The usefulness of olfactory bulb kindling as a model for evaluation of antiepileptics.

PURPOSE: The present study was undertaken to clarify the behavioral and electroencephalographic characteristics of olfactory bulb (OB) kindling in rats, in comparison with those of amygdala (AMG) kindling. In addition, the usefulness of OB kindling as a model to evaluate antiepileptics was studied. METHODS: Bipolar electrical stimulation was applied to the OB or AMG every day until generalized seizure was achieved. Antiepileptics (carbamazepine, sodium valproate, zonisamide, clobazam, and topiramate), which are used for complex partial epilepsy or secondary generalized epilepsy in clinical practice, were orally administrated to kindled rats. RESULTS: The afterdischarge (AD) threshold of OB kindling is not different from that of AMG kindling. OB-kindled rats showed more rapid development of the seizure stage and AD duration than AMG-kindled rats; however, fully kindled AD duration did not differ between groups. In AMG kindled rats, AD on day 1 was localized only at the stimulation site, whereas in OB-kindled rats, AD on day 1 was observed at not only the stimulation site (OB) but also in the frontal cortex, hippocampus, and AMG. All five antiepileptics significantly inhibited both the seizure stage and AD duration in OB-kindled rats. In addition, carbamazepine, zonisamide, and topiramate were more effective in suppressing OB-kindled seizures. Zonisamide was not effective at any dose tested in AMG-kindled rats. DISCUSSION: OB kindling can be used as a new valuable model to evaluate antiepileptic drugs, with the advantage of its rapid development and the efficacy of antiepileptics.

Seizure characteristics and control following resection in 332 patients with low-grade gliomas.

OBJECT: Seizures play an important role in the clinical presentation and postoperative quality of life of patients who undergo surgical resection of low-grade gliomas (LGGs). The aim of this study was to identify factors that influenced perioperative seizure characteristics and postoperative seizure control. METHODS: The authors performed a retrospective chart review of all cases involving adult patients who underwent initial surgery for LGGs at the University of California, San Francisco between 1997 and 2003. RESULTS: Three hundred and thirty-two cases were included for analysis; 269 (81%) of the 332 patients presented with >or=1 seizures (generalized alone, 33%; complex partial alone, 16%; simple partial alone, 22%; and combination, 29%). Cortical location and oligodendroglioma and oligoastrocytoma subtypes were significantly more likely to be associated with seizures compared with deeper midline locations and astrocytoma, respectively (p=0.017 and 0.001, respectively; multivariate analysis). Of the 269 patients with seizures, 132 (49%) had pharmacoresistant seizures before surgery. In these patients, seizures were more likely to be simple partial and to involve the temporal lobe, and the period from seizure onset to surgery was likely to have been longer (p=0.0005, 0.0089, and 0.006, respectively; multivariate analysis). For the cohort of patients that presented with seizures, 12-month outcome after surgery (Engel class) was as follows: seizure free (I), 67%; rare seizures (II), 17%; meaningful seizure improvement (III), 8%; and no improvement or worsening (IV), 9%. Poor seizure control was more common in patients with longer seizure history (p<0.001) and simple partial seizures (p=0.004). With respect to treatment-related variables, seizure control was far more likely to be achieved after gross-total resection than after subtotal resection/biopsy alone (odds ratio 16, 95% confidence interval 2.2-124, p=0.0064). Seizure recurrence after initial postoperative seizure control was associated with tumor progression (p=0.001). CONCLUSIONS: The majority of patients with LGG present with seizures; in approximately half of these patients, the seizures are pharmacoresistant before surgery. Postoperatively, >90% of these patients are seizure free or have meaningful improvement. A shorter history of seizures and gross-total resection appear to be associated with a favorable prognosis for seizure control.

Brain homocarnosine and seizure control of patients taking gabapentin or topiramate.

PURPOSE: To assess the relation between seizure control and brain homocarnosine and gamma-aminobutyric acid (GABA) levels of patients with complex partial seizures taking gabapentin (GBP) or topiramate (TPM) as adjunctive therapy. METHODS: In vivo measurements of GABA and homocarnosine were made of a 14-cc volume in the occipital cortex by using (1)H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Poor seizure control was defined as more recent seizures than the median for the two groups of patients studied. RESULTS: Homocarnosine levels were higher in patients with better seizure control than in those with poor control. No differences were found in the intracellular GABA levels between the patients who responded to GBP or TPM compared with those who did not. CONCLUSIONS: In the visual neocortex, which is remote from the presumed seizure-onset zone, higher homocarnosine levels were associated with better seizure control in the patients taking GBP or TPM as adjunctive therapy; elevated intracellular GABA levels appeared to offer no additional protection.

