Resection of focal cortical dysplasia located in the upper pre‐central gyrus

The primary motor cortex of the oro‐facial level can be removed without permanent deficits, because of the bilateral representation of the innate functions. In contrast, resective surgery of the hand motor cortex or higher levels presents more challenges. We treated two adult patients with intractable epilepsy caused by small focal cortical dysplasia in the pre‐central gyrus located between the foot and hand primary motor cortices. Focal cortical resection was guided by cortical EEG and intra‐operative motor evoked potential, resulting in seizure freedom without neurological deficits in both cases. These cases illustrate that resective surgery can be safely performed in the primary motor cortex even dorsal to the oro‐facial level, as long as the critical regions of the hand and foot motor cortices remain intact. Accurate delineation of the anatomical lesion and functional areas using intra‐operative neurophysiological monitoring is crucial for successful outcome of the surgery.     

Surgical outcome and predictive factors in adult patients with intractable epilepsy and focal cortical dysplasia

OBJECTIVES: To determine the surgical outcome and prognostic factors in adult patients with intractable epilepsy and focal cortical dysplasia (FCD). MATERIALS AND METHODS: We retrospectively studied the operative outcome in 21 consecutive adult patients with FCD who underwent surgical treatment for intractable partial epilepsy. RESULTS: The mean age at surgery was 32.7 years (range, 18-58 years). The median post-operative follow-up was 2.5 years. The FCD was extratemporal in 11 patients, involved the temporal lobe in 10 patients, and was multilobar in eight patients. Eleven patients (52%) were rendered seizure-free, four patients (19%) had >95% reduction in seizures, and two patients (10%) had an 80-94% reduction in seizures. A seizure-free outcome was associated with shorter duration of epilepsy (P = 0.02). CONCLUSION: Adult patients with FCD may be candidates for surgical treatment of intractable partial epilepsy. Most individuals have neocortical, extrahippocampal seizures and approximately 50% of patients are rendered seizure-free.     

Epilepsy surgery for patients with genetic refractory epilepsy: a systematic review

Aims. In recent years, many different DNA mutations underlying the development of refractory epilepsy have been discovered. However, genetic diagnostics are still not routinely performed during presurgical evaluation and reports on epilepsy surgery outcome for patients with genetic refractory epilepsy are limited. We aimed to create an overview of the literature on seizure outcome following epilepsy surgery in patients with different genetic causes of refractory epilepsy. Methods. We systematically searched PubMed and Embase prior to January 2017 and included studies describing treatment outcome following epilepsy surgery in patients with genetic causes of epilepsy. We excluded studies in which patients were described with epilepsy due to Tuberous Sclerosis Complex or Sturge‐Weber syndrome (since this extensive body of research has recently been described elsewhere) and articles in which surgery was aimed to be palliative. Results. We identified 24 eligible articles, comprising a total of 82 patients who had undergone surgery for (mainly childhood‐onset) refractory epilepsy due to 15 different underlying genetic causes. The success rate of surgery varied widely across these different genetic causes. Surgery was almost never effective in patients with epilepsy due to mutations in genes involved in channel function and synaptic transmission, whereas surgery was significantly more successful regarding seizure control in patients with epilepsy due to mutations in the mTOR pathway. Patients with a lesion on MRI tended to have higher seizure freedom rates than those who were MRI‐negative. Conclusion. Although the evidence is still scarce, this systematic review suggests that studying genetic variations in patients with refractory epilepsy could help guide the selection of surgical candidates.     

Taylor’s focal cortical dysplasia increases the risk of sleep‐related epilepsy

Purpose: To analyze the topography of the epileptogenic zone (EZ) and the etiologic substrate as risk factors for sleep‐related focal epilepsy. Methods: Three hundred three patients (172 males and 131 females, mean age at surgery 25.6 ± 13.1 years), who were seizure‐free after resective surgery for drug‐resistant focal epilepsy, were retrospectively reviewed. Statistical analysis was conducted to evaluate the risk of presenting sleep‐related epilepsy (SRE) against topography of resection (assumed to correspond or to include the EZ) and results of histology. Results: Thirty‐nine patients (12.8%) presented with an SRE. At bivariate analysis, a higher frequency of SRE was associated with a frontal lobe EZ (p = 1.94 × 10^?9) and Taylor’s FCD (TFCD, p = 2.20 × 10^?16), whereas architectural FCD (p = 0.00977), ganglioglioma (p = 0.02508), and mesial temporal sclerosis (p = 2.47 × 10^?5) were correlated with a reduced frequency of SRE. Multivariate analysis demonstrated that the only variable significantly associated with SRE was the presence of a TFCD, which increased 14‐fold the risk of SRE [p = 1.66 × 10^?10; risk ratio (RR) = 14.44]. Discussion: In this study, we have demonstrated a significant and strong association between SRE and TFCD in a select population of patients with drug‐resistant focal epilepsy submitted to surgical resection of the EZ. Although our results cannot be applied to the entire spectrum of SRE, the presence of TFCD as the underlying etiology should be considered when evaluating patients with SRE, because surgery can provide excellent results on seizures in these cases.     

