Predictors of epilepsy surgery outcome: a meta-analysis

The potential efficacy of temporal and extratemporal resection in patients with partial epilepsy uncontrolled by anti-epileptic drugs is undisputed. However, there are still uncertainties about which patients will benefit most. A systematic review of the available literature has been undertaken by four pairs of reviewers to assess the overall outcome of epilepsy surgery and to identify factors better correlated to seizure outcome. A Medline search for studies on epilepsy surgery published since 1984 was performed. Studies were included if they had a well-defined population and design, a sample size of at least 30 patients, an MRI performed in least 90% of cases, an expected duration of follow-up of at least one year, and a post-operative outcome measured as seizure remission. A good outcome was considered as seizure control or seizure-free status for at least one year or Engel class I. Based on the review of 47 articles meeting all the eligibility criteria, febrile seizures (odds ratio, OR, 0.48; 95% confidence interval, CI, 0.27-0.83), mesial temporal sclerosis (OR 0.47; 95% CI 0.35-0.64), tumors (OR 0.58; 95% CI 0.42-0.80), abnormal MRI (OR 0.44; 95% CI 0.29-0.65), EEG/MRI concordance (OR 0.52; 95% CI 0.32-0.83), and extensive surgical resection (OR 0.24; 95% CI 0.16-0.36) were the strongest prognostic indicators of seizure remission (positive predictors); by contrast, post-operative discharges (OR 2.41; 95% CI 1.37-4.27) and intracranial monitoring (OR 2.72; 95% CI 1.60-4.60) predicted an unfavorable prognosis (negative predictors). Firm conclusions cannot be drawn for extent of resection, EEG/MRI concordance and post-operative discharges for the heterogeneity of study results. Neuromigrational defects, CNS infections, vascular lesions, interictal spikes, and side of resection did not affect the chance of seizure remission after surgery. Despite a number of limitations, the results of the review provide some insight into the selection of the best surgical candidates in clinical practice but raise concerns on the quality of published reports, and may serve as the basis for the identification of better standards to assess surgical outcome in observational studies.     

Headache in patients with epilepsy: a prospective incidence study

High prevalence of headache has been reported in patients with refractory epilepsy in cross-sectional surveys based on retrospective recall. We conducted a prospective study to document the incidence of headache over a 3-month observation period in a cohort of 227 adult patients with less refractory epilepsy. The mean seizure frequency was 2.46 per month. Fifty (22%) patients reported to have had at least one headache episode, 45 (19.8%) had interictal headache, 11 (4.8%) had periictal headache, and 5 (2.2%) had both interictal and periictal headache. Forty-nine percent of the patients with headache took over-the-counter analgesics as acute treatment. The headache was rated to have made very severe or substantial impact on their lives by 34% of patients. A formal headache diagnosis was not made in any of the patients prior to the survey. Although the incidence of headache in epilepsy patients appeared to be low, it was underdiagnosed and associated with substantial negative impact.     

Quality of life after extratemporal epilepsy surgery: a prospective clinical study

PURPOSE: The purpose of this prospective clinical study was to assess quality of life (QOL) and impact of seizure status on QOL in patients with extratemporal epilepsy after surgery. PATIENTS AND METHODS: Twenty-three consecutive patients who had been operated due to extratemporal epilepsy were included in this study. Quality of Life Inventory in Epilepsy-10 (QOLIE-10) questionnaire was completed by all patients before 6 months and 2 years after surgery. Results obtained from short- and long-term follow-up were compared to baseline. Furthermore, patients who were seizure-free since surgery and those who had seizure were also compared in terms of outcome in QOL after surgery. RESULTS: All patients showed significantly improved QOL in both short- and long-term follow-ups compared to preoperative status regardless of seizure status (p<0.001). Seizure-free patients showed better QOL than those of patients who continued to have seizure during postoperative period. Furthermore, improved QOL was correlated with seizure status and shorter duration of epilepsy (p=0.001). CONCLUSION: Our findings showed that improved QOL is related to postoperative seizure status. However, future clinical studies including larger population of patients with extratemporal epilepsy are required to elucidate the role of other factors.     

