Nadia Colombo

The clinicopathologic spectrum of focal cortical dysplasias: A consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission†

Purpose:  Focal cortical dysplasias (FCD) are localized regions of malformed cerebral cortex and are very frequently associated with epilepsy in both children and adults. A broad spectrum of histopathology has been included in the diagnosis of FCD. An ILAE task force proposes an international consensus classification system to better characterize specific clinicopathological FCD entities.

Imaging of malformations of cortical development

Malformations of cortical development (MCD) include a broad range of disorders that result from disruption of the major steps of cortical development: cell proliferation in germinal zones, neuronal migration and cortical organization. With the improvement and increased utilization of modern imaging techniques, MCD have been increasingly recognized as a major cause of seizure disorders. The advent of Magnetic Resonance Imaging (MRI), in particular, has revolutionized the investigation and the treatment of patients with epilepsy. High-resolution MRI may elucidate the type, the extension and the localization of MCD; therefore, in a group of patients suffering from drug-resistant partial epilepsy (DRPE), MRI greatly contributes to the identification of subjects who are suitable for surgical treatment. In the recent past, many efforts were addressed to establish the MRI diagnostic criteria for a peculiar group of MCD, namely focal cortical dysplasias (FCD), histopathologically distinguished as types I and II. Some subtle FCD, which were previously cryptic to imaging investigation, can now be recognized by MRI, however their detection and specification remains challenging. This review will re-visit the neuroimaging findings, including structural MRI, PET, co-registered PET/MRI, MEG and diffusion tensor imaging (DTI) of FCD types I and II. Three major issues will be discussed: 1) the morphological MRI features of the FCDs, 2) the utility of PET and MEG and the use of co-registration methods and 3) diffusion tensor imaging (DTI) as a future modality of investigation, which may add additional informations regarding the microstructure of the grey matter (GM) and white matter (WM) in cortical dysplasia.

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.

Sensitivities and predictive values of paraclinical tests for diagnosing multiple sclerosis.

The sensitivities and predictive values of visual, somatosensory, and brain auditory evoked potentials (EPs), cerebrospinal fluid oligoclonal banding (CSF-OB) and magnetic resonance imaging (MRI) were evaluated for the early diagnosis of clinically definite multiple sclerosis (CDMS). Paraclinical evidence of asymptomatic lesions allows a diagnosis of CDMS. Eighty-two patients in whom MS was suspected but diagnosis of CDMS was not possible entered the study prospectively. Paraclinical examinations were performed at entry. Patients were examined and underwent EPs every 6 months, and MRI yearly. After a mean follow-up of 2.9 years, 28 patients (34%) had developed CDMS (McDonald-Halliday criteria). The initial MRI was strongly suggestive of MS in 19 of these (68%), while 27 (96%) had at least one MS-like abnormality in the initial MRI. CSF-OB and EPs had lower sensitivities. CDMS developed during follow-up in 19 of the 36 patients (53%) who had an initial MRI strongly suggestive of MS but in only 1 of the 25 who had normal MRI when first studied. These results support previous conclusions that MRI is the most sensitive test for detecting white matter asymptomatic lesions, and the most predictive for the diagnosis of CDMS.

Magnetic resonance diagnosis of intramedullary tumors of the spinal cord.

SummaryFifty patients with intramedullary space occupying lesions were studied with MR from October 1983. Of these 32 were operated on and histological diagnosis together with gross morphological description was available. MR findings were reviewed in search for morphological and signal characteristics capable of providing a better preoperative diagnosis. There were 11 astrocytomas, 10 ependymomas, 5 vascular lesions and 6 “gliomas”.All lesions usually had signal characteristics different from those of the normal cord, mainly because of prolonged T1 and T2 relaxation times. No specific patterns related either to morphology or signal were found, capable of differentiating the two main histological types. Vascular malformations may be suspected from the presence of serpiginous areas without signal.Tumor nodules within cysts can however be well recognized, thus providing the neurosurgeon with very useful preoperative information.Some characteristics of signal and morphology, are more common for one or the other of the two main groups of tumors. A tumor involving all the cord with a homogeneously prolonged T2 relaxation time is most likely to be an astrocytoma. A small nodule with signal close to normal parenchyma, associated with extensive cysts, is most likely to be an ependymoma.

Sleep-related hyperkinetic seizures: always a frontal onset?

Hyperkinetic seizures are considered a typical manifestation of nocturnal frontal lobe epilepsy (NFLE). Patients with temporal lobe epilepsy with mainly sleeprelated seizures have been described; however they commonly lack hyperkinetic activity and seizure frequency is low. We retrospectively analysed our population of 442 consecutive patients surgically treated between January 1996 and January 2004. Among these there were 25 patients with sleep-related hyperkinetic epileptic seizures, with a frontal lobe onset in 18 cases and a temporal lobe onset in 7. Patients with sleep-related hyperkinetic seizures with temporal lobe origin had anamnestic and clinical features strikingly similar to those with a frontal onset, with agitated movements, high seizure frequency and no history of febrile convulsions. We confirm our previous findings that this kind of epileptic manifestation is not only peculiar to frontal lobe epilepsy.