Cytokine induction in fetal rat brains and brain injury in neonatal rats after maternal lipopolysaccharide administration.

Induction of proinflammatory cytokines has been proposed to be a link between prenatal maternal intrauterine infection and neonatal brain damage. It is known that the endotoxin, lipopolysaccharide (LPS), released during bacterial infection crosses the placenta. Cytokine induction in the fetal rat brain after maternal administration of LPS was determined by reverse transcriptase-polymerase chain reaction method. LPS suspension in pyrogen-free saline was administered (i.p.) to pregnant rats at 18 d of gestation. The control group was treated with pyrogen-free saline. Expression of the proinflammatory cytokines, tumor necrosis factor-alpha and IL-1beta mRNA, in the fetal rat brain was increased in a dose-dependent manner at 1 h after LPS administration. The great increase in expression of IL-1beta mRNA was only observed at 1 h after injection of LPS (4 mg/kg), whereas the increased expression of tumor necrosis factor-alpha was still detectable from 4 to 24 h after LPS administration. Brain injuries were examined by immunohistochemistry in 8-d-old rat pups born to the dams that were consecutively treated with LPS (500 microg/kg) or pyrogen-free saline on gestation d 18 and 19. No apparent necrotic tissue damage was found in either the LPS group or the control group. Myelin basic protein staining, as a marker of myelin, was clearly observed in the internal capsule and the fimbria hippocampus in the rat brain from the control group. Myelin basic protein staining was much less and weaker in the brains of the LPS-treated group. Glial fibrillary acidic protein-positive astrocytes were observed in both the control and the LPS-treated groups. The LPS-treated group appeared to have more glial fibrillary acidic protein-positive astrocytes in the hippocampal and the cortex areas of the brain than the control group. Immunoblotting data showed that glial fibrillary acidic protein content in the cortex or the hippocampus of the LPS-treated rat brain was higher than in the control group. OX-42-positive staining (a marker of the type 3 complement receptors) of microglial cells was greatly reduced in the 8-d-old rat brain after maternal LPS administration. However, histochemistry with tomato lectin showed that staining of both amoeboid and ramified microglial cells in the LPS-treated rat brain was similar to that in the control group. The overall results indicate that maternal LPS administration induces an increased expression of IL-1beta and tumor necrosis factor-alpha mRNA in the fetal brain. Maternal LPS administration also increases glial fibrillary acidic protein-positive astrocytes, decreases myelin basic protein and alters immunoreactivity of microglia in the brain of offspring. Although results from the current study do not provide direct evidence linking LPS-induced cytokines with the abnormalities in the neonatal rat brain, our animal model may be appropriate for exploring the mechanisms involved in the effects of maternal infection on glial cells in the brains of offspring.

Lethal neonatal autosomal recessive axonal sensorimotor polyneuropathy.

Peripheral neuropathy is an uncommon cause of generalized hypotonia and weakness in infancy. It occurs as a part of the clinical syndrome in some neurodegenerative disorders of infancy, but seldom causes respiratory failure or swallowing difficulties. We report a lethal autosomal recessive axonal polyneuropathy with neonatal onset in a large kindred from Northern Mississippi. One patient was studied in detail at our medical center and the information on 12 other affected infants in this large family were gathered from medical records and by interviewing the family members. Patients were symptomatic for the polyneuropathy before birth and died in the first year of life from respiratory complications. Thirteen babies were affected by this clinical phenotype in four generations of this family with a high frequency of consanguinity. Affected babies were of both sexes and were born to healthy consanguineous parents. The clinical phenotype of polyneuropathy in our index patient and other affected babies in this family was similar, and represents a unique form of hereditary neonatal polyneuropathy.

Guillain-Barré syndrome.

GBS is an acquired, monophasic illness of the peripheral nervous system that usually presents with a gait disturbance and clinical features of pain, weakness, and areflexia. The etiology of the disease is immune-mediated and directed against the peripheral nervous system myelin, axon, or both. A careful history, physical examination, and routine laboratory tests are necessary to make a clinical diagnosis and to exclude other disorders that cause acute weakness. Laboratory tests that support the diagnosis, such as an increased CSF protein and abnormal electrodiagnostic studies, may be normal early in the illness. The most serious complications during the acute phase of the disease are respiratory failure and autonomic disturbances. Plasma exchange or IVIG shortens the duration and severity of the disease significantly. The prognosis for children who have GBS generally is excellent for full and functional recovery, using modern intensive care for respiratory support and the management of other complications.

Muscle rigidity due to fentanyl infusion in the pediatric patient.

Two cases of fentanyl-induced muscle rigidity are presented. Significant features of these cases include the unusual pattern of rigidity and the use of fentanyl doses lower than those usually associated with muscle rigidity.

