Presurgical seizure frequency and tumoral etiology predict the outcome after extratemporal epilepsy surgery

OBJECTIVE: To examine the predictive value of demographic data for the seizure outcome after extratemporal epilepsy surgery. METHODS: Eightyone patients who underwent resective extratemporal epilepsy surgery were retrospectively studied concerning (a) age at surgery, (b) onset of epilepsy, (c) duration of epilepsy, (d) number of seizures at the time of presurgical evaluation, (d) number of presurgically tested antiepileptic substances and (f) number of seizure types. The data were correlated to the postoperative seizure outcome after two years. RESULTS: 33 patients (40.7%) were seizure free two years after surgery. Univariate and multivariate analysis revealed that both tumor etiology and low presurgical seizure frequency were independently associated with seizure freedom after epilepsy surgery. The recurrence rate in patients with one or more seizures per day was more than two-fold if compared with patients with fewer seizures. The remaining demographic factors did not show a significant association with seizure outcome in our 81 patients. CONCLUSIONS: Fewer than daily seizures prior to surgery and a tumoral etiology independently increase the likelihood of remaining seizure free two years after extratemporal epilepsy surgery.     

The duration of temporal lobe epilepsy and seizure outcome after epilepsy surgery

To assess the effect of the duration of epilepsy on the outcome of epilepsy surgery in non-lesional medically refractory temporal lobe epilepsy we reviewed the outcome of 76 patients.MethodsAll patients had anterior temporal resections for “non-lesional” temporal epilepsy (excluding any patient with tumours or vascular malformations but including patients with hippocampal sclerosis). Outcome at one year was assessed using Engel's scale.Results67% had a good outcome (Engel I or II). The mean duration of epilepsy was 23.0 years (range 2.9–46.9 years). Overall, there was no significant difference between patients with good outcome (mean duration 22.4 years) and poor outcome (mean duration 24.2 years) (p = 0.49). The proportion of patients with good outcome was slightly higher in the shorter duration groups. (Duration less than 10 years 75%, 10–19 years 71%, 20–29 years 65%, 30–39 years 62%, and 40–49 years 60% good outcome, p = 0.95).ConclusionWe found no significant associations between outcome and duration of epilepsy.     

Late seizures in patients initially seizure free after epilepsy surgery

PURPOSE: Surgery for medically intractable epilepsy is currently the most effective means of achieving seizure control. Although relatively few long-term outcome studies have been performed, evidence is mounting that the possibility of late seizure recurrence exists, even after an early seizure-free period. No published reports document the rate and predictors of late recurrence in a large series of patients undergoing surgery in the magnetic resonance imaging (MRI) era. METHODS: We retrospectively queried the databases of two epilepsy surgery centers. Patients eligible for study had preoperative MRI scans, were seizure free for 1 year after surgery, and had a minimal follow-up period of 3 years. Patients with tumors or vascular lesions were excluded. We performed log-rank comparison of Kaplan-Meier product limit estimates for categoric variables and used a Cox proportional hazards model for continuous variables. Variables that were significant (p<0.05) on a univariate screen were entered into a multivariate forward step-wise Cox regression. RESULTS: The study included 285 patients, 254 with medial temporal lobe (MTLE) and 31 with neocortical epilepsy. The probability of having a single seizure after being seizure free for 1 year was 18.3% at 5 years and 32.7% at 10 years. However, only 13% were not seizure free at the last follow-up. Predictors of late recurrences on both uni- and multivariate analysis were the presence of preoperative generalized tonic-clonic (GTC) seizures in patients with neocortical epilepsy and late age at surgery in patients with MTLE. MRI results and location of surgery were not predictive. CONCLUSIONS: Although the risk of at least one recurrent seizure after initially successful epilepsy surgery is relatively high, the rate of recurrent intractability is low. The finding that late age at surgery and presence of preoperative GTC seizures are predictors of late recurrence indicates the importance of patient selection and early surgery for persistent seizure control.     

