A comparison of rectal diazepam gel and placebo for acute repetitive seizures.

BACKGROUND: Acute repetitive seizures are readily recognizable episodes involving increased seizure frequency. Urgent treatment is often required. Rectal diazepam gel is a promising therapy. METHODS: We conducted a randomized, double-blind, parallel-group, placebo-controlled study of home-based treatment for acute repetitive seizures. Patients were randomly assigned to receive either rectal diazepam gel, at a dosage varying from 0.2 to 0.5 mg per kilogram of body weight on the basis of age, or placebo. Children received one dose at the onset of acute repetitive seizures and a second dose four hours later. Adults received three doses -- one dose at onset, and two more doses 4 and 12 hours after onset. Treatment was administered by a care giver, such as a parent, who had received special training. The number of seizures after the first dose was counted for 12 hours in children and for 24 hours in adults. RESULTS: Of 125 study patients (64 assigned to diazepam and 61 to placebo) with a history of acute repetitive seizures, 91 (47 children and 44 adults) were treated for an exacerbation of seizures during the study period. Diazepam treatment was superior to placebo with regard to the outcome variables related to efficacy: reduced seizure frequency (P<0.001) and improved global assessment of treatment outcome by the care giver (frequency and severity of seizures and drug toxicity) (P<0.001). Post hoc analysis showed diazepam to be superior to placebo in reducing seizure frequency in both children (P<0.001) and adults (P=0.02), but only in children was it superior with regard to improvement in global outcome (P<0.001). The time to the first recurrence of seizures after initial treatment was longer for the patients receiving diazepam (P<0.001). Thirty-five patients reported at least one adverse effect of treatment; somnolence was the most frequent. Respiratory depression was not reported. CONCLUSIONS: Rectal diazepam gel, administered at home by trained care givers, is an effective and well-tolerated treatment for acute repetitive seizures.

Congenital lymphocytic choriomeningitis virus syndrome: a disease that mimics congenital toxoplasmosis or Cytomegalovirus infection.

OBJECTIVE: To describe the clinical characteristics of intrauterine infection with lymphocytic choriomeningitis (LCM) virus, an uncommonly recognized cause of congenital viral infection. PATIENTS: Three infants born in the midwestern United States in 1994 and 1995 with clinical features and serologic studies consistent with congenital LCM virus infection and cases of congenital infection identified by review of the medical literature between 1955 and 1996. RESULTS: Twenty-six infants with serologically confirmed congenital LCM virus infection were identified. Twenty-two infants were products of term gestations, and birth weights ranged from 2384 to 4400 g (median, 3520 g). Ocular abnormalities, macrocephaly, or microcephaly were the most commonly identified neonatal features. Twenty-one infants (88%) had chorioretinopathy, 10 (43%) had macrocephaly (head circumference >90th percentile) at birth, and 3 (13%) were microcephalic (head circumference <10th percentile). Macrocephaly and hydrocephalus developed postnatally in one of the latter infants. Hydrocephalus or intracranial calcifications were documented in five infants by computed tomography or magnetic resonance imaging. Nine infants (35%) died, and 10 (63%) of the 16 reported survivors had severe neurologic sequelae, consisting of spastic quadriparesis, seizures, visual loss, or mental retardation. One-half of the mothers reported illnesses compatible with LCM virus infection, and 25% reported exposures to rodents during their pregnancies. CONCLUSIONS: These cases suggest that congenital LCM virus infection could be an underrecognized cause of congenital infection among infants born in the United States. Because of the clinical similarities of these congenital infections, cases of congenital LCM virus infection can be confused with infections with cytomegalovirus or Toxoplasma gondii.

Acquired immobility of the right arm.

The occurrence of an asymmetrical motor dysfunction is an event that frequently results in referral to the pediatric neurologist. The differential diagnosis is not extensive but is somewhat larger than superficial evaluation might indicate. This 4-year-old boy developed intermittent painful motor dysfunction of the right arm over a 1-year period of time resulting from an unusual cause of unilateral motor dysfunction.

Sudden attacks of head pain in a young child.

In the evaluation of headaches at any age, the clinical features of the episodes are the most important diagnostic information available. In the patient presented, the nature of the headaches suggests the need for further study as well as the most fruitful location in which to look.

Headaches of recent onset and long-term learning disability.

