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.     

Coregistration of multimodal imaging is associated with favourable two‐year seizure outcome after paediatric epilepsy surgery

Aims. Multimodal coregistration uses multiple image datasets coregistered to an anatomical reference (i.e. MRI), allowing multiple studies to be viewed together. Commonly used in intractable epilepsy evaluation and generally accepted to improve localization of the epileptogenic zone, data showing that coregistration improves outcome is lacking. We compared seizure freedom following epilepsy surgery in paediatric patients, evaluated before and after the use of coregistration protocols at our centre, to determine whether this correlated with a change in outcome. Methods. We included paediatric epilepsy surgery patients with at least one anatomical and one functional neuroimaging study as part of their presurgical evaluation. Preoperatively designated palliative procedures and repeat surgeries were excluded. Multiple pre‐, peri‐, and postoperative variables were compared between groups with the primary outcome of seizure freedom. Results. In total, 115 were included with an average age of 10.63 years (0.12–20.7). All evaluations included video‐EEG (VEEG) and MRI. Seven (6%) had subtraction single‐photon emission CT (SPECT), 46 (40%) had positron emission tomography (PET), and 62 (54%) had both as part of their evaluation. Sixty (52%) had extratemporal epilepsy and 25 (22%) were MRI‐negative. Sixty‐eight (59%) had coregistration. Coregistered patients were less likely to undergo invasive EEG monitoring (p=0.045) and were more likely to have seizure freedom at one (p=0.034) and two years (p<0.001) post‐operatively. A logistic regression accounting for multiple covariates supported an association between the use of coregistration and favourable post‐surgical outcome. Conclusions. Coregistered imaging contributes to favourable postoperative seizure reduction compared to visual analysis of individual modalities. Imaging coregistration is associated with improved outcome, independent of other variables after surgery. Coregistered imaging may reduce the need for invasive EEG monitoring, likely due to improved confidence in presurgical localization. These findings support the use of multimodal coregistered imaging as part of the presurgical assessment in patients evaluated for surgical treatment of intractable epilepsy.     

Drug‐resistant parietal lobe epilepsy: clinical manifestations and surgery outcome

Aim. We reviewed a large surgical cohort to investigate the clinical manifestations, EEG and neuroimaging findings, and postoperative seizure outcome in patients with drug‐resistant parietal lobe epilepsy (PLE). Methods. All drug‐resistant PLE patients, who were investigated for epilepsy surgery at Jefferson Comprehensive Epilepsy Center between 1986 and 2015, were identified. Demographic data, seizure data, EEG recordings, brain MRI, pathological findings, and postsurgical seizure outcome were reviewed. Results. In total, 18 patients (11 males and seven females) were identified. Sixteen patients (88%) had tonic‐clonic seizures, 12 (66%) had focal seizures with impaired awareness, and 13 (72%) described auras. Among 15 patients who had brain MRI, 14 patients (93%) had parietal lobe lesions. Only three of 15 patients (20%) who had interictal scalp EEG recordings showed parietal interictal spikes. Of 12 patients with available ictal surface EEG recordings, only three patients (25%) had parietal ictal EEG onset. After a mean follow‐up duration of 8.6 years, 14 patients (77.7%) showed a favourable postoperative seizure outcome. Conclusion. In patients with PLE, semiology and EEG may be misleading and brain MRI is the most valuable tool to localize the epileptogenic zone. Postsurgical seizure outcome was favourable in our patients with drug‐resistant parietal lobe epilepsy.     

