Julia Scholly

Selective amygdalohippocampectomy versus standard temporal lobectomy in patients with mesial temporal lobe epilepsy and unilateral hippocampal sclerosis.

Several studies have demonstrated the positive effect of resective epilepsy surgery in drug-resistant temporal lobe epilepsy (TLE). However, it is still a matter of debate whether selective amygdalohippocampectomy (SAH) or standard temporal lobectomy (STL) are the most effective approaches concerning seizure outcome, quality of life and memory. In each of the two centers participating in this study either SAH or STL was the neurosurgical standard procedure irrespective of contextual aspects. Thus, with this postoperative assessment of resected patients we sought to avoid any selection bias that usually impaired comparative trials of both surgical approaches. We finally identified and studied 95 adult patients who had undergone either SAH (n=46) or STL (n=49) between 1999 and 2009 and fulfilled the inclusion criteria, namely drug-resistant unilateral mesial TLE with hippocampal sclerosis without any further structural lesions. We assessed the postoperative seizure outcome according to the ILAE criteria and postoperative quality of life by means of standardized questionnaires. Finally, we compared postoperative neuropsychological performance in 60 completely seizure-free patients (n=27 after SAH, n=33 after STL) prior to, one year after surgery and at a long-term follow-up with a mean of seven years. 78.2% of SAH and 85.7% of STL were seizure-free at the last observation. Quality of life had improved in 95.6% of the SAH patients and 89.8% of the STL patients. These differences were not statistically significant. Left-sided TLE patients had a significantly worse verbal memory outcome irrespective of the surgical method. However, SAH patients had a significantly better outcome concerning visual encoding, verbal and visual short-term memory and visual working memory. In this study, seizure outcome and quality of life did not differ depending on the surgical approach. However, a more selective resection led to better neuropsychological performances.

First clinical experiences with perampanel—The Kork experience in 74 patients

Perampanel (PER) has been approved for adjunctive treatment of partial‐onset seizures in patients age 12 years and older. In Germany, PER was licensed and marketed in September of 2012. At our tertiary referral epilepsy center, a couple of difficult‐to‐treat patients were awaiting this introduction of PER; therefore, we were able to initiate treatment in many patients within a short period of time. For this report we collected and analyzed the data of the first patients who had been started on add‐on PER between September and December of 2012, so that we were able to evaluate at least 6 months of treatment when we made this analysis. At cutoff in June of 2013, 74 patients could be analyzed. Mean age was 38.4 years (range 15–71 years). PER doses ranged from 4 to 14 mg (mean 8.8 mg). All patients took PER once daily at bedtime. Seventy‐one patients had focal epileptic seizures; the remaining four patients had Lennox‐Gastaut syndrome. Considering the last 3 months of observation compared with baseline, 34 patients (46%) were responders with a reduction of seizure frequency of at least 50%. Ten patients of these (14% of all) were seizure‐free. Adverse events were reported in 40 patients (54%). Leading side effects were somnolence (n = 31, 42%) and dizziness (n = 13, 18%), followed by ataxia, irritability, falls, cognitive slowing, and depression in single cases. Six‐month retention rate was 70%. Our first clinical experiences with add‐on PER in a highly selected group of difficult‐to‐treat epilepsies are promising.

Current use of imaging and electromagnetic source localization procedures in epilepsy surgery centers across Europe

In 2014 the European Union–funded E‐PILEPSY project was launched to improve awareness of, and accessibility to, epilepsy surgery across Europe. We aimed to investigate the current use of neuroimaging, electromagnetic source localization, and imaging postprocessing procedures in participating centers.

Hypothalamic hamartoma: is the epileptogenic zone always hypothalamic? Arguments for independent (third stage) secondary epileptogenesis.