In the evaluation of headaches, history is everything! Usually. However, sometimes the headaches are associated with unrelated conditions simply because of their frequency. The evaluation of a child with a learning disability is also a common exercise and the trick, with both conditions, is to recognize the occasional patient who warrants further evaluation.

Class I major histocompatibility complex-restricted cytotoxic T lymphocytes are not necessary for heterotypic immunity to influenza.

Mice transgenic for beta 2-microglobulin deletion (beta 2M-/-) were immunized intranasally with either a recombinant vaccinia virus that expressed both nucleoprotein and interleukin-2 or by infection with H3N2 influenza virus; 3-4 weeks later they were challenged with H1N1 influenza virus. The immunized beta 2M-/- mice had increased survival and enhanced clearance of virus relative to nonimmune controls. This protection correlated with the development of class II major histocompatibility complex-restricted pulmonary cytotoxic T lymphocyte activity and nasal IgA anti-nucleoprotein antibody. Heterotypic immunity can therefore be generated by a mechanism that does not involve class I major histocompatibility complex-restricted T cells.

Myelinoclastic diffuse sclerosis (Schilder's disease): report of a case and review of the literature.

The clinical, neuroimaging, and neuropathologic features of Schilder's disease in a 17-year-old girl are presented and compared to 11 well-documented cases reported since 1912. The evolution of knowledge about Schilder's disease and the confusion in nomenclature are reviewed. Signs and symptoms in this case and others reported in the literature are nonspecific and may mimic mass lesions. Neuroimaging studies also may mimic brain tumor or abscess; however, the absence of significant edema, the irregular and incomplete ring enhancement, the discrepancy between size of the lesions and the associated mass effect, and the absence of other lesions elsewhere in the brain may help differentiate Schilder's disease from neoplasm, infection, and other demyelinating lesions. Although frozen sections of these lesions are often interpreted as astrocytoma, the inflammatory, primarily histiocytic, nature of Schilder's disease is more easily recognized in paraffin-embedded material. Unique features of this case include multiple unilateral lesions and the cyst-like degeneration present in both lesions. Multiple lesions in Schilder's disease are characteristically bilateral. The examination of aspirated fluid is the first such report in Schilder's disease. The limitation of multiple lesions in our case to one hemisphere calls for reexamination of the restrictive 1985 criteria of Poser for the diagnosis of Schilder's disease.

Evaluation of bromfenac and ibuprofen for pain after orthopedic surgery.

STUDY OBJECTIVES: To determine the relative analgesic potency and adverse effect liability of bromfenac 25, 50, and 100 mg, and ibuprofen 200 and 400 mg in the treatment of postoperative pain after orthopedic surgery. DESIGN: Randomized, double-blind, single-dose, parallel-group relative potency assay with evaluations at 30 minutes and then at hourly intervals for up to 6 hours. SETTING: Two wards of the orthopedic surgery department at the Centralsjukhuset (Central Hospital) in Karlstad, Sweden. PATIENTS: Two hundred inpatients with steady, moderate or severe pain within 72 hours after orthopedic surgery. INTERVENTIONS: Patients received a single oral dose of bromfenac 25, 50, or 100 mg, or ibuprofen 200 or 400 mg, when they experienced steady, moderate or severe pain that, in their opinion, required an analgesic. Using a self-rating record, subjects rated their pain and its relief for 6 hours after medicating. MEASUREMENTS AND MAIN RESULTS: The study was a valid relative potency assay with estimates of bromfenac's potency relative to ibuprofen ranging from 10.9 (nurse's global evaluation) to 16.7 (sum of hourly analog pain intensity difference scores). That is, 11-16 times the dose of ibuprofen must be administered to equal the analgesic effect of bromfenac. Patients who had eaten breakfast or lunch within 60 minutes before or 30 minutes after receiving the study medication ("fed" patients) had lower efficacy scores than those who had not ingested food within these time constraints before or after receiving the study medication ("fasted" patients). Furthermore, patients who had eaten before receiving the study medication had significantly lower efficacy scores than those who had eaten after receiving the study medication. CONCLUSIONS: The relative potency of the analgesic effect of bromfenac to ibuprofen is 11-16.7 in patients with pain after orthopedic surgery. Fed patients may have lower analgesic efficacy than fasted patients. Adverse effects for both bromfenac and ibuprofen were transient and consistent with the pharmacologic profiles of the drugs.

Evaluation of two opioid-acetaminophen combinations and placebo in postoperative oral surgery pain.

