Detection of somatic and germline pathogenic variants in adult cohort of drug-resistant focal epilepsies.

OBJECTIVE: This study investigates the prevalence of pathogenic variants in the mechanistic target of rapamycin (mTOR) pathway in surgical specimens of malformations of cortical development (MCDs) and cases with negative histology. The study also aims to evaluate the predictive value of genotype-histotype findings on the surgical outcome. METHODS: The study included patients with drug-resistant focal epilepsy who underwent epilepsy surgery. Cases were selected based on histopathological diagnosis, focusing on MCDs and negative findings. We included brain tissues both as formalin-fixed, paraffin-embedded (FFPE) or fresh frozen (FF) samples. Single-molecule molecular inversion probes (smMIPs) analysis was conducted, targeting the MTOR gene in FFPE samples and 10 genes within the mTOR pathway in FF samples. Correlations between genotype-histotype and surgical outcome were examined. RESULTS: We included 78 patients for whom we obtained 28 FFPE samples and 50 FF tissues. Seventeen pathogenic variants (22 %) were identified and validated, with 13 being somatic within the MTOR gene and 4 germlines (2 DEPDC5, 1 TSC1, 1 TSC2). Pathogenic variants in mTOR pathway genes were exclusively found in FCDII and TSC cases, with a significant association between FCD type IIb and MTOR genotype (P = 0.003). Patients carrying mutations had a slightly better surgical outcome than the overall cohort, however it results not significant. The FCDII diagnosed cases more frequently had normal neuropsychological test, a higher incidence of auras, fewer multiple seizure types, lower occurrence of seizures with awareness impairment, less ictal automatisms, fewer Stereo-EEG investigations, and a longer period long-life of seizure freedom before surgery. SIGNIFICANCE: This study confirms that somatic MTOR variants represent the primary genetic alteration detected in brain specimens from FCDII/TSC cases, while germline DEPDC5, TSC1/TSC2 variants are relatively rare. Systematic screening for these mutations in surgically treated patients' brain specimens can aid histopathological diagnoses and serve as a biomarker for positive surgical outcomes. Certain clinical features associated with pathogenic variants in mTOR pathway genes may suggest a genetic etiology in FCDII patients.

Focal lesions induce large-scale percolation of sleep-like intracerebral activity in awake humans.

Focal cortical lesions are known to result in large-scale functional alterations involving distant areas; however, little is known about the electrophysiological mechanisms underlying these network effects. Here, we addressed this issue by analysing the short and long distance intracranial effects of controlled structural lesions in humans. The changes in Stereo-Electroencephalographic (SEEG) activity after Radiofrequency-Thermocoagulation (RFTC) recorded in 21 epileptic subjects were assessed with respect to baseline resting wakefulness and sleep activity. In addition, Cortico-Cortical Evoked Potentials (CCEPs) recorded before the lesion were employed to interpret these changes with respect to individual long-range connectivity patterns. We found that small structural ablations lead to the generation and large-scale propagation of sleep-like slow waves within the awake brain. These slow waves match those recorded in the same subjects during sleep, are prevalent in perilesional areas, but can percolate up to distances of 60 mm through specific long-range connections, as predicted by CCEPs. Given the known impact of slow waves on information processing and cortical plasticity, demonstrating their intrusion and percolation within the awake brain add key elements to our understanding of network dysfunction after cortical injuries.

fMRI-Based Effective Connectivity in Surgical Remediable Epilepsies: A Pilot Study.

Simultaneous EEG-fMRI can contribute to identify the epileptogenic zone (EZ) in focal epilepsies. However, fMRI maps related to Interictal Epileptiform Discharges (IED) commonly show multiple regions of signal change rather than focal ones. Dynamic causal modeling (DCM) can estimate effective connectivity, i.e. the causal effects exerted by one brain region over another, based on fMRI data. Here, we employed DCM on fMRI data in 10 focal epilepsy patients with multiple IED-related regions of BOLD signal change, to test whether this approach can help the localization process of EZ. For each subject, a family of competing deterministic, plausible DCM models were constructed using IED as autonomous input at each node, one at time. The DCM findings were compared to the presurgical evaluation results and classified as: "Concordant" if the node identified by DCM matches the presumed focus, "Discordant" if the node is distant from the presumed focus, or "Inconclusive" (no statistically significant result). Furthermore, patients who subsequently underwent intracranial EEG recordings or surgery were considered as having an independent validation of DCM results. The effective connectivity focus identified using DCM was Concordant in 7 patients, Discordant in two cases and Inconclusive in one. In four of the 6 patients operated, the DCM findings were validated. Notably, the two Discordant and Invalidated results were found in patients with poor surgical outcome. Our findings provide preliminary evidence to support the applicability of DCM on fMRI data to investigate the epileptic networks in focal epilepsy and, particularly, to identify the EZ in complex cases.