Predicting memory decline following epilepsy surgery: a multivariate approach

BACKGROUND: While some patients experience a decline in memory function following an anterior temporal lobe resection, there is considerable individual variation in the extent, nature, and direction of postoperative memory change. Patients with surgically remediable temporal lobe epilepsy differ in etiology, the extent and type of underlying pathology, and on demographic and epilepsy-related variables, all of which may have an impact on their pre- and postoperative neuropsychological functioning. This study examined the relationship between these variables and postoperative memory decline. METHODS: Logistic regression was used to examine the effects of age, laterality of surgery, age of onset of epilepsy, underlying pathology and preoperative level of memory function on postoperative verbal learning in 288 patients who had undergone an anterior temporal lobe resection. One hundred twenty-five patients underwent a right temporal lobe resection (RTL), 163 patients underwent a left temporal lobe resection (LTL). RESULTS: In the group as a whole, 25% of the patients demonstrated a significant postoperative deterioration in verbal learning. Postoperative deterioration in verbal learning was significantly associated with higher levels of preoperative function in both the RTL and LTL groups. Older age at the time of the operation and a lower verbal IQ were additional significant predictors for the RTL group. The presence of cortical dysgenesis was a significant predictor of postoperative decline in the LTL group. The logistic regression models accurately identified 3/4 of those who experienced a postoperative decline in memory, using a cutoff of 0.25 or above to identify high risk. CONCLUSIONS: Our analyses suggest that the majority of patients with a high risk of significant postoperative memory decline can be reliably identified preoperatively. These models are valuable tools helping patients make an informed decision regarding surgery.     

Impact of an optimized epilepsy surgery imaging protocol for focal epilepsy: A monocentric prospective study

Objective

To evaluate in a real clinical scenario the impact of the ILAE-recommended “Harmonized neuroimaging of epilepsy structural sequences”- HARNESS protocol in patients affected by focal epilepsy.

Methods

We prospectively enrolled focal epilepsy patients who underwent a structural brain MRI between 2020 and 2021 at Modena University Hospital. For all patients, MRIs were: (a) acquired according to the HARNESS-MRI protocol (H-MRI); (b) reviewed by the same neuroradiology team. MRI outcomes measures were: the number of positive (diagnostic) and negative MRI; the type of radiological diagnosis classified in: (1) Hippocampal Sclerosis; (2) Malformations of cortical development (MCD); (3) Vascular malformations; (4) Glial scars; (5) Low-grade epilepsy-associated tumors; (6) Dual pathology. For each patient we verified for previous MRI (without HARNESS protocol, noH-MRI) and the presence of clinical information in the MRI request form. Then the measured outcomes were reviewed and compared as appropriate.

Results

A total of 131 patients with H-MRI were included in the study. 100 patients out from this cohort had at least one previous noH-MRI scan. Of those, 92/100 were acquired at the same Hospital than H-MRI and 71/92 on a 3T scanner. The HARNESS protocol revealed 81 (62%) positive and 50 (38%) negative MRI, and MCD was the most common diagnosis (60%). Among the entire pool of 100 noH-MRI, 36 resulted positive with a significant difference (p < .001) compared to H-MRI. Similar findings were observed when accounting for the expert radiologists (H-MRI = 57 positive; noH-MRI = 33, p < .001) and the scanner field strength (H-MRI 43 = positive, noH-MRI = 23, p < .001), while clinical information were more present in H-MRI (p < .002).

Significance

The adoption of a standardized and optimized MRI acquisition protocol together with adequate clinical information contribute to identify a higher number of potentially epileptogenic lesions (especially FCD) thus impacting concretely on the clinical management of patients with focal epilepsy.     

Gamma knife surgery in mesial temporal lobe epilepsy: a prospective multicenter study

PURPOSE: This article is the first prospective documentation of the efficacy and safety of gamma knife surgery (GKS) in the treatment of drug-resistant epilepsies of mesial temporal lobe origin. METHODS: From July 1996 to March 2000, three European centers selected 21 patients with mesial temporal lobe epilepsy (MTLE) for a temporal lobectomy. The preoperative investigations included video-EEG with foramen ovale electrodes, magnetic resonance imaging, neuropsychological testing, and the ESI-55 quality-of-life questionnaire. In place of a cortectomy, radiosurgical treatment was performed by using the Leksell Gamma Knife (LGK) at a dose of 24 +/- 1 Gy at the margin. The target included the anterior parahippocampal cortex and the basal and lateral part of the amygdala and anterior hippocampus (head and body). One patient (a heavy smoker) died of a myocardial infarction. Twenty patients were available for prospective evaluation. A minimum 2-year follow-up period included clinical, neuropsychological, and radiologic evaluations. RESULTS: At each 6-month follow-up evaluation, the frequency of seizures was significantly smaller than that at the previous visit. The median seizure frequency of 6.16 the month before treatment was reduced to 0.33 at 2 years after treatment. At 2 years, 65% of the patients (13 of 20) were seizure free. Five patients had transient side effects, including depression, headache, nausea, vomiting, and imbalance. There was no permanent neurological deficit reported except nine visual field deficits. No neuropsychological deterioration was observed 2 years after treatment. The quality of life was significantly better than that before surgery. CONCLUSIONS: The safety and efficacy of the radiosurgical treatment of MTLEs appears good in this group of patient over short-to-middle term. Delay of the seizure cessation was the major disadvantage of GKS. A longer follow-up period is required for confirmation of these results.     

