Richard S. K. Young

Isoflurane for refractory status epilepticus: a clinical series

General anesthesia has been recommended to control convulsive status epilepticus that is refractory to conventional anticonvulsant therapy. Halothane has been the recommended agent, but without experimental justification. Isoflurane, which has no reported organ toxicity and produces electrographic suppression at clinically useful concentrations in normal humans, should be a better volatile anesthetic for this purpose. The efficacy and safety of isoflurane administered to control convulsive status epilepticus were assessed on 11 occasions in nine patients in seven North American hospitals. Isoflurane, administered for 1-55 h, stopped seizures in all patients and was able to be titrated to produce burst-suppression patterns on electroencephalograms. Blood pressure support with iv fluids and/or pressor infusions was required in all of the patients. Seizures resumed upon discontinuation of isoflurane on eight of 11 occasions. Six of the nine patients died. The three survivors sustained cognitive deficits. In one patient urine fluoride concentrations were elevated, although not to nephrotoxic levels. These cases suggest that isoflurane 1) is an effective, rapidly titratable anticonvulsant; 2) does not reverse underlying causes of the refractory seizures; and 3) usually necessitates hemodynamic support with fluids and/or pressors. Isoflurane may be administered for seizures, but only when iv agents in anesthetic doses are ineffective or produce unacceptable side effects.

Systemic and Neuropathologic Effects of E. coli Endotoxin in Neonatal Dogs

Summary: The acute systemic and neuropathologic effects of E. coli endotoxin were determined in neonatal dogs. Administration of sublethal (LD0), moderate (LD50), or lethal (LD100) doses of endotoxin produced significant arterial hypotension, metabolic (lactic) acidosis, and hypoglycemia. Neuropathologic changes consisted of widespread inflammation in both grey and white matter; however, necrotic lesions were found only in forebrain white matter.

Effects of Dexamethasone in Hypoxic-Ischemic Brain Injury in the Neonatal Rat

To clarify the effects of corticosteroids in neonatal hypoxic-ischemic brain injury, 7-day-old rats were subjected to unilateral common carotid artery ligation and hypoxia (Levine procedure) after being injected subcutaneously with saline, low-dose dexamethasone (4 mg/kg) or high-dose dexamethasone (40 mg/kg). Neither low-dose nor high-dose dexamethasone ameliorated the brain edema, lactacidemia, or hypoglycemia associated with hypoxia-ischemia. In addition, dexamethasone did not alter the pattern of neuropathologic damage or reduce the fall in brain high-energy phosphates. Finally, high-dose dexamethasone-treated animals experienced significantly more mortality than did either saline- or low-dose dexamethasone-treated animals. In this model of neonatal hypoxia-ischemia, dexamethasone did not confer any significant cerebral protection.

Orbital pseudotumor and Crohn disease

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Is Werdnig-Hoffmann disease a pure lower motor neuron disorder?

SummaryIt is not widely recognized that the pathology of Werdnig-Hoffman disease (WHD) may include cells other than the lower motor neuron. In the early infantile (acute) forms of this degenerative disease, neuropathologic involvement may extend well beyond the lower motor neuron territory to include neurons in spinal sensory ganglion and thalamus.The present report describes the neuropathologic findings of four patients with early infantile degenerative motor neuron disease, compares them to other reported patients, and discusses the relationship of these patients to those with classic WHD. We found involvement of thalamic and primary sensory neurons, although mild, to be a common finding in classic WHD. We suggest that early infantile forms of degenerative lower motor neuron disease which show prominent involvement of thalamic, primary sensory, and other neurons are but one end of the spectrum of WHD.

