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At least 19 recordsLinked to original sources
PubMed1994

Seizures and other neurologic manifestations of allergy.

Numerous disease entities affecting the nervous system can be attributed at least in part to immune responses. Neurons have been shown to have receptors from many of the vasoactive neurotransmitter and neuromodulator molecules first studied as mediators of inflammation and immediate hypersensitivity (Type 1 response). Immune responses have now been proven to affect CNS and peripheral neurons. In the diagnostic workup, consideration should be given to the possibility of immune-related causes for seizures and some other neurologic disorders.

Animals↗
PubMed1994

[Schizophrenia and partial complex seizures--case report in diagnosis and differential diagnosis of psychoses and epilepsy].

We report on a 57 year-old patient with schizophrenia. After a 30 years course of the disease, he developed previous unknown psychopathological symptoms, and therapeutic interventions (neuroleptic drugs and electroconvulsive therapy) failed. Neurological examination and EEG revealed the diagnosis of complex partial epileptic seizures. MRI showed bitemporal localized cerebral lesions. Discussion focusses on generalization of microseizures in deep brain structures, and "kindling effect" of electroconvulsive therapy in a patient with pre-existing cerebral lesions.

Antipsychotic Agents↗
PubMed2004

Evidence of the antiepileptic potential of amiloride with neuropharmacological benefits in rodent models of epilepsy and behavior.

Sodium-hydrogen exchangers (NHEs) in the brain play a key role in regulating neuronal pH and, hence, modulate bioelectric and seizure activity. In this study, we investigated the anticonvulsant effect of amiloride (a NHE inhibitor) on increasing current electroshock (ICES) and pentylenetetrazole (PTZ)-induced seizures in mice. Further, the effect of amiloride on mood, memory, grip strength, and rotarod performance was also evaluated. The forced swimming test (FST) and spontaneous alternation behavior (SAB) models were employed to assess the effects on mood and memory, respectively. Amiloride produced a dose-dependent increase in seizure threshold in both rodent models of epilepsy. It was observed that amiloride reduced behavioral depression in the FST in mice. In addition, it resulted in memory improvement in the SAB model. Amiloride did not affect grip strength and rotarod performance, suggesting it is devoid of behavioral impairment. The results indicate the potential antiseizure activity of amiloride along with additional neurological advantages.

Amiloride↗
PubMed1996

Anticonvulsant activity of novel derivatives of 2- and 3-piperidinecarboxylic acid in mice and rats.

The relative ability of derivatives of 2-piperidinecarboxylic acid (2-PC; pipecolic acid) and 3-piperidinecarboxylic acid (3-PC; nipecotic acid) to block maximal electroshock (MES)-induced seizures, elevate the threshold for electroshock-induced seizures and be neurotoxic in mice was investigated. Protective index (PI) values, based on the MES test and rotorod performance, ranged from 1.3 to 4.5 for 2-PC benzylamides and from < 1 to > 7.2 for 3-PC derivatives. PI values based on elevation of threshold for electroshock-induced seizures and rotorod performance ranged from > 1.6 to > 20 for both types of derivatives. Since preliminary data indicated that benzylamide derivatives of 2-PC displace [3H]1-[1-(2-thienyl)-cyclohexyl]piperidine (TCP) binding to the phencyclidine (PCP) site of the N-methyl-D-aspartate (NMDA) receptor in the micromolar range and such low affinity uncompetitive antagonists of the NMDA receptor-associated ionophore have been shown to be effective anticonvulsants with low neurological toxicity, the 2-PC derivatives were evaluated in rat brain homogenates for binding affinity to the PCP site. Although all compounds inhibited [3H]TCP binding, a clear correlation between pharmacological activity and binding affinity was not apparent. Select compounds demonstrated minimal ability to protect against pentylenetetrazol-, 4-aminopyridine- and NMDA-induced seizures in mice. Corneal and amygdala kindled rats exhibited different sensitivities to both valproic acid and the nonsubstituted 2-PC benzylamide, suggesting a difference in these two models. Enantiomers of the alpha-methyl substituted benzylamide of 2-PC showed some ability to reduce seizure severity in amygdala kindled rats.

4-Aminopyridine↗
PubMed1988

Carbamazepine in the treatment of aggression: a case report and a review of the literature.