Intervertebral disk calcification: an unusual cause of acquired torticollis in childhood.

Intervertebral disk calcification in children can result in a syndrome of neck pain, muscle spasm, and torticollis. Usually the clinical course is benign with spontaneous recovery; however, occasionally nerve root or spinal cord compression can be seen. We report a seven-year-old patient with symptomatic cervical disk calcification and briefly discuss the salient clinical and radiographic features.

Treatment of childhood dermatomyositis with high dose intravenous immunoglobulin.

Two children with chronic dermatomyositis who were treated with intravenous immunoglobulin (IVIG) for 28 and 12 months, respectively, are reported. Both patients had received prednisone and immunosuppressive agents prior to IVIG treatments and had experienced significant side effects. Strength and functional abilities improved in both patients in a gradual stepwise fashion with IVIG treatment. One patient achieved remission and continues to do well without any immunosuppressive agents; in the other patient, the dose of oral steroids was reduced and other immunosuppressive agents were discontinued. Use of IVIG was associated with headaches, nausea, and vomiting in both patients. IVIG was an useful adjuvant therapy in these 2 children with dermatomyositis without any significant side effects.

Rapid-fractionation pre-operative chemoradiation for malignant periampullary neoplasms.

The multimodality treatment of adenocarcinoma of the pancreatic head has been shown to improve survival compared with surgery alone. The delivery of chemotherapy and radiation therapy (chemoradiation) before rather than after pancreaticoduodenectomy ensures that all patients who undergo surgery receive the other components of multimodality therapy. In an effort to reduce overall treatment time and cost, the use of rapid-fractionation preoperative chemoradiation was explored. Radiation therapy was delivered with 18-MeV photons to a total dose of 30 Gy given in 10 fractions over 2 weeks. 5-Fluorouracil was given concurrently by continuous infusion at a dose of 300 mg m-2 day-1. Four weeks after the completion of chemoradiation, patients underwent pancreaticoduodenectomy and electron-beam intraoperative radiation therapy (10 Gy). All patients completed the treatment programme without delay. The rapid-fractionation programme was delivered at nearly half the cost of standard chemoradiation and histologic evidence of tumour cell injury was present in all resected specimens. There were no perioperative anastomotic complications, and median hospital stay was 20 days. Rapid-fractionation chemoradiation warrants further study in the neoadjuvant setting.

Vogt-Koyanagi-Harada syndrome in a 4-year-old child.

Vogt-Koyanagi-Harada syndrome is an acquired illness with ocular, cutaneous, and/or neurologic features. A 4-year-old child who acutely developed visual disturbances and headache and was found to have serous retinal detachments and aseptic meningitis is presented. Improvement was rapid with corticosteroid therapy. This is the youngest reported patient with Vogt-Koyanagi-Harada syndrome.

Fat embolism syndrome in a child with muscular dystrophy.

Fat embolism syndrome is a relatively common complication of orthopedic trauma. Once thought to be rare in children, it probably occurs with a similar frequency as in adults, but is often subclinical. Clinically apparent fat embolism syndrome may exhibit neurologic, pulmonary, and cutaneous manifestations. It often resolves without sequelae if it is recognized promptly and supportive treatment is provided. We present a pediatric case of fat embolism syndrome and review the literature on its diagnosis and management in children.

Prematurity and early-onset juvenile myasthenia gravis.

A child manifested ocular myasthenia gravis at age 16 months which progressed to bulbar and mild systemic weakness over a 3-year period. The medical history was significant for premature birth at 32 weeks gestation and birth weight 940 gm. A review of reported patients with juvenile myasthenia gravis with adequate documentation of the birth history, noncongenital onset, typical clinical course and diagnostic findings, and elevated titers of antiacetylcholine receptor antibodies revealed that 55% with onset before age 3 years had a history of prematurity. This association of myasthenia gravis and prematurity may provide insights to the pathogenesis of the disease.

Local anesthetic mortality: report of case.

The case of a healthy five-year-old, thirty-six pound female patient scheduled for multiple extractions is reported. The child received a total dose of 270 mg of mepivacaine, instead of the correct dose of 72 mg, which resulted in multiple seizures, hospital admission, pneumonia, and death caused by anoxic brain injury secondary to cardiopulmonary arrest following the overdose.

MK-801 does not protect against hypoxic-ischemic brain injury in piglets.

