Cynthia V. Stack

Long-term outcome of patients with intraspinal neuroblastoma

BACKGROUND Chemotherapy, radiotherapy, and surgical decompression with laminectomy are effective therapeutic options in the treatment of cord compression from neuroblastoma (NB). We report the long-term outcome of patients with intraspinal NB treated with or without laminectomy at two large pediatric oncology centers. PROCEDURE We reviewed the medical records and radiographs of 26 children with intraspinal NB treated at Childrens Memorial Hospital in Chicago, Illinois, between 1985 and 1994 or at St. Jude Childrens Research Hospital in Memphis, Tennessee, between 1967 and 1992. RESULTS Twenty-four of the 26 patients are alive and disease-free (follow-up of 2-29 years; median, 10 years 2 months). Fifteen of the 23 patients with neurologic impairment underwent initial laminectomy. Nine of these 15 patients recovered neurologic function, including 3 patients who presented with paraplegia. Eleven of the 15 patients who underwent laminectomy have developed mild to severe spinal deformities. Eight patients with neurologic symptoms consequent to cord compression were treated with initial chemotherapy and/or surgery, but did not undergo laminectomy. Three patients with mild to moderate deficits recovered neurologic function. Four of 11 patients with intraspinal NB who did not undergo laminectomy have mild to severe scoliosis. CONCLUSIONS A low incidence of neurologic recovery was seen in patients with long-standing severe cord compression regardless of treatment modality. For patients with partial neurologic deficits, recovery was seen in most patients following chemotherapy or surgical decompression with laminectomy. A higher incidence of spinal deformities was seen in the patients treated with initial laminectomy.

Outcome of children with opsoclonus-myoclonus regardless of etiology

Within the past 11 years, 11 patients with opsoclonus and myoclonus, with or without a history of neuroblastoma, have been admitted to Childrens Memorial Hospital. Eight of the 11 children had an occult neuroblastoma. Eight children have had subsequent delayed development with motor incoordination and speech delay (7 with neuroblastoma, 1 without). Nine of 11 children initially were treated with ACTH, 1 child was treated with prednisone, and 1 was not treated. Nine of the 10 children who were treated had recurrences of symptoms during the gradual withdrawal or discontinuation of ACTH. Often the ACTH had to be restarted or increased, although several times the episodes were self-limited, not requiring treatment after ACTH was withdrawn. We found prednisone was ineffective in controlling opsoclonus-myoclonus regardless of etiology. The majority of children with opsoclonus-myoclonus, regardless of etiology, have developmental delay, more severe and at a higher rate than previously reported. When a neuroblastoma was present, tumor removal did not improve symptoms. Although limited in size, our study indicates patients with opsoclonus-myoclonus without an associated neuroblastoma have a better chance for normal neurologic development (2/3 versus 1/8).

Folinic acid therapy in treatment of dihydropteridine reductase deficiency

We gave folinic acid to three siblings, and to a fourth child, who have or had dihydropteridine reductase (DHPR) deficiency. The youngest began folinic acid therapy in addition to neurotransmitter precursors and a phenylalanine-restricted diet at age 2 months, and at 2 years of age has near normal development without evidence of neurologic impairment. His older brother began similar treatment at 5 1/2 months of age, when early neurologic findings were evident. At age 6 years his mental retardation and neurologic impairment are less severe than reported in most patients with DHPR deficiency. Little improvement occurred in their sister, who first received treatment at 2 years of age, when she already had severe neurologic impairment. An unrelated boy with profound neurologic impairment showed subtle signs of improvement after he began treatment with folinic acid alone at age 9 years. These results provide evidence that folinic acid is important in the treatment of DHPR deficiency and, if begun early in infancy, may prevent irreversible neurologic damage. The mechanism of folinic acid action in DHPR deficiency may be to increase indirectly the synthesis of 5-methyltetrahydrofolate.

Utility of the Electroencephalogram in Attention Deficit Hyperactivity Disorder

An electroencephalogram (EEG) has not been routinely utilized in the evaluation of children with attention deficit hyperactivity disorder (ADHD). The utility of the EEG in ADHD is unclear. A recent study in our laboratory using sleep and sleep deprivation routinely found one in four non-epileptic children evaluated for attention deficit disorder has epileptiform discharges in the EEG, more than half focal. The majority of abnormalities (97.5%) occur in sleep and sleep-deprived records compared to 7% in prior wake only records. A review of eight publications showed that laboratories using awake only as routine EEG recordings report a relatively low prevalence of epileptiform discharges, whereas the higher prevalence of epileptiform discharges is seen in those with more prolonged sleep recordings. We have determined that sleep deprivation and sleep are essential to rule out an abnormal EEG in attention deficit disorder. In patients with attention deficit disorder complicated by epilepsy, stimulant therapy is generally safe, provided seizures are controlled by antiepileptic medication. Patients with epilepsy or subclinical electrographic abnormalities not treated with anticonvulsants are at increased risk of seizures when stimulant therapy is introduced, especially extended-release methylphenidate. Apart from an increase in risk of seizures and need for caution in use of stimulants, studies show that epileptiform discharges in the electroencephalogram are linked to a better response of attention deficit to methylphenidate and a higher cognitive performance. Transient cognitive impairment related to sub-clinical electrographic abnormalities responds to antiepileptic medication. An EEG is important in selected cases of attention deficit disorder and is useful in choice of medication, especially in children with lack of awareness and transient cognitive impairment.

