G. Di Gennaro

Tissue plasminogen activator and urokinase plasminogen activator in human epileptogenic pathologies

A growing body of evidence demonstrates the involvement of plasminogen activators (PAs) in a number of physiologic and pathologic events in the CNS. Induction of both tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) has been observed in different experimental models of epilepsy and tPA has been implicated in the mechanisms underlying seizure activity. We investigated the expression and the cellular distribution of tPA and uPA in several epileptogenic pathologies, including hippocampal sclerosis (HS; n=6), and developmental glioneuronal lesions, such as focal cortical dysplasia (FCD, n=6), cortical tubers in patients with the tuberous sclerosis complex (TSC; n=6) and in gangliogliomas (GG; n=6), using immuno-cytochemical, western blot and real-time quantitative PCR analysis. TPA and uPA immunostaining showed increased expression within the epileptogenic lesions compared to control specimens in both glial and neuronal cells (hippocampal neurons in HS and dysplastic neurons in FCD, TSC and GG specimens). Confocal laser scanning microscopy confirmed expression of both proteins in astrocytes and microglia, as well as in microvascular endothelium. Immunoblot demonstrated also up-regulation of the uPA receptor (uPAR; P<0.05). Increased expression of tPA, uPA, uPAR and tissue PA inhibitor type mRNA levels was also detected by PCR analysis in different epileptogenic pathologies (P<0.05). Our data support the role of PA system components in different human focal epileptogenic pathologies, which may critically influence neuronal activity, inflammatory response, as well as contributing to the complex remodeling of the neuronal networks occurring in epileptogenic lesions.

Temporal lobe epilepsy surgery: different surgical strategies after a non-invasive diagnostic protocol

Aim: To test a non-invasive presurgical protocol for temporal lobe epilepsy (TLE) based on “anatomo–electro–clinical correlations”. Methods: All consecutive patients with suspected TLE and seizure history <2 years were entered into the protocol, which included video-electroencephalographic (EEG) monitoring and magnetic resonance imaging (MRI). Three different TLE subsyndromes (mesial, lateral, mesiolateral) were identified by combined anatomical, electrical, and clinical criteria. “Tailored” surgery for each subsyndrome was offered. Patients with seizure history <2 years, MRI evidence of temporal mass lesion, and concordant interictal EEG and clinical data bypassed video-EEG monitoring and were directly scheduled for surgery. Results: Lesionectomy was performed without video-EEG recording in 11 patients with tumorous TLE. Of 146 patients studied with video-EEG, 133 received a TLE diagnosis. Four were excluded for neuropsychological risks, eight refused surgery, and 121 underwent surgery. Of 132 consecutive patients who underwent surgery, 101 had at least one year of follow up. They were divided into a “hippocampal sclerosis/cryptogenic” group (n = 57) and a “tumours/cortical organisation disorders” group (n = 44). In the first group, extensive temporal lobectomy (ETL) was performed in 40 patients, anteromesial temporal lobectomy (AMTL) in 17 patients. At follow up, 47 patients were seizure free. In the second group, lesionectomy plus ETL was performed in 23 patients, lesionectomy plus AMTL in six patients, and lesionectomy alone in 15 patients. Thirty nine patients were seizure free. Conclusions: These findings suggest that different TLE subsyndromes can be identified accurately using non-invasive anatomo–electro–clinical data and can be treated effectively and safely with tailored surgery.

Stop-event-related potentials from intracranial electrodes reveal a key role of premotor and motor cortices in stopping ongoing movements

In humans, the ability to withhold manual motor responses seems to rely on a right-lateralized frontal–basal ganglia–thalamic network, including the pre-supplementary motor area and the inferior frontal gyrus (IFG). These areas should drive subthalamic nuclei to implement movement inhibition via the hyperdirect pathway. The output of this network is expected to influence those cortical areas underlying limb movement preparation and initiation, i.e., premotor (PMA) and primary motor (M1) cortices. Electroencephalographic (EEG) studies have shown an enhancement of the N200/P300 complex in the event-related potentials (ERPs) when a planned reaching movement is successfully stopped after the presentation of an infrequent stop-signal. PMA and M1 have been suggested as possible neural sources of this ERP complex but, due to the limited spatial resolution of scalp EEG, it is not yet clear which cortical areas contribute to its generation. To elucidate the role of motor cortices, we recorded epicortical ERPs from the lateral surface of the fronto-temporal lobes of five pharmacoresistant epileptic patients performing a reaching version of the countermanding task while undergoing presurgical monitoring. We consistently found a stereotyped ERP complex on a single-trial level when a movement was successfully cancelled. These ERPs were selectively expressed in M1, PMA, and Brodmanns area (BA) 9 and their onsets preceded the end of the stop process, suggesting a causal involvement in this executive function. Such ERPs also occurred in unsuccessful-stop (US) trials, that is, when subjects moved despite the occurrence of a stop-signal, mostly when they had long reaction times (RTs). These findings support the hypothesis that motor cortices are the final target of the inhibitory command elaborated by the frontal–basal ganglia–thalamic network.