Temporo-mesial extraventricular neurocytoma and cortical dysplasia in focal temporal lobe epilepsy

We describe a 17-year-old boy with a left extraventricular temporo-mesial neurocytoma associated with cortical dysplasia causing focal pharmacoresistant temporal lobe epilepsy. He presented with a long history of medically refractory, temporal complex partial seizures. MRI showed a left temporo-mesial lesion suspect to be a low-grade tumor. Based on the pre-operative non-invasive neurophysiological studies, the patient underwent a left tailored temporal antero-mesial resection. Histopathological examination showed an extraventricular neurocytoma associated with architectural dysplasia (Type 1a) of the temporal pole. The patient was seizure-free at 2 years follow-up. Extraventricular neurocytomas must be considered in the differential diagnosis of the plethora of low-grade tumors associated with focal epilepsy that typically involve the temporal lobe, and are frequently associated with focal cortical dysplasia.     

Risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia

Objective

The purpose of this study was to identify the risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia (FCD).

Sleep related epilepsy in focal cortical dysplasia type 2: Insights from sleep recordings in presurgical evaluation

ObjectiveTo determine the relationship between seizure onset, sleep stage and focal cortical dysplasia type 2 (FCD2) location in sleep related epilepsy (SRE).MethodsWe reviewed scalp video-EEG data of 77 patients with SRE among 130 surgically treated patients with histologically confirmed FCD2. Seizure onset was classified as occurring during NREM, REM and after arousal.ResultsSleep recordings were available for 65 patients (37 males, 7–49 years old). FCD2 was located in frontal lobe in 46 (71%) and in extra-frontal regions in 19, including the temporal lobe in 6. MRI was negative/doubtful in 35 cases. Interictal rhythmic/pseudorhythmic spike rate increased from 31% during waking to 65% during sleep. Seizure onset occurred from NREM in 46 cases (71%), mostly from stage 2, and after arousal in 14 (22%). Seizures occurring from NREM/REM sleep were significantly more frequent in frontal (89%) compared to extra-frontal location (42%), whilst arousal preceded seizure onset more often in extra-frontal (58%) compared to frontal location (7%).ConclusionsNREM seizure onset is the most common ictal pattern in SRE due to frontal FCD2 whereas preceding arousal points to extra-frontal regions.SignificanceSleep recordings may help for FCD2 localisation and suggest topography dependent impact on sleep related epileptic networks.     

Neuroimaging in identifying focal cortical dysplasia and prognostic factors in pediatric and adolescent epilepsy surgery

Purpose: The purpose of this study is to determine the sensibility of each imaging tool in identifying focal cortical dysplasia (FCD) in children and adolescents with epilepsy and to define the prognostic factors of pediatric and adolescent epilepsy surgery. Methods: We identified 48 children with FCD who underwent resective surgery and analyzed their preoperative data. The results of various anatomic and functional neuroimaging studies were compared for accuracy in locating the lesion. We also investigated clinical factors that affected the outcome of surgical treatment. Key Findings: Brain magnetic resonance imaging (MRI) was able to localize FCD in 30 patients and fluorodeoxyglucose positron emission tomography (FDG‐PET) and/or subtraction ictal single photon emission computed tomography (SPECT) coregistered with MRI provided additional information that helped to define the lesion in 13 patients. When comparing the pathologic results between a mild malformation of cortical development (MCD) and FCD type I and II, we noted a strong tendency for patients with FCD to have MRI abnormalities (p = 0.005). In addition, severe pathologic features (Palmini’s classification, FCD type II) (p = 0.025) showed significant correlation with a better surgical outcome. To define the primary epileptogenic area, various interictal epileptiform discharges and the results of multimodal neuroimaging studies were helpful, and younger age at the time of operation could aid in more favorable surgical outcomes (p = 0.048). Significance: Our study showed a significant relationship between pathologic grade and the detectability of FCD by brain MRI. In addition, early surgery can be justified by showing that advanced neuroimaging studies in children with FCD and even with extensive epileptiform discharges have a higher rate of success.     

