Concept of epilepsy surgery and presurgical evaluation

Epilepsy surgery is a well‐accepted treatment for drug‐resistant epilepsy. The success of the epilepsy surgery depends upon an appropriate presurgical evaluation process which should ensure the selection of suitable patients who are likely to become seizure‐free following surgery without any unacceptable deficit. The two basic goals of the presurgical evaluation are the accurate localization and delineation of the extent of the epileptogenic zone, and its complete and safe resection. The process of the presurgical evaluation requires a multimodality approach wherein each modality provides unique and complimentary information which is combined with the information provided by other modalities to generate a hypothesis with regard to the likely epileptogenic zone. The basic modalities for the presurgical evaluation are clinical history, long‐term video‐EEG recording, high‐resolution MRI, and neuropsychological evaluation. The additional modalities include functional imaging studies, electrical and magnetic source imaging, functional MRI, and intracranial monitoring. Each modality has its own limitations and the information provided by none of them is absolute. Hence, a concordance among the different modalities is the key to surgical success. The presurgical evaluation is a step‐wise process starting form the most basic and most reliable tests and progressing to more complex and invasive modalities. The number of tests required varies according to the complexity involved and may include very basic minimum investigations in a given case, to the use of all the available investigations in more complex cases. The proper selection of various investigations and their accurate interpretation at each stage is required to ensure a successful outcome. In this article, we intend to review some of these basic concepts of presurgical evaluation and epilepsy surgery, and try to provide a frame work of the presurgical evaluation process.     

Occipital ulegyria causing epilepsy and visual impairment: an easily overlooked epilepsy syndrome

Ulegyria refers to scarring of the cerebral cortex usually arising from perinatal ischaemia. The scarring has a specific configuration in which small atrophic circumvolutions at the bottom of a sulcus underlie an intact spared gyral apex. This disconnection of overlying cortex may allow an “epileptogenic” island of cortex to generate seizures. Ulegyria is often associated with epilepsy and developmental delay, however, the syndromic association of visual impairment with epilepsy due to occipital ulegyria may not be recognised as a specific entity. Here, we report a series of five patients with occipital ulegyria who presented with widely variable seizure semiology and an array of visual deficits. In some patients, the link between the epilepsy and the visual impairment was not appreciated until they attended an epilepsy clinic.     

ILAE survey of neuropsychology practice in pediatric epilepsy surgery evaluation

Aims. To determine the extent to which specific neuropsychological measures are in common use around the world for the assessment of children who are candidates for epilepsy surgery. Materials and methods. As part of the work of the International League Against Epilepsy Pediatric Surgical Task Force, a survey was developed and distributed online. The survey consisted of questions related to demographics, training experience, general practice, and specific measures used and at what frequency. Results. Seventy‐eight clinicians with an average of 13.5 years of experience from 19 countries responded to the survey; 69% were English‐speaking. Pre‐ and post‐neuropsychological evaluations were conducted with a majority of children undergoing surgical resection for epilepsy. There was high consistency (>90%) among the domains evaluated, while consistency rate among specific measures was more variable (range: 0–100%). Consistency rates were also lower among respondents in non‐English‐speaking countries. For English‐speaking respondents, at least one measure within each domain was used by a majority (>75%) of clinicians; 19 specific measures met this criterion. Conclusion. There is consensus of measures used in neuropsychological studies of pediatric epilepsy patients which provides a basis for determining which measures to include in establishing a collaborative data repository to study surgical outcomes of pediatric epilepsy. Challenges include selecting measures that promote collaboration with centers in non‐English‐speaking countries and providing data from children under age 5.     

Defecation reflex seizures: a case report with long‐term VEEG monitoring,neuroimaging and comprehensive epilepsy evaluation

Reflex seizures are consistently elicited by a specific afferent sensory stimulus or an activity undertaken by the patient. Among many known stimuli, defecation has rarely been reported. We describe the case of a child with reflex seizures triggered by defecation, considering the diagnostic challenge, epilepsy evaluation with video‐EEG monitoring, as well as impact on neuropsychology, behaviour and quality of life. The child was a 10‐year‐old boy with seizure onset at age four with epilepsy diagnosis established one and a half years later. Seizures were focal with impaired awareness triggered by defecation. Video‐EEG and structural and functional neuroimaging were performed and all pointed to the left temporal region. The patient became seizure‐free with carbamazepine and valproic acid. Neuropsychological and quality of life assessments suggested global impairment, both before and after seizure control. This is the third case of epilepsy induced by defecation reported in the literature. The rarity of this entity may be a diagnostic challenge and postpone specific treatment. Reporting of cases of defecation reflex epilepsy may provide a better understanding of its physiopathology and optimize effective treatment, avoiding cognitive, behavioural and poor social consequences. [Published with video sequence]     

Drug‐resistant epilepsy after treatment for childhood acute lymphocytic leukaemia: from focal epilepsy to Lennox‐Gastaut syndrome