The natural history of epilepsy in tuberous sclerosis complex

Background : Although epilepsy affects most patients with tuberous sclerosis complex (TSC), little is known about the natural history of epilepsy in this genetic disease. Methods : A retrospective chart review of all patients with TSC seen between January 2002 and October 2008. Charts were reviewed for a history of infantile spasms (IS), seizure other than IS, refractory epilepsy, Lennox‐Gastaut syndrome (LGS), anticonvulsant medication use, ages of seizure onset, last seizure, last clinic visit, clinical seizure phenotype(s), cognitive impairment, and genetic mutation. Results : Two hundred ninety‐one patients were included. Among these patients, 37.8% had a history of IS; 85.2% had a history of seizure; 54.1% developed multiple seizure types, not including IS; 63.2% had seizure onset in the first year of life; and 12.1% of adults without a seizure history developed epilepsy. Of epilepsy patients, 62.5% developed refractory epilepsy and 33.5% achieved epilepsy remission; 37.5% of these patients achieved medication freedom. IS was a risk factor for refractory epilepsy (p<0.0001) and LGS (p<0.0001). History of seizure, IS, age at seizure onset, and refractory epilepsy each correlated with poor cognitive outcome (p<0.0001). Epilepsy remission correlated with better cognitive outcome (p<0.0001). TSC2 was a risk factor for IS and epilepsy; patients without an identified mutation were more likely to achieve remission. Conclusion : Most patients with TSC develop epilepsy and most develop multiple seizure types. Onset typically occurs in the first year of life; however, adults remain at risk. Although refractory epilepsy is common, many patients achieve seizure control. Many features of seizure history are predictive of cognitive and epilepsy outcome.     

Epilepsy due to mutations in the mitochondrial polymerase gamma (POLG) gene: A clinical and molecular genetic review

We performed a systematic review of the clinical, molecular, and biochemical features of polymerase gamma (POLG)–related epilepsy and current evidence on seizure management. Patients were identified from a combined electronic search of articles using Ovid Medline and Scopus databases, published from January 2000 to January 2015. Only patients with a confirmed genetic diagnosis of POLG mutations were considered. Seventy‐two articles were included for analysis. We identified 128 pathogenic variants in 372 patients who had POLG‐related epilepsy. Among these, 84% of the cases harbored at least one of these pathogenic variants: p.Ala467Thr, p.Trp748Ser, and p.Gly848Ser. A bimodal distribution of disease onset was present in early childhood (<5 years) and adolescence; female patients had a later presentation than male patients (median age 4.00 vs. 1.83 years, p‐value = 0.041). Focal‐onset seizure including convulsive, myoclonus, and occipital seizures was common at the outset and was refractory to pharmacotherapy. We confirmed that homozygous pathogenic variants located in the linker region of POLG were associated with later age of onset and longer survival compared to compound heterozygous variants. In addition, biochemical and molecular heterogeneities in different tissues were frequently observed. POLG‐related epilepsy is clinically heterogeneous, and the prognosis is, in part, influenced by the location of the variants in the gene and the presence of hepatic involvement. Normal muscle and fibroblast studies do no exclude the diagnosis of POLG‐related mitochondrial disease and direct sequencing of the POLG gene should be the gold standard when investigating suspected cases.     

Temporal patterns and mechanisms of epilepsy surgery failure

Epilepsy surgery is an accepted treatment option in patients with medically refractory focal epilepsy. Despite various advances in recording and localization noninvasive and invasive techniques (including electroencephalography (EEG), magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetoencephalography (MEG), subdural grids, depth electrodes, and so on), the seizure outcome following surgical resection remains suboptimal in a significant number of patients. The availability of long‐term outcome data on an increasing number of patients suggests two major temporal patterns of seizure recurrence (early vs. late) that implicate the following two different mechanisms for seizure recurrence: (1) a failure to either define/resect the epileptogenic zone, and (2) the nonstatic nature of epilepsy as a disease through the persistence of proepileptic cortical pathology. We describe the temporal patterns of epilepsy surgery failures and discuss their potential clinical, histopathologic, genetic, and molecular mechanisms. In addition, we review predictors of successful surgical interventions and analyze the natural history of epilepsy following surgical intervention. We hypothesize that the acute/early postoperative failures are due to errors in localizing and/or resecting the epileptic focus, whereas late recurrences are likely due to development/maturation of a new and active epileptic focus (de novo epileptogenesis).     