Magnetic source imaging versus intracranial electroencephalogram in epilepsy surgery: a prospective study

OBJECTIVE: Noninvasive brain imaging tests can potentially supplement or even replace the use of intracranial electroencephalogram (ICEEG), an invasive, costly procedure used in presurgical epilepsy evaluation. This study prospectively examined the agreement between magnetic source imaging (MSI) and ICEEG localization in epilepsy surgery candidates. METHODS: Patients completing video monitoring with scalp EEG who had intractable partial epilepsy based on ictal electro-clinico-anatomical features were screened. Forty-nine enrolled patients (mean age, 27 years; range, 1-61 years) completed MSI and ICEEG studies. Decisions about ICEEG and surgery were made at a consensus conference where MSI could only influence ICEEG coverage by indicating supplemental coverage to that already planned by an original hypothesis. RESULTS: The positive predictive value of MSI for seizure localization was 82 to 90%, depending on whether computed against ICEEG alone or in combination with surgical outcome. The kappa score of agreement for MSI with ICEEG was 0.2744 (p < 0.01) INTERPRETATION: MSI yields localizing information with a high positive predictive value in epilepsy surgery candidates who typically require ICEEG. This finding suggests that enough clinical validity exists for MSI to potentially replace ICEEG for seizure localization.     

Posterior quadrant epilepsy surgery: Predictors of outcome

PurposeTo identify predictors of seizure recurrence following posterior quadrant epilepsy surgery.MethodsBetween 1983 and 2008, 43 medically refractory epilepsy patients underwent posterior quadrant epilepsy surgery. Epilepsy surgery involved the occipital lobe in all cases; some cases also included resection of the adjacent parietal or temporal cortex. Using a logistic regression model, we evaluated the relationship between outcome (Engel class I–IV) and 5 outcome predictors: absence of a visual aura, a temporal lobe type aura, versive head movement unaccompanied by a visual aura, non-focal interictal scalp EEG, and surgical pathology other than low grade tumor or cortical dysplasia. We also determined the relative risk for significant post-operative cognitive decline of Wechsler intelligence test score among those receiving complete lobectomies compared to those receiving partial lobectomies.ResultsOverall, outcome was favorable at 1 year following surgery: 22 (51.2%) patients Engel class I, 10 (24%) patients Engel class II, 5 (12%) patients Engel class III, and 6 (14%) patients Engel class IV. The 3 best univariate predictors of seizure recurrence were versive head movement unaccompanied by visual aura, non-focal interictal scalp EEG, and pathology other than low grade tumor or cortical dysplasia. A multivariate predictor combining temporal lobe type aura, versive head movement unaccompanied by visual aura, non-focal interictal scalp EEG, and pathology other than low grade tumor or cortical dysplasia was optimum. Complete lobectomy significantly increased the risk of post-operative decline of Wechsler intelligence score.ConclusionsThese findings indicate that posterior quadrant epilepsy surgery may provide sustained seizure control. A multivariate model combining temporal lobe type aura, versive head movement unaccompanied by a visual aura, non-focal interictal scalp EEG, and pathology other than low grade tumor or cortical dysplasia may contribute to predicting seizure recurrence following posterior quadrant epilepsy surgery. The extent of cortical resection may predict significant cognitive decline in post-operative Wechsler intelligence score.     

Attention and psychomotor speed decline in patients with temporal lobe epilepsy: a longitudinal study

PURPOSE: To assess the possible cognitive alterations in epilepsy patients compared with controls over 5 years, and to investigate the clinical variables mainly implied in mental impairment. METHODS: In our longitudinal single-center study, 50 patients with temporal lobe epilepsy (TLE) and 50 controls were administered the same battery of comprehensive neuropsychological tests at baseline and after 5 years. RESULTS: TLE patients showed a significant impairment in attention and psychomotor speed compared with controls after 5 years, while the other cognitive domains did not exhibit any important changes. This worsening was mainly related to the duration of epilepsy, the age at onset, a history of tonic-clonic seizures and a low educational level. CONCLUSIONS: We believe that tapping the attention and psychomotor speed decline in TLE patients should be considered relevant for future research, in order to achieve a deeper understanding of the cognitive dimensions of this field.     