Suppression of interictal spikes during phasic rapid eye movement sleep: a quantitative stereo-electroencephalography study.

Tonic and phasic rapid eye movement (REM) sleep seem to represent two different brain states exerting different effects on epileptic activity. In particular, interictal spikes are suppressed strongly during phasic REM sleep. The reason for this effect is not understood completely. A different level of synchronization in phasic and tonic REM sleep has been postulated, yet never measured directly. Here we assessed the interictal spike rate across non-REM (NREM) sleep, phasic and tonic REM sleep in nine patients affected by drug resistant focal epilepsy: five with type II focal cortical dysplasia and four with hippocampal sclerosis. Moreover, we applied different quantitative measures to evaluate the level of synchronization at the local and global scale during phasic and tonic REM sleep. We found a lower spike rate in phasic REM sleep, both within and outside the seizure onset zone. This effect seems to be independent from the histopathological substrate and from the brain region, where epileptic activity is produced (temporal versus extra-temporal). A higher level of synchronization was observed during tonic REM sleep both on a large (global) and small (local) spatial scale. Phasic REM sleep appears to be an interesting model for understanding the mechanisms of suppression of epileptic activity.

Genetic and cellular basis of cerebral cavernous malformations: implications for clinical management.

Cerebral cavernous malformations (CCMs) are a diffuse cerebrovascular disease affecting approximately 0.5% of the population. A CCM is characterized by abnormally enlarged and leaky capillaries arranged in mulberry-like structures with no clear flow pattern. The lesion might predispose to seizures, focal neurological deficits or fatal intracerebral hemorrhage. However, a CCM can also remain neurologically silent. It might either occur sporadically or as an inherited disorder with incomplete penetrance and variable expressivity. Due to advances in imaging techniques, the incidence of CCM diagnoses are increasing, and the patient must be managed on a multidisciplinary basis: genetic counselling, treatment if needed, and follow-up. Advances have been made using radiological and pathological correlates of CCM lesions adding to the accumulated knowledge of this disease, although management of these patients is very variable among centers. This review is aimed at providing an update in genetic and molecular insights of this condition. Included are implications for genetic counselling, and possible approaches to prevention and treatment that derive from the understanding of pathogenetic mechanisms.

Seizure outcome after epilepsy surgery in tuberous sclerosis complex: Results and analysis of predictors from a multicenter study.

Epilepsy surgery is recommended in selected patients with Tuberous Sclerosis Complex (TSC). However, reports on predictive factors of seizure outcome are variable. Here we report on seizure and cognitive outcome of 35 TSC patients who received surgery for refractory epilepsy in 7 Italian centers over a period of 22 years (1997-2019). The rate of seizure-free individuals at last follow-up (mean 7.5 years, range 1-21 years) was 51%. Patients with longer follow-up (≥10 years) had a lower rate of Engel I outcome (11.1%) than those who received surgery in the last 10 years (65.4%, p = 0.003). Factors associated with Engel II, III, IV outcome in our cohort included: high number of cortical tubers (≥5); presence of subependymal nodules (SENs); seizure onset before age 1 year; and multifocal interictal epileptic discharges (IEDs) on electroencephalogram (EEG). A subset of patients evaluated with Vineland Adaptive Behaviour Scales (VABS) showed developmental gains, in line with their developmental trajectories, but no improvement in standard scores after surgery was noted. Our study demonstrates that the rates of successful seizure outcome of epilepsy surgery in TSC have improved in the last 10 years. More than half of the patients achieved seizure freedom, and a high proportion of affected individuals experienced a reduction in seizure burden and in antiseizure medications. A comprehensive assessment after surgery should be performed in TSC patients to evaluate the overall neurodevelopmental outcome, as measures that are based only on seizure control do not adequately identify the benefits of surgery on global functioning in these patients.

A cross-sectional survey among physicians on internet use for epilepsy-related information.

