Anatomical and Neurochemical Substrates of Clonic and Tonic Seizures

Gale, Karen; Browning, Ronald A.

doi:10.1007/978-1-4684-5556-4_8

Cited by 18 publications

(11 citation statements)

References 115 publications

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“…This differential effect on GTCSs and TSs may indirectly indicate the mechanism by which CS decreases seizures. In animal experiments using transections at different brainstem and diencephalic levels, GTCSs induced by systemic convulsive drugs were decreased or abolished after mesencephalic transections, whereas TSs were increased in intensity and duration (30,31). These experiments concluded that whereas GTCSs were dependent on supradiencephalic structures, TSs were a function of the brainstem.…”

Section: Discussionmentioning

confidence: 99%

Double‐blind, Randomized Controlled Pilot Study of Bilateral Cerebellar Stimulation for Treatment of Intractable Motor Seizures

et al. 2005

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Summary: Purpose:The efficacy and safety of cerebellar stimulation (CS) was reevaluated in a double-blind, randomized controlled pilot study on five patients with medically refractory motor seizures, and especially generalized tonic-clonic seizures.Methods: Bilateral modified four-contact plate electrodes were placed on the cerebellar superomedial surface through two suboccipital burr holes. The implanted programmable, batteryoperated stimulator was adjusted to 2.0 µC/cm 2 /phase with the stimulator case as the anode; at this level, no patient experienced the stimulation. Patients served as their own controls, comparing their seizure frequency in preimplant basal phase (BL) of 3 months with the postimplant phases from 10 months to 4 years (average, eight epochs of 3 months each). During the month after implantation, the stimulators were not activated. The patient and the evaluator were blinded as to the next 3-month epoch, as to whether stimulation was used. The patients were randomized into two groups: three with the stimulator ON and two with the stimulator OFF. After a 4-month postimplantation period, all patients had their stimulator ON until the end of the study and beyond. Medication was maintained unchanged throughout the study. EEG paroxysmal discharges also were measured.Results: Generalized tonic-clonic seizures: in the initial 3-month double-blind phase, two patients were monitored with the stimulation OFF; no change was found in the mean seizure rate (patient 1, 100%, and patient 5, 85%; mean, 93%), whereas the three patients with the stimulation initially ON had a reduction of seizures to 33% (patient 2, 21%; patient 3, 46%; patient 4, 32%) with a statistically significant difference between OFF and ON phase of p = 0.023. All five patients then were stimulated and monitored. At the end of the next 6 months of stimulation, the five patients had a mean seizure rate of 41% (14-75%) of the BL. The second patient developed an infection in the implanted system, which had to be removed after 11 months of stimulation; the seizures were being reduced with stimulation to a mean of one per month from a mean of 4.7 per month (BL level) before stimulation. At the end of 24 months, three patients were monitored with stimulation, resulting in a further reduction of seizures to 24% (11-38%). Tonic seizures: four patients had these seizures, which at 24 months were reduced to 43% (10-76%). Follow-up surgery was necessary in four patients because of infection in one patient and lead/electrode displacement needing repositioning in three patients. The statistical analysis showed a significant reduction in tonic-clonic seizures (p < 0.001) and tonic seizures (p < 0.05).Conclusions: The superomedial cerebellar cortex appears to be a significantly effective and safe target for electrical stimulation for decreasing motor seizures over the long term. The effect shows generalized tonic-clonic seizure reduction after 1-2 months and continues to decrease over the first 6 months and then maintains this effectiveness over the st...

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Section: Discussionmentioning

confidence: 99%

Double‐blind, Randomized Controlled Pilot Study of Bilateral Cerebellar Stimulation for Treatment of Intractable Motor Seizures

et al. 2005

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“…An association between increased GABA levels in the brains of rats and mice and inhibition of audiogenic seizures has been previously demonstrated in rodents receiving the anticonvulsant drug sodium n-dipropylacetate (Godin et al, 1969;Simler et al, 1973). More recently, a GABAergic projection from the substantia nigra to the striatum has been postulated to function as a gating mechanism to limit susceptibility to a variety of seizures (Gale and Browning, 1988). The decrease observed in GABA levels of EP mice in the present study could be interpreted as evidence for a relationship between seizure susceptibility and loss of GABAergic inhibition.…”

Section: Amino Acid Concentrations In E P Micementioning

confidence: 90%

Determination of Amino Acids and Monoamine Neurotransmitters in Caudate Nucleus of Seizure‐Resistant and Seizure‐Prone BALB/c Mice

