Initiating an epilepsy surgery program with limited resources in Indonesia.

To share the experiences of organizing the epilepsy surgery program in Indonesia. This study was divided into two periods based on the presurgical evaluation method: the first period (1999-2004), when interictal electroencephalogram (EEG) and magnetic resonance imaging (MRI) were used mainly for confirmation, and the second period (2005-2017), when long-term non-invasive and invasive video-EEG was involved in the evaluation. Long-term outcomes were recorded up to December 2019 based on the Engel scale. All 65 surgical recruits in the first period possessed temporal lobe epilepsy (TLE), while 524 patients were treated in the second period. In the first period, 76.8%, 16.1%, and 7.1% of patients with TLE achieved Classes I, II, and III, respectively, and in the second period, 89.4%, 5.5%, and 4.9% achieved Classes I, II, and III, respectively, alongside Class IV, at 0.3%. The overall median survival times for patients with focal impaired awareness seizures (FIAS), focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures were 9, 11 and 11 years (95% CI: 8.170-9.830, 10.170-11.830, and 7.265-14.735), respectively, with p = 0.04. The utilization of stringent and selective criteria to reserve surgeries is important for a successful epilepsy program with limited resources.

Left ventricle end-systolic elastance, arterial-effective elastance, and ventricle-arterial coupling in Epilepsy.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is a tragic event. Cardiac models of sudden death state that, paradoxically, healthy individuals compose most of the victims of this event. Exploration of cardiac physiological variables related to outcome could help unveil risk markers for sudden death in epilepsy. We investigated left ventricle end-systolic elastance, arterial-effective elastance and ventricle-arterial coupling (VAC) in PWE compared with controls. MATERIAL & METHODS: Adult patients with temporal lobe epilepsy without known cardiovascular diseases were submitted to treadmill test and transthoracic echocardiogram. Individuals without epilepsy matched by sex, age, and body mass index composed the control group. Cardiac risk factors, exercise performance, autonomic data from treadmill test, systolic and diastolic function, morphological cardiac data, and left ventricle pressure-volume loop were recorded. RESULTS: Sixty subjects were consecutively enrolled (30 PWE and 30 controls). Epilepsy duration was 22.5 ± 10.7 years (age of onset 15.2 ± 10.1 years). Treadmill variables were significantly worse in TLE patients compared with controls. End-systolic elastance, arterial-effective elastance, and ventricle-arterial coupling were similar between groups. Female sex, percentage of maximal predicted heart rate achieved in exercise, exercise time, and epilepsy duration explained 28,4% of VAC in PWE in multiple stepwise linear regression (P = .018). CONCLUSIONS: Some aspects of the cardiac pressure-volume curves, mainly linked to left ventricle systolic performance, contractile function and their interaction with afterload appears normal in young PWE and cannot explain their increase risk to adverse outcomes or lower physical fitness.

Identification of Hub Genes of Mesio Temporal Lobe Epilepsy and Prognostic Biomarkers of Brain Low-grade Gliomas Based on Bioinformatics Analysis.

Mesio temporal lobe epilepsy (MTLE) syndrome is the most common form of intractable epilepsies. Meanwhile, seizures are common in patients with cancer as a consequence of brain tumors, including brain low-grade gliomas (LGG). However, the underlying molecular mechanisms of MTLE remain poorly understood. Also, the relationship between MTLE and LGG needs our attention. In this study, we aimed to investigate the hub genes and potential mechanism in MTLE, and the relationship between MTLE and LGG, the gene expression profiles (GSE88992) were downloaded from the Gene Expression Omnibus (GEO) database. Difference analysis for MTLE versus control groups under the three time points was conducted to select the differentially expressed genes (DEGs). Time series clustering analysis was used to select the trend genes. Then a series of bioinformatics analyses including functional enrichment analysis, protein-protein interaction (PPI) network and module analyses, and transcription factor (TF) and miRNA prediction were performed. Also, the overall survival analysis and expression of hub genes in LGG were performed using UALCAN from TCGA database. At 6 h, there were 351 upregulated and 80 downregulated DEGs. At 12 h, there were 499 upregulated and 231 downregulated DEGs. Additionally, 532 upregulated and 402 downregulated DEGs were obtained at 24 h. After time series clustering analysis of the DEGs, we obtained 323 uptrend and 248 downtrend genes. We identified 10 key genes with higher degrees, including C3, TIMP1, PENK, CKAP4, etc. Five PPI modules were identified by MCODE. TF analysis predicted four TFs: JUN, STAT3, NR4A2, and Myc. A total of 26,834 miRNA-mRNA pairs were predicted. Moreover, survival analysis of UALCAN suggested that C3, TIMP1, PENK, GNG2, CKAP4, TNC, JUN, STAT3, NR4A2, and Myc can be potential biomarkers for the prognosis of LGG. In summary, DEGs and hub genes were identified in the present study, which provides novel insight into the development of MTLE.