Aggressive behaviour is an inescapable clinical problem confronting practitioners of medicine, neurology and psychiatry. Several drugs have been used to treat it, with limited success. Successful use of carbamazepine in the treatment of aggressive behaviour in a patient with limbic dysfunction is reported, and varieties of aggressive behaviour that respond to carbamazepine are examined. The authors suggest that carbamazepine may have a specific anti-aggressive effect perhaps due to an anti-kindling effect, but caution that double-blind studies are needed before firm conclusions are drawn.

Adolescent↗
PubMed2000

Chlormethiazole: effectiveness against toxic effects of cocaine in mice.

Chlormethiazole positively modulates the gamma-aminobutyric acid (GABA)(A) receptor complex and is primarily used to treat certain life-threatening neurological events (e.g., refractory seizures and ethanol withdrawal syndrome). On account of several experimental and clinical studies reporting effectiveness against the toxic effects of heroin and methamphetamine, chlormethiazole was systematically tested in the present study for its effectiveness against cocaine-induced seizures and lethality in mice. The protective effects of chlormethiazole were evaluated against single, submaximal convulsive (75 mg/kg) or lethal (110 mg/kg) doses of cocaine. Chlormethiazole also was tested against the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures, and against fully developed kindled seizures. Cocaine-kindled seizures were produced by a total of five daily treatments with 60 mg/kg cocaine. The inverted-screen test was used to assess behavioral side effects of chlormethiazole. Chlormethiazole protected against acute cocaine-induced convulsions (ED(50) = 7.0 mg/kg) and lethality (ED(50)= 21.8 mg/kg) with a robust separation [protective index (PI) = TD(50)/ED(50) = 22.3 and 7.2, respectively] from doses producing behavioral side effects (TD(50) = 156 mg/kg). Chlormethiazole suppressed the behavioral expression of cocaine-kindled seizures and prevented the development of sensitization to the convulsant effects of cocaine. It was also effective in suppressing fully developed kindled seizures. Relative to cocaine seizures in naive mice, chlormethiazole was equieffective, less potent (ED(50) = 22.3 mg/kg), and had a reduced protective index (PI = 3.7) against cocaine-induced seizures in kindled mice. The protective profile and protective index of chlormethiazole were superior to those of the benzodiazepines clonazepam and diazepam, which were of limited efficacy and had low protective indices (PI = approximately 1). The results of this study predict the potential utility of chlormethiazole for the treatment of life-threatening complications of cocaine abuse for which no specific treatment has yet been identified.

Animals↗
PubMed1998

A critical analysis of multiple chemical sensitivities.

Multiple chemical sensitivities (MCS) is a chronic condition of irritation and inflammation of sensory organs, gastrointestinal distress, fatigue, and compromised neurological function, including learning and memory deficits, unpleasant smells, tingling of nerves, and sensory discomfort. Victims report these symptoms after exposure to unfamiliar chemicals. Some studies have linked MCS to immune system dysregulation. MCS is believed to be a disease that spreads between various target organs, and is caused by sensitization to chemicals with very different structures. MCS is often attributed to free radical production and stress, which indirectly cause spreading because of damage to the immune system.

Free Radicals↗
PubMed1992

Synthesis and anticonvulsant activity of enaminones.

A new series of novel enaminones has been synthesized from cyclic beta-dicarbonyl precursors which were condensed with morpholine, pyrrolidine, phenethylamine, hydrazines, substituted benzyl amines, and substituted anilines. These compounds were subsequently evaluated for anticonvulsant activity in a variety of anticonvulsant models by the National Institute of Neurological and Communicative Disorders and Stroke and in our laboratory. Several of these compounds exhibited potent anticonvulsant activity with a remarkable lack of neurotoxicity. The most active analog, methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxo-cyclohex-3-en-1-oate++ + (27), was protective in the maximal electroshock (MES) seizure test in the rat with an oral ED50 of 5.8 mg/kg with no toxicity noted at doses up to 380 mg/kg, thus providing a protective index (TD50/ED50) of greater than 65.5. A similar protective index for 27 was noted upon intraperitoneal (ip) administration in mice. The anticonvulsant effect of 27 occurred within 15 min of administration and the compound remained active beyond 4 h. Compound 27 was also active in the rat corneal kindled model. The application of Free-Wilson analysis to structure-activity correlation in this series is discussed.