Early‐life epileptic encephalopathy secondary to SZT2 pathogenic recessive variants

Advances in genetic testing have led to the identification of increasing numbers of novel gene mutations that underlie infantile‐onset epileptic encephalopathies. Recently, a mutagenesis screen identified a novel gene, SZT2, with no known protein function that has been linked to epileptogenesis in mice. Thus far, two clinical reports have identified children with different recessive mutations in SZT2 and varying clinical phenotypes. One case report described patients with epileptic encephalopathy and the other noted patients with cognitive deficiencies, but normal MRI and no epilepsy. This case report identifies novel mutations (a compound heterozygous frameshift and a nonsense variant) in the SZT2 gene with distinct clinical and radiographic findings relative to those previously reported. Our patient presented with intractable epilepsy at 2 months of age. Seizures were refractory to numerous antiepileptic medications and the patient finally achieved seizure cessation at age 3 years with a combination of divalproex and lamotrigine. Our patient had similar facial dysmorphisms (macrocephaly, high forehead, and down‐slanted palpebral fissures) to a previous case with truncating mutation. While developmental delay and cognitive deficiencies were present, our case had unique MRI findings suggesting migrational abnormalities not previously reported in other cases.     

7 tesla T2*‐weighted MRI as a tool to improve detection of focal cortical dysplasia

Focal cortical dysplasia is one of the most common underlying pathologies in patients who undergo surgery for refractory epilepsy. Absence of a MRI‐visible lesion necessitates additional diagnostic tests and is a predictor of poor surgical outcome. We describe a series of six patients with refractory epilepsy due to histopathologically‐confirmed focal cortical dysplasia, for whom pre‐surgical 7 tesla T₂*‐weighted MRI was acquired. In four of six patients, T₂* sequences showed areas of marked superficial hypointensity, co‐localizing with the epileptogenic lesion. 7 tesla T₂* hypointensities overlying focal cortical dysplasia may represent leptomeningeal venous vascular abnormalities associated with the underlying dysplastic cortex. Adding T₂* sequences to the MRI protocol may aid in the detection of focal cortical dysplasias.     

Ictal SPECT is useful in localizing the epileptogenic zone in infants with cortical dysplasia

Aims. To assess the localizing value of ictal SPECT in very young epilepsy surgery candidates when cerebral haemodynamic responses are known to be immature. Methods. We retrospectively studied 13 infants with intractable focal epilepsy caused by focal cortical dysplasia (FCD). Completeness of resection of the (1) ictal SPECT hyperperfusion zone and (2) cerebral cortex with prominent ictal and interictal abnormalities on intracranial EEG (ECoG or long‐term invasive monitoring) and the MRI lesion, when present, were correlated with postoperative seizure outcome. Results. All five patients with complete resection of the ictal SPECT hyperperfusion zone were seizure‐free compared to only one of eight patients with incomplete or no excision of hyperperfusion zones (p=0.00843). Similar results were noted for the MRI/iEEG‐defined epileptogenic region; five of six patients with complete removal were seizure‐free, whereas only one of seven incompletely resected patients was seizure‐free (p=0.02914). All four patients who underwent complete resection of both regions were seizure‐free compared to none of the six with incomplete resection (p=0.01179). Conclusion. Despite age‐related differences in cerebral perfusion, ictal SPECT provides useful localization data in infants with FCD. Complete resection of the hyperperfused regions is a strong predictor of favourable outcome. The added information may alleviate the need for invasive EEG evaluations in some patients.     