Gelastic seizures associated with hypothalamic hamartomas (HHs) are a clinicoradiologic syndrome presenting with a variety of symptoms, including pharmacoresistant epilepsy with multiple seizure types, electroencephalography (EEG) abnormalities, precocious puberty, behavioral disturbances, and progressive cognitive deterioration. Surgery in adults provides seizure freedom in only one third of patients. The poor results of epilepsy surgery could be explained by an extrahypothalamic epileptogenic zone. The existence of an independent, secondary epileptogenic area with persistent seizures after resection of the presumably primary lesion supports the concept of a “hypothalamic plus” epilepsy. “Hypothalamic plus” epilepsy could be related to either an extrahypothalamic structural lesion (visible on magnetic resonance imaging [MRI] or on neuropathology) or if the former is absent, to a functional alteration with enhanced epileptogenic properties due to a process termed secondary epileptogenesis. We report two patients with gelastic seizures with HH (gelastic seizures isolated or associated with dyscognitive seizures of temporal origin). Both patients underwent two‐step surgery: first an endoscopic resection of the HH, followed at a later time by temporal lobectomy. Both patients became seizure‐free only after the temporal lobectomy. In both cases, neuropathology failed to demonstrate a significant structural lesion in the temporal lobe. To our knowledge, for the first time, these two cases suggest the existence of independent secondary epileptogenesis in humans.

Hyperkinetic seizures in patients with temporal lobe epilepsy: Clinical features and outcome after temporal lobe resection

Purpose:  Temporal lobe epilepsy (TLE) is usually associated with automatisms. Hyperkinetic seizures are supposed to be unusual. Because we witnessed several patients with TLE and ictal hyperkinetic symptoms, we retrospectively assessed the number, clinical findings, and seizure outcome in such patients who had undergone temporal lobe resection.

Selective amygdalohippocampectomy versus standard temporal lobectomy in patients with mesiotemporal lobe epilepsy and unilateral hippocampal sclerosis: post-operative facial emotion recognition abilities

Surgical treatment of mesial temporal lobe epilepsy (mTLE) patients involves the removal either of the left or the right hippocampus. Since the mesial temporal lobe is responsible for emotion recognition abilities, we aimed to assess facial emotion recognition (FER) in two homogeneous patient cohorts that differed only in the administered surgery design since anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH) were performed independently of the underlying electroclinical conditions. The patient selection for the two respective surgical procedures was carried out retrospectively between 2000 and 2009 by two independent epilepsy centres, the Kork Epilepsy Centre, Germany and the University Hospital of Strasbourg, France. All included patients had presented with unilateral hippocampus sclerosis (HS) without associated dysplasia or white matter blurring and had become seizure-free postoperatively. Psychometric evaluation was carried out with the Ekman 60 Faces Test and screened for depression and psychosomatic symptoms with the SCL-90 R and the BDI. Thirty healthy volunteers participated as control subjects. Sixty patients were included, 27 had undergone SAH and 33 ATL. Patients and controls obtained comparable scores in FER for surprise, happiness, anger and sadness. Concerning fear and disgust the patient group scored significantly worse. Left-sided operations led to the the most pronounced impairment. The ATL group scored significantly worse for recognition of fear compared with SAH patients. Inversely, after SAH scores for disgust were significantly lower than after ATL, independently of the side of resection. Unilateral temporal damage impairs FER. Different neurosurgical procedures may affect FER differently.

Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy.

Genetic generalized epilepsy (GGE), formerly known as idiopathic generalized epilepsy, is the most common form of epilepsy and is thought to have predominant genetic etiology. GGE are clinically characterized by absence, myoclonic, or generalized tonic-clonic seizures with electroencephalographic pattern of bilateral, synchronous, and symmetrical spike-and-wave discharges. Despite their strong heritability, the genetic basis of generalized epilepsies remains largely elusive. Nevertheless, recent advances in genetic technology have led to the identification of numerous genes and genomic defects in various types of epilepsies in the past few years. In the present study, we performed whole-exome sequencing in a family with GGE consistent with the diagnosis of eyelid myoclonia with absences. We found a nonsense variant (c.196C>T/p.(Arg66*)) in RORB, which encodes the beta retinoid-related orphan nuclear receptor (RORβ), in four affected family members. In addition, two de novo variants (c.218T>C/p.(Leu73Pro); c.1249_1251delACG/p.(Thr417del)) were identified in sporadic patients by trio-based exome sequencing. We also found two de novo deletions in patients with behavioral and cognitive impairment and epilepsy: a 52-kb microdeletion involving exons 5–10 of RORB and a larger 9q21-microdeletion. Furthermore, we identified a patient with intellectual disability and a balanced translocation where one breakpoint truncates RORB and refined the phenotype of a recently reported patient with RORB deletion. Our data support the role of RORB gene variants/CNVs in neurodevelopmental disorders including epilepsy, and especially in generalized epilepsies with predominant absence seizures.