Drug‐resistant epilepsy, not associated with acute brain complications or central nervous system leukaemic involvement, can develop in patients treated for acute lymphocytic leukaemia during childhood. It has been postulated that this rare complication may be due to CNS oncological treatment neurotoxicity, related to intrathecal drugs, such as methotrexate, and brain radiotherapy. We report four patients who developed drug‐resistant epilepsy sometime after receiving treatment for acute lymphocytic leukaemia. All patients were female and received intrathecal methotrexate. One received additional intrathecal cytarabine, and two concomitant brain radiotherapy. Two developed Lennox‐Gastaut type syndrome, one multifocal epilepsy, and one focal epilepsy related to a radiotherapy‐induced cavernous angioma. The development of drug‐resistant epilepsy after treatment for acute lymphocytic leukaemia is a rare complication that may vary, from focal epilepsy to an epileptic encephalopathy. This may appear even years after the treatment has finished and is most likely associated with treatment‐related neurotoxicity.     

Wada testing and fMRI in a polyglot evaluated for epilepsy surgery

Despite advancements in the neurophysiology of language and presurgical evaluation for epilepsy surgery, there is a paucity of information in the literature regarding presurgical evaluation of multilingual patients. We present a case of a 52‐year‐old right‐handed woman with refractory epilepsy who was fluent in six languages and underwent subsequent trilingual presurgical evaluation which included neuropsychological testing, Wada testing, functional magnetic resonance imaging (fMRI), and electrocortical stimulation. These studies suggested a seizure focus in the left temporal lobe and language localization that was predominantly right‐hemispheric; she subsequently underwent left temporal laser interstitial thermal therapy without clinical disturbance in language function while remaining seizure‐free. A multidisciplinary effort was integral in providing an optimal outcome for this patient.     

顽固性癫癎病人的术前综合评估(附40例报告)

目的探讨常规脑电图(REEG)、视频脑电图(VEEG)、MRI、SPECT检查对癫病人术前综合评估致灶定位的意义。方法对40例顽固性癫病人进行REEG、VEEG、MRI及SPECT检查,其中32例行手术治疗,术中行皮质电极(ECoG)和深部电极监测,同时对REEG、VEEG、MRI、SPECT定位致灶的情况进行对比研究。结果REEG异常40例,局灶棘波17例(42.5%);VEEG异常40例,局灶棘波35例(87.5%),两组局灶棘波检出率有显著性差异(P <0.01)。SPECT异常32例(80%),MRI异常31例(77.5%)。在32例手术病人中,VEEG与ECoG病灶一致者30例(93.7%),MRI与ECoG一致者27例(84.3%)。结论VEEG、MRI、EEG、SPECT检查结合临床表现,对顽固性癫病人术前致灶的定位和指导手术治疗有较大的应用价值。     

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.     

Surgery for drug‐resistant tuberous sclerosis complex‐associated epilepsy: who,when, and what

Objective: Tuberous sclerosis complex (TSC) is a multisystem genetic disorder associated with refractory early‐onset epilepsy. Current evidence supports surgery as the intervention most likely to achieve long‐term seizure freedom, but no specific guidelines are available on TSC pre‐surgical workup. This critical review assesses which TSC patients are suitable for surgical treatment, when pre‐surgical evaluation should start, and what degree of surgical resection is optimal for postsurgical outcome. Methods: We searched for publications from 2000 to 2020 in Pubmed and Embase using the terms “tuberous sclerosis,” “epilepsy,” and “epilepsy surgery”. To evaluate postsurgical seizure outcome, we selected only studies with at least one year of follow‐up. Results: Overall, we collected data on 1,026 patients from 34 studies. Age at surgery ranged from one month to 54 years. Mean age at surgery was 8.41 years. Of the diagnostic non‐invasive pre‐surgical tools, MRI and video‐EEG were considered most appropriate. Promising data for epileptogenic tuber detection is provided from invasive SEEG studies. Data on surgery and related outcome were available for 769 patients. Seizure freedom was seen in 64.4% of patients who underwent tuberectomy, 68.9% treated with lobectomy and 65.1% with multilobar resection. The most effective surgical approach was lobectomy, even though more recently tuberectomy associated with the resection of the perituberal area seems to be the best approach to reach seizure freedom. Published postsurgical seizure freedom rates in patients with TSC were between 65% and 75%, but reduced to 48%‐57% over longer follow‐up periods. Early surgery might positively affect neurodevelopmental trajectory in some patients, even though data on cognitive outcome are still to be confirmed with longitudinal studies. Significance: Considering the strong correlation between epilepsy duration and neurocognitive outcome, all patients with TSC ought to be referred early to a dedicated epilepsy centre for individually tailored pre‐surgical evaluation by a multi‐disciplinary epilepsy surgery team.     