Contralateral MRI abnormalities in candidates for hemispherectomy for refractory epilepsy

Purpose: To assess the impact of contralateral magnetic resonance imaging (MRI) findings on seizure outcome after hemispherectomy for refractory epilepsy. Methods: We retrospectively reviewed 110 children, 0.4–18 (median 5.9) years of age, who underwent hemispherectomy for severe refractory epilepsy at Cleveland Clinic Children’s Hospital. In children with contralateral (as well as ipsilateral) MRI findings appreciated preoperatively, the decision to proceed to surgery was based on other features concordant with the side with the most severe MRI abnormality, including ipsilateral epileptiform discharges, lateralizing seizure semiology, and side of hemiparesis. Results: We retrospectively observed contralateral MRI abnormalities (predominantly small hemisphere, white matter loss or abnormal signal, or sulcation abnormalities) in 81 patients (74%), including 31 of 43 (72%) with malformations of cortical development (MCD), 31 of 42 (73%) with perinatal injury from infarction or hypoxia, and 15 of 25 (60%) with Rasmussen’s encephalitis, Sturge‐Weber syndrome, or posttraumatic encephalomalacia. Among 84 children (76%) with lesions that were congenital or acquired pre‐ or perinatally, 67 (83%) had contralateral MRI abnormalities (p = 0.02). Contralateral findings were subjectively judged to be mild or moderate in 70 (86%). At follow‐up 12–84 (median 24) months after surgery, 79% of patients with contralateral MRI abnormalities were seizure‐free compared to 83% of patients without contralateral MRI findings, with no differences based on etiology group or type or severity of contralateral MRI abnormality. Discussion: MRI abnormalities, usually mild to moderate in severity, were seen in the contralateral hemisphere in the majority of children who underwent hemispherectomy for refractory epilepsy due to various etiologies, especially those that were congenital or early acquired. The contralateral MRI findings, always much less prominent than those in the ipsilateral hemisphere, did not correlate with seizure outcome and may not contraindicate hemispherectomy in otherwise favorable candidates.     

Additional clinical value of voxel‐based morphometric MRI post‐processing for MRI‐negative epilepsies: a prospective study

Aims: Magnetic resonance imaging is of paramount importance in the presurgical evaluation of drug resistant epilepsy. Detection of a potentially epileptogenic lesion significantly improves seizure outcome after surgery. To optimize the detection of subtle lesions, MRI post‐processing techniques may be of essential help. Methods: In this study, we aimed to evaluate the detection rate of the voxel‐based morphometric analysis program (MAP) in a prospective trial. We aimed to study the MAP+ findings in terms of their clinical value in the decision‐making process of the presurgical evaluation. Results: We included, prospectively, 21 patients who had negative MRI by visual analysis. In a first step, results of the conventional non‐invasive presurgical evaluation were discussed, blinded to the MAP results, in multidisciplinary patient management conferences to determine the possible seizure onset zone and to set surgical or invasive evaluation plans. Thereafter, MAP results were presented, and the change of initial clinical plan was recorded. All MAP detections were reaffirmed by a neuroradiologist with epilepsy expertise. For the 21 patients included, mean age at the time of patient management conference was 26 years (SD 15 +/‐ years, range: 5–54 years). In total, 4/21 had temporal lobe epilepsy and 17/21 had extra‐temporal lobe epilepsy. MAP was positive in 10/21 (47%) patients and in 6/10 (60%) a diagnosis of focal cortical dysplasia was confirmed after neuroradiologist review, corresponding to a 28% detection rate. MAP+ findings had a clear impact on the initial management in 7/10 patients (7/21, 33% of all patients), which included an adaptation of the intracranial EEG plan (6/7 patients), or the decision to proceed directly to surgery (1/7 patients). Conclusion: MRI post‐processing using the MAP method yielded an increased detection rate of 28% for subtle dysplastic lesions in a prospective cohort of MRI‐negative patients, indicating its potential value in epilepsy presurgical evaluation.     

Parahippocampal epilepsy with subtle dysplasia: A cause of “imaging negative” partial epilepsy