STUDY OBJECTIVE: To determine the relative analgesic potency and adverse effect liability of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, and placebo in the treatment of pain following oral surgery. DESIGN: Randomized, double-blind, single-dose, placebo-controlled, parallel-group study with self-ratings at 30 minutes and then at hourly intervals from hour 1 to hour 6. SETTING: Private, oral surgery practice sites. PATIENTS: Three hundred twenty-four outpatients with moderate or severe pain after the surgical removal of impacted third molars were selected. One was lost to follow-up and 32 did not need an analgesic; 232 patients had valid efficacy data. INTERVENTIONS: Patients were treated with a single oral dose of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, or placebo when they experienced steady, moderate or severe pain that, in their opinion, required an analgesic. Using a self-rating record, subjects rated their pain and its relief for 6 hours after medicating; estimates of peak and total analgesia were derived from these subjective reports. MEASUREMENTS AND MAIN RESULTS: This study was a valid analgesic assay. Both active treatments were significantly superior to placebo for all measures of analgesic efficacy. The hydrocodone-acetaminophen combination was significantly superior to the codeine-acetaminophen combination for total pain relief and the number of evaluations with 50% relief. Both active treatments manifested an analgesic effect within 30 minutes; the effect persisted for 5 hours for the codeine combination and 6 hours for the hydrocodone combination. Adverse effects were transient, consistent with the pharmacologic profiles of opioids, and none required treatment. CONCLUSIONS: A slight advantage in analgesic efficacy was demonstrated in this single-dose study for the hydrocodone-acetaminophen combination. Repeat-dose studies, however, should be conducted to determine the clinical significance of the difference in analgesic effect of these opioid combinations.

Tests for juvenile myasthenia gravis: comparative diagnostic yield and prediction of outcome.

The clinical picture, family history, laboratory data, treatment modalities, and outcome in 27 juvenile myasthenics seen over a 25-year period are presented. Onset was after 10 years of age in the majority of patients. Half presented with ocular signs, the other half with generalized-onset myasthenia. Half of those with ocular-onset myasthenia progressed to generalized myasthenia. The female-to-male ratio was 3.5:1. Myasthenia gravis was reported in the mother of one patient. Ptosis was the most common presenting sign. It was unilateral at onset in 33% of patients and remained unilateral in 11%. Pharmacologic tests (neostigmine methylsulfate and edrophonium chloride) were positive in 92% of patients. Serology was positive in 63%, whereas repetitive nerve stimulation was positive in 33% when distal nerves were stimulated and in 66% when proximal and distal nerves were stimulated. Seropositivity tended to increase with generalization of the myasthenic process. No statistically significant difference in seropositivity was noted between males and females. Anti-striated muscle antibodies were detected in two patients, neither of whom had thymoma. The yield of repetitive stimulation increased with generalization of the myasthenic process and when proximal nerves were stimulated. No statistically significant difference was noted in the decremental response between seropositive and seronegative patients. The majority of ocular myasthenics were treated with pyridostigmine bromide monotherapy. With generalization of the myasthenic process, other modes of medical and surgical therapies were needed. All patients given corticosteroids ultimately underwent thymectomy. The mean age at presentation and the duration of symptoms at presentation were longer in thymectomized patients than in those without thymectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased sensitivity to cAMP in the in vitro generation of memory splenic cytotoxic T-lymphocytes from aged mice: role of phosphodiesterase.

The effects of increased intracellular concentration of cyclic AMP (cAMP) on cellular immune function of young and aged mice were examined by using an in vitro anti-influenza cytotoxic T-lymphocyte (CTL) assay. We found that increasing intracellular concentrations of cAMP with either the cAMP analog, N,6O2'-dibutyryl cAMP, or the beta adrenergic agonist, metaproterenol, significantly inhibited the in vitro development of memory CTL activity of young mice. The development of CTL activity of aged mice, however, was less sensitive to the effects of these agents. We found that the S-isomer of cAMPS, a cAMP analog resistant to the effects of PDE, caused equivalent inhibition of CTL activity in the young and aged mice. This suggested that the cause of the decreased cAMP sensitivity in aging was increased PDE activity. In subsequent experiments, we found that the PDE from T-cells of aged mice have higher KM and higher Vmax for cAMP than the PDE from T-cells of young mice. Because beta-agonists probably act as a counter-regulatory hormone at an inflammatory site, the decreased sensitivity to cAMP in aging may be a compensatory response to the age-related decline in immune function.