BACKGROUND AND PURPOSE: The excitatory amino acid inhibitor MK-801 has been shown in many animals species to protect against hypoxic-ischemic brain injury. We sought to determine whether hypoxic-ischemic injury to the newborn pig's brain could be prevented by the use of MK-801. METHODS: Hypoxic-ischemic injury to the brain was induced in forty 0-3-day-old piglets. They were randomized to receive either 3 mg/kg MK-801 (MK-801 group, n = 20) or vehicle (control group, n = 19) prior to insult. At time 0, the carotid arteries were ligated and the blood pressure was reduced by one third by hemorrhage. At 15 minutes, inspired oxygen was reduced from 50% to 6%. At 30 minutes, inspired oxygen was changed to 100%, carotid ligatures were released, and the withdrawn blood was reinfused. An additional 14 piglets received 3 mg/kg MK-801 but not hypoxic-ischemic injury (drug-only group), and a final group of 11 piglets were subjected to only a sham operation (sham group). RESULTS: Neurological examination scores at 24, 48, and 72 hours showed that MK-801 and drug-only piglets were significantly worse than the controls. Pathological examination of the brains at 72 hours showed significantly greater damage in the brains of the MK-801 and control pigs relative to the sham and drug-only groups. No differences were found between the control and the MK-801 groups. No differences were found between the sham and drug-only groups. CONCLUSIONS: MK-801, at a dose of 3 mg/kg, causes neurological dysfunction in piglets lasting at least 72 hours, but neither causes brain damage nor ameliorates the effects of hypoxic-ischemic injury to the brain of the newborn pig.

Fructose-1,6-bisphosphate, when given immediately before reoxygenation, or before injury, does not ameliorate hypoxic ischemic injury to the central nervous system in the newborn pig.

BACKGROUND AND METHODS: We demonstrated earlier in our laboratories that fructose-1,6-bisphosphate (FDP) would improve the outcome of hypoxic ischemic injury to the brain in the adult rabbit. Since many human newborns suffer hypoxic injury to the brain, with a secondary ischemic component due to hypoxic cardiac failure, we set out to reproduce similar experiments in newborn piglets. Hypoxic ischemic CNS damage was induced by ligating both carotid arteries and reducing BP to 66% of normal for 30 min; in the last 15 min, FIO2 was reduced to 0.6. Twelve piglets were randomized to receive either 175 mg/kg of FDP in the last 5 min before reoxygenation or the equivalent volume of saline. The other 20 piglets received 75 mg/kg of FDP in the 5 min immediately before carotid ligation, followed by 1.8 mg/kg.min continuous infusion for the 30 min of hypoxia and ischemia or an equivalent volume of saline. RESULTS: There were no significant differences in the neurologic exam scores or pathologic exam scores between the FDP and control animals at either dose level. CONCLUSIONS: In this animal model, FDP at the doses given was not effective in ameliorating hypoxic ischemic injury to the CNS.

Fructose-1,6-diphosphate, when given five minutes after injury, does not ameliorate hypoxic ischemic injury to the central nervous system in the newborn pig.

Hypoxic ischemic injury to the brain was induced in 12 0- to 3-day-old piglets. At time 0, the carotid arteries were ligated, and the blood pressure was reduced by one third by hemorrhage. At 15 min, inspired FIO2 was reduced from 50 to 6%. After 10 min of flat EEG, the FIO2 was changes to 100%, the carotid ligations were released, and the withdrawn blood was reinfused. Five minutes after reoxygenation, the piglets were randomly assigned to either receive 350 mg of fructose-1,6-diphosphate over 5 min, followed by 6 mg/kg/min for the ensuing 50 min, or an equivalent volume of normal saline. 3 days after the experiment, the animals received a neurologic examination by a blinded observer, were then sacrificed, and the brains examined by a blinded observer. There were no significant differences in the degree of damage between the two groups.

Mistaken diagnoses in continuous muscle fiber activity of peripheral nerve origin.

The syndrome of continuous muscle fiber activity of peripheral nerve origin has manifestations that resemble those of many other more common neurologic disorders during childhood and infancy. This similarity often leads to misdiagnosis when an adequate index of suspicion is not entertained and a comprehensive electromyographic examination is not performed. Two affected patients from 1 family are reported to illustrate the type of diagnostic errors that were made before the establishment of the correct diagnosis.

Hematologic monitoring in children with epilepsy treated with carbamazepine.

One hundred seventy-six children treated with carbamazepine for epilepsy were monitored over a 12-month period to determine the effects of carbamazepine on the hematologic system. There were no significant changes within the total population in the mean hematocrit or platelet count. The white blood cell count and total neutrophil count showed declines at 1, 8, and 12 months, but the differences did not achieve statistical significance. There was no correlation between the hematologic parameters and carbamazepine blood level, age or sex, or the presence of other drugs. Pretreatment leukopenia and neutropenia were present in 2.8% and 4.0% of children, respectively. During carbamazepine therapy, 8.0% and 17.0% of the children developed leukopenia and neutropenia, respectively, and it was persistent in 1.7% and 2.8%, respectively. The changes in the white blood cell count could be attributed to the changes in the total neutrophil count.