Purpose: Lesion‐negative refractory partial epilepsy is a major challenge in the assessment of patients for potential surgery. Finding a potential epileptogenic lesion simplifies assessment and is associated with good outcome. Here we describe imaging features of subtle parahippocampal dysplasia in five cases that were initially assessed as having imaging‐negative frontal or temporal lobe epilepsy. Methods: We analyzed the clinical and imaging features of five patients with seizures from the parahippocampal region. Results: Five patients had subtle but distinctive magnetic resonance imaging (MRI) abnormalities in the parahippocampal gyrus. This was a unilateral signal abnormality in the parahippocampal white matter extending into gray matter on heavily T₁‐ and T₂‐weighted images with relative preservation of the gray–white matter boundary on T₁‐weighted volume sequences. Only one of these patients had typical electroclinical unilateral temporal lobe epilepsy (TLE); one mimicked frontal lobe epilepsy, two showed bitemporal seizures, and one had unlocalized partial seizures. All have had surgery; four are seizure‐free (one has occasional auras only, follow‐up 6 months to 10 years), and one has a >50% seizure reduction. Histopathologic evaluation suggested dysplastic features in the surgical specimens in all. Discussion: In patients with lesion‐negative partial epilepsy with frontal or temporal semiology, or in cases with apparent bitemporal seizures, subtle parahippocampal abnormalities should be carefully excluded. Recognizing the MRI findings of an abnormal parahippocampal gyrus can lead to successful surgery without invasive monitoring, despite apparently incongruent electroclinical features.     

Utility of electrocorticography in the surgical treatment of cavernomas presenting with pharmacoresistant epilepsy

Aim. To describe the general aspects of cavernomas and epilepsy and review the available literature on the utility of electrocorticography (ECoG) in cerebral cavernoma surgery. Methods. We searched studies in PubMed, MedLine, Scopus, Web of Science, and Google Scholar (from January 1969 to December 2013) using the keywords “electrocorticography” or “ECoG” or “prognosis” or “outcome” and “cavernomas”. Original articles that reported utility of ECoG in epilepsy surgery were included. Four review authors independently selected the studies, extracted data, and assessed the methodological quality of the studies using the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines, and Jadad Scale. A meta‐analysis was not possible due to methodological, clinical, and statistical heterogeneity of included studies. We analysed six articles with a total of 219 patients. Results. The most common surgical approach was lesionectomy using ECoG in the temporal lobe with Engel I outcome range from 72.7 to 100%. Conclusions. Small controlled studies suggest that ECoG‐guided resection offers the best functional results in seizure control for subjects undergoing cavernoma surgery, especially in the temporal lobe.     

Whole‐exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel,de novo GRIN2A mutation

We present a 4‐year‐old girl with profound global developmental delay and refractory epilepsy characterized by multiple seizure types (partial complex with secondary generalization, tonic, myoclonic, and atypical absence). Her seizure semiology did not fit within a specific epileptic syndrome. Despite a broad metabolic and genetic workup, a diagnosis was not forthcoming. Whole‐exome sequencing with a trio analysis (affected child compared to unaffected parents) was performed and identified a novel de novo missense mutation in GRIN2A, c.2449A>G, p.Met817Val, as the likely cause of the refractory epilepsy and global developmental delay. GRIN2A encodes a subunit of N‐methyl‐d ‐aspartate (NMDA) receptor that mediates excitatory transmission in the central nervous system. A significant reduction in the frequency and the duration of her seizures was observed after the addition of topiramate over a 10‐month period. Further prospective studies in additional patients with mutations in GRIN2A will be required to optimize seizure management for this rare disorder. This report expands the current phenotype associated with GRIN2A mutations. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .     

Mutational analysis of paediatric patients with tuberous sclerosis complex in Korea: genotype and epilepsy