Brain energy state and lactate metabolism during status epilepticus in the neonatal dog : in vivo 31P and 1H nuclear magnetic resonance study

ABSTRACT: The purpose of these experiments was to determine whether flurothyl-induced status epilepticus causes progressive decline of brain high-energy phosphates and progressive increase in brain lactate in neonatal dogs who are paralyzed and oxygenated. In vivo 31P nuclear magnetic resonance spectroscopic measurements showed that the fall in brain pH occurred early in the course of seizure. The decline in phosphocreatine was more gradual, i.e. 50% reduction, during the 1st h of seizure. There was no reduction in ATP during the 3 h of status epilepticus. In vivo 1H nuclear magnetic resonance measurement of brain lactate disclosed a steep rise that stabilized by 60 min. Brain and blood lactate were closely related during the initial phase of seizure, suggesting rapid efflux of lactate from brain or systemic production of lactate. Blood lactate exceeded brain lactate after 1 h of status epilepticus. The new steady state for cerebral phosphocreatine and lactate during status epilepticus was achieved much more slowly during neonatal status epilepticus than has been reported during status epilepticus in the adult experimental animal. The lack of change in ATP during 3 h of seizure indicates that brain energy state is not radically altered during prolonged seizure if oxygenation is maintained.

Effects of glutamate, quisqualate, and N-methyl-D-aspartate in neonatal brain.

The intracerebral injection of the excitotoxins, glutamate (GLU), or its analogues, quisqualic acid (QA) and N-methyl-D-aspartate (NMDA), produces neuropathologic changes which resemble those induced by hypoxic-ischemic injury. We employed proton magnetic resonance spectroscopy to investigate the acute biochemical changes which follow injection of these excitotoxins in the neonatal rat brain. Aspartate and GLU increased in animals injected with GLU or NMDA. Alanine, glycine, and taurine increased with all three excitotoxins. There was no decrease in phosphocreatine (PCr) or glucose and only a modest increase in lactate after excitotoxin injection, but there was substantial change in these metabolites after hypoxia. GABA rose only after hypoxic-ischemic injury. Although NMDA and QA produced morphological changes which resembled those following hypoxic-ischemic injury, the effect of these excitotoxins on levels of PCr, glucose, and excitatory and inhibitory amino acids was considerably different.

Effect of Experimental Escherichia coli Meningitis on Concentrations of Excitatory and Inhibitory Amino Acids in the Rabbit Brain: In Vivo Microdialysis Study

ABSTRACT: Excessive extracellular fluid concentrations of the amino acids glutamate and aspartate play an important role in the pathogenesis of neuronal cell damage during hypoxia, hypoglycemia, and seizure. The purpose of these investigations was to test the hypothesis that bacterial meningitis causes progressive increase in excessive extracellular fluid concentrations of excitatory and inhibitory neurotransmitters. To test this hypothesis, Escherichia coli was injected intracisternally in juvenile rabbits after which neurotransmitter concentrations were measured with in vivo microdialysis. The data showed significant elevation of the excitatory amino acids aspartate and glutamate, as well as of the inhibitory neurotransmitters γ-amino butyric acid and taurine in the excessive extracellular fluid of animals injected with E. coli compared with control animals injected with saline. However, concentrations of these excitatory and inhibitory amino acids rose late in the course of meningitis, at a time when the animals were hypotensive (mean blood pressure ≤40 mm Hg). These data show that the major increase in excitatory neurotransmitters during experimental meningitis occurs in association with the cerebral ischemia produced by septic shock rather than being produced by the meningitis itself.

Preferential Utilization of Lactate in Neonatal Dog Brain: In vivo and in vitro Proton NMR Study

In vivo proton nuclear magnetic resonance spectroscopy was utilized to determine whether lactate is preferentially utilized as metabolic fuel by the neonatal dog brain. The data showed that during lactate influx, metabolism of lactate could account for most of the fuel needed for oxidative metabolism. The in vivo nuclear magnetic resonance measurements were corroborated by conventional arteriovenous determinations which showed steep decline of arteriovenous difference of glucose and sharp increase in arteriovenous difference of lactate during lactate infusion.

Magnetic resonance imaging in leukodystrophies of childhood

Magnetic resonance imaging (MRI) is particularly valuable in the diagnosis of childhood brain disorders with abnormal myelination because MRI may identify lesions not always seen with x-ray CT scans. We report the clinical and magnetic resonance findings of six children with leukodystrophy. T2 weighted (spin-echo) images disclosed striking asymmetric involvement of cerebral white matter, particularly in periventricular white matter and visual radiations. Calculated T1 values were significantly elevated in the children with leukodystrophy.