Maximal/exhaustive treadmill test features in patients with temporal lobe epilepsy: Search for sudden unexpected death biomarkers.

Autonomic dysfunction may account for sudden unexpected death in patients with epilepsy (PWE). On the other hand, low cardiovascular fitness, which may affect autonomic function, is a risk factor for sudden death and all-cause mortality in the general population. Little is known about autonomic variables and cardiovascular response to exercise in PWE. We submitted thirty consecutive PWE with no known cardiovascular diseases to maximal treadmill test, comparing them with matched controls. All individuals were submitted to clinical assessment, 12-lead electrocardiogram (ECG) and echocardiogram to exclude cardiovascular disease. Maximal/exhaustive treadmill test using the Bruce protocol was then performed. Clinical-epidemiological features were similar in both groups, regarding age, sex, body mass index and traditional cardiovascular risk factors. PWE achieved a lower peak heart rate (163.8±21.28bpm×180.9±12.52bpm; p=0.002), lower duration of exercise (673.6±148.27s×784.4±155.72s; p=0.004), lower Duke Score (11.8±2.48×13.4±2.28; p=0.02) and lower achieved metabolic equivalent of task (MET) (12.8±2.49×14.5±2.46; p=0.006). Chronotropic incompetence was more frequent in PWE. Female gender, age of epilepsy onset, number of secondarily generalized seizures and polytherapy were associated to lower cardiovascular fitness in multiple linear regression. Increased risk for SUDEP in PWE may be associated with autonomic disturbances of the cardiovascular system secondary to low cardiovascular fitness.

The Role of Gastrodin on Hippocampal Neurons after N-Methyl-D-Aspartate Excitotoxicity and Experimental Temporal Lobe Seizures.

Tian ma (Gastrodia elata, GE) is an ancient Chinese herbal medicine that has been suggested to be effective as an anticonvulsant and analgesic, and to have sedative effects against vertigo, general paralysis, epilepsy and tetanus. The primary active ingredient isolated from GE is termed gastrodin, which is the glucoside of 4-hydroxybenzyl alcohol (4-HBA). Gastrodin can abolish hypoxia-, glutamate- and N-methyl-D-aspartate (NMDA) receptor-induced toxicity in primary culture of rat cortical neurons, and reduces seizure severity in seizure-sensitive gerbils. We evaluated the effect of gastrodin on NMDA excitotoxicity in hippocampal slice cultures (HSCs) with propidium iodide (PI) fluorescence measurement. We also evaluated the effects of gastrodin for treating active in vivo temporal lobe seizures induced by lithium/pilocarpine. Seizure severity, time span to seizure onset, mortality rate and hippocampal histology for survivors were compared. The effect of gastrodin was evaluated for treating in vitro seizures induced by Mg²âº-free medium in hippocampal slices. Frequencies and amplitudes of epileptiform discharges were compared. The effect of gastrodin on synaptic transmission was evaluated on hippocampal CA1 Schaffer collaterals. Application of 25 µM gastrodin significantly suppressed NMDA excitotoxicity in CA3 but not in CA1 hippocampus and dentate gyrus. Intraventricular gastrodin accelerated seizure onset for 12 min after intraperitoneal pilocarpine injection (P = 0.051). Three of five rats (60%) in the gastrodin group, and three of four (75%) in the dimethyl sulfoxide (DMSO) group died within 3 days after status epilepticus (SE). Gastrodin also failed to inhibit epileptiform discharges in hippocampal slices induced by Mg²âº-free medium, believed to be NMDA receptor-mediated spontaneous activity. The frequencies of the spontaneous epileptiform discharges were similar under treatments with 25 µM gastrodin, 200 µM gastrodin and DMSO. For the evaluation of gastrodin on synaptic transmission, application of DMSO, 25 µM or 200 µM gastrodin had no significant effect on excitatory postsynaptic potential (EPSP) slopes. Gastrodin at 200 µM decreased paired-pulse facilitation (PPF) from 1.23 ± 0.04 to 1.12 ± 0.04 (P = 0.002). In conclusion, gastrodin failed to suppress in vivo and in vitro seizures in our study. Gastrodin showed no effect on hippocampal Schaffer collateral EPSP. These findings suggest that gastrodin does not interact with ionotropic glutamate receptors to inhibit NMDA receptor-facilitated seizures. However, gastrodin showed protective effects against NMDA toxicity on cultured hippocampal slices. Nevertheless, gastrodin is still a potential neuroprotective agent against NMDA excitotoxicity, with potential benefits for stroke and patients with epilepsy.

