Manuela Bramerio

Inhibitory circuits in human dysplastic tissue

Summary: Purpose: Different types of epilepsies and seizures depend on the nature and location of the primary disturbance and are presumably mediated by different physiopathological mechanisms. We immunocytochemically investigated possible changes in the inhibitory ‐aminobutyric acid (GABA)ergic system in specimens taken from four patients who underwent surgery for intractable epilepsy and presented two different types of focal cortical dysplasia in the temporal lobe.

Epilepsy Surgery in Children: Results and Predictors of Outcome on Seizures

Purpose: To retrospectively analyze the results on seizures of surgery in children with drug‐resistant focal epilepsy. To identify the factors predicting seizure control among several presurgical, surgical, and postsurgical variables.

Type I focal cortical dysplasia: surgical outcome is related to histopathology

Pre-surgical and post-surgical data were examined and compared from 215 consecutive patients undergoing surgery for intractable epilepsy. Patients were selected on the basis of a proven histopathological diagnosis of type I focal cortical dysplasia (FCD I), alone or associated with other lesions. The patients were divided into five sub-groups: i) 66 with isolated FCD I, ii) 76 with FCD I and hippocampal sclerosis, iii) 49 with FCD I and tumours, iv) 16 with FCD I and other malformations of cortical development and v) eight with FCD I and anoxic-ischaemic or inflammatory diseases. The duration of epilepsy was greatest in patients with FCD I associated with hippocampal sclerosis, and those with isolated FCD I showed the highest seizure frequency at the time of surgery. Hippocampal sclerosis and tumours were the most frequent pathological lesions associated with FCD I in temporal lobe epilepsy. Febrile seizures significantly correlated with the presence of hippocampal sclerosis and FCD I. Isolated FCD I was observed in 31% of the patients, characterized by frequent seizures, negative magnetic resonance imaging, and frequent frontal or multilobar involvement. In comparison to patients with FCD I associated with hippocampal sclerosis, MCD or tumours, the patients with isolated FCD I had a worse post-surgical outcome (46% in class I). Our findings indicate that there is a high incidence of FCD I associated with other apparently distinct pathologies, particularly those affecting the temporal lobe, and highlight the need for a comprehensive clinicopathological approach for the classification of FCD I.

Temporal lobe epilepsy: neuropathological and clinical correlations in 243 surgically treated patients

The present study included analysis of data from 243 patients surgically treated for Temporal Lobe Epilepsy (TLE). Resection was confined to the temporal lobe, with at least two years of follow-up, and specimens sufficiently preserved to allow a precise evaluation of both lateral neocortex and hippocampus. The frequency of different types of lesion and hippocampal sclerosis (HS), isolated or associated with neocortical lesions, risk factors and surgical outcomes in relation to neuropathological findings were evaluated. We found tumours in 33% of patients, malformations of cortical development (MCD) in 45%, isolated HS in 14%, no lesion in 5% and less common lesions in 3%. HS was present in 8% of tumour cases and 70% of MCD. Statistical analysis of antecedents was significantly associated only with febrile seizures (FS). In MCD patients with no history of FS, a strong association between HS and duration of epilepsy was revealed. A Class I outcome was identified in 87% of cases with tumours and 79% in cases with MCD. In 93 patients the antiepileptic drug therapy was withdrawn. Our findings show that MCD, which is significantly associated with HS, is the most common lesion in TLE and support the concept that an optimal outcome is obtained when mesial and neocortical structures are removed. FS are particularly relevant in patients with focal cortical dysplasia and HS.