Predictors of relapse in Chinese schizophrenia patients: a prospective,multi-center study

Objective  

Relapse prevention is the main goal of maintenance treatment in schizophrenia. This study aimed to determine the rate and the socio-demographic and clinical predictors of relapse in Chinese schizophrenia patients following treatment of the acute phase of the illness.     

How patients' psycho-social profiles contribute to decision-making in epilepsy surgery: A prospective study

Objective

Identifying factors associated with surgical decision-making is important to understand reasons for underutilization of epilepsy surgery. Neurologists' recommendations for surgery and patients' acceptance of these recommendations depend on clinical epilepsy variables, for example, lateralization and localization of seizure onset zones. Moreover, previous research shows associations with demographic factors, for example, age and sex. Here, we investigate the relevance of patients' psycho-social profile for surgical decision-making.

Methods

We prospectively studied 296 patients from two large German epilepsy centers. Multiple logistic regression analyses were used to investigate variables linked to neurologists' recommendations for and patients' acceptance of surgery or intracranial video-electroencephalographic monitoring. Patients' psycho-social profiles were assessed via self-reports and controlled for various clinical–demographic variables. Model selection was performed using the Akaike information criterion.

Results

As expected, models for neurologists' surgery recommendations primarily revealed clinical factors such as lateralization and localization of the seizure onset zone, load with antiseizure medication (ASM), and site of the epilepsy-center. For this outcome, employment was the only relevant psycho-social aspect (odds ratio [OR] = .38, 95% confidence interval [CI] = .13–1.11). In contrast, three of the five relevant predictors for patients' acceptance were psycho-social. Higher odds were found for those with more subjective ASM adverse events (OR = 1.04, 95% CI = .99–1.00), more subjective seizure severity (OR = 1.12, 95% CI = 1.01–1.24), and lower subjective cognitive impairment (OR = .98, 95% CI = .96–1.00).

Significance

We demonstrated the relevance of the patients' psycho-social profile for decision-making in epilepsy surgery, particularly for patients' decisions. Thus, in addition to clinical–demographic variables, patients' individual psycho-social characteristics add to the understanding of surgical decision-making. From a clinical perspective, this calls for individually tailored counseling to assist patients in finding the optimal treatment option.     

Nodular heterotopia: a neuropathological study of 24 patients undergoing surgery for drug-resistant epilepsy

Purpose:   Despite the availability of detailed electroclinical and imaging data, only a few neuropathological studies of nodular heterotopia have been published. The aim of this study was to describe the neuropathological features of various types of nodular heterotopia obtained from patients undergoing surgery for intractable epilepsy.
Methods: Specimens of heterotopic nodules taken from 24 patients were neuropathologically investigated using routine and immunocytochemical procedures, and the data were compared with magnetic resonance imaging (MRI), electroclinical findings, and surgical outcomes.
Results: The neuropathological data distinguished two groups. Group 1 (14 patients, 78% in Engel class 1) had similar characteristics regardless of the size, number, or location of the nodules, with both projecting and local circuit neurons in the nodules intermingled with glial cells. Thirteen patients had focal cortical dysplasia. The nodules were identified by MRI in all cases. In group 2 (10 patients, 90% in Engel class 1), all of the nodules were within the temporal lobe and associated with hippocampal sclerosis or gangliogliomas. They were very small (undetected by MRI) and mainly formed by projecting neurons with no evidence of glial cells. All of the patients had cortical dysplasia.
Discussion: The distinctive neuropathological features of the nodules in the two groups suggest different etiopathogenetic mechanisms. In group 2, the presence of nodular formations in association with cortical dysplasia and either hippocampal sclerosis or ganglioglioma raises a question concerning so-called dual pathology in the temporal lobe.     

Selecting patients for epilepsy surgery: identifying a structural lesion

One of the most important components of presurgical evaluation of patients with epilepsy is structural imaging, predominantly using magnetic resonance imaging. This study is now part of the basic assessment of patients with epilepsy and is as important as the electroencephalogram. Epilepsy protocol magnetic resonance imaging studies must be part of the overall assessment of the patient. To understand the basis of the epileptic disorder, interpretation of these investigations relies on knowledge of the clinical details and features of the seizures, the functional abnormality in the brain as shown on the electroencephalogram, and structural assessment of the brain with a magnetic resonance imaging study optimized for epilepsy. This review considers the essential elements of this issue and gives a broad overview of what imaging options are available for the investigation of the patient with epilepsy from the perspective of the practicing epileptologist.     