Identifying clinical correlates for suicide among epilepsy patients in South Korea: A case-control study.

OBJECTIVE: Suicide is a major cause of premature mortality in patients with epilepsy. We aimed to identify the clinical correlates of suicide in these patients. METHODS: We conducted a matched, case-control study based on a clinical case registry of epilepsy patients (n = 35,638) treated between January 1994 and December 2011 at an academic tertiary medical center in Seoul, Korea. Each epilepsy patient in the suicide group (n = 74) was matched with three epilepsy patients in the nonsuicide group (n = 222) by age, gender, and approximate time at first treatment. The clinical characteristics of the patients in both groups were then compared. RESULTS: In a univariate analysis, seizure frequency during the year before suicide, use of antiepileptic drug polytherapy, lack of aura before seizure, diagnosis of temporal lobe epilepsy, use of levetiracetam, psychiatric comorbidity, and use of antidepressants were all significantly higher in the suicide group than in the nonsuicide group. Multivariate analysis revealed that a high seizure frequency (odds ratio [OR] 3.3, 95% confidence interval [CI] 1.04-10.2), a lack of aura before seizure (OR 4.0, 95% CI 1.7-9.3), temporal lobe epilepsy (OR 3.7, 95% CI 1.6-8.6), and use of levetiracetam (OR 7.6, 95% CI 1.1-53.7) and antidepressants (OR 7.2, 95% CI 1.5-34.1) were all associated with a higher probability of suicide. SIGNIFICANCE: Patients with temporal lobe epilepsy who experience seizures weekly or more frequently, experience a lack of aura, use levetiracetam, or take antidepressants are all at a higher risk of suicide and should be monitored closely.

Mortality in patients with refractory temporal lobe epilepsy at a tertiary center in Cuba.

OBJECTIVES: We aimed to investigate the prevalence and risk of mortality in patients with refractory temporal lobe epilepsy. METHODS: Eligible patients included all adults referred to the National Institute of Neurology (NIN) in Havana, Cuba. All patients were followed up for 9 years. All analyses were made with the data available at the last follow-up. The frequency of death related to refractory TLE was analyzed taking into account the total number of patients included in the study. We analyzed the causes of death for each case. Multivariate analysis was made to determine the specific variables related to the death. All values were statistically significant if p<0.05. RESULTS: Six out of 117 patients died during follow-up. Fifty percent of patients died because of suicide. Only the presence of aura, specifically experiential psychic auras, and prodromal depressive disorders were associated significantly with the deaths (p<0.05). Patients who died had a higher concern about their seizures than patients who were still alive at last follow-up (p<0.01); they also had a poor perception of the overall QOL (p<0.01); and they were more concerned about the possible medication side effects than patients who did not die (p<0.05). Logistic regression provided only one variable related to the deaths in our cohort in multivariate analysis: presence of prodromal depressive disorder. CONCLUSION: The causes of death in patients with refractory temporal lobe epilepsy were similar to those documented in the general population of patients with epilepsy.

Anterior temporal lobectomy compared with laser thermal hippocampectomy for mesial temporal epilepsy: A threshold analysis study.