OBJECTIVE: We investigated views towards the Internet in a sample of Italian healthcare specialists involved in epilepsy field, to identify factors associated with the attitude of being influenced by information found on the Internet. METHODS: This study was a self-administered survey conducted in a group of members of the Italian Chapter of the International League Against Epilepsy (ILAE) in January 2018. RESULTS: 184 questionnaires were analyzed. 97.8 % of responders reported to seek online information on epilepsy. The Internet was most frequently searched to obtain new information (69.9 %) or to confirm a diagnostic or therapeutic decision (37.3 %). The influence of consulting the Internet on clinical practice was associated with registration to social network(s) (OR: 2.94; 95 %CI: 1.28-6.76; p = 0.011), higher frequency of Internet use (OR: 3.66; 95 %CI: 1.56-9.21; p = 0.006) and higher confidence in reliability of online information (OR: 2.61; 95 %CI: 1.09-6.26; p = 0.031). No association was found with age, sex, years in epilepsy practice or easiness to find online information. CONCLUSION: Internet is frequently used among healthcare professionals involved in the epilepsy to obtain information about this disease. The attitude of being influenced by the Internet for diagnostic and/or therapeutic decisions in epilepsy is independent on age and years of experience in epilepsy, and probably reflects an individual approach towards the Web.

Neuroethological approach to frontolimbic epileptic seizures and parasomnias: The same central pattern generators for the same behaviours.

The aim of this report is not to make a differential diagnosis between epileptic nocturnal seizures and non-epileptic sleep-related movement disorders, or parasomnias. On the contrary, our goal is to emphasize the commonly shared semiological features of some epileptic seizures and parasomnias. Such similar features might be explained by the activation of the same neuronal networks (so-called 'central pattern generators' or CPG). These produce the stereotypical rhythmic motor sequences - in other words, behaviours - that are adaptive and species-specific (such as eating/alimentary, attractive/aversive, locomotor and nesting habits). CPG are located at the subcortical level (mainly in the brain stem and spinal cord) and, in humans, are under the control of the phylogenetically more recent neomammalian neocortical structures, according to a simplified Jacksonian model. Based on video-polygraphic recordings of sleep-related epileptic seizures and non-epileptic events (parasomnias), we have documented how a transient "neomammalian brain" dysfunction - whether epileptic or not - can 'release' (disinhibition?) the CPG responsible for involuntary motor behaviours. Thus, in both epileptic seizures and parasomnias, we can observe: (a) oroalimentary automatisms, bruxism and biting; (b) ambulatory behaviours, ranging from the classical bimanual-bipedal activity of 'frontal' hypermotor seizures, epileptic and non-epileptic wanderings, and somnambulism to periodic leg movements (PLM), alternating leg muscle activation (ALMA) and restless legs syndrome (RLS); and (c) various sleep-related events such as ictal fear, sleep terrors, nightmares and violent behaviour.

Ultra-High-Field Targeted Imaging of Focal Cortical Dysplasia: The Intracortical Black Line Sign in Type IIb.

BACKGROUND AND PURPOSE: Conventional MR imaging has limitations in detecting focal cortical dysplasia. We assessed the added value of 7T in patients with histologically proved focal cortical dysplasia to highlight correlations between neuropathology and ultra-high-field imaging. MATERIALS AND METHODS: Between 2013 and 2019, we performed a standardized 7T MR imaging protocol in patients with drug-resistant focal epilepsy. We focused on 12 patients in whom postsurgical histopathology revealed focal cortical dysplasia and explored the diagnostic yield of preoperative 7T versus 1.5/3T MR imaging and the correlations of imaging findings with histopathology. We also assessed the relationship between epilepsy surgery outcome and the completeness of surgical removal of the MR imaging-visible structural abnormality. RESULTS: We observed clear abnormalities in 10/12 patients using 7T versus 9/12 revealed by 1.5/3T MR imaging. In patients with focal cortical dysplasia I, 7T MR imaging did not disclose morphologic abnormalities (n = 0/2). In patients with focal cortical dysplasia II, 7T uncovered morphologic signs that were not visible on clinical imaging in 1 patient with focal cortical dysplasia IIa (n = 1/4) and in all those with focal cortical dysplasia IIb (n = 6/6). T2*WI provided the highest added value, disclosing a peculiar intracortical hypointense band (black line) in 5/6 patients with focal cortical dysplasia IIb. The complete removal of the black line was associated with good postsurgical outcome (n = 4/5), while its incomplete removal yielded unsatisfactory results (n = 1/5). CONCLUSIONS: The high sensitivity of 7T T2*-weighted images provides an additional tool in defining potential morphologic markers of high epileptogenicity within the dysplastic tissue of focal cortical dysplasia IIb and will likely help to more precisely plan epilepsy surgery and explain surgical failures.

Surgical treatment of drug-resistant nocturnal frontal lobe epilepsy.