To date, only a few studies have reported that, in tuberous sclerosis, TSC2 mutations are more frequently associated with infantile spasms and cognitive impairment compared to TSC1 mutations. We analyzed the mutational spectrum of patients with tuberous sclerosis in Korea and attempted to explore the associations between genotype and seizure type/outcome. We performed mutational analyses on 70 unrelated patients with clinically confirmed tuberous sclerosis by using direct DNA sequencing and/or multiplex ligation‐dependent probe amplification. The patients’ medical records, including epilepsy type and outcome, were reviewed retrospectively. We identified pathogenic mutations in 55 patients (79%), 25 of which were novel. There were 12 TSC1 mutations and 43 TSC2 mutations. TSC1 mutations included 8 frameshift and 4 nonsense mutations. TSC2 mutations included 12 frameshift, 10 nonsense, 6 splicing, and 6 missense mutations, as well as 4 in‐frame deletions and 5 large deletions. Fifty‐eight patients had epilepsy (83%), including 19 patients with a history of infantile spasms. Compared to patients with TSC1 mutations, individuals with TSC2 mutations had a significantly higher frequency of epilepsy (p<0.05) and tended to have a higher frequency of infantile spasms (37% vs 17%; p<0.3). Most of the patients with TSC2 mutations who developed infantile spasms exhibited subsequent epilepsy (13/14; 93%). However, the presence/absence of infantile spasms did not influence seizure remission or cognitive outcome.     

A comprehensive clinico‐pathological and genetic evaluation of bottom‐of‐sulcus focal cortical dysplasia in patients with difficult‐to‐localize focal epilepsy

Aims. We comprehensively studied the clinical presentation, stereo‐EEG and MRI findings, histopathological diagnosis, and brain somatic mutations in a retrospective series of drug‐resistant patients with difficult‐to‐localize epilepsy due to focal cortical dysplasia at the bottom of a sulcus (BOS‐FCD). Methods. We identified 10 patients with BOS‐FCD from the Cleveland Clinic epilepsy surgery database submitted for intracranial video‐EEG monitoring. Brain MRI, including voxel‐based morphometric analysis and surgical tissue submitted for histopathology, was reviewed. Paraffin tissue samples from five patients were made available for targeted next‐generation sequencing. Postsurgical follow‐up was available in nine patients. Results. BOS‐FCD was identified in the superior frontal sulcus in six patients, inferior frontal sulcus in one patient, central sulcus in one patient, and intraparietal sulcus in two patients. All patients had stereotyped seizures. Intracranial EEG recordings identified ictal onset at the BOS‐FCD in all 10 patients, whereas ictal scalp EEG had a localizing value in only six patients. Complete resection was achieved by lesionectomy or focal corticectomy in nine patients. Histopathologically, six patients had FCD type IIb and three had FCD type IIa. Next‐generation sequencing analysis of DNA extracted from lesion‐enriched (micro‐dissected) tissue from five patients with FCD type II led to the identification of a germline frameshift insertion in DEPDC5, introducing a premature stop in one patient. Eight out of nine patients with available follow‐up were completely seizure‐free (Engel Class IA) after a mean follow‐up period of six years. Conclusion. Our results confirm previous studies classifying difficult‐to‐localize BOS‐FCD into the emerging spectrum of FCD ILAE type II mTORopathies. Further studies with large patient numbers and ultra‐deep genetic testing may help to bridge the current knowledge gap in genetic aetiologies of FCD.     

Autosomal dominant lateral temporal lobe epilepsy associated with a novel reelin mutation

Aims. Reelin mutations are responsible for a minority of families with autosomal dominant lateral temporal lobe epilepsy. Here, we report a novel nuclear family with distinct clinical and neuroradiological findings. Methods. We studied the proband and her mother by means of EEG, video‐EEG, 3T MRI, FDG‐PET and genetic testing. Results. Both patients had a focal drug‐resistant epilepsy with onset at the age of 16 and focal seizures with typical auditory features combined with fear, followed by loss of contact or evolving to bilateral tonic‐clonic seizures. The proband's ictal EEG showed clear left temporal seizure onset, and cerebral MRI revealed subtle left temporal changes (mild hypotrophy, slight blurring of the white and grey matter and hyperintensity) with corresponding left temporal mesial focal hypometabolism on FDG‐PET. Genetic testing identified a missense variant, c.6631C>T (p.Arg2211Cys), in reelin repeat #5 in both patients, which markedly affected the secretion of the protein. Conclusion. The data from this family support previous findings indicating that reelin mutations are a cause of autosomal dominant lateral temporal lobe epilepsy which has a clinical spectrum that may also encompass drug‐resistant epilepsy associated with mild MRI temporal changes.     

