Eliseu Paglioli

Resection of the lesion in patients with hypothalamic hamartomas and catastrophic epilepsy

BackgroundPatients with hypothalamic hamartomas (HH) often have severe refractory epilepsy, incapacitating behavioral abnormalities, and cognitive decline. Attempts to control the seizure disorder by resection of apparently epileptogenic mesial temporal or other cortical structures have failed consistently. Objective To report a series of 13 patients in whom the hamartoma itself was resected. Methods All patients underwent preoperative evaluation between ages 2 and 33 years and had subtotal or complete resection of the hamartoma. Follow-up ranged from 1 to 5.5 years (mean: 2.8 y). Results Preoperatively, all patients had variable combinations of gelastic, complex partial, and generalized seizures. Eight had drop attacks. In addition, all had marked behavior abnormalities and cognitive impairment. Postoperatively, two patients are completely seizure-free and 11 are either seizure-free or have achieved a greater than 90% reduction of drop attacks and generalized tonic-clonic seizures. However, minor gelastic, complex partial, and atypical absence seizures have persisted in 11 patients, although at significantly reduced rates. In addition, there has been a dramatic improvement in behavior and cognition. Three patients had an anterior thalamic and one a capsular infarct, which left only minimal long-term deficits. Exact location of the lesion in relation to the interpeduncular fossa and the walls of the third ventricle correlated with extent of excision, seizure control, and complication rate. Conclusion Resection can alleviate both the seizures and the behavioral and cognitive abnormalities of hypothalamic hamartomas, but complications are frequent.

Survival Analysis of the Surgical Outcome of Temporal Lobe Epilepsy Due to Hippocampal Sclerosis

Summary:  Purpose: Surgical results in patients with mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS) are often reported in conjunction with other etiologies of TLE.

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).

Surgical Resection for Intractable Epilepsy in “Double Cortex” Syndrome Yields Inadequate Results

PURPOSE To analyze the results of surgical treatment of intractable epilepsy in patients with subcortical band heterotopia, or double cortex syndrome, a diffuse neuronal migration disorder. METHODS We studied eight patients (five women) with double cortex syndrome and intractable epilepsy. All had a comprehensive presurgical evaluation including prolonged video-EEG recordings and magnetic resonance imaging (MRI). RESULTS All patients had partial seizures, with secondary generalization in six of them. Neurologic examination was normal in all. Three were of normal intelligence, and five were mildly retarded. Six patients underwent invasive EEG recordings, three of them with subdural grids and three with stereotactic implanted depth electrodes (SEEG). Although EEG recordings showed multilobar epileptic abnormalities in most patients, regional or focal seizure onset was recorded in all. MRI showed bilateral subcortical band heterotopia, asymmetric in thickness in three. An additional area of cortical thickening in the left frontal lobe was found in one patient. Surgical procedures included multiple subpial transections in two patients, frontal lesionectomy in one, temporal lobectomy with amygdalohippocampectomy in five, and an additional anterior callosotomy in one. Five patients had no significant improvement, two had some improvement, and one was greatly improved. CONCLUSION Our results do not support focal surgical removal of epileptogenic tissue in patients with double cortex syndrome, even in the presence of a relatively localized epileptogenic area.

An 18-year follow-up of seizure outcome after surgery for temporal lobe epilepsy and hippocampal sclerosis.

Objectives To evaluate the very long-term clinical outcome of surgery for mesial temporal lobe epilepsy and unilateral hippocampal sclerosis (MTLE/HS) without atypical features. The impact of surgical technique and postoperative reduction of medication on this outcome was investigated. Design Prospective longitudinal cohort follow-up study for up to18 years. Setting Epilepsy surgery centre in a university hospital. Patients 108 patients who underwent unilateral MTLE/HS. Intervention Surgery for MTLE/HS. Main outcome measure Engel classification (I). Clinical evaluations were based on systematic interviews in person or by phone. Kaplan-Maier survival curves estimated the probability of remaining seizure free. The impact of medication management in the postoperative outcome was analysed using Cox regression. Results The probability of remaining completely seizure-free at 12 and 18 years after MTLE/HS surgery was 65% and 62%, respectively. The risk of having any recurrence was 22% during the first 24 months and increased 1.4% per year afterwards. Type of surgical technique (selective amygdalohippocampectomy vs anterior temporal lobectomy) did not impact on outcome. Remaining on antiepileptic drugs and history of generalised clonic seizure diminished the probability of remaining seizure free. Conclusions MTLE/HS surgery is able to keep patients seizure free for almost up to two decades. Removal of the neocortex besides the mesial portion of the temporal lobe does not lead to better chances of seizure control. These findings are applicable to the typical unilateral MTLE/HS syndrome and cannot be generalised for all types of TLE. Future longitudinal randomised controlled studies are needed to replicate these findings.

Developmental tumors and adjacent cortical dysplasia: Single or dual pathology?

Developmental tumors often lead to refractory partial seizures and constitute a well‐defined, surgically remediable epilepsy syndrome. Dysplastic features are often associated with these tumors, and their significance carries both practical and conceptual relevance. If associated focal cortical dysplasia (FCD) relates to the extent of the epileptogenic tissue, then presurgical evaluation and surgical strategies should target both the tumor and the surrounding dyslaminated cortex. Furthermore, the association has been included in the recently revised classification of FCD and the epileptogenicity of this associated dysplastic tissue is crucial to validate such revision. In addition to the possibility of representing dual pathology, the association of developmental tumors and adjacent dysplasia may instead represent a single developmental lesion with distinct parts distributed along a histopathologic continuum. Moreover, the possibility that this adjacent dyslamination is of minor epileptogenic relevance should also be entertained. Surgical data show that complete resection of the solid tumors and immediately adjacent tissue harboring satellites may disrupt epileptogenic networks and lead to high rates of seizure freedom, challenging the epileptogenic relevance of more extensive adjacent dyslaminated cortex. Whether the latter is a primary or secondary abnormality and whether dyslaminated cortex in the context of a second lesion may produce seizures after complete resection of the main lesion is still to be proven.