Electroclinical, MRI and surgical outcomes in 100 epileptic patients with type II FCD

Focal cortical dysplasias (FCDs) are highly epileptogenic malformations associated with drug-resistant epilepsy, susceptible to surgical treatment. Among the different types of FCD, the type II includes two subgroups based on the absence (IIa) or presence (IIb) of balloon cells. The aim of this retrospective study was to investigate possible differences in electroclinical presentations and surgical outcomes between the two subgroups in 100 consecutive surgically treated patients with type II FCDs. All patients underwent a comprehensive presurgical assessment including stereo-EEG (SEEG) when necessary. No significant differences in gender, age at epilepsy onset, duration of epilepsy, age at surgery or seizure frequency were found between the two subgroups. Patients with type IIb FCD frequently showed sleep-related epilepsy. Their peculiar electrographic pattern was characterised by localised rhythmic or pseudo-rhythmic spikes or polyspikes (“brushes”) enhanced during non-REM sleep and also associated with well-localised, brief, low-voltage fast activity. The incidence and frequency of short bursts of fast discharges, interrupted by activity suppression, increased during slow-wave sleep and often recurred pseudo-periodically. The occurrence of “brushes”, present in 76% of the patients with type IIb FCD, was significantly associated (p<0.001) with the presence of balloon cells. We discuss the possible pathogenetic mechanisms underlying this activity. MRI diagnosis of type II FCD was made in 93% of the patients with balloon cells (BCs), suggesting that the presence of balloon cells might be, at least partially, responsible for the MRI features. Patients had very good postsurgical outcomes (83% in Engel class I) even after a long period of follow-up.

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.

Architectural (Type IA) focal cortical dysplasia and parvalbumin immunostaining in temporal lobe epilepsy.

Summary:  Purpose: We analyzed 26 surgically treated patients operated on for intractable epilepsy associated with type IA (architectural) cortical dysplasia, to investigate neuropathologic and immunocytochemical features, particularly of the γ‐aminobutyric acid (GABA)ergic system, and to compare the findings with those observed in normal cortex.

Nodular heterotopia: a neuropathological study of 24 patients undergoing surgery for drug-resistant epilepsy.

Purpose:  Despite the availability of detailed electroclinical and imaging data, only a few neuropathological studies of nodular heterotopia have been published. The aim of this study was to describe the neuropathological features of various types of nodular heterotopia obtained from patients undergoing surgery for intractable epilepsy.

7T MRI in focal epilepsy with unrevealing conventional field strength imaging

To assess the diagnostic yield of 7T magnetic resonance imaging (MRI) in detecting and characterizing structural lesions in patients with intractable focal epilepsy and unrevealing conventional (1.5 or 3T) MRI.

Epilepsy surgery of focal cortical dysplasia-associated tumors.

The goal of the present study was to evaluate the clinical characteristics and postoperative seizure outcome of epileptogenic tumors associated with focal cortical dysplasias (FCDs) compared to both solitary FCD type I and solitary tumors. Particular attention is given to FCD type IIIb (tumors associated with FCD type I), which have been recently classified as a separate entity. We retrospectively reviewed the clinical charts of 1,109 patients who were operated on for drug‐resistant focal epilepsy, including 492 patients with a histologic diagnosis of solitary FCD I and II (83 and 157 cases, respectively), solitary tumors (179 cases), and FCD‐associated tumors (73 cases, 58 of which met the criteria of FCD IIIb of the new International League Against Epilepsy [ILAE] classification). The different subgroups were evaluated for clinical characteristics and postoperative surgical outcome. Clinical variables and postoperative seizure outcome of patients with coexisting tumor and FCDs (FCD IIIb and tumor associated FCD II) were similar to those of patients with a solitary tumor and differed significantly from patients with solitary FCDs. Nevertheless, tumors associated with FCDs are characterized by a striking male predominance and a higher seizure frequency as compared to solitary tumors. Patients with drug‐resistant focal epilepsy secondary to a solitary tumor or with a tumor‐associated FCD have similar basic clinical presentation and postoperative seizure outcome. Nevertheless, the epileptogenic contribution of the associated FCDs can be crucial, and it needs to be adequately assessed. The impact of FCD on tumor‐related epilepsy deserves future research in order to optimize the surgical strategies aimed at seizure relief.