PURPOSE: Anterior Temporal Lobectomy (ATL) is the gold standard surgical treatment for refractory temporal lobe epilepsy (TLE), but it carries the risks associated with invasiveness, including cognitive and visual deficits and potential damage to eloquent structures. Laser thermal hippocampectomy (LTH) is a new procedure that offers a less invasive alternative to the standard open approach. In this decision analysis, we determine the seizure freedom rate at which LTH would be equivalent to ATL. METHODS: MEDLINE searches were performed for studies of ATL from 1995 to 2014. Using complication and success rates from the literature, we constructed a decision analysis model for treatment with ATL and LTH. Quality-adjusted life years (QALYs) were derived from examining patient preferences in similar clinical conditions. LTH data were obtained from a preliminary multicenter study report following patients for 6-12 months. A sensitivity analysis in which major parameters were systematically varied within their 95% CIs was used. RESULTS: 350 studies involving 25,144 cases of ATL were included. Outcomes of LTH were taken from a recently presented multicenter series of 68 cases. Over a 10-year postoperative modeling period, LTH value was 5.9668 QALYs and ATL value was 5.8854. Sensitivity analysis revealed that probabilities of seizure control and late morbidity of LTH are most likely to affect outcomes compared to ATL. We calculated that LTH would need to stop disabling seizures (Engel class I) in at least 43% of cases and have fewer than 40% late mortality/morbidity to result in quality of life at least as good as that after ATL. CONCLUSIONS: This decision analysis based on early follow-up data suggests LTH has similar utility to ATL. These early data support LTH as a potentially comparable less invasive alternative to ATL in refractory TLE. LTH utility may remain comparable to ATL even if long-term seizure control is less than that of ATL. Larger prospective studies with long-term follow up will be needed to validate the true role of LTH in the refractory epilepsy patient population.

Delayed complication after Gamma Knife surgery for mesial temporal lobe epilepsy.

OBJECT: Despite the controversy over the clinical significance of Gamma Knife surgery (GKS) for refractory mesial temporal lobe epilepsy (MTLE), the modality has attracted attention because it is less invasive than resection. The authors report long-term outcomes for 7 patients, focusing in particular on the long-term complications. METHODS: Between 1996 and 1999, 7 patients with MTLE underwent GKS. The 50% marginal dose covering the medial temporal structures was 18 Gy in 2 patients and 25 Gy in the remaining 5 patients. RESULTS: High-dose treatment abolished the seizures in 2 patients and significantly reduced them in 2 others. One patient in this group was lost to follow-up. However, 2 patients presented with symptomatic radiation necrosis (SRN) necessitating resection after 5 and 10 years. One patient who did not need necrotomy continued to show radiation necrosis on MRI after 10 years. One patient died of drowning while swimming in the sea 1 year after GKS, before seizures had disappeared completely. CONCLUSIONS: High-dose treatment resulted in sufficient seizure control but carried a significant risk of SRN after several years. Excessive target volume was considered as a reason for delayed necrosis. Drawbacks such as a delay in seizure control and the risk of SRN should be considered when the clinical significance of this treatment is evaluated.

Generation and characterization of pilocarpine-sensitive C57BL/6 mice as a model of temporal lobe epilepsy.

C57BL/6 (B6) is the most widely used inbred mouse strain, but its use in epilepsy research is compromised by low sensitivity to various convulsants, including pilocarpine. We recently identified a subline of B6NCrl mice in a barrier (#8) of a German vendor (Charles River) that was much more sensitive to status epilepticus (SE) induction than B6NCrl mice from four other barriers of the same vendor and other B6 substrains. Breeding experiments indicated that the observed differences have a genetic basis, thus offering a unique opportunity to identify the genes and pathways involved and contributing to a better understanding of the underlying molecular mechanisms of seizure susceptibility. Since the pilocarpine-sensitive B6 subline (B6NCrl#8) is not further available from the breeder, we decided to generate a new highly pilocarpine-sensitive B6NCrl subline by crossing female B6NCrl#8 mice with male F1 hybrids. Further sister-brother mating of the resulting F2 generation generated a highly susceptible F3 generation. Similar to B6NCrl#8 mice, mice from the F3 generation were significantly more susceptible to SE induction than any other B6 substrain, including B6J (JAX) mice, which were particularly insensitive to seizure induction. In contrast to the marked inter-subline differences in susceptibility to induction of SE, B6 sublines did not differ in the long-term consequences of SE, i.e., development of spontaneous seizures and neurodegeneration in the hippocampus, although hippocampal damage was much less severe than previously reported for other mouse strains. We have started to search for genetic loci underlying the high seizure susceptibility of B6NCrl#8 and filial generations obtained by cross-breeding with this B6 subline. Further characterization of the genetic variations underlying high susceptibility to convulsants such as pilocarpine will facilitate our understanding of the pathomechanisms involved in the evolution of single seizures to a self-sustained SE and provide new opportunities for interventions.