Epilepsy surgery in the first months of life: a large type IIb focal cortical dysplasia causing neonatal drug‐resistant epilepsy

Focal cortical dysplasia is a common cause of medically refractory epilepsy in infancy and childhood. We report a neonate with seizures occurring within the first day of life. Continuous video‐EEG monitoring led to detection of left motor seizures and a right frontal EEG seizure pattern. Brain MRI revealed a lesion within the right frontal lobe without contrast enhancement. The patient was referred for epilepsy surgery due to drug resistance to vitamin B6 and four antiepileptic drugs. Lesionectomy was performed at the age of two and a half months, and histopathological evaluation confirmed the diagnosis of focal cortical dysplasia type IIb (FCD IIb). The patient is free of unprovoked seizures without medication (Engel Class I) and is normally developed at 36 months after surgery. The case study demonstrates that FCD IIb may cause seizures within the first day of life and that epilepsy surgery can be successfully performed in medically intractable patients with a clearly identifiable seizure onset zone within the first three months of life. Although radical surgery such as hemispherectomy and multi‐lobar resections are over‐represented in early infancy, this case also illustrates a favourable outcome with a more limited resection in this age group.     

The Epilepsy Surgery Grading Scale: Validation in an independent population with drug‐resistant focal epilepsy

The Epilepsy Surgery Grading Scale (ESGS) is a simple tool that predicts a patient's likelihood of progressing to resective surgery and becoming seizure‐free. The aim of our study was to validate the ESGS in an independent patient cohort. We retrospectively calculated the ESGS score for adult patients with drug‐resistant focal epilepsy undergoing presurgical evaluation at two reference centers for drug‐resistant epilepsy in Belgium. We classified patients into ESGS grade 1 (most favorable), grade 2 (intermediate), and grade 3 (least favorable). We assessed progression to surgery and postsurgical seizure freedom. A total of 238 patients underwent presurgical evaluation (presurgical cohort), of whom 140 progressed to surgery (surgical cohort). In the presurgical cohort, we observed significant differences in rates of surgery and in rates of seizure freedom between grades 1, 2, and 3. In the surgical cohort, we observed significant differences in rates of seizure freedom between grades 1 and 2 and between grades 1 and 3. We confirm the usefulness of the ESGS for the prognostic stratification of patients with drug‐resistant focal epilepsy undergoing presurgical evaluation. Our results support the use of the ESGS in the decision process of presurgical evaluation in clinical practice.     

Focal cortical dysplasia: prevalence, clinical presentation and epilepsy in children and adults

Focal cortical dysplasias (FCD) are defined as circumscribed malformations of cortical development. They result from an impairment of neuronal proliferation, migration and differentiation. In the diagnosis of focal epilepsy FCD prevalence ranges between 5% and 25%, depending on patient collective and imaging techniques. Several 'cryptogenic' epilepsies may be caused by FCD but have not been diagnosed because of the lack of high-quality magnetic resonance imaging assessment. Retrospective analysis of patients who have undergone epilepsy surgery can be biased because of the fact that they represent a mere subset of potential FCD diagnoses. Epilepsy typically manifests within the first years of life, but has been documented up to the age of 60 years. Cognitive impairment commonly accompanies early onset. Epilepsy is often refractory to antiepileptic drug (AED) treatment. Clinical observations and pathophysiological findings illustrate intrinsic epileptogenicity. Upregulation of drug transporter proteins has been found in FCD tissue. There is no specific drug treatment in FCD, as any AED used in focal epilepsy could prove effective. A sequential AED therapy should be designed individually and take side effects as well as developmental progresses into consideration. Fifty to sixty-five percent of FCD patients are rendered seizure-free after surgery. Presurgical evaluation should be initiated after two unsuccessful AED trials. Both risks and potential benefits regarding seizure control and developmental impairment need to be considered on an individual basis when deciding between surgical intervention and conservative treatment. Current knowledge on epilepsy course and psychomotor development in FCD is limited in the absence of qualified long-term studies combining imaging with cognitive evaluation.     

Long‐term health‐related quality of life in drug‐resistant temporal lobe epilepsy after anterior temporal lobectomy

Epilepsy surgery is beneficial to patients suffering from drug‐resistant temporal lobe epilepsy in the short term, but fewer reports of long‐term outcomes have been published. To clarify the long‐term outcomes of seizure control and health‐related quality of life after epilepsy surgery, we enrolled 48 patients suffering from drug‐resistant temporal lobe epilepsy. All of the patients received comprehensive presurgical evaluations, including the Quality of Life in Epilepsy Inventory‐89 (QOLIE‐89) questionnaire to measure their health‐related quality of life. Among the patients, 28 patients received surgery (surgical group) and 20 patients remained under medication (medical group). Eight years later, the seizure frequency and QOLIE‐89 were evaluated. The seizure‐free rate was much higher in the surgical group (53.6%) than in the medical group (5%), eight years after the initial evaluation. The follow‐up QOLIE‐89 score was significantly higher in the surgical group than in the medical group. Moreover, the seizure frequency inversely correlated to the QOLIE‐89 score, regardless of the treatment group. Our results provide evidence that epilepsy surgery confers benefits with respect to seizure control and health‐related quality of life for drug‐resistant temporal lobe epilepsy patients based on long‐term follow‐up.     