5-HT1A receptor agonists modify epileptic seizures in three experimental models in rats.

The effects of two serotonergic (5-HT1A) receptor agonists (8-OH-DPAT; 0.01, 0.1, 0.3, 1 mg/kg, s.c., and Indorenate; 1, 3, 10 mg/kg, i.p.) were evaluated in three type of seizures in male Wistar rats: clonic-tonic convulsions induced by pentylenetetrazol (PTZ, 60 mg/kg, i.p.), status epilepticus (SE) of limbic seizures produced by kainic acid (KA, 10 mg/kg, i.p.) and tonic-clonic seizures by amygdala kindling. 8-OH-DPAT decreased the incidence of tonic seizures and the mortality rate induced by PTZ. Indorenate increased the latency to the PTZ-induced seizures and decreased the percentage of rats showing tonic extension and death. Concerning KA, 8-OH-DPAT augmented the latency and reduced the frequency of wet-dog shake (WDS) and generalized seizure (GS). At high doses it diminished the occurrence and delayed the establishment of SE. Indorenate augmented the latency to WDS, GS and SE, and diminished the number of GS. 8-OH-DPAT and Indorenate did not alter the expression of kindled seizures. However, Indorenate enhanced the refractoriness to subsequent seizures during the postictal depression. Some effects induced by 8-OH-DPAT and Indorenate on seizures evaluated and postictal depression were fully or partially blocked by WAY100635. These results suggest that 5-HT1A receptor agonists modify epileptic activity depending on the type of seizure.

Postoperative seizure outcome in patients with cerebral arteriovenous malformations.

This study was intended to investigate the pre- and postoperative profile of seizures in the patients with cerebral arteriovenous malformations (AVMs). The patients consisted of 46 consecutive cases with supratentorial AVMs operated on from May 1987 to May 1993. Their postoperative mean follow-up duration was 60 months. The overall incidences of seizure were 50% preoperatively and 52% postoperatively, and the incidence of intractable seizure was 15% in both pre- and postoperative period. The presence of preoperative seizure and large AVM size were significant indicators of high risk of postoperative seizures (P < 0.05). About 70% of the patients with preoperative seizures showed seizures postoperatively, while those without preoperative seizures developed seizures postoperatively in 35%. Regarding postoperative intractable seizures, 57% of the group with preoperative intractable seizures remained intractable postoperatively. In conclusion, removal of AVMs did not change the overall incidence of seizures, and patients with large sized AVMs and preoperative seizure had a higher possibility of postoperative seizures.

A neurobehavioral treatment for unilateral complex partial seizure disorders: a comparison of right- and left-hemisphere patients.

This study looked at the efficacy of a multi-disciplinary neurobehavioral approach for treating patients with complex partial seizure disorders. Patients with a seizure focus in either the left or right hemisphere were compared for overall effectiveness of this approach in achieving control of complex partial seizures. Patients in this study received short-term treatment based on a model of self-control developed by the Andrews/Reiter Epilepsy Research Program. This research selected all patients who met the lateralization criterion from among cases receiving short-term treatment between 1992 and 1996. Forty-four patients were identified, a group of 21 right-hemisphere subjects and a second group of 23 left-hemisphere subjects. These patients were treated in a short-term (5 consecutive days) treatment protocol and then released, with weekly phone contact for 6 months following treatment. They were then followed for an additional 19 months through the continued submission of their seizure logs and journals. Subjects in both groups kept seizure records throughout the study starting with a two-month baseline period. Other data collected allowed study of the interaction of emotional states with seizure occurrence. This project produced valuable and relevant information regarding neurobehavioral management interventions as an effective adjunctive or alternative treatment for obtaining seizure control in epilepsy patients. Overall, 79% of patients treated achieved seizure control. More than 64% identified a recognizable emotional state that triggered seizures. The emotional trigger was specific for either the right or left hemisphere.

Anticonvulsant activity of PNU-151774E in the amygdala kindled model of complex partial seizures.