Mortality after temporal lobe epilepsy surgery.

PURPOSE: To report mortality, after a longer interval, in a cohort of patients with drug-resistant epilepsy treated by temporal lobe surgery between 1975 and 1995. A previous audit of these patients ending December 1, 1997 observed a standardized mortality ratio (SMR) of 4.5. METHODS: We analyzed mortality in a cohort of 306 patients with temporal lobe epilepsy (TLE) who underwent temporal lobe resections between December 1, 1975 and December 1, 1995. Deaths occurring after December 1,1997 and until December 1, 2009 were evaluated. Medical records, death certificates, postmortem examination reports, coroner officer's reports, and coroner's inquest reports were sought, and causes of death were ascertained. Sudden unexpected death in epilepsy (SUDEP) cases were identified. KEY FINDINGS: In 3,569 person-years of follow-up 19 deaths occurred, [SMR 2.00, 95% confidence interval (CI) 1.27-3.13], 14 men (SMR 2.01, 95% CI 1.19-3.39) and 5 women (SMR 1.68, 95% CI 0.70-4.03). On analysis of subgroups, SMRs were significantly elevated in patients with mesial temporal sclerosis (MTS) (SMR 2.50, 95% CI 1.38-4.51), men with MTS (SMR 3.12, 95% CI 1.56-6.25), men with nonspecific lesions (SMR 2.68, 95% CI 1.00-7.09), and right-sided resections in MTS (SMR 3.33, 95% CI 1.39-8.00). During follow-up, six SUDEP cases were observed with a rate of 1/595 person-years. SIGNIFICANCE: In this cohort, the risk for premature death in patients undergoing TLE surgery decreased over time but remained above the standard population. Men had a slightly higher risk than women, as did right-sided resections in MTS, confirming this observation in the original cohort. Although lower, the risk of SUDEP remained. Without up-to-date information on seizure outcome, we were unable to directly relate this to mortality.

Redistribution of CB1 cannabinoid receptors in the acute and chronic phases of pilocarpine-induced epilepsy.

The endocannabinoid system plays a central role in retrograde synaptic communication and may control the spread of activity in an epileptic network. Using the pilocarpine model of temporal lobe epilepsy we examined the expression pattern of the Type 1 cannabinoid receptor (CB1-R) in the hippocampi of CD1 mice at survival times of 2 hours, 1 day, 3 days and 2 months (acute, latent and chronic phases). Based on the behavioral signs of the acute seizures, animals were classified as "weakly" or "strongly" epileptic using the modified Racine scale. Mice of the weak group had mild seizures, whereas seizures in the strong group were frequent with intense motor symptoms and the majority of these animals developed sclerosis in the chronic phase. In control samples the most intense staining of CB1-R-positive fibers was found in the molecular layer of the dentate gyrus and in str. pyramidale of the cornu Ammonis. In weak animals no significant changes were seen at any survival time compared to controls. In strong animals, however, in the acute phase, a massive reduction in CB1-R-stained terminals occurred in the hippocampus. In the latent phase CB1-R immunoreactivity gradually recovered. In the chronic phase, CB1-immunostaining in sclerotic samples was stronger throughout the hippocampus. Quantitative electron microscopic analysis showed an increase in the number of CB1-R-positive terminals in the dentate gyrus. Moreover, the number of immunogold particles significantly increased in GABAergic terminals. Our results suggest a proconvulsive downregulation of CB1 receptors in the acute phase most probably due to receptor internalization, followed by compensatory upregulation and sprouting in the chronic phase of epilepsy. In conclusion, the changes in CB1 receptor expression pattern revealed in this study are associated with the severity of hippocampal injury initiated by acute seizures that ultimately leads to sclerosis in the vulnerable regions in the chronic phase.

An experimental study on dynamic morphological changes and expression pattern of GFAP and synapsin i in the hippocampus of MTLE models for immature rats.

