Historical Risk Factors Associated with Seizure Outcome After Surgery for Drug-Resistant Mesial Temporal Lobe Epilepsy.

OBJECTIVE: To investigate the possible influence of risk factors on seizure outcome after surgery for drug-resistant temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS). METHODS: This retrospective study recruited patients with drug-resistant MTS-TLE who underwent epilepsy surgery at Jefferson Comprehensive Epilepsy Center and were followed for a minimum of 1 year. Patients had been prospectively registered in a database from 1986 through 2014. After surgery outcome was classified into 2 groups: seizure-free or relapsed. The possible risk factors influencing long-term outcome after surgery were investigated. RESULTS: A total of 275 patients with MTS-TLE were studied. Two thirds of the patients had Engel\u27s class 1 outcome and 48.4% of the patients had sustained seizure freedom, with no seizures since surgery. Patients with a history of tonic-clonic seizures in the year preceding surgery were more likely to experience seizure recurrence (odds ratio, 2.4; 95% confidence interval 1.19-4.80; P = 0.01). Gender, race, family history of epilepsy, history of febrile seizure, history of status epilepticus, duration of disease before surgery, intelligence quotient, and seizure frequency were not predictors of outcome. CONCLUSIONS: Many patients with drug-resistant MTS-TLE respond favorably to surgery. It is critical to distinguish among different types and etiologies of TLE when predicting outcome after surgery

Mesial temporal lobe epilepsy with childhood febrile seizure.

OBJECTIVES: To evaluate the demographic and clinical manifestations of patients with mesial temporal sclerosis and temporal lobe epilepsy (MTS-TLE) with childhood febrile seizure (FS) and establishing the potential differences as compared to those without FS. We also investigated the surgery outcome in these two groups of patients. MATERIALS AND METHODS: In this retrospective study, all patients with a clinical diagnosis of drug-resistant TLE due to mesial temporal sclerosis, who underwent epilepsy surgery at Jefferson Comprehensive Epilepsy Center, were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups; seizure-free or relapsed. Clinical manifestations and outcome were compared between patients with MTS-TLE with FS and those without FS. RESULTS: Two hundred and sixty-two patients were eligible for this study. One hundred and seventy patients (64.9%) did not have FS in their childhood, while 92 patients (35.1%) reported experiencing FS in their childhood. Demographic and clinical characteristics of these two groups of patients were not different. Postoperative seizure outcome was not statistically different between these two groups of patients (P = 0.19). CONCLUSIONS: When MTS is the pathological substrate of TLE, clinical manifestations and response to surgical treatment of patients are very similar in patients with history of febrile seizure in their childhood compared to those without such an experience. In other words, when the subgroup of patients with MTS-TLE and drug-resistant seizures is examined history of childhood febrile seizure loses its value as a distinguishing factor in characteristics or predictive factor for surgery outcome

Patient historical risk factors associated with seizure outcome after surgery for drug-resistant nonlesional temporal lobe epilepsy.

OBJECTIVE: To investigate the possible influence of risk factors on seizure outcome after surgery for drug-resistant nonlesional temporal lobe epilepsy (TLE). METHODS: This retrospective study recruited patients with drug-resistant nonlesional TLE who underwent epilepsy surgery at Jefferson Comprehensive Epilepsy Center and were followed for a minimum of one year. Patients had been prospectively registered in a database from 1991 through 2014. Postsurgical outcome was classified into two groups; seizure free or relapsed. The possible risk factors influencing long-term seizure outcome after surgery were investigated. RESULTS: Ninety-five patients (42 males and 53 females) were studied. Fifty-four (56.8%) patients were seizure free. Only a history of febrile seizure in childhood affected the risk of post-operative seizure recurrence (odds ratio 0.22; 95% CI: 0.06-0.83; p = 0.02). Gender, race, family history of epilepsy, history of status epilepticus, duration of disease before surgery, aura symptoms, intelligence quotient, and seizure type or frequency were not predictors of outcome. CONCLUSION: Many patients with drug-resistant nonlesional TLE responded favorably to surgery. The only factor predictive of seizure outcome after surgery was a history of febrile seizure in childhood. It is critical to distinguish among different types of TLE when assessing outcome after surgery

Auras in patients with temporal lobe epilepsy and mesial temporal sclerosis.