Bacterial meningitis in children. Selected aspects.

Accumulating clinical experience has gradually outlined the epidemiology of acute bacterial meningitis, including the epidemic and the sporadic forms, the customary clinical signs related to different age groups and causative organisms, and methods of rapid diagnosis by laboratory examinations. Effective treatment, which continues to evolve, emerged in the 1940s with the development of antibacterial antimicrobials, first with the sulfonamides and then with the penicillins. The literature relative to these aspects of the disease has been abundant in the past few years. This article is directed to a variety of topics that have direct bearing on the disorder but are less often addressed to those who deal with infants and children.

Etiology of lateral rectus palsy in infancy and childhood.

The etiologies of lateral rectus palsy in 132 infants and children seen over a period of 22 years in a university medical center were retrospectively reviewed and compared with similar reports in the literature. Unlike most reports, which lump children with adults, this study focuses on childhood etiologies of lateral rectus palsy. In contrast to the only two studies in the literature on childhood lateral rectus palsy, which reflect a purely ophthalmologic perspective, this study reflects experiences of pediatric neurology and pediatric neurosurgery, as well as ophthalmology. Most lateral rectus palsies were unilateral, almost equally distributed between right and left sides. Trauma, tumor, and congenital etiologies were the most prevalent. The relative frequency of each of these etiologies varies by service (neurology, neurosurgery, ophthalmology). In 10.6% of patients, etiology could not be determined. The majority of patients had an isolated lateral rectus palsy. Association of lateral rectus palsy with other cranial nerve palsies and/or long tract signs characterized trauma and tumor. The majority of tumors were primary and infratentorial. A small number of patients had benign recurrent lateral rectus palsy.

Epidermal nevus syndrome: subgroup with neuronal migration defects.

Epidermal nevus syndrome is one of the sporadic congenital hamartoses in which neurologic abnormalities have been frequently reported. We report two cases with severe primary brain involvement, seizures, mental retardation, and facial hemihypertrophy. We emphasize the superiority of magnetic resonance imaging over other radiographic studies in outlining the primary central nervous system anomalies associated with this syndrome. Although attempts were made to distinguish between several variants of epidermal nevus syndrome, it is clear that these are one entity. Proteus syndrome, encephalocraniocutaneous lipomatosis, and epidermal nevus syndrome have several overlapping phenotypic features. We suggest that they represent a phenotypic continuum, which in turn suggests a common pathogenetic process. While the cause of these syndromes is unknown, observations point to a somatic mutation leading to variable patterns of mosaicism.

Brain tumors occurring before 1 year of age: a retrospective reviews of 22 cases in an 11-year period (1977-1987).

Congenital brain tumors have been reported infrequently and their management remains ill defined. An 11-year review (1977-1987) of all children with brain tumors with the onset of symptoms before 1 year of age was completed. Twenty-two children with the following histological diagnoses were treated: astrocytoma (7 patients), primitive neuroectodermal tumor (6 patients), papilloma or carcinoma of the choroid plexus (3 patients), malignant teratoma (2 patients), dermoid tumor (2 patients), embryonal rhabdomyosarcoma (1 patient), and chloroma (1 patient). Fifteen tumors were supratentorial in location, and 7 were infratentorial. Initial symptoms were hydrocephalus (32%), focal neurological deficit (23%), asymptomatic increase in head circumference (18%), failure to thrive (14%), and seizures (4.5%). The goal of treatment was a radical excision when possible, with primary chemotherapy in the last 6 years of the review period. Radiation therapy was the adjunct to surgery in the initial 5-year period. All patients with papillomas of the choroid plexus and dermoid lesions underwent a total resection with no recurrence. All 7 astrocytomas were supratentorial, with 6 occurring in the diencephalon. Five of the seven patients with astrocytomas survived more than 5 years. The 6 primitive neuroectodermal tumors were located equally between the supra- and infratentorial spaces. Four of the 6 infants with these tumors received chemotherapy (2 received chemotherapy alone; 2 received chemotherapy and radiation therapy) and are tumor free 2 to 9 years later. A fifth child received radiation therapy alone early in the series and survived only 4 months. The family of the other child refused adjunctive treatment.(ABSTRACT TRUNCATED AT 250 WORDS)