Amines↗
PubMed2005

Effect of neonatal isolation on outcome following neonatal seizures in rats--the role of corticosterone.

Emerging evidence indicates that early maternal care permanently modifies the activity of hypothalamic-pituitary-adrenal (HPA) axis and is a critical factor in determining the capacity of the brain to compensate for later encountered insults. The purpose of this study was to determine the role of corticosterone (CORT) in the detrimental effects of neonatal isolation (NI) on seizures. Rats were assigned randomly to the following five groups: (1) control (CONT) rats; (2) NI rats that underwent daily separation from their dams from postnatal day 2 (P2) to P9; (3) status epilepticus (SE) rats, induced by lithium-pilocarpine (Li-Pilo) model at P10; (4) NI plus SE (NIS) rats and (5) NISM rats, a subset of NIS rats receiving metyrapone (100 mg/kg), a CORT synthesis inhibitor, immediately after SE induction. At P10, plasma CORT levels were compared at baseline in CONT and NI rats and in response to Li-Pilo-induced SE among SE, NIS and NISM rats. We evaluated the spatial memory in the Morris water maze at P50 approximately 55, the expression of hippocampal cyclic adenosine monophosphate (cAMP)-responsive element-binding protein phosphorylation at serine-133 (pCREBSer-133) at P55, hippocampal neuronal damage at P80 and seizure threshold at P100. The isolated rats exhibited higher CORT release in response to SE than non-isolated rats, and the NIS rats had greater cognitive deficits and decreased seizure threshold compared to the CONT, NI and SE groups. By contrast, the NISM group, compared to the NIS group, showed a normal CORT response to SE and better spatial memory but no difference in seizure threshold. Compared to the CONT group, the hippocampal pCREBSer-133 level was significantly reduced in all experimental groups (NI, SE, NIS, NISM) with no differences between groups. All rats were free of spontaneous seizures later in life and had no discernible neuronal loss in the hippocampus. Results in this model demonstrate repetitive NI enhances response of plasma CORT to SE, and exacerbates the neurological consequences of neonatal SE. Amelioration of neurological sequelae following reduction of the SE-induced excessive rise in plasma CORT implicates CORT in the pathogenesis of NI increasing the vulnerability to seizures.

Animals↗
PubMed1993

A pathogenetic hypothesis of temporal lobe epilepsy.

Temporal lobe epilepsy is the most common type of epilepsy in adults. It frequently develops in previously normal nervous tissue, secondary to trauma, tumour or stroke. The disease has a tendency to progress toward generalization and neurologic deficits. The pathogenesis of temporal lobe epilepsy is still unclear. In this article, a hypothesis is proposed suggesting that a cascade of biological events may underlie its development and progression. These include increased excitatory amino acid release, NMDA receptor activation, influx of calcium into neurones, activation of calcium-dependent enzymes (including phospholipase A2), immediate early gene expression, and synthesis of new proteins. Positive and negative feedback loops as well as other events, taking place in parallel, are also hypothesized. The clinical and pharmacological ramifications of this working hypothesis are discussed.

Epilepsy, Temporal Lobe↗
PubMed2001

Association of fear auras with mood and anxiety disorders after temporal lobectomy.

PURPOSE: Epilepsy has been associated with increased occurrence of behavioral disorders. Auras reflect abnormal stimulation of brain areas in close proximity to regions from which clinical seizures originate. The purpose of our study was to investigate whether fear auras are associated with a higher rate of mood and anxiety disorders before and 1 year after temporal lobectomy. METHODS: Twenty-two patients with fear auras were compared with matched groups with other auras and no auras. Neurologic and neuropsychological evaluations before, 1-2 months after, and 1 year after temporal lobectomy were reviewed for mood and anxiety disorders and psychotropic medication treatment. A logistic regression model examined effects of patient group and psychiatric status on postoperative psychiatric status. RESULTS: The majority of patients in the three groups experienced mood and anxiety disorders before surgery. Mood and anxiety disorders declined in the control, but not in the fear aura group after surgery. Presence of auras at 1 year after surgery was not related to psychiatric outcome. Postoperative mood and anxiety disorders were more common in patients with persistence of seizures and in those in the fear group who were seizure free. The minority of patients in all groups underwent psychotropic treatment before surgery, but the majority with fear auras underwent treatment after surgery. CONCLUSIONS: Postoperative mood and anxiety disorders were more common in fear aura patients after temporal lobectomy, in particular, if seizure free. Possible mechanisms include the role of the amygdala in fear conditioning, the concepts of forced normalization, and kindling.