Adult absence semiology misinterpreted as mesial temporal lobe epilepsy

Correct diagnosis of seizure type and epilepsy syndrome is the foundation for appropriate antiepileptic drug selection. Inappropriate medication choices occur in the treatment of generalized epilepsy and may aggravate some seizure types, including absence seizures, potentially leading to pseudo‐drug resistance. Fortunately, a correct diagnosis of absence seizures is usually not difficult, though rarely demonstrates electroclinical overlap with focal seizures. EEG can be especially misleading when secondary bilateral synchronous discharges occur in patients with focal seizures. However, the semiology of focal seizures associated with mesial temporal lobe epilepsy has a characteristic and consistent semiology that is the mark of this common epilepsy syndrome in adulthood. We recently encountered a 53‐year‐old female with refractory seizures and a semiology strongly suggesting mesial temporal lobe epilepsy. Instead of focal seizures, prolonged absence seizures were validated by video‐EEG monitoring and she became seizure‐free after a change to broad‐spectrum antiepileptic drugs. This case further expands our understanding of the complexity of semiology in electroclinical classification and the spectrum that may occur in adult absence seizures. It serves to underscore the need for ictal EEG recordings and the importance of concordance with the clinical course during the pre‐surgical evaluation of patients with lesions and drug‐resistant epilepsy. [Published with video sequences]     

Outcome of vagus nerve stimulation for drug‐resistant epilepsy: the first three years of a prospective Japanese registry

Aims. Vagus nerve stimulation (VNS) is an established option of adjunctive treatment for patients with drug‐resistant epilepsy, however, evidence for long‐term efficacy is still limited. Studies on clinical outcomes of VNS in Asia are also limited. We report the overall outcome of a national, prospective registry that included all patients implanted in Japan. Methods. The registry included patients of all ages with all seizure types who underwent VNS implantation for drug‐resistant epilepsy in the first three years after approval of VNS in 2010. The registry excluded patients who were expected to benefit from resective surgery. Efficacy analysis was assessed based on the change in frequency of all seizure types and the rate of responders. Changes in cognitive, behavioural and social status, quality of life (QOL), antiepileptic drug (AED) use, and overall AED burden were analysed as other efficacy indices. Results. A total of 385 patients were initially registered. Efficacy analyses included data from 362 patients. Age range at the time of VNS implantation was 12 months to 72 years; 21.5% of patients were under 12 years of age and 49.7% had prior epilepsy surgery. Follow‐up rate was >90%, even at 36 months. Seizure control improved over time with median seizure reduction of 25.0%, 40.9%, 53.3%, 60.0%, and 66.2%, and responder rates of 38.9%, 46.8%, 55.8%, 57.7%, and 58.8% at three, six, 12, 24, and 36 months of VNS therapy, respectively. There were no substantial changes in other indices throughout the three years of the study, except for self/family‐accessed QOL which improved over time. No new safety issues were identified. Conclusions. Although this was not a controlled comparative study, this prospective national registry of Japanese patients with drug‐resistant epilepsy, with >90% follow‐up rate, indicates long‐term efficacy of VNS therapy which increased over time, over a period of up to three years. The limits of such trials, in terms of AED modifications and during follow‐up and difficulties in seizure counting are also discussed.     

Failure to use new breakthrough treatments for epilepsy

Despite the approval of ~20 additional antiseizure medications (ASMs) since the 1980s, one-third of epilepsy patients experience seizures despite therapy. Drug-resistant epilepsy (DRE) is associated with cognitive and psychiatric comorbidities, socioeconomic impairment, injuries, and a 9.3–13.4 times higher mortality rate than in seizure-free patients. Improved seizure control can reduce morbidity and mortality. Two new ASMs were launched in the United States in 2020: cenobamate for focal epilepsy in adults and fenfluramine for Dravet syndrome (DS). They offer markedly improved efficacy. Cenobamate achieved 21% seizure freedom with the highest dose and decreased tonic–clonic seizures by 93% during maintenance treatment in a randomized clinical trial (RCT). In long-term, open-label studies, 10%–36% of patients were seizure-free for a median duration of ~30–45 months. Fenfluramine treatment in DS reduced convulsive seizure frequency by 56% over placebo at the highest dose, with 8% of patients free of convulsive seizures, and 25% with only one convulsive seizure over 14 weeks. These results were sustained for up to 3 years in open-label extension studies. Mortality was reduced 5-fold. These results are superior to all other approved ASMs, placing these two drugs among the most effective antiseizure therapies. The adverse event profiles resemble those of other ASMs. Despite greater efficacy and similar toxicity, these medications are infrequently used. Two years after US market entry, < 5% of either adults with focal DRE or patients with DS were treated with either cenobamate or fenfluramine. We believe this is a failure of our medical system, resulting from limited knowledge about these drugs stemming partly from the separation of academia from industry; restrictions to access created by health care payors, hospitals, and regulatory agencies; and insufficient post-launch information about the efficacy and safety of these ASMs.