Wada memory performance predicts seizure outcome after epilepsy surgery in children

PURPOSE: Wada memory asymmetries were examined in children from four comprehensive epilepsy surgery centers who subsequently underwent epilepsy surgery to determine whether Wada memory performance could predict degree of seizure relief in children. METHODS: One hundred fifty-six children (between ages 5 and 16 years) with intractable epilepsy underwent Wada testing before resective epilepsy surgery (93 within the left hemisphere, and 63 within the right hemisphere). Memory stimuli were presented soon after intracarotid amobarbital injection, and recognition memory for the items was assessed after return to neurologic baseline. Eighty-eight children underwent unilateral temporal lobe resection, and 68 had extratemporal lobe resections. One hundred four (67%) children were seizure free (Engel class I), and 52 (33%) were not seizure free (Engel classes II-IV) at follow-up (mean follow-up interval, 2.3 years). RESULTS: Seizure-free children recalled 19.3% more Wada memory items after ipsilateral injection than did non-seizure-free children (p = 0.008). If analysis was restricted to youngsters with temporal lobectomies (TLs), seizure-free children recalled 27.7% more items after ipsilateral injection than did non-seizure-free TL children (p = 0.004). With regard to individual patient prediction, 75% of children who had memory score asymmetries consistent with the seizure focus were seizure free. In contrast, only 56% of children whose memory score asymmetries were inconsistent with the seizure focus were seizure free (p = 0.01). CONCLUSIONS: Results suggest that Wada memory performance asymmetries are related to the degree of seizure relief after epilepsy surgery in children and adolescents.     

Long-term seizure and psychosocial outcomes after resective surgery for intractable epilepsy

Resective surgery is considered an effective treatment for refractory localization-related epilepsy. Most studies have reported seizure and psychosocial outcomes of 2–5 years postsurgery and a few up to 10 years. Our study aimed to assess long-term (up to 15 years) postsurgical seizure and psychosocial outcomes at our epilepsy center. The Henry Ford Health System Corporate Data Store was accessed to identify patients who had undergone surgical resection for localization-related epilepsy from 1993 to 2011. Demographics including age at epilepsy onset and surgery, seizure frequency before surgery, and pathology were gathered from electronic medical records. Phone surveys were conducted from May 2012 to January 2013 to determine patients' current seizure frequency and psychosocial metrics including driving and employment status and use of antidepressants. Surgical outcomes were based on Engel's classification (classes I and II = favorable outcomes). McNemar's tests, chi-square tests, two sample t-tests, and Wilcoxon two sample tests were used to analyze the relationships of psychosocial and surgical outcomes with demographic and surgical characteristics. A total of 470 patients had resective epilepsy surgery, and of those, 50 (11%) had died since surgery. Of the remaining, 253 (60%) were contacted with mean follow-up of 10.6 ± 5.0 years (27% of patients had follow-up of 15 years or longer). Of the patients surveyed, 32% were seizure-free and 75% had a favorable outcome (classes I and II). Favorable outcomes had significant associations with temporal resection (78% temporal vs 58% extratemporal, p = 0.01) and when surgery was performed after scalp EEG only (85% vs 65%, p < 0.001). Most importantly, favorable and seizure-free outcome rates remained stable after surgery over long-term follow-up [i.e., < 5 years (77%, 41%), 5–10 years (67%, 29%), 10–15 years (78%, 38%), and > 15 years (78%, 26%)]. Compared to before surgery, patients at the time of the survey were more likely to be driving (51% vs 35%, p < 0.001) and using antidepressants (30% vs 22%, p = 0.013) but less likely to be working full-time (23% vs 42%, p < 0.001). A large majority of patients (92%) considered epilepsy surgery worthwhile regardless of the resection site, and this was associated with favorable outcomes (favorable = 98% vs unfavorable = 74%, p < 0.001). The findings suggest that resective epilepsy surgery yields favorable long-term postoperative seizure and psychosocial outcomes.     

Long-term seizure outcome and risk factors for recurrence after extratemporal epilepsy surgery