Vriend

Alexiuk

Green-Johnson

et al. 1993

Journal of Neurochemistry

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Amino acid and monoamine concentrations were examined in tissue extracts of caudate nucleus of genetic substrains of BALB/c mice susceptible or resistant to audiogenic seizures. Amino acids [aspartate, glutamate, glycine, taurine, serine, gamma-aminobutyric acid (GABA)], monoamines, and related metabolites were separated by isocratic reverse-phase chromatography and detected by a coulometric electrode array system. In situ activity of tyrosine hydroxylase and tryptophan hydroxylase were determined by measuring the accumulation of L-DOPA and 5-hydroxytryptophan after administration of the decarboxylase inhibitor NSD-1015. Highly significant decreases in concentrations of both excitatory (glutamate and aspartate) and inhibitory amino acids (GABA and taurine) were observed in extracts of caudate nucleus of seizure-prone mice. Substantial decreases in concentrations of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, were also noted. Decreased accumulation of L-DOPA after NSD-1015 administration provided evidence for decreased tyrosine hydroxylase activity and decreased DA synthesis in striatum of seizure-prone mice compared with seizure-resistant mice. Decreased concentrations of the DA metabolite 3-methoxytyramine (after NSD-1015 administration) suggested that DA release was also compromised in seizure-prone mice. No significant difference in 5-hydroxytryptophan accumulation in striatum of seizure-prone and seizure-resistant mice suggested that tryptophan hydroxylase activity and serotonin synthesis were not affected. The data suggest that seizure-prone BALB/c mice have a deficiency in intracellular content of both excitatory and inhibitory amino acids. The data also raise the issue of whether GABAergic interactions with the nigrostriatal DA system are important in the regulation of audiogenic seizure susceptibility.

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“…Apparently, repetitive seizure activity in one circuit may alter the susceptibility of other circuitry to seizure induction, possibly by inducing long-term changes in structures and pathways (e.g., substantia nigra, midline thalamic nuclei, superior colliculus, ascending noradrenergic projections) that serve a general gating function (Dean and Gale, 1989; Gale, 1990;Brown-ing et al, 1991;Miller et al, 1991). Such gating mechanisms which can modulate susceptibility to a wide variety of seizures of both forebrain and hindbrain origin (Gale and Browning, 1988;Gale, 1990;Miller and Ferrendelli, 1990) are not typically an integral part of any specific seizure-conducting circuit per se.…”

Section: Methodsmentioning

confidence: 99%

“…Seizures consisting of facial and forelimb clonus with rearing and falling occur within minutes after a single application of y-aminobutyric (GABA) antagonists, glutamate agonists, or muscarinic agonists in the AT (Gale, 1990). This model allowed us to restrict the convulsive stimulation to the forebrain so that our results would not be complicated by brainstem-evoked convulsions such as occur after administration of systemic chemoconvulsants (Gale and Browning, 1988). For evoking seizures from AT, we chose the GABA receptor antagonist, bicuculline (BIC); because BIC acts by removing GABAergic inhibition, we believed the resulting seizure response would best reflect the endogenous excitatory drive in the prepiriform cortex.…”

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confidence: 99%

Role of Brainstem Structures in Seizures Initiated from the Deep Prepiriform Cortex of Rats

et al. 1993

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Summary: Previous studies showed that brainstem sei zures can still be evoked after transections that separate forebrain from brainstem. We sought to determine wheth er forebrain‐evoked electrographic seizures require brain stem connections for initiation and generalization. Male Sprague‐Dawley rats weighing 295–320 g implanted with epidural electrodes had brain transections placed at the pre‐, mid‐, or postcollicular level. In experiment 1, the transections were limited to severing the brainstem, spar ing the telencephalon laterally; these are referred to as “core” transections. In experiment 2, the transections severed the brainstem and also cut through the lateral telencephalon. These “extended” transections were ei ther (a) bilateral, (b) unilateral (i.e., a hemitransection confined to one hemisphere), or (c) partial (sparing path ways ventral to the pretectal nuclei). All transections were performed under ether anesthesia, and seizures were initiated 3 h later by focal infusion of bicuculline (BIC) into the area tempestas (AT) through a previously implanted guide cannula. In experiment 1, bilateral fore brain electrographic seizures occurred in the complete absence of connections between forebrain and brainstem, showing that the brainstem is not required for forebrain evoked seizures. In experiment 2, forebrain seizures evoked by BIC in AT were suppressed by bilateral ex tended transections which interrupted connections be tween AT and the caudal lateral telencephalon. Under these circumstances, application of carbachol with BIC reinstated the forebrain seizure response. These results indicate that carbachol application served to compensate for loss of an excitatory influence on AT resulting from the severing of connections with the caudal telencepha lon. The demonstration of direct projections from ento rhinal cortex to AT using Fluoro‐Gold tracing together with the finding that extended brain transections caudal to the telencephalon do not suppress focally evoked fore brain seizures provided further support for the notion that AT afferents from the caudal telencephalon regulate the sensitivity of AT to BIC. The present findings provide further evidence that seizure substrates in the forebrain and brainstem are separable and independent.

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Anatomical and Neurochemical Substrates of Clonic and Tonic Seizures

Cited by 18 publications

References 115 publications

Double‐blind, Randomized Controlled Pilot Study of Bilateral Cerebellar Stimulation for Treatment of Intractable Motor Seizures

Double‐blind, Randomized Controlled Pilot Study of Bilateral Cerebellar Stimulation for Treatment of Intractable Motor Seizures

Determination of Amino Acids and Monoamine Neurotransmitters in Caudate Nucleus of Seizure‐Resistant and Seizure‐Prone BALB/c Mice

Role of Brainstem Structures in Seizures Initiated from the Deep Prepiriform Cortex of Rats

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