OBJECTIVE: To establish an animal model resembling human mesial temporal lobe epilepsy (MTLE); observe the dynamic changes of mossy fiber sprouting (MFS) and neuron loss in the hippocampus; and investigate the expression changes of Glial fibrillary acidic protein (GFAP) and Synapsin I in the hippocampus in immature rats. METHODS: MTLE models of immature rats were induced by lithium-pilocarpine. The surviving animals were continually monitored for 8 weeks. Nissl staining was used to observe the neuron loss and Timm staining was performed to evaluate MFS. Western blot (WB) and immunohistochemical methods were performed to detect the expression of GFAP and Synapsin I. RESULTS: Status epilepticus (SE) was successfully induced in 94.1% of the rats with a high mortality of 68.8%; 75% of the survived rats were observed for spontaneous recurrent seizures (SRS) which resembles the features of human MTLE. Expression levels of glial fibrillary acidic protein and Synapsin I fluctuated in correspondence with the different stages of MTLE development. CONCLUSION: We established an animal model depicting the human MTLE by using immature rats. GFAP and Synapsin I expressions are involved in MTLE development. Neuron loss and mossy fiber sprouting may have a role in epileptogenesis.

Population-based analysis of morbidity and mortality following surgery for intractable temporal lobe epilepsy in the United States.

OBJECTIVE: To assess the morbidity of temporal lobe epilepsy (TLE) surgery on a nationwide level in order to address reservations regarding the morbidity of anterior temporal lobectomy (ATL) for TLE despite class I evidence demonstrating the superiority of ATL over continued medical therapy. DESIGN: Retrospective cohort study. SETTING: The Nationwide Inpatient Sample from 1988 to 2003 was used for analysis. PATIENTS: Only patients who were admitted for ATL for TLE (International Classification of Diseases, Ninth Revision, Clinical Modification codes 345.41 and 345.51; primary procedure code, 01.53) were included. MAIN OUTCOME MEASURES: Morbidity and mortality. Analysis was adjusted for several variables including patient age, race, sex, admission type, primary payer for care, income in zip code of residence, and hospital volume of care. RESULTS: Multivariate analyses revealed that the overall morbidity (postoperative morbidity and/or adverse discharge disposition) following ATL for TLE was 10.8%, with no mortality. Private insurance decreased postoperative morbidity (odds ratio [OR] = 0.52; 95% confidence interval [CI] = 0.28-0.98; P = .04) and adverse discharge disposition (OR = 0.31; 95% CI = 0.12-0.81; P = .02). Increased patient age increased postoperative morbidity (OR = 1.04; 95% CI = 1.01-1.07; P = .03) and adverse discharge disposition (OR = 1.08; 95% CI = 1.02-1.13; P = .004). Neither sex, income, race, nor hospital volume was predictive of postoperative morbidity. The degree of medical comorbidity directly correlated with the incidence of postoperative morbidity. CONCLUSIONS: Morbidity following ATL for TLE is low throughout the United States regardless of sex, race, insurance status, or income. Younger age and private insurance status are independently predictive of reduced postoperative morbidity. In patients with low medical comorbidity, ATL for TLE is safe, with low morbidity and no mortality.

Cox-2 inhibition can lead to adverse effects in a rat model for temporal lobe epilepsy.

PURPOSE: Status epilepticus (SE) leads to upregulation of pro-inflammatory proteins including cyclooxygenase-2 (cox-2) which could be implicated in the epileptogenic process and epileptic seizures. Recent studies show that cox-2 can regulate expression of P-glycoprotein (P-gp) during epileptogenesis and epilepsy. P-gp could cause pharmacoresistance by reducing brain entry of anti-epileptic drugs such as phenytoin (PHT). Here we have investigated the effects of cox-2 inhibition on epileptogenesis, spontaneous seizures and PHT treatment in a rat model for temporal lobe epilepsy (TLE). METHODS: A 3-day treatment with the cox-2 inhibitor SC-58236 (SC) was started 1 day before electrically induced SE. Chronic epileptic rats were treated with SC for 14 days, which was followed by a 7-day period of SC/PHT combination treatment. Seizure activity was monitored continuously using electroencephalography. RESULTS: SC treatment did not affect SE duration, but led to an increased number of rats that died during the first 2 weeks after SE. Cox-2 inhibition during the chronic period led to an increased number of seizures in the 2nd week of treatment in 50% of the rats. SC/PHT treatment reduced seizures significantly for only 2 days. CONCLUSIONS: Both SC treatment that started before SE and the 14-day treatment in chronic epileptic rats led to adverse effects in the TLE rat model. Despite a temporal reduction in seizure frequency with SC/PHT treatment, SC does not seem to be a suitable approach for anti-epileptogenic or anti-epileptic therapy.