Cerebral cavernous malformations in the setting of focal epilepsies: pathological findings, clinical characteristics, and surgical treatment principles

Cavernous cerebral malformations (CCMs) are a well-defined epilepsy-associated pathology. They represent lesions/conglomerates of abnormally configured vessels leading to seizures either as a result of physiological changes affecting the cerebral cortex immediately surrounding the CCM (an epileptogenic mechanism that is relevant for both temporal and extratemporal lesions), or as a result of promoting epileptogenicity in remote but anatomo-functionally connected brain regions (a mechanism that is particularly relevant for temporal lobe lesions). This review details the pathological findings in CCMs and discusses the mechanisms of epileptogenicity in this context. The bulk of the review will focus on therapeutic strategies. Medical therapy using antiepileptic drugs is recommended as a first-line therapy, but surgical removal of the CCM with the surrounding cortex should be pursued if seizures prove to be drug resistant. Early timing of the resection and complete removal of any associated epileptic pathology are critical for best outcomes. In addition to reviewing the available data from prior series, we present original research from two specialized epilepsy centers targeted at answering particularly pressing clinical questions mainly related to the ideal timing and extent of surgery. Further research is needed to define the best surgical strategies in patients with temporal lobe CCMs and structurally normal hippocampi.

Variables associated with co-existing epileptic and psychogenic nonepileptic seizures: a systematic review

PURPOSE Epileptic seizures (ES) have many mimickers, perhaps the most relevant being psychogenic nonepileptic seizures (PNES). The picture is even more challenging when PNES are associated with ES in a given patient. The aim of this research paper was to delineate the demographic, epileptological and psychiatric profile of that specific population. METHODS A systematic review was carried out from 2000 to 2015 for articles in English, French, Italian, Spanish and Portuguese in PUBMED and EMBASE. Cohort or case-control studies reporting prospective or retrospective original data comparing patients with co-existing ES and PNES with those who had PNES only and ES only have been included. In retained studies, the presence of PNES was confirmed by video-electroencephalography (V-EEG). Forty-eight abstracts were identified. RESULTS Nine studies were retained. Most showed that female gender predominated in both groups with PNES. Patients with co-existing ES and PNES take higher number of antiepileptic drugs (AEDs) than PNES alone. Two studies showed association of concomitant ES and PNES with earlier age of seizure onset. Localizing EEG features and ES type were evaluated in only two studies and their association with either group was inconclusive. Somatoform, conversion or cluster B personality disorders were more frequent in subjects with PNES than with ES. DISCUSSION Patients with concomitant ES and PNES are highly heterogeneous, challenging differentiation on clinical grounds. A diagnosis of conversion or somatoform, anxiety disorders, and the use of a higher number of AEDs than psychiatric medications may have an association with co-existing ES and PNES. Further studies are warranted to differentiate patients who only have PNES from those with co-existing ES and PNES.

Selective posterior callosotomy for drop attacks: A new approach sparing prefrontal connectivity

Objective: To evaluate a novel approach to control epileptic drop attacks through a selective posterior callosotomy, sparing all prefrontal interconnectivity. Methods: Thirty-six patients with refractory drop attacks had selective posterior callosotomy and prospective follow-up for >4 years. Falls, episodes of aggressive behavior, and IQ were quantified. Autonomy in activities of daily living, axial tonus, and speech generated a functional score ranging from 0 to 13. Subjective effect on patient well-being and caregiver burden was also assessed. Results: Median monthly frequency of drop attacks decreased from 150 to 0.5. Thirty patients (83%) achieved either complete or >90% control of the falls. Need for constant supervision decreased from 90% to 36% of patients. All had estimated IQ below 85. Median functional score increased from 7 to 10 (p = 0.03). No patient had decrease in speech fluency or hemiparesis. Caregivers rated the effect of the procedure as excellent in 40% and as having greatly improved functioning in another 50%. Clinical, EEG, imaging, and cognitive variables did not correlate with outcome. Conclusions: This cohort study with objective outcome assessment suggests that selective posterior callosotomy is safe and effective to control drop attacks, with functional and behavioral gains in patients with intellectual disability. Results are comparable to historical series of total callosotomy and suggest that anterior callosal fibers may be spared. Classification of evidence: This study provides Class III evidence that selective posterior callosotomy reduces falls in patients with epileptic drop attacks.

Immediate improvement of motor function after epilepsy surgery in congenital hemiparesis

Hemispherectomy often leads to a loss of contralateral hand function. In some children with congenital hemiparesis, however, paretic hand function remains unchanged. An immediate improvement of hand function has never been reported. A 17‐year‐old boy with congenital hemiparesis and therapy‐refractory seizures due to a large infarction in the territory of the middle cerebral artery underwent epilepsy surgery. Intraoperatively, electrical cortical stimulation of the affected hemisphere demonstrated preserved motor projections from the sensorimotor cortex to the (contralateral) paretic hand. A frontoparietal resection was performed, which included a complete disconnection of all motor projections originating in the sensorimotor cortex of the affected hemisphere. Surprisingly, the paretic hand showed a significant functional improvement immediately after the operation. This observation demonstrates that, in congenital hemiparesis, crossed motor projections from the affected hemisphere are not always beneficial, but can be dysfunctional, interfering with ipsilateral motor control over the paretic hand by the contralesional hemisphere.