Purpose: We aimed to assess long‐term seizure outcome and risk factors for seizure recurrence in a cohort of patients who have undergone extratemporal resection for management of refractory seizures. Methods: Eighty‐one patients underwent extratemporal resection at Austin Health, Melbourne, Australia (1991–2004). Seizure recurrence was any postoperative disabling seizure (complex partial seizure [CPS] ± secondary generalization). Multivariate Cox proportional hazards regression models examined potential preoperative and perioperative risk factors and the risk associated with early postoperative seizures (≤28 days postsurgery). The change between preoperative and postoperative seizure frequency was also measured. Key Findings: Median follow‐up was 10.3 years (range 1–17.7). The probabilities of freedom from disabling seizures (on or off antiepileptic medication) were 40.7% (95% confidence interval [CI] 30–51) at 1 month, 23.5% (95% CI 15–33) at 1 year, and 14.7% (95% CI 8–23) at 5 years postoperative. Reduction of disabling seizures to at least 20% of preoperative frequency was attained by 57% of patients at 5 postoperative years. Of the preoperative/perioperative factors, focal cortical dysplasia (FCD) type 1 (hazard ratio [HR] 1.90, 95% CI 1.08–3.34, p = 0.025) and incomplete resection (HR 1.71, 95% CI 1.06–2.76, p = 0.028) were independent recurrence risks. After surgery, an early postoperative seizure was the only factor associated with higher risk (HR 4.28 [2.42–7.57], p = 0.00). Significance: Distinction between subtypes of focal cortical dysplasia, which can be made using magnetic resonance imaging (MRI) criteria, may be useful for preoperative prognostication. Early seizures after surgery are not benign and may be markers of factors that contribute to seizure recurrence. Most patients achieve substantial reduction in seizure frequency. Further study of the significance of this reduction in terms of surgical “success” or otherwise is required.     

Postoperative routine EEG correlates with long-term seizure outcome after epilepsy surgery.

We investigated the correlation of interictal epileptiform discharges (IED) in routine EEG 6 and 24 months after epilepsy surgery with regard to long-term seizure outcome. In 148 patients (74% temporal lobe epilepsy (TLE), 26% extratemporal epilepsy) EEG results (IED present or absent) were correlated with the postoperative outcome using the Engel classification 6 and 24 months after resection (PO6m and PO2y, respectively). Self-evaluation was conducted 3 and 5 years after resection (PO3y and PO5y, respectively). Ninety-one patients (62%) were seizure-free 5 years after resection; 88% of them showed no IED in PO6m. Twenty-eight patients (19%) displayed IED in routine EEG 6 months after resection; 61% of them had recurrent seizures at PO5y, whereas of 120 patients without IED only 33% had recurrent seizures at PO5y; p=0.01. Absence of IED in PO6m and PO2y correlated with good outcome: 71% without IED remained seizure-free, whereas only 25% with IED at PO6m and PO2y remained seizure-free; p=0.001. Seizure-free patients (Engel 1) and patients with less favourable outcome (Engel 3-4) at PO6m and PO2y rarely changed categories of outcome during the following years (p<0.001). Half of the patients with favourable seizure reduction (Engel 2) changed to seizure-free (Engel 1) or to a worse outcome category (Engel 3-4). Postoperative routine EEG is a good prognostic instrument for the prediction of long-term seizure outcome, especially for TLE. It predicts the running up and down of fits in patients with rare seizures (Engel 2).     

Spike frequency is dependent on epilepsy duration and seizure frequency in temporal lobe epilepsy.

OBJECTIVES: We wanted to investigate factors that are associated with frequency of interictal epileptiform discharges by investigating 303 patients with temporal lobe epilepsy (TLE). METHODS: We included all patients who consecutively underwent the adult presurgical evaluation program at our center and who had intractable, medial TLE with complex partial seizures due to unilateral medial temporal lobe lesions. The interictal EEG samples were automatically recorded and stored on computer. The location and frequency of interictal epileptiform discharges were assessed by visual analysis of interictal EEG samples of 2-minute duration every hour. RESULTS: There were 303 patients (aged 16-63) who met the inclusion criteria. The median interictal epileptiform discharge frequency was 15 IED/h, the median seizure frequency was 4 seizures/month. According to univariate analyses, we found that age at monitoring, epilepsy duration, and higher seizure frequency were associated with higher interictal epileptiform discharge frequency. In the logistic regression analysis, we found that higher seizure frequency (p < 0.001) and longer epilepsy duration (p = 0.007) were independently associated with higher spike frequency, while the age at monitoring was not. CONCLUSIONS: Seizure frequency and epilepsy duration (years of patient's life with seizure activity) were independently associated with IED frequency, suggesting that IED are modulated by seizures.     