Predictors of outcome in pediatric epilepsy surgery

OBJECTIVE: To determine the correlation between pre- and perioperative variables on the outcome of children undergoing focal resections for medically intractable partial epilepsy. METHODS: Retrospective analysis of pre- and perioperative variables in a cohort of 75 patients younger than 12 years of age who underwent excisional surgery and had at least 1 year of follow-up. Outcome, measured by postoperative seizure frequency, was analyzed as a function of age at seizure onset, duration of epilepsy, presence of cognitive impairment, lobe of seizure origin, presence of a lesion, histopathology, and completeness of resection. Completeness of resection was defined on the basis of excising both the entire structural lesion if present and the region revealing prominent interictal and ictal abnormalities on intracranial EEG. RESULTS: Seventy-seven percent of patients had good outcomes (class 1 or 2), and 59% were seizure-free. Lesional status, site of resection, and pathologic diagnoses were not significant predictors of outcome except for in multilobar resection, for which overall outcome was relatively poor (44% class 3 or 4; 22% seizure-free). Completeness of resection was the only significant predictor of good outcome (p < 0.001), with 92% of patients who underwent complete resection of the epileptogenic zone achieving good outcome compared with 50% of patients who had incomplete resections. CONCLUSION: In this series of pediatric patients, complete resection of the lesion and the electrographically abnormal region was the main determinant of outcome after focal resections. Except for multilobar resections, other factors examined in this study did not significantly influence postoperative seizure prognosis and should not influence candidate selection for the surgical process.     

Intelligence in epilepsy: a prospective study in children

A prospective study tested the stability of the IQ in children with seizure disorders. Seventy-two children with epilepsy underwent psychological evaluations within two weeks of initial diagnosis and yearly thereafter for an average of 4 years. Forty-five of the patients also had a nonepileptic sib evaluated in parallel. The mean IQ for all the children with epilepsy was 99.7 (+/- 20.2, standard deviation) at the time of the initial test, not significantly different from the siblings. This score did not change appreciably with time. Eight of the 72 epileptic patients (11.1%), however, had a persistent decrease in IQ of 10 points or more. These patients had a higher incidence of drug levels in the toxic range (p less than 0.001), their epilepsy was more difficult to control (p less 0.005), and their seizures began at an earlier age (p less than 0.05). Discriminant analysis is revealed that the number of drugs to which the patient became toxic and the age at seizure onset were the two best predictors of ultimate IQ. These two predictors correctly classified 71% of all patients as to whether their IQ would drop by 10 or more points during the test period, remain within 10 points of the initial test score, or increase by more than 10 points. Total number of seizures and seizure control were less good predictors, according to this method of analysis. The findings suggest that, in younger children in particular, total seizure control should not be achieved at the price of repeated episodes of drug toxicity.     

Topiramate in refractory epilepsy: a prospective observational study

PURPOSE: This prospective observational study explored the efficacy and tolerability of topiramate (TPM) in patients with refractory epilepsy attending a single outpatient clinic. METHODS: One hundred seventy patients (82 men, 88 women, aged 18-75 years) with refractory localization-related (n = 134) or idiopathic generalized epilepsy (n = 36) were started on adjunctive TPM using a standard titration schedule. TPM was introduced after a 3-month prospective baseline, and doses were adjusted according to clinical response. End points were seizure freedom for 6 months, > or =50% seizure reduction for 6 months compared with baseline at the highest tolerated TPM dose (responder), or discontinuation of TPM because of side effects, lack of efficacy, or both. RESULTS: Thirty-nine (23%) patients were seizure-free, and 80 (47%) more patients had a useful therapeutic response. Thirteen seizure-free patients and 16 responders took 100 mg of TPM daily or less. TPM was discontinued in 51 (30%) patients. The most common side effects resulting in withdrawal were fatigue, weight loss, irritability, paresthesia, depression, and headache. Concomitant antiepileptic drugs (AEDs) were stopped in 30 patients. Twelve were established on TPM monotherapy, eight of whom remained seizure-free. Final TPM doses and concentrations varied widely among the three outcome groups. CONCLUSIONS: TPM was efficacious as add-on and monotherapy in patients with refractory partial and generalized seizures in everyday clinical use. A good response was obtained in many patients with TPM doses substantially lower than those studied in regulatory clinical trials. The wide variation in dose-response and dose-toxicity relationships may reflect different neurobiologies causing refractory epilepsy and differential efficacy of AED combinations.