Objective 3D surface evaluation of intracranial electrophysiologic correlates of cerebral glucose metabolic abnormalities in children with focal epilepsy

To determine the spatial relationship between 2‐deoxy‐2[¹⁸F]fluoro‐D‐glucose (FDG) metabolic and intracranial electrophysiological abnormalities in children undergoing two‐stage epilepsy surgery, statistical parametric mapping (SPM) was used to correlate hypo‐ and hypermetabolic cortical regions with ictal and interictal electrocorticography (ECoG) changes mapped onto the brain surface. Preoperative FDG‐PET scans of 37 children with intractable epilepsy (31 with non‐localizing MRI) were compared with age‐matched pseudo‐normal pediatric control PET data. Hypo‐/hypermetabolic maps were transformed to 3D‐MRI brain surface to compare the locations of metabolic changes with electrode coordinates of the ECoG‐defined seizure onset zone (SOZ) and interictal spiking. While hypometabolic clusters showed a good agreement with the SOZ on the lobar level (sensitivity/specificity = 0.74/0.64), detailed surface‐distance analysis demonstrated that large portions of ECoG‐defined SOZ and interictal spiking area were located at least 3 cm beyond hypometabolic regions with the same statistical threshold (sensitivity/specificity = 0.18–0.25/0.94–0.90 for overlap 3‐cm distance); for a lower threshold, sensitivity for SOZ at 3 cm increased to 0.39 with a modest compromise of specificity. Performance of FDG‐PET SPM was slightly better in children with smaller as compared with widespread SOZ. The results demonstrate that SPM utilizing age‐matched pseudocontrols can reliably detect the lobe of seizure onset. However, the spatial mismatch between metabolic and EEG epileptiform abnormalities indicates that a more complete SOZ detection could be achieved by extending intracranial electrode coverage at least 3 cm beyond the metabolic abnormality. Considering that the extent of feasible electrode coverage is limited, localization information from other modalities is particularly important to optimize grid coverage in cases of large hypometabolic cortex. Hum Brain Mapp 38:3098–3112, 2017. © 2017 Wiley Periodicals, Inc.     

Clinical and experimental studies of epilepsy associated with focal cortical dysplasia

The results of clinical and experimental studies on epilepsy associated with focal cortical dysplasia (FCD) are presented. We have been interested in the findings of abnormal increases in the numbers of small vessels in specimens of FCD resected from epilepsy patients. In the clinical study of 13 patients with epilepsy, specimens of FCD or dysembryoplastic neuroepithelial tumor (DNT) were examined using immunohistochemistry. The number of vessels in both lesions were greater than those in cortical specimens of autopsy cases without epilepsy. Because the vessels showed negative staining of VEGF, it was thought that the phenomenon of increase in the number of vessels was simply a hypervascularity, not a neovascularity. The local hypervascularity was expected to show local hyperperfusion in CBF-SPECT study, but interictal SPECT demonstrated local hypoperfusion and ictal SPECT showed hyperperfusion. This may have been caused by a functional change in those vessels. In the experimental study, we tried to make a new animal model of FCD to study epileptogenicity of FCD. When kainic acid had been infused into the neocortex in the neonatal rats, FCD was induced in adult Wistar rats. Histopathological examination revealed cortical dyslamination and abnormal neurons. On EEG, local spike bursts were elicited from the lesions, however, clinical seizures were not detected. Although the data are preliminary and observation over a longer period is required to determine whether spontaneous seizures will occur in this model, it is expected that this new model will be useful for studying epilepsy associated with FCD.     

Desmoplastic infantile ganglioglioma with focal cortical dysplasia: A rare double pathology in an infant with history of seizures

We describe an extremely rare case of double pathology arising in an infant girl presenting with a history of intractable seizures, delayed milestones and enlarging head. The pathology included desmoplastic infantile ganglioglioma (DIG) and extensive focal cortical dysplasia in the overlying cortex. While tumors such as ganglioglioma have been commonly described to occur as concomitant pathology with cortical dysplasia, DIG in such an association has not been described in the literature. As DIG are voluminous supratentorial tumors, awareness about such an association is pertinent for correct diagnosis.     

Review: Mechanistic target of rapamycin (mTOR) pathway,focal cortical dysplasia and epilepsy

Over the last decade, there has been increasing evidence that hyperactivation of the mechanistic target of rapamycin (mTOR) pathway is a hallmark of malformations of cortical development such as focal cortical dysplasia (FCD) or hemimegalencephaly. The mTOR pathway governs protein and lipid synthesis, cell growth and proliferation as well as metabolism and autophagy. The molecular genetic aetiology of mTOR hyperactivation has only been recently clarified. This article will review the current and still evolving genetic advances in the elucidation of the molecular basis of FCD. Activating somatic mutations in the MTOR gene are to date the most frequent mutations found in FCD brain specimens.