A rapid and reliable procedure to localize subdural electrodes in presurgical evaluation of patients with drug-resistant focal epilepsy

OBJECTIVES To evaluate a novel method for localization of subdural electrodes in presurgical assessment of patients with drug-resistant focal epilepsy. METHODS We studied eight consecutive patients with posterior epilepsy in whom subdural electrodes were implanted for presurgical evaluation. Electrodes were detected on post-implantation brain CT scans through a semiautomated procedure based on a MATLAB routine. Then, post-implantation CT scans were fused with pre-implantation MRI to localize the electrodes in relation to the underlying cortical structures. The reliability of this procedure was tested by comparing 3D-rendered MR images of the electrodes with electrode position as determined by intraoperative digital photography. RESULTS In each patient, all electrodes could be correctly localized and visualized in a stereotactic space, thus allowing optimal surgery planning. The agreement between the procedure-generated images and the digital photographs was good according to two independent raters. The mean mismatch between the 3D images and the photographs was 2 mm. CONCLUSIONS While our findings need confirmation on larger samples including patients with anterior epilepsy, this procedure allowed to localize subdural electrodes and to establish the spatial relationship of each electrode to the underlying brain structure, either normal or damaged, on brain convessity, basal and medial cortex. SIGNIFICANCE Being simple, rapid, unexpensive, and reliable, this procedure holds promise to be useful to optimize epilepsy surgery planning.

Severe amnesia following bilateral medial temporal lobe damage occurring on two distinct occasions.

A comprehensive neuropsychological assessment was performed on a 38-year-old woman with drug-resistant right temporal lobe epilepsy before temporal lobectomy, during a 2-year follow-up period, and approximately 3 years after surgery when she developed a malignant glioma in the left medial temporal lobe (MTL). Both before and after epilepsy surgery, memory function was normal. When the tumour was discovered, the patient suffered from severe retrograde and anterograde amnesia, whereas working memory and the other cognitive abilities were preserved. Compared with other cases of bilateral temporal lesion, this case is peculiar because the damage occurred on two distinct occasions. It suggests that only one MTL can allow normal memory function, or can take over the function normally subserved by a dysfunctional contralateral MTL when the dysfunction is marked and prolonged, such as in chronic epilepsy.

Lateralizing value of memory tests in drug-resistant temporal lobe epilepsy

Our aim was to test the lateralizing value of a neuropsychological battery including several memory tests on a large sample of consecutive patients with drug‐resistant temporal lobe epilepsy (TLE) evaluated for epilepsy surgery. We studied 73 right‐handed patients (56% males, mean age 35.3 ± 11.2 years, 49% left TLE) aged 16 years or older with normal IQ who underwent a preoperative neuropsychological assessment including several memory tests and were seizure‐free after at least 1 year of follow‐up. Forty‐seven had TLE due to hippocampal sclerosis, whilst 26 had TLE secondary to tumors or other lesions. Receiver Operating Characteristic (ROC) analysis and discriminant function analysis were used to evaluate the lateralization value of selected tests and of the battery as a whole, respectively. In patients with TLE secondary to tumors or other lesions, no test showed significant lateralizing value. In patients with TLE due to hippocampal sclerosis, the immediate (P < 0.01) and delayed (P < 0.001) Rey Auditory Verbal Learning Test (RAVLT) displayed substantial discriminatory ability. The battery as a whole correctly classified 82% of patients with respect to side of epileptogenesis. Our findings suggest that a non‐invasive, relatively short and unexpensive neuropsychological battery based on memory tests may profitably complement other well‐established diagnostic procedures such as video‐EEG or magnetic resonance imaging (MRI), at least in patients with drug‐resistant TLE due to hippocampal sclerosis.

Cardiac asystole during right frontal lobe seizures: a case report

The association between partial seizures and cardiac asystole has rarely been reported in the literature. This potentially life-threatening symptom has been observed principally in left-sided epilepsies, in particular during seizures originating in temporal lobe. We describe a case with ictal bradycardia followed by cardiac asystole during right frontal lobe seizures. Video-EEG monitoring recorded two partial seizures with electro-clinical findings suggestive of a right frontal lobe origin, associated with ictal bradycardia followed by prolonged asystole. The brain MRI showed a lesion located in the cingulate gyrus of the right frontal lobe. The patient required a subsequent placement of a pacemaker. In conclusion, cardiac asystole may be a potentially life-threatening symptom during seizures of frontal lobe origin. The right fronto-mesial structures may play a role in autonomic regulation of cardiovascular responses.

Movement‐Induced Seizures: A Case Report

: Reflex seizures induced by movement are typically evoked by sudden or unattended motor actions. However, tonic seizures may also be triggered by slow movements as observed in nonketotic hyperglycemia or in “praxis‐induced epilepsy.” We report the case of a young, nondiabetic patient affected by recurrent partial tonic postural seizures precipitated by slow movements which were unrelated to cognitive tasks. Ictal EEG did not permit location of the epileptogenic brain region. However, the clinical features suggest possible involvement of the supplementary motor area.

Clinical dissection of childhood occipital epilepsy of Gastaut and prognostic implication

Our aim was to describe the clinical and electrical features and the long‐term evolution of childhood occipital epilepsy of Gastaut (COE‐G) in a cohort of patients and to compare long‐term prognosis between patients with and without other epileptic syndromes.

Hypoglycaemia induced by phenytoin treatment for partial status epilepticus

A 22 year old woman was admitted at our epilepsy unit in status epilepticus. On examination, seizures were characterised by a confusional state with little response to external stimuli, and recurrent, brief, tonic motor manifestations lateralised to the left side. Family history was negative for epilepsy and metabolic disorders. Full term birth was uncomplicated and first psychomotor developmental milestones were normal. In the past medical history there was no sign of any metabolic diseases. There were no reports of cognitive dysfunction or personality disturbances. At the age of 16, the patient presented with epilepsy, which was characterised by two types of seizures: global tonic seizures, which occurred yearly, and brief episodes of loss of contact without any other manifestations, which were rare. The patient was treated for many years with 20 mg of clobazam twice daily. The awake EEGs that were performed routinely during the years of treatment with …