Hypermetabolism during resting-state FDG-PET suggesting intrinsic epileptogenicity in focal cortical dysplasia.

We report the case of a 21-year-old man who presented drug-resistant epilepsy since the age of 3 years. The underlying type Ia left prefrontal focal cortical dysplasia was revealed by focal hypermetabolism of FDG-PET several years later. The stereo-electroencephalography showed continuous interictal rhythmic spike discharges, suggesting the dysplastic character of the cortex explored by depth electrodes placed into and at the margins of PET abnormalities. The surgical limits of resection were defined based on interictal activity, spontaneous and induced seizures. The patient is seizure-free, with normal electroencephalography and clear improvement of neuropsychological performance, without functional deficit at 3 years postsurgery.

Quality control of elective surgery for drug-resistant epilepsy in a German reference centre—A long-term outcome study

PURPOSE Resective epilepsy surgery is the recommended treatment for a well-defined group of patients with drug-resistant epilepsy. Long-term outcome studies are an appropriate quality control to assess the value of elective surgical procedures ethically and economically. This paper reports the long-term post-surgical follow-up of adult patients of the Kork Epilepsy Centre. METHOD Data collection was performed by means of a questionnaire to obtain updated information about postsurgical outcome, frequency and postsurgical seizure semiology in case of relapse, postsurgical use of antiepileptic drugs, social issues and satisfaction rates. We classified seizure outcome according to the ILAE surgery outcome scale (OC 1-OC 6). RESULTS Outcome data of 340 adult patients were obtained. Mean post-operative follow-up was 6.7 years (range 1.0-21.6 years). Seizure remission was 67% if comprising patients with postoperative auras only (OC 1+OC 2). Sixty-two per cent of patients were completely seizure free. The majority of patients (78%) underwent temporal lobe resections. Sixty-four per cent of these and 52% of the patients with extra-temporal resections became completely seizure-free (OC 1). Only 34% of the patients with negative MRI achieved complete seizure-freedom. CONCLUSION In line with others our huge cohort sample that covers decades of experience with epilepsy surgery revealed satisfying long-term outcome results. Best results were obtained in lesional temporal lobe epilepsy, least favourable results in MRI-negative epilepsy.

Is routine electroencephalography (EEG) a useful biomarker for pharmacoresistant epilepsy

People with seizure disorders who have been treated at the Kork Epilepsy Center over a prolonged time period and who thus provide data concerning the chronic course of epilepsy were investigated in order to address the potential role of electroencephalography (EEG) as a biomarker for pharmacoresistant epilepsy. Clinical course and the corresponding findings from their first recorded EEG, their first EEG following appropriate treatment, and their last EEG were compared. Furthermore, we investigated if interictal epileptiform discharges (IEDs) differ in amplitude and morphology if recorded in long‐term seizure‐free patients. The early cessation of IEDs was a relatively good marker for a good prognosis, especially in idiopathic generalized epilepsies. However, persistent IEDs had no major impact on the long‐term prognosis. We found no differences between IEDs in seizure‐free patients or patients with ongoing seizures. Therefore, in our hands, routine EEG was not an appropriate biomarker for the prediction of pharmacoresistant epilepsy. Additional factors such as etiology and pathophysiology also need to be considered.