Biomedical subjects
Publications and source records attributed to E P Vining.
Barbiturates and benzodiazepines may be very effective in controlling seizures, especially status epilepticus. However, their chronic use may be associated with serious sedative-hypnotic effects that interfere with cognitive function and behavior. When utilized, patients must be carefully monitored to be certain that these side effects are not occurring.
Antiepileptic medications were discontinued in 88 children with epilepsy of various causes who had been free of seizures for two to four years. The subjects were then followed for six months to five years (mean, 22 months). Sixty-six (75 per cent) remained free of seizures. Electroencephalographic characteristics, type of seizure, and age at onset were important in predicting outcome. Specific electroencephalographic features (such as the presence or absence of slowing or spikes) were more predictive than simple classification of an electroencephalogram as normal or abnormal. A history of complex partial seizures that had been controlled for two years carried a relatively favorable prognosis (P less than 0.05), whereas a history of atypical febrile seizures carried a poor prognosis (P less than 0.05). The variable of a younger age at onset was also associated with a better outcome (P less than 0.05), but only if accompanied by electroencephalographic slowing. Altogether, six variables (the interaction of age at onset with electroencephalographic slowing, electroencephalographic spikes, atypical febrile seizures, complex partial seizures, electroencephalographic slowing, and electroencephalographic change) were statistically significant (P less than 0.05) in predicting outcome. We conclude that in most children with epilepsy who have been free of seizures for two or more years, antiepileptic medications can safely be discontinued, and that it is possible to predict reasonably well which children will remain free of seizures.
Twelve segments of ventral nerve cord (VNC) from donor earthworms, Eisenia foetida, were transplanted into recipient worms from which a comparable length of VNC had been removed. Within the first few days after transplantation, bud-like formations, containing outgrowths of the giant nerve fibers, were evident at the ends of transplanted and recipient VNC. Morphological and electrophysiological evidence indicated that by 4-10 days after transplantation, medial (MGF) and lateral (LGF) giant fibers within the transplanted VNC formed cell-specific connections with their counterparts in the recipient VNC. Although the diameters of the giant fiber connections in the transplant-recipient junctions were often larger than normal, spike conduction across the junction was initially slow (approximately 1.0 m/s) but gradually increased over the next 2-3 weeks. Within the transplant, giant fibers were initially normal in appearance, but spike conduction was slow (1-2 m/s). During the next few weeks velocities increased by as much as fourfold and then stabilized for the next several months. However, by 4-5 weeks after transplantation, giant fiber morphology within the transplant was altered significantly, as indicated by the formation of numerous branch-like extensions along the length of each giant fiber. By 9-10 months there were further morphological changes in the transplant, as indicated by decreased branching of the giant fibers and altered neuropile. Despite these morphological changes, through-conduction of giant fiber spikes remained reliable.
Twelve segments of earthworm ventral nerve cord (VNC) were excised from either segments 10-22 (i.e., within the MGF sensory field) or segments 75-87 (i.e., within the LGF sensory field) in donor worms and heterotopically, or homotopically, transplanted into recipient animals. Morphological evidence indicated that by four days after transplantation, peripheral connections were formed between the transplanted VNC and the body wall of the recipient, many of these connections involving novel pathways projecting ventrally from the transplant. Restoration of giant fiber touch sensitivity in the transplant occurred from 4-14 days after transplantation. Regardless of the site of transplantation, the restored sensitivity (i.e., MGF versus LGF sensory field) always reflected the origin of the donor VNC. Restoration of MGF-mediated motor activity in the transplant occurred approximately 17-22 days after transplantation. In the case of heterotopic transplants (i.e., anterior VNC into posterior segments), the restored MGF-mediated muscle potentials were facilitating, indicating at least some tendency for persistence of this feature after transplantation. Behavioral observations suggested that reconnections involving other reflex pathways (e.g., those controlling setal movements and peristaltic locomotion) were made within the transplant region and that properties of the restored reflexes reflected those of the donor VNC. The rapid restoration of sensory and motor connections, despite heterotopic placement, indicates a significant capacity for peripheral regeneration by the transplanted VNC. On the other hand, the maintenance of various properties of reflex function, despite heterotopic transplantation, suggests a limited capacity for rearrangement of established central connections in the transplanted VNC.
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Status epilepticus is a serious medical emergency requiring immediate and rational therapy. Rapid initial management is directed at stabilization of vital functions and a quick but thorough assessment of clinical and laboratory studies to determine etiologies. Initial drug management is directed at the rapid control of status with prevention of recurrence by sustaining a therapeutic level of a long acting anticonvulsant. Few patients should remain in status more than 30 minutes after initiation of therapy.
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Grids of recording electrodes etched onto printed circuit boards were used for noninvasive recording of medial (MGF) and lateral (LGF) giant nerve fiber spikes in developing earthworms, Eisenia foetida. Stereotyped patterns of through-conducted giant fiber spikes, evoked by light tactile stimulation, were first detectable in the normal crawling embryonic stage and continued to be detectable throughout postembryonic development. Giant fiber spiking activity in normal crawling embryos was accompanied by stereotyped muscle activity and rapid escape withdrawal, suggesting that giant fiber reflex pathways are functionally intact before the worm hatches. For both the MGF and LFG, several age-dependent changes were noted, including the following: increases in spike conduction velocity, increases in giant fiber diameter, and decreases in spike duration. The MGF conduction velocity in normal crawling embryos was 1.1-1.6 m s-1 (6-7 micrometers diameter) and increased to 7.0-8.5 m s-1 (20-25 micrograms diameter) by 60 days after hatching. The LGF conduction velocity in normal crawling embryos was 0.7-1.1 m s-1 (2.5-4.0 micrometers diameter) and increased to 4.0-5.5 m s-1 (8-14 micrometers diameter) by 60 days after hatching. During postembryonic development MGF and LGF conduction velocities were linearly related to fiber diameter.
Noninvasive electrophysiological recording methods were used to study the effects of prolonged food deprivation on the postembryonic patterns of giant fiber growth, as indicated by age-dependent changes in giant fiber conduction velocity and diameter, in the earthworm, Eisenia foetida. In addition, giant fiber growth was compared to patterns of somatic growth, as indicated by increases in body weight. Within a wide range of food deprivation levels, normal age-dependent increases in conduction velocity and diameter occurred in spite of marked stunting of somatic growth. Stunting of giant fiber velocity and diameter occurred only during severe food deprivation, but giant fiber spikes and associated rapid escape responses were still readily evoked. The stunting effects of prolonged and severe food deprivation upon giant fiber conduction velocity and diameter were readily reversed by replenishing food. The results demonstrate the persistence of rapid escape reflex functioning, as well as the priority of giant fiber growth relative to somatic growth, during severe and prolonged food deprivation. As a consequence of the priority of giant fiber growth during limited food availability, giant fiber conduction velocity appears to be a more reliable predictor of animal age then body size.
Anticonvulsant therapy was discontinued in 68 children with epilepsy who had had no seizures for four years, in an attempt to find the risk of relapse and the factors predictive of recurrence. In this population the probability of remaining free of seizures for four years after discontinuation of medication was 69 per cent. Children were more likely to have recurrent seizures if they were mentally retarded, if their seizures had begun before two years of age, if they had had many generalized seizures before control, or if they had had a definitely abnormal electroencephalogram before medication was discontinued. Multivariate analysis showed that the best predictors of outcome were the electroencephalogram taken at cessation of medication and the number of seizures before control. We conclude that in the normal child who has not had many seizures and whose electroencephalogram is normal or mildly abnormal, the risks of discontinuing medication after four seizure-free years are acceptable.