Acute postoperative seizures after epilepsy surgery – a long‐term outcome predictor?

Alfstad KÅ, Lossius MI, Røste GK, Mowinckel P, Scheie D, Borota OC, Larsson PG, Nakken KO. Acute postoperative seizures after epilepsy surgery – a long‐term outcome predictor?
Acta Neurol Scand: 2011: 123: 48–53.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives – The prognostic value of acute postoperative seizures (APS) after epilepsy surgery is much debated. This study evaluated APS, defined as seizures in the first week post‐surgery, as a predictor of long‐term seizure outcome, and investigated the utility of other potential outcome predictors. Materials and methods – Medical records of 48 patients with temporal and extra‐temporal epilepsy surgery were studied. Forty patients had lesional surgery. All had at least 2 year postoperative follow‐up. Results – At 2 year follow‐up, 25 patients (53%) were seizure free. Univariate analysis showed that APS (P = 0.048), using ≥six AEDs prior to surgery (P = 0.03), pathological postoperative EEG (P = 0.043) and female gender (P = 0.012) were associated with seizure recurrence. Conclusions – Univariate analysis indicate that APS, a high number of AEDs used prior to surgery, and pathological postoperative EEG are possible predictors of seizure recurrence after epilepsy surgery. Only gender retained significance in the multivariate analysis.     

Correlation of widespread preoperative magnetic resonance imaging changes with unsuccessful surgery for hippocampal sclerosis

Despite meticulous preoperative assessment, about 30% of patients with refractory partial epilepsy due to hippocampal sclerosis fail to become seizure free after appropriate temporal lobe surgery. Perioperative complications, hippocampal remnants, and bitemporal disease do not account for all failures; extrahippocampal epileptogenic tissue must persist in some patients. Such dual pathology is detected on routine visual inspection of magnetic resonance images in about 15% of patients with hippocampal sclerosis, but most such patients are excluded from surgery. We postulated that some patients have occult extrahippocampal cerebral structural abnormalities (i.e., subtle dual pathology) and that the presence of these abnormalities would be associated with a poor surgical outcome. Quantitative postprocessing of preoperative magnetic resonance images from 27 patients subsequently proved to have hippocampal sclerosis demonstrated extrahippocampal structural abnormalities in 14, 10 of whom did not become seizure free, while 11 of 13 patients without such changes did become seizure free (χ², p < 0.005). Such structural information may supplement clinical decision making in some patients being evaluated for epilepsy surgery and help to explain the biological basis of poor outcome from such surgery.     

Myoclonic jerks are commonly associated with absence seizures in early‐onset absence epilepsy

Aim. Typical absence seizures are observed in various epilepsy syndromes, however, few series have focused on early‐onset absence epilepsy (EOAE). We aimed to evaluate the occurrence of this seizure type in children under 4 years of age in order to evaluate their electroclinical characteristics and outcome. Methods. We retrospectively studied (2006–2014) the electroclinical features of children with normal development and typical absence seizures starting before the age of 4 (with available pre‐treatment video‐EEG). Results. Nine patients were included. Among them, eight patients had rhythmic myoclonic jerks involving the muscles of the upper face (eyebrows and eyelids) or neck, present from the onset to the end of the typical absence discharge. The myoclonia were synchronous with spike‐wave complexes. One patient with GLUT‐1 deficiency was refractory to antiepileptic polytherapy. The other eight became seizure‐free; five with one antiepileptic drug and three with a combination of two drugs. The treatment was successfully withdrawn in five of the six patients who achieved two years of seizure freedom. None of them exhibited any other seizure type. Four of the eight patients with normal schooling required some support. We observed a positive correlation between the duration of absence seizure and the age of the patient at examination. Conclusion. Most of the patients under four years with only typical absence seizures had EOAE, and the motor symptoms may represent a distinctive age‐related feature of EOAE. Further investigations are required to better correlate the role of brain maturation with the duration of the absence. [Published with video sequence on www.epilepticdisorders.com ]