Adult↗
PubMed1999

[Universal cerebral mechanisms in the pathogenesis of paroxysmal states].

Paroxysmal disorders are conventionally divided into paroxysms of epileptic and nonepileptic origin. In spite of the different mechanisms of their development, paroxysmal states of different types have some similar clinical features: short duration of the disorders, frequent combination of emotional, motor and autonomic disorders during paroxysm, normal neurologic status between the attacks, possible positive reaction to anticoagulants. These facts allow to consider a "paroxysm" as a possible universal pathogenetic mechanism of brain's reaction to endogenic and exogenic stimulus. A comparative study of 4 types of paroxysmal states was performed: partial epileptic fits, attacks of paroxysmal dystonia, pseudofits, panic attacks. The elevation of general power of spontaneous electric activity, an interhemispheric assymmetry of the power of theta-range, the reaction of hypersynchronization as the reply to 24-hours of sleep deprivation, the increase of the total amplitude of contingent negative deviation were general neurophysiologic characteristics of the states. "Readiness" of brain to the development of paroxysm was characterised by the dynamic elevation of the indices of spontaneous and evoked biologic activity mentioned above.

Brain↗
PubMed2003

Prevention of epilepsy after head trauma: do we need new drugs or a new approach?

Annually in the U.S. about 500,000 head injuries are severe enough to require hospitalization. Past studies of severe head trauma estimate the risk of late seizures, which are synonymous with epilepsy, to be from 26 to 53%. Furthermore, head trauma accounts for 5% of all epilepsy cases and 20% of symptomatic epilepsy. Although potentially preventable, no effective prophylaxis for posttraumatic epilepsy currently exists. Prior attempts to prevent posttraumatic epileptogenesis used various anticonvulsants, usually given many hours after injury. Generally these studies showed these agents suppressed seizures in the first week after trauma, but had no effect on the incidence of late posttraumatic seizures. Brain trauma engages a rapid excitotoxic process triggered by glutamate release, similar to that seen with ischemia. For ischemic cell damage early and rapid delivery of agents has been a key to rescuing or protecting neurons. Yet, no study has addressed whether the rapidity of drug delivery is critical in the prophylaxis of late seizures. Perhaps excitotoxicity proximate to the brain injury also leads to the neurological deficits seen after severe trauma, initiating and promoting epileptogenesis, and that disrupting this process may prevent epilepsy. While experimental models of epileptogenesis have shown that GABAergic drugs, including valproate (VPA), may be antiepileptogenic, the timing of treatment with putative prophylactic drugs has not been studied. Recent laboratory work explored this issue using an in vitro model of posttraumatic epileptogenesis. The data suggest that a limited time domain exists for VPA to intervene in the epileptogenic process, requiring the earliest possible intervention. We contend that protection from posttraumatic epileptogenesis can be conferred only if agents are given soon after trauma. A pilot study is proposed to begin to translate these findings to explore the feasibility of early VPA delivery to severe head trauma patients admitted to Kings County Hospital Center in Brooklyn, NY, a Level 1 trauma center.

Animals↗
PubMedDate not supplied

Responses of rat hippocampal slices in a high-K+ medium following in vivo global ischaemia.

1. We hypothesized that burst activity induced in rat hippocampal tissue by a high-K+ medium in vitro would be increased by a previous episode of global ischaemia, severe enough to induce persistent neurological dysfunction. 2. Male Wistar rats that were subjected to 9 min of chest compression, sufficient to reduce blood pressure (BP) to zero, showed evidence of neurological damage attributed to a global ischaemic insult. Hindlimb function was impaired for 24-48 h and a susceptibility to sound-induced seizures was induced in 25 to 35 rats. The seizure susceptibility cleared spontaneously within 2 weeks in 10 of 25 rats. 3. Hippocampal slices from postischaemic rats were prepared, tested for viability and were then exposed to an 8.0 mmol/L K+ artificial cerebrospinal fluid in vitro. Spontaneous epileptiform bursting activity in the high-K+ medium was not increased. Instead, burst size decreased with time after ischaemia. 4. The decrement in bursting activity is attributed to loss of cellular activity or integrity. These changes correlate with functional changes described by others, but not necessarily to histologically verifiable cell death. The time course of these changes was remarkably long, continuing for almost 3 weeks. Thus, a less-than-lethal ischaemia appears to induce neuronal changes, possibly reversible, that continue for at least 20 days after the global ischaemic insult.