Ictal hypoventilation contributes to cardiac arrhythmia and SUDEP: report on two deaths in video-EEG-monitored patients.

Sudden unexplained death in epilepsy (SUDEP) is a common cause of death in patients with epilepsy, with cardiorespiratory dysfunction and a primary cessation of cerebral function proposed as causes. We report two cases of SUDEP in patients with intractable temporal lobe epilepsy undergoing video-EEG (electroencephalography) telemetry at two centers. Both had secondarily generalized convulsions. EEG, electrocardiography (ECG), and respiratory changes in these two patients are reported herein. Ictal/postictal hypoventilation may contribute to SUDEP with the resulting hypoxemia and acidosis leading to failure of recovery of cortical function and eventual cardiac failure.

The effect of preoperative body mass index on outcome after temporal lobe epilepsy surgery.

PURPOSE: The increasing prevalence of obesity is a significant health care concern. Individuals with obesity, i.e., a body mass index (BMI)>or=30, may have significant comorbid conditions that may increase the risk of general anesthesia and operative procedures. The rationale for the present investigation is to evaluate the importance of obesity on operative outcome in patients with intractable temporal lobe epilepsy undergoing surgical treatment. METHODS: This study involved a retrospective analysis of 244 adult patients who underwent epilepsy surgery at Mayo Clinic in Rochester, Minnesota between 1990 and 1996. The mean age of patients at surgery was 35 years (range, 18-68 years). There were 108 male patients (44%). Seventy-three patients (30%) were overweight (BMI 26-29), 56 patients (23%) were obese (BMI 30-39), and nine patients (4%) had extreme obesity (BMI>or=40) at the time of surgery. RESULTS: The BMI was not predictive of the duration of intensive care unit or hospital stay following surgery, perioperative morbidity, or long-term seizure control following epilepsy surgery. Fifteen deaths occurred in the study period remote from the surgical procedure. The mortality during follow-up was increased for patients with extreme obese (p<0.007). CONCLUSIONS: The perioperative morbidity and seizure outcome following epilepsy surgery was independent of the patient's body weight. However, long-term mortality was significantly increased in the individuals with extreme obesity. The effect of morbid obesity on long-term quality of life after epilepsy surgery may need to be considered in selecting operative candidates.

Ictal apnea linked to contralateral spread of temporal lobe seizures: Intracranial EEG recordings in refractory temporal lobe epilepsy.

PURPOSE: Respiratory mechanisms are implicated in sudden unexpected death in epilepsy (SUDEP). We previously demonstrated a high incidence of ictal hypoxemia in temporal lobe seizures. We now report on the temporal relationship between ictal apnea and seizure onset and spread in patients undergoing video-EEG (electroencephalography) telemetry (VET) with intracranial electrodes. METHODS: Ten patients with medically refractory temporal lobe epilepsy (TLE) undergoing VET were studied. Data from synchronously recorded digital pulse oximetry (SaO(2)), end-tidal CO(2) (ETCO(2)), nasal airflow, abdominal excursions, and electrocardiography were obtained. RESULTS: Sixty-one seizures were captured. SaO(2) in the ictal/postictal period was available for 52 seizures, apnea onset times for 27 seizures, and ETCO(2) for 16 seizures. Apneas occurred only when seizures spread to the contralateral temporal lobe. The mean delay to apnea onset was significantly shorter after contralateral seizure spread (2.87 s) than after seizure onset (58.4 s); p < 0.001. The mean SaO(2) nadir with partial seizures or partial seizures prior to secondary generalization was 89.4 +/- 8.6% (91.5, 69-100). Following generalized convulsions the mean oxygen saturation nadir was 75.8 +/- 10.6% (78.5, 58-90). ETCO(2) elevations occurred with each ictal desaturation below 85%. CONCLUSIONS: There is a close temporal relationship between spread of seizures to the contralateral hemisphere and the onset of seizure-associated apnea. Apnea onsets are more tightly linked to time of contralateral spread than to time of seizure onset. Patients with TLE in whom there is evidence of contralateral seizure spread may be at higher risk for ictal-related respiratory dysfunction than those in whom seizures remain unilateral.