We investigated auras in patients with drug-resistant temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS). We also investigated the clinical differences between patients with MTS and abdominal auras and those with MTS and non-mesial temporal auras. All patients with drug-resistant TLE and unilateral MTS who underwent epilepsy surgery at Jefferson Comprehensive Epilepsy Center from 1986 through 2014 were evaluated. Patients with good postoperative seizure outcome were investigated. One hundred forty-nine patients (71 males and 78 females) were studied. Thirty-one patients (20.8%) reported no auras, while 29 patients (19.5%) reported abdominal aura, and 30 patients (20.1%) reported non-mesial temporal auras; 16 patients (10.7%) had sensory auras, 11 patients (7.4%) had auditory auras, and five patients (3.4%) reported visual auras. A history of preoperative tonic-clonic seizures was strongly associated with non-mesial temporal auras (odds ratio 3.8; 95% CI: 1.15-12.98; p=0.02). About one-fifth of patients who had MTS in their MRI and responded well to surgery reported auras that are historically associated with non-mesial temporal structures. However, the presence of presumed non-mesial temporal auras in a patient with MTS may herald a more widespread epileptogenic zone

Brainstem atrophy in focal epilepsy destabilizes brainstem-brain interactions: Preliminary findings.

BACKGROUND: MR Imaging has shown atrophy in brainstem regions that were linked to autonomic dysfunction in epilepsy patients. The brainstem projects to and modulates the activation state of several wide-spread cortical/subcortical regions. The goal was to investigate 1. Impact of brainstem atrophy on gray matter connectivity of cortical/subcortical structures and autonomic control. 2. Impact on the modulation of cortical/subcortical functional connectivity. METHODS: 11 controls and 18 patients with non-lesional focal epilepsy (FE) underwent heart rate variability (HRV) measurements and a 3 T MRI (T1 in all subjects, task-free fMRI in 7 controls/ 12 FE). The brainstem was extracted, and atrophy assessed using deformation-based-morphometry. The age-corrected z-scores of the mean Jacobian determinants were extracted from 71 5x5x5 mm grids placed in brainstem regions associated with autonomic function. Cortical and non-brainstem subcortical gray matter atrophy was assessed with voxel-based-morphometry and mean age corrected z-scores of the modulated gray matter volumes extracted from 380 cortical/subcortical rois. The profile similarity index was used to characterize the impact of brainstem atrophy on gray matter connectivity. The fMRI was preprocessed in SPM12/Conn17 and the BOLD signal extracted from 398 ROIs (16 brainstem). A dynamic task-free analysis approach was used to identify activation states. Connectivity HRV relationship were assessed with Spearman rank correlations. RESULTS: HRV was negatively correlated with reduced brainstem right hippocampus/parahippocampus gray matter connectivity in controls (p \u3c .05, FDR) and reduced brainstem to right parietal cortex, lingual gyrus, left hippocampus/amygdala, parahippocampus, temporal pole, and bilateral anterior thalamus connectivity in FE (p \u3c .05, FDR). Dynamic task-free fMRI analysis identified 22 states. The strength of the functional brainstem/cortical connectivity of state 15 was negatively associated with HRV (r = -0.5, p = .03) and positively with decreased brainstem-cortical (0.49, p = .03) gray matter connectivity. CONCLUSION: The findings of this small pilot study suggest that impaired brainstem-cortex gray matter connectivity in FE negatively affects the brainstem\u27s ability to control cortical activation

Seizure outcome after switching antiepileptic drugs: A matched, prospective study.

OBJECTIVE: Outcomes after changing antiepileptic drugs (AEDs) have largely been studied in single cohort series. We recently reported the first study to examine this question in a controlled manner. Here we expand on these results by using a matched, prospective methodology applied to both uncontrolled and well-controlled patients taking any AED. METHODS: We reviewed all outpatient notes over a 9-month period and identified patients with focal epilepsy who were on monotherapy. We classified those who switched AEDs as case patients, with those remaining on the same drug serving as controls. We matched cases with controls for seizure status (seizure-free in the preceding 6 months or not), current AED, and number of failed AEDs. We subsequently assessed outcome 6 months later. RESULTS: Seizure-free patients who switched drug (n = 12) had a 16.7% rate of seizure recurrence at 6 months, compared to 2.8% among controls remaining on the same drug (n = 36, p = 0.11). There was a 37% remission rate among uncontrolled patients who switched drug compared to 55.6% among controls (n = 27 per group, p = 0.18). Uncontrolled patients who had previously tried more than one AED were somewhat less likely to enter remission (p = 0.057). Neither AED mechanism of action nor change in dosage impacted outcome. SIGNIFICANCE: Herein we provide further estimation of the modest risk (~14%) associated with switching AEDs in patients in remission compared to being maintained on the same regimen. Uncontrolled patients were no more likely to enter remission after a drug switch than they were after remaining on the same drug, suggesting that spontaneous changes in disease state, and not drug response, underlie remission in this population

Carbamazepine treatment of generalized tonic–clonic seizures in idiopathic generalized epilepsy

AbstractPurposeEvaluate the efficacy of carbamazepine in the treatment of idiopathic generalized epilepsy (IGE).MethodThe response of five patients with IGE, who experienced primarily generalized tonic–clonic seizures which were refractory to multiple antiepileptic drugs, is reported.ResultsCarbamazepine controlled multiple seizure types and did not induce or increase the frequency of myoclonic or absence seizures in these patients. Many family members also responded favorably to carbamazepine.ConclusionCarbamazepine can be used with caution as an alternative treatment option for refractory IGE, especially in cases in which the main seizure type is generalized tonic–clonic

Long-term effect of antiepileptic drug switch on serum lipids and C-reactive protein.