Preoperative estimation of seizure control after resective surgery for the treatment of epilepsy

PurposePredicting seizure control after epilepsy surgery is difficult. The objectives of this work are: (a) to estimate the value of surgical procedure, presence of neuroimaging abnormalities, need for intracranial recordings, resection lobe, pathology, durations of epilepsy and follow-up period to predict postsurgical seizure control after epilepsy surgery and (b) to provide empirical estimates of successful outcome after different combinations of the above factors in order to aid clinicians in advising patients presurgically about the likelihood of success under their patients’ individual circumstances.MethodsWe report postsurgical seizure control from all 243 patients who underwent resective surgery for epilepsy at King's College Hospital between 1999 and 2011. Among the 243 patients, 233 had lobar or sub-lobar resections, 8 had multilobar resections and 2 had excision of a hypothalamic hamartoma. We examined the relation between postsurgical seizure control and type of surgical procedure, presence of neuroimaging abnormalities, pathology, resection lobe and the need of intra-cranial electrodes to identify seizure onset.ResultsAmong the 243 patients, 126 (52%) enjoyed outcome grade I, 40 (16%) had grade II, 51 (21%) had grade III and 26 (11%) had grade IV (mean follow-up 41.1 months). Normal neuroimaging or need for intracranial recordings was not associated with poorer outcome. Patients undergoing temporal resections showed better outcome than those with frontal resections, due to the poor outcome seen in frontal patients with normal neuroimaging. Among temporal resections, there was no difference in outcome between patients with and without neuroimaging abnormalities. Among patients with lesions on imaging, temporal and frontal resections showed similar outcomes. Likelihood of favourable outcome under the patient's individual circumstances was estimated by the tables provided. There was an 8–9% decrease in the percentage of grade I between follow-up at 12 and >36 months.ConclusionOverall, nearly 70% of patients undergoing resective surgery enjoy favourable post-surgical seizure control. Normal neuroimaging should not discourage surgery in temporal patients but is a negative prognostic sign in normal MRI frontal patients. There were no statistical differences in outcome between patients with neuroimaging lesions in frontal or temporal lobes.     

Intentional seizure interruption may decrease the seizure frequency in drug-resistant temporal lobe epilepsy.

We investigated the nature of preictal subjective phenomena and whether they had any effect on the seizure frequency in 95 adult patients with medial temporal lobe epilepsy. Seventy-three (77%) patients indicated that they experienced seizure-provoking factors. Ten patients (11%) had prodromas independent of auras, while auras occurred in 89%. Forty-four patients (46%) reported that that they had tried to stop their seizures in the presence of prodroma or aura and this action had resulted in success at least once. Twenty-one patients (22%) regularly tried to stop their seizures because this effort was often successful according to their interpretation. Patients who reported that they could frequently inhibit their seizures had 1.8 +/- 1.6 seizures/month, a significantly lower mean seizure frequency than those 74 patients who did not do it regularly (4.6 +/- 4.8 seizures/month, P<0.001). Patients who reported regular experience in inhibiting intentionally their seizures more often had affective (P=0.05) and vertiginous auras (P<0.01) as well as isolated auras (P<0.05). Patients who experienced provoking factors showed the same seizure frequency as those who did not. Our results suggest that intentional seizure inhibition had an impact on the severity of drug-resistant epilepsy.     

A prospective study of anxiety with respect to seizure outcome after epilepsy surgery.

PURPOSE: To evaluate if degree of anxiety proneness is affected by seizure outcome after epilepsy surgery. METHODS: Five scales related to anxiety, which are part of the Karolinska Scales of Personality (KSP), were administered pre-operatively and 2-8 years post-operatively to 31 female and 26 male patients. High scores indicate a high degree of anxiety. Seizure outcome was either Engel I or Engel II-IV. RESULTS: Mean age of the patients was 39 years (S.D. 10). Forty-seven patients had temporal surgery and 10 patients had extra-temporal surgery. The outcome in 34 patients was classified as Engel I and in 23 patients as Engel II-IV. There were statistically significant decreases (paired t test) in t scores for the Somatic Anxiety scale (expected mean 50, from 55.4 to 50.2, P = 0.001) and the Psychic Anxiety scale (expected mean 50, from 56.2 to 51.6, P = 0.006) in patients in Engel I. No other significant differences were observed. After taking baseline imbalances into account (ANCOVA), there were no statistically significant differences in the change in degree of anxiety proneness between patients in the two outcome groups. CONCLUSION: Patients undergoing successful epilepsy surgery experienced small decreases in somatic anxiety and psychic anxiety. Since there were important pre-operative imbalances between the two outcome groups, these differences could not be attributed to the effect of seizure freedom after epilepsy surgery.     