Frequency of epileptiform discharges in the sleep-deprived electroencephalogram in children evaluated for attention-deficit disorders.

The authors determined the frequency of epileptiform discharges in the electroencephalogram (EEG) of a cohort of children and adolescents referred to a neurology specialty clinic for evaluation of attention-deficit disorders. Of 624 records, 461 (73.9%) were normal and 163 (26.1%) abnormal. Of abnormal EEGs, 70 (42.9%) had focal epileptiform discharges only, 68 (41.7%) had generalized epileptiform discharges only, and 19 (11.6%) had both independent focal and generalized spikes. Focal spikes were localized chiefly in central, frontal, and temporal regions. Of 163 records with abnormalities, 154 (94.5%) were sleep deprived and 159 (97.5%) were sleep records. One-quarter of the nonepileptic children evaluated for attention-deficit disorder have epileptiform discharges in the EEG, and just more than half are focal. Sleep-deprived sleep is essential to exclude epileptiform abnormalities. The utility of the EEG in the management of attention-deficit disorders and selection of stimulant or nonstimulant medication deserves further study.

Systemic lymphoma mimicking acute disseminated encephalomyelitis

We describe a 10-year-old immunocompetent male whose initial presentation was consistent with the diagnosis of acute disseminated encephalomyelitis. He relapsed 3 months later, with new neurologic signs and lymphadenopathy. T-cell lymphoma was diagnosed by lymph node and stereotaxic brain biopsy. This patient represents a rare report of T-cell lymphoma in an immunocompetent child presenting with central nervous system symptoms.

Ictal Asystole and Anti–N-Methyl-d-aspartate Receptor Antibody Encephalitis

Anti–N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis is a recently identified autoimmune disorder that is increasingly recognized in children. Most cases occur in girls and women and may be paraneoplastic with an associated ovarian teratoma. Characteristic clinical features include neuropsychiatric symptoms, dyskinesias, decreased consciousness, and autonomic instability. We report the first case of asystole associated with temporal lobe seizures in this disorder and highlight the need for careful monitoring for this potentially fatal complication. A 15-year-old previously healthy girl presented with focal seizures and personality changes that progressed to periods of agitation and confusion alternating with catatonia. Anti-NMDAR antibodies were detected in the cerebrospinal fluid and serum. Twenty-six days after initial presentation, new seizures developed characterized by bradycardia and oxygen desaturation. Continuous video-electroencephalogram monitoring captured 3 seizures with left-temporal onset and associated asystole. An ovarian teratoma was diagnosed by pelvic ultrasound and computed tomography, and surgical resection was followed by gradual improvement in her neuropsychiatric symptoms. Treatment with phenobarbital beginning on day 26 lead to the cessation of seizures. However, asymptomatic bradycardia and pauses of 3 seconds continued. After insertion of a demand pacemaker on day 46, there were no further cardiac events. The patient was also treated with 2 courses of intravenous immunoglobulin. Outpatient follow-up at 4 months revealed near-complete neurologic recovery and no cardiac events. To our knowledge, ictal asystole has not previously been described as a complication of anti-NMDAR encephalitis; it is a preventable cause of death in this emerging pediatric disorder, which presents with protean symptoms and is easily misdiagnosed.

Alexander disease with serial MRS and a new mutation in the glial fibrillary acidic protein gene

Alexander disease is a progressive disorder characterized by macrocephaly, a frontal-occipital progression of MRI signal abnormalities, and the presence of Rosenthal fibers in the CNS.1-4⇓⇓⇓ Recently, Alexander disease has been associated with mutations in the glial fibrillary acidic protein (GFAP) gene, a member of the evolutionarily conserved intermediate filament (IF) family of genes.1-3⇓⇓ The authors describe rare findings in a case of infantile Alexander disease with rapid clinical deterioration and unique MRI progression in a patient with a novel GFAP mutation. A full-term boy of mixed Philippine and western European ancestry died at 38 days of life after prolonged seizures and respiratory failure. The mother had raised concerns about the neonate’s poor feeding on the first day of life. On day 5, the baby presented to the pediatrician with emesis and poor feeding. On day 9, the child was seen in an emergency room for emesis. On day 13, the child …

Developmental normo-maturation of brainstem auditory evoked potentials in children with asymptomatic meningo-myelocele during the first year of life

Abstract It is difficult to predict the onset of clinical symptoms due to Chiari II malformation. Brainstem auditory evoked potentials (BAEPs) may be useful to select potential candidates for surgery. We studied 158 BAEPs in 134 asymptomatic children with meningomyelocele (MMC) during the first year of life. Both wave latencies (WLs) and interpeak latencies (IPLs) in asymptomatic children with MMC gradually became shorter during the first year of life. In particular, the shortening of III–V IPLs was observed in the asymptomatic children with MMC from 2 or 3 weeks to 4–6 months of age. This may be a characteristic parameter of the development of the intrinsic brainstem function in patients with MMC. Comparison of these data on BAEPs in asymptomatic children with MMC with the published data on BAEPs in normal neonates and infants showed that the maturation of brainstem function was delayed in the asymptomatic children with MMC during the first year of life. These data on asymptomatic neonates and infants with MMC could potentially be a good reference for selecting the modalities of treatment in patients with MMC associated with symptomatic Chiari II malformation.

The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium

The multicenter National Infantile Spasms Consortium prospective cohort was used to compare outcomes and phenotypic features of patients with infantile spasms with and without hypsarrhythmia.