the levels of beta-endorphin immunoreactivity were measured in the cerebrospinal fluid (CSF) of five groups of infants: (1) infants with proved apnea, (2) infants with histories of an apparent life-threatening event (ALTE), (3) siblings of victims of the sudden infant death syndrome (SIDS), (4) infants with suspected but unproved apnea, and (5) infants undergoing investigation for other acute illnesses. Twenty-two infants considered at risk for an ALTE (groups 1 to 3) had significantly higher CSF beta-endorphin equivalents (88 +/- 7 pg/mL) than did the 22 control patients in groups 4 and 5 (31 +/- 3 pg/mL). Plasma beta-endorphin immunoreactivity, which was also measured in some of the infants, did not correlate with levels in CSF and, in fact, was significantly lower in the groups at risk for an ALTE (50 +/- 9 pg/mL; n = 14) than in the control subjects (80 +/- 6 pg/mL; n = 11). These studies indicate that elevated beta-endorphin immunoreactivity in CSF may be a marker in infants who have apnea and who may be considered at risk for an ALTE.

Tolusa-Hunt syndrome: resolution of a 12-year course after tonsillectomy.

The authors review the symptoms, physical findings, possible causes, and treatment of Tolusa-Hunt syndrome (THS). The authors present a patient with THS and tonsillitis. The symptoms, except for blindness, were alleviated after tonsillectomy. Anatomical relationships of the tonsils to the cavernous sinus are demonstrated and tonsillitis as a possible trigger mechanism of THS is suggested.

The early evaluation of survivors after extracorporeal membrane oxygenation for neonatal pulmonary failure.

Excluding mortality data, there is little information regarding patients' development after extra corporeal membrane oxygenation (ECMO). In six of nine neonates surviving ECMO for predictably fatal pulmonary failure, examination 15 to 21 months afterward showed (1) physical growth and development, normal in six; (2) chest x-ray, normal pulmonary parenchyma; (3) average arterial blood gases, PO2 80, Pco2 35, pH 7.35; (4) echocardiogram, normal, without evidence of pulmonary hypertension; (5) cerebrovascular dopplers, normal ophthalmic artery flow in five patients, retrograde in one; (6) CT scan, EEG, neurologic survey, normal in five, cerebral atrophy in one patient who had an air embolus during decannulation; (7) psychologic examination, normal in all. This early evaluation of ECMO survivors should encourage its further application in those newborns who would otherwise die.

Parainfectious optic neuritis. Report and review following varicella.

Severe loss of vision and bilateral optic disc edema occurred in a 10-year-old girl 38 days after the rash of varicella first appeared and subsequent encephalitis developed. Recovery of visual function was nearly complete, but optic atrophy persisted. Parainfectious optic neuritis following other viral infections, with the exception of herpes zoster, has a similar clinical profile: delayed onset, severe visual loss, optic disc edema, bilaterality, good recovery, and residual optic atrophy. Conduction delays in our patient's patterned visual evoked potentials implicated demyelination within the optic nerves. The often favorable recovery, frequency of delayed onset, and bilateral involvement of the optic nerves support an autoimmune process in the pathogenesis of parainfectious optic neuritis.

Morphology and distribution of cytoplasmic inclusions in adrenoleukodystrophy.

We report some additional observations on the pathognomonic cytoplasmic inclusions in a typical case of adrenoleukodystrophy (ALD). Study of the linear inclusions by means of tilt-stage electron microscopy indicated that they represent trilaminar sheet-like structures distinct from materials seen in various other storage disorders. This study emphasizes that the inclusions in the adrenal and testicular parenchymal cells morphologically differ from those in the brain macrophages. In the latter they occur as membrane-bound discrete structures while in the parenchymal cells they are always seen lying free in the cytoplasm and associated with cleft-like spaces. This morphologic variation of the inclusions is noteworthy and probably reflects a biochemical difference in the storage materials in these two most severely affected organs. In addition, this study demonstrates the presence of linear inclusions within macrophages in otherwise normal-appearing liver, spleen, thymus and also in the renal tubular cells. These findings suggest that the abnormal materials containing very long chain fatty acids enter the blood stream and become sequestered in the reticuloendothelial system and possibly are also excreted in the urine. Detection of these abnormal fatty acids in blood and urine may simplify diagnosis of ALD.

Pathologic findings in mucopolysaccharidosis type IIIB (Sanfilippo's sydnrome B).

The pathologic changes in a rare case of mucopolysaccharidosis (MPS) type IIIB or Sanfilippo's syndrome B (absence of alpha-N-acetylglucosaminidase) are presented, along with the biochemical findings. Comparisons were made with other reported cases of MPS III subtypes and related storage disorders in terms of clinical, light microscopic, electron microscopic, and chemical findings, and a correlation of the ultrastructural changes made with the severe neurological dysfunction noted in this disorder. At present, MPS III subtypes cannot be separated from one another by morphological means because the same expression and distribution of lesions may be encountered among differing subtypes.