PURPOSE: PNU-151774E [(S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino) propanamide, methanesulfonate] is a novel antiepileptic drug (AED) with a broad spectrum of activity in a variety of chemically and mechanically induced seizures. The objective of this study was to evaluate the activity of PNU-151774E in the amygdala fully kindled rat model of complex partial seizures, and to compare its effects with those of carbamazepine (CBZ), phenytoin (PHT), lamotrigine (LTG), and gabapentin (GBP), drugs used to treat this disease state. METHODS: Male Wistar rats were stimulated daily through electrodes implanted in the amygdala with a threshold current until fully generalized seizures developed. The rats were then treated with various doses of a single compound. Control values for each rat and drug dose were determined after vehicle administration followed by electrical stimulation 1 day before drug treatment. RESULTS: PNU-151774E (1, 10, 30 mg/kg; i.p.) reduced the duration of behavioral seizures significantly and dose-dependently at doses starting from 1 mg/kg. Higher doses significantly reduced seizure severity and afterdischarge duration. In contrast, no dose-related effects were noted after administration of PHT, whereas after CBZ treatment, a plateau of activity was noted from the intermediate to higher doses. The effects of PNU-151774E were comparable to those of LTG and GBP. CONCLUSIONS: The activity shown by PNU-151774E at doses similar to those that are active in models of generalized seizures indicates that PNU-151774E would also have potential efficacy in the treatment of complex partial seizures.

Can patients perform volitional motor acts at the start of a seizure?

A seizure warning device might allow some individuals with partial seizures to protect themselves against consequences of seizures, but a prerequisite is the ability to take volitional action in response to a warning. The authors reviewed consecutive seizures in their epilepsy monitoring unit to determine whether patients could squeeze an event bulb, as instructed, at the start of their seizure. Only complex partial seizures with EEG changes and with the patient on camera were analyzed. Data were obtained from 77 patients, 42 with scalp monitoring and 35 with depth electrodes. Forty-seven percent had a left-hemisphere focus, 42% a right-hemisphere focus, and 11% multifocal seizures. The seizure focus was temporal in 68%. A magnetic resonance imaging consistent with mesial temporal sclerosis was seen in 29% of patients. Overall, 44% of the patients made at least one attempt to reach for the event bulb at the start of their seizures. Among the 72% of patients who gave a history of auras, 53% were able to press the event bulb compared to 20% with no history of auras (P = 0.016). EEG changes occurred a mean of 2.9+/-30.5 seconds after reaching for the bulb for scalp-recorded seizures (n = 20), and 16.2+/-13.7 seconds before behavior for depth-recorded seizures (n = 14, difference significant at P = 0.02). Neither seizure focus nor seizure laterality influenced the ability to press the event bulb. The authors conclude that nearly half of individuals with complex partial seizures can take volitional motor action at the start of their seizure. A method to enhance the intensity and timeliness of a seizure warning would not be wasted.

Neuropsychiatric complications after temporal lobe limbic system surgery.

Although control of seizure activity is the main goal of temporal lobectomies for complex partial epilepsy, the results of surgery must be viewed within the larger context of possible ramifications of limbic system disruption. The neuropsychiatric complications may be significant and influence the patient's perceived qualify of life, thus detracting from the benefits of seizure control. It is apparent from the previous studies that the modalities affected are influenced by the laterality of the resection, with left-sided lobectomies more often affecting verbal memory and learning, whereas right-sided resections may cause visual/spatial memory and cognitive declines. Preoperative neuropsychologic testing may help to predict these possible complications. General psychosocial function, memory, and cognition all seem to be less affected when complete seizure control is attained, with nearly 80% experiencing no significant change in neuropsychologic testing and the gain and losses being equal in magnitude. Also, younger patients and those with a shorter history of seizure activity may fare better after surgery because of a greater capacity for neuronal plasticity to subserve these functions. These findings support the contention that early diagnosis and surgical treatment may help to minimize potential neuropsychiatric complications in conjunction with improved postoperative seizure control.

Lesionectomy versus electrophysiologically guided resection for temporal lobe tumors manifesting with complex partial seizures.