Animals↗
PubMed2003

An animal model of generalized nonconvulsive status epilepticus: immediate characteristics and long-term effects.

Absence seizures are traditionally believed to have no significant long-term neurological consequences, but few basic scientific studies have examined the effects of absence seizures on neuronal function, especially regarding absence status epilepticus. We developed a model of generalized nonconvulsive status epilepticus (GNCSE) in rats to study behavioral, functional, and histological effects of GNCSE. Using repetitive timed injections of low-dose pentylenetetrazol (PTZ), a state of prolonged behavioral arrest and immobility associated with frequent generalized spike-wave discharges on EEG could be induced for hours, consistent with GNCSE. GNCSE occurred reproducibly in adult rats, but surprisingly not in juvenile rats or adult mice. There was no evidence of pathological damage following GNCSE using Fluoro-Jade B and Cresyl Violet histological methods. Although a transient, subtle deficit in place learning occurred in PTZ-treated rats, there were no long-term behavioral effects of GNCSE on spatial learning or sensorimotor function. However, 1 week after a single episode of GNCSE, there was an increase in absence seizures in response to a repeat dose of PTZ compared to controls. These results indicate that an animal model of GNCSE can be generated and that even in the absence of overt neuronal damage, GNCSE may produce functional changes in neurons that alter electrical excitability of neural circuits.

Age Factors↗
PubMed1995

Parietal lobe epilepsy. Clinical manifestations and outcome in 82 patients treated surgically between 1929 and 1988.

We report the clinical manifestations and outcome of 82 patients with nontumoural parietal lobe epilepsy treated surgically at the Montreal Neurological Institute between 1929 and 1988. Patients with extensive resections extending outside the parietal lobe were excluded. Ninety-four percent exhibited aurae: the most common were somatosensory, described by 52 patients; 13 of these also described pain. Other aurae included disturbances of body image, visual illusions, vertiginous sensations and aphasia or dysphasia. A few patients exhibited complex visual or auditory hallucinations and elementary visual hallucinations. Intraoperative cortical stimulation reproduced the habitual aurae in 44 patients. Often the clinical manifestations indicated ictal spread to the frontal, supplementary motor area, or temporo-limbic areas: 28% of patients exhibited tonic posturing of the extremities, 57% unilateral clonic activity, 17% oral or gestural automatisms and 4% complex automatisms. Sixty-one percent of patients with tonic posturing had epileptogenic zones which included the superior parietal lobe, and in 79% of patients with automatisms the epileptogenic zones extended to the inferior parietal lobe, suggesting different spread patterns. Forty-three patients underwent right, and 39 left parietal corticectomies. Postoperative sensory deficits were seen only when the corticectomy extended into the post-central gyrus. Early in the series extensive nondominant inferior parietal resections led to disturbances of body image in a few patients. Follow-up ranging from 2 to 50 years was available for 79 patients. Sixty-five percent had a complete or nearly complete cessation of seizures. Those patients with no post-resection electrocorticographic epileptiform discharges had a more favourable outcome.

Adolescent↗
PubMed1984

Effect of a single brief seizure on subsequent seizure susceptibility in the immature rat.

To determine whether a single seizure permanently affects the brain's susceptibility to further seizures, 27-day-old rats were subjected to a single seizure induced by either an electroshock or the administration of pentylenetetrazol. Three days following the seizure, the rats, along with age- and weight-matched control rats, underwent kindling. The rate of kindling did not differ between the control rats and those rats that had previously experienced a single electroshock or pentylenetetrazol-induced seizure. At the present time, there is no conclusive evidence that a single brief seizure results in permanently increased susceptibility to future convulsions.

Animals↗