High frequency oscillations in intra-operative electrocorticography before and after epilepsy surgery

ObjectiveRemoval of brain tissue showing high frequency oscillations (HFOs; ripples: 80–250 Hz and fast ripples: 250–500 Hz) in preresection electrocorticography (preECoG) in epilepsy patients seems a predictor of good surgical outcome. We analyzed occurrence and localization of HFOs in intra-operative preECoG and postresection electrocorticography (postECoG).MethodsHFOs were automatically detected in one-minute epochs of intra-operative ECoG sampled at 2048 Hz of fourteen patients. Ripple, fast ripple, spike, ripples on a spike (RoS) and not on a spike (RnoS) rates were analyzed in pre- and postECoG for resected and nonresected electrodes.ResultsRipple, spike and fast ripple rates decreased after resection. RnoS decreased less than RoS (74% vs. 83%; p = 0.01). Most fast ripples in preECoG were located in resected tissue. PostECoG fast ripples occurred in one patient with poor outcome. Patients with good outcome had relatively high postECoG RnoS rates, specifically in the sensorimotor cortex.ConclusionsOur observations show that fast ripples in intra-operative ECoG, compared to ripples, may be a better biomarker for epileptogenicity. Further studies have to determine the relation between resection of epileptogenic tissue and physiological ripples generated by the sensorimotor cortex.SignificanceFast ripples in intra-operative ECoG can help identify the epileptogenic zone, while ripples might also be physiological.     

Reduction of seizure frequency by clonazepam during cobalt experimental epilepsy

Adult female Sprague-Dawley rats rendered epileptic by bilateral cerebral implantation of cobalt wire were simultaneously prepared with permanent cortical and temporalis muscle electrodes for continuous recording of electroencephalographic (EEG) and electromyographic (EMG) activities. Clonazepam (4, 10 or 40 mg/kg) dissolved in gum acacia was administered once daily intraperitoneally for 5 days beginning 9 days after cobalt implantation. The 40 mg/kg dose completely suppressed generalized seizure activity. Although no tolerance to this effect developed by the fifth day of treatment, generalized seizure activity two days after the last injection was significantly greater in epileptic rats than in control animals. These results suggest that the cobalt model of epilepsy may be useful in the study of mechanisms underlying both anticonvulsant effectiveness and rebound excitability after anticonvulsant drug withdrawal.     

Reduction of seizure frequency after epilepsy surgery in a patient with STXBP1 encephalopathy and clinical description of six novel mutation carriers

Mutations in STXBP1 have been identified in a subset of patients with early onset epileptic encephalopathy (EE), but the full phenotypic spectrum remains to be delineated. Therefore, we screened a cohort of 160 patients with an unexplained EE, including patients with early myoclonic encephalopathy (EME), Ohtahara syndrome, West syndrome, nonsyndromic EE with onset in the first year, and Lennox‐Gastaut syndrome (LGS). We found six de novo mutations in six patients presenting as Ohtahara syndrome (2/6, 33%), West syndrome (1/65, 2%), and nonsyndromic early onset EE (3/64, 5%). No mutations were found in LGS or EME. Only two of four mutation carriers with neonatal seizures had Ohtahara syndrome. Epileptic spasms were present in five of six patients. One patient with normal magnetic resonance imaging (MRI) but focal seizures underwent epilepsy surgery and seizure frequency dropped drastically. Neuropathology showed a focal cortical dysplasia type 1a. There is a need for additional neuropathologic studies to explore whether STXBP1 mutations can lead to structural brain abnormalities.     

Bumetanide reduces seizure frequency in patients with temporal lobe epilepsy

Alterations in the balance of K‐Na‐2Cl cotransporter (NKCC1) and Na‐Cl cotransporter (KCC2) activity may cause depolarizing effect of γ‐aminobutyric Acid (GABA), and contribute to epileptogenesis in human temporal lobe epilepsy. NKCC1 facilitates accumulation of chloride inside neurons and favors depolarizing responses to GABA. In the current pilot study we provide the first documented look at efficacy of bumetanide, a specific NKCC1 antagonist, on reduction of seizure frequency in adult patients with temporal lobe epilepsy. According to our results, seizure frequency was reduced considerably in these patients. Furthermore, epileptiform discharges decreased in two of our patients. If the efficacy of bumetanide is proven in large scale studies, it can be used as a supplemental therapy in temporal lobe epilepsy.