Complex partial seizures associated with tumors and other mass lesions are readily diagnosed by modern imaging techniques but their optimum surgical treatment remains unresolved. Lesionectomy has been reported to produce seizure outcomes equal to outcomes after resection that ablates the epileptogenic cortex with the lesion. However, some evidence suggests that when the lesion is in the temporal lobe, simple excision of the tumor or lesion more often fails to control seizures. After retrospectively reviewing the records of 30 patients with complex partial seizures and temporal lobe tumors who underwent surgical treatment at the University of Cincinnati hospitals (1985-1992), the authors divided them into two groups: Group A (16 patients) underwent lesionectomy only and Group B (14 patients) received surgical treatment for seizures with electroencephalographic delineation of the epileptogenic zone and resection of the lesion. Seizure control was best achieved in Group B patients with 13 (92.8%) seizure free at follow up (mean 52 months). Only three (18.8%) of the Group A patients became seizure free after lesionectomy at follow up (mean 33 months). In eight Group A patients, who underwent temporal lobectomy as a second procedure after lesionectomy failed to control seizures, five (62.5%) became seizure free. Group B patients had a longer duration of seizures and were more likely to have lesions smaller than 2.5 cm compared with Group A. Analysis of covariance demonstrated that the differences in outcome between the groups remained significant even with adjustment for the variation in duration of seizures (p = 0.0006) and size of tumor (p = 0.0001). Based on this study, the authors found that the probable relief from seizures caused by a temporal lobe lesion is greater if the region of epileptogenicity, usually the amygdalohippocampal complex, is resected along with the tumor in a temporal lobectomy.

Anticonvulsant effect of fluoxetine on focally evoked limbic motor seizures in rats.

Fluoxetine was evaluated for anticonvulsant effects in a rat model of focally evoked complex partial seizures (CPS) secondarily generalized. Fluoxetine was administered intraperitoneally (i.p.) 1 h before seizures were induced by focal intracerebral application of the GABAA receptor antagonist, bicuculline methiodide (118 pmol) unilaterally into a discrete epileptogenic site in the deep prepiriform cortex ("area tempestas," AT) of rats. Significant dose-dependent protection from clonic motor seizures was obtained after 5-, 10-, and 20-mg/kg doses of fluoxetine, with 50% protection occurring after the 5-mg/kg dose. Suppression of electrographic seizure activity was concomitant with suppression of motor seizures. These observations support and extend previous findings of other investigators who showed that fluoxetine exerts anticonvulsant actions against maximal electroshock (MES) convulsions and audiogenic convulsions in genetically seizure-prone rodents.

Action of antiepileptic drugs against kainic acid-induced seizures and automatisms during ontogenesis in rats.

Kainic acid (KA 4-14 mg/kg) administered intraperitoneally (i.p.) produces automatisms (scratching until third postnatal week, "wet dog" shakes thereafter), and clonic and tonic-clonic seizures in rats aged 7, 12, 18, 25, and 90 days. Administration of carbamazepine (CBZ) i.p. (25 or 50 mg/kg), phenobarbital (PB 20-80 mg/kg), clonazepam (CZP 0.2 or 1 mg/kg), or valproate (VPA 200 mg/kg) influenced neither incidence nor latency of automatisms. Clonic seizures that are regularly observed after the third postnatal week in controls were either abolished or substantially suppressed by any of the aforementioned antiepileptic drugs (AEDs). Tonic-clonic seizures observed in the first 3 postnatal weeks were suppressed only by solvent [including propyleneglycol (PEG), ethanol, and water]; the effect of AEDs on tonic-clonic seizures was proconvulsant instead. The automatisms were most resistant to AED therapy. These results induce some doubts about the adequacy of the KA model for identifying AEDs effective against complex partial seizures, but forthcoming AEDs that suppress automatisms in the KA rat model might also be active against human complex partial seizures.

The anticonvulsant effects of vitamin E: a further evaluation.

Vitamin E (d-alpha-tocopherol) has proven to be a useful adjunct to anticonvulsant drugs in clinical studies. Improvement has occurred even in patients with complex partial seizures, which are often resistant to drug therapy. In animals, vitamin E is effective against ferrous chloride seizures, hyperbaric oxygen seizures and penicillin-induced seizures. It has failed, however, to show anticonvulsant effects in the standard animal models used for drug screening--the maximal electroshock and threshold pentylenetetrazol tests. The present experiments were designed to further explore the anti-epileptic actions of vitamin E in animals. Three models related to complex partial epilepsy were used: 1) the development of amygdala-kindled seizures; 2) the development of electrically-induced status in kindled animals; and 3) the development of kainic-acid seizures. Vitamin E failed to produce significant effects in any of the models.

[Focal crisis induced by movement in a patient with nonketotic hyperglycemia]. / Crises focais desencadeadas por movimento em paciente com hiperglicemia não cetótica.

Case report of a long term diabetic patient with partial motor crisis originating from passive movement of the right arm. This is a rare type of crisis when compared to spontaneous partial crisis in diabetic patients. Partial crises are often the initial manifestation of diabetes mellitus (about 19% of the cases reported). As in those cases registered in the literature, crisis control in this case was obtained by normalization of glycose serum levels. Possible mechanisms involved in the pathogenesis are discussed.