BACKGROUND: Prior studies have shown that switching patients from inducing antiepileptic drugs (AEDs) to lamotrigine, levetiracetam, or topiramate reduces serum lipids and C-reactive protein (CRP). These studies were all of short duration, and some drugs, such as zonisamide, have not been investigated. METHODS: We recruited 41 patients taking phenytoin or carbamazepine who were being switched to zonisamide, lamotrigine, or levetiracetam. We measured serum lipids and CRP before the switch, \u3e6weeks after, and \u3e6months after. An untreated control group (n=14) underwent similar measurement. We combined these data with those of our previous investigation (n=34 patients and 16 controls) of a very similar design. RESULTS: There were no differences in outcome measures between the two inducing AEDs nor among the three noninducing AEDs. Total cholesterol (TC), atherogenic lipids, and CRP were higher under inducer treatment than in controls. All measures were elevated under inducer treatment relative to noninducer treatment, including TC (24mg/dL higher, 95% CI: 17.5-29.9, p CONCLUSIONS: We demonstrate that switching from inducing to noninducing AEDs produces an enduring reduction in serum lipids and CRP. These results provide further evidence that inducing AEDs may be associated with elevated vascular disease risk. These are the first vascular risk marker data in patients taking zonisamide, which shows a profile similar to that of other noninducing AEDs

Type of preoperative aura may predict postsurgical outcome in patients with temporal lobe epilepsy and mesial temporal sclerosis.

PURPOSE: As the initial symptoms of epileptic seizures, many types of auras have significant localizing or lateralizing value. In this study, we hypothesized that the type of aura may predict postsurgical outcome in patients with medically refractory temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS). METHODS: In this retrospective study, all patients with a clinical diagnosis of medically refractory TLE due to unilateral mesial temporal sclerosis who underwent epilepsy surgery at the Jefferson Comprehensive Epilepsy Center were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups: seizure freedom or relapse. Outcome was compared between seven groups of patients according to their preoperative auras. RESULTS: Two hundred thirty-seven patients were studied. The chance of becoming free of seizures after surgery in patients with abdominal aura was 65.1%, while in other patients, this was 43.3% (P=0.01). In two-by-two comparisons, no other significant differences were observed. CONCLUSION: Patients with medically refractory TLE-MTS who reported abdominal auras preceding their seizures fared better postoperatively with regard to seizure control compared with those who did not report auras, which may indicate bitemporal dysfunction, and to patients with other auras, which may indicate a widespread epileptogenic zone in the latter group of patients

Postictal serotonin levels are associated with peri-ictal apnea.

ObjectiveTo determine the relationship between serum serotonin (5-HT) levels, ictal central apnea (ICA), and postconvulsive central apnea (PCCA) in epileptic seizures.MethodsWe prospectively evaluated video EEG, plethysmography, capillary oxygen saturation (SpO2), and ECG for 49 patients (49 seizures) enrolled in a multicenter study of sudden unexpected death in epilepsy (SUDEP). Postictal and interictal venous blood samples were collected after a clinical seizure for measurement of serum 5-HT levels. Seizures were classified according to the International League Against Epilepsy 2017 seizure classification. We analyzed seizures with and without ICA (n = 49) and generalized convulsive seizures (GCS) with and without PCCA (n = 27).ResultsPostictal serum 5-HT levels were increased over interictal levels for seizures without ICA (p = 0.01), compared to seizures with ICA (p = 0.21). In patients with GCS without PCCA, serum 5-HT levels were increased postictally compared to interictal levels (p < 0.001), but not in patients with seizures with PCCA (p = 0.22). Postictal minus interictal 5-HT levels also differed between the 2 groups with and without PCCA (p = 0.03). Increased heart rate was accompanied by increased serum 5-HT levels (postictal minus interictal) after seizures without PCCA (p = 0.03) compared to those with PCCA (p = 0.42).ConclusionsThe data suggest that significant seizure-related increases in serum 5-HT levels are associated with a lower incidence of seizure-related breathing dysfunction, and may reflect physiologic changes that confer a protective effect against deleterious phenomena leading to SUDEP. These results need to be confirmed with a larger sample size study