Of the cases with nocturnal frontal lobe epilepsy (NFLE) approximately 30% are refractory to antiepileptic medication, with several patients suffering from the effects of both ongoing seizures and disrupted sleep. From a consecutive series of 522 patients operated on for drug-resistant focal epilepsy, 21 cases (4%), whose frontal lobe seizures occurred almost exclusively (>90%) during sleep, were selected. All patients underwent a comprehensive pre-surgical evaluation, which included history, interictal EEG, scalp video-EEG monitoring, high-resolution MRI and, when indicated, invasive recording by stereo-EEG (SEEG). There were 11 males and 10 females, whose mean age at seizure onset was 6.2 years, mean age at surgery was 24.7 years and seizure frequency ranged from <20/month to >300/month. Nine patients reported excessive daytime sleepiness (EDS). Prevalent ictal clinical signs were represented by asymmetric posturing (6 cases), hyperkinetic automatisms (10 cases), combined tonic posturing and hyperkinetic automatisms (4 cases) and mimetic automatisms (1 case). All patients reported some kind of subjective manifestations. Interictal and ictal EEG provided lateralizing or localizing information in most patients. MRI was unrevealing in 10 cases and it showed a focal anatomical abnormality in one frontal lobe in 11 cases. Eighteen patients underwent a SEEG evaluation to better define the epileptogenic zone (EZ). All patients received a microsurgical resection in one frontal lobe, tailored according to pre-surgical evaluations. Two patients were operated on twice owing to poor results after the first resection. Histology demonstrated a Taylor-type focal cortical dysplasia (FCD) in 16 patients and an architectural FCD in 4. In one case no histological change was found. After a post-operative follow-up of at least 12 months (mean 42.5 months) all the 16 patients with a Taylor's FCD were in Engel's Class Ia and the other 5 patients were in Engel's Classes II or III. After 6 months post-surgery EDS had disappeared in the 9 patients who presented this complaint pre-operatively. It is concluded that patients with drug-resistant, disabling sleep-related seizures of frontal lobe origin should be considered for resective surgery, which may provide excellent results both on seizures and on epilepsy-related sleep disturbances. An accurate pre-surgical evaluation, which often requires invasive EEG recording, is mandatory to define the EZ. Further investigation is needed to explain the possible causal relationships between FCD, particularly Taylor-type, and sleep-related seizures, as observed in this cohort of NFLE patients.

Microanatomy of the dysplastic neocortex from epileptic patients.

Focal cortical dysplasia (FCD) is a pathology that is characterized by the abnormal development of the neocortex. Indeed, a wide range of abnormalities in the cortical mantle have been associated with this pathology, including cytoarchitectonic alterations and the presence of dysmorphic neurons, balloon cells and ectopic neurons in the white matter. FCD is commonly associated with epilepsy, and hence we have studied the ultrastructure of cortical tissue resected from three subjects with intractable epilepsy secondary to cortical dysplasia to identify possible alterations in synaptic circuitry, using correlative light and electron microscopic methods. While the balloon cells found in this tissue do not appear to receive synaptic contacts, the ectopic neurons in the white matter were abnormally large and were surrounded by hypertrophic basket formations immunoreactive for the calcium-binding protein parvalbumin. Furthermore, these basket formations formed symmetrical (inhibitory) synapses with both the somata and the proximal portion of the dendrites of these giant ectopic neurons. A quantitative analysis revealed that in the dysplastic tissue, the density of excitatory and inhibitory synapses was different from that of the normal adjacent cortex. Both increases and decreases in synaptic density were observed, as well as changes in the proportion of excitatory and inhibitory synapses. However, we could not establish a common pattern of changes, either in the same patients or between different patients. These results suggest that cortical dysplasia leads to multiple changes in excitatory and inhibitory synaptic circuits. We discuss the possible relationship between these alterations and epilepsy, bearing in mind the possible limitations that preclude the extrapolation of the results to the whole population of epileptic patients with dysplastic neocortex.

Electroclinical, MRI and neuropathological study of 10 patients with nodular heterotopia, with surgical outcomes.

We present the results of a retrospective study on 10 patients operated on for intractable epilepsy associated with nodular heterotopia as identified by high resolution MRI. Seven patients had unilateral heterotopia, one patient had symmetric bilateral heterotopia and two patients had asymmetric bilateral heterotopia. By stereo-electroencephalogram (SEEG) (nine patients) interictal activity within nodules was similar in all cases, and ictal activity never started from nodules alone but from the overlying cortex or simultaneously in nodules and cortex. Excellent outcomes (Engel class Ia, 1987) were achieved in the seven patients with unilateral heterotopia, showing that surgery can be highly beneficial in such cases when the epileptogenic zone is carefully located prior to surgery by MRI and particularly SEEG. For the bilateral cases surgical outcomes were Engel IIa (one patient) or Engel IIIa (two patients). Histological/immunohistochemical studies of resected specimens showed that all nodules had similar microscopic organization, even though their extent and location varied markedly. The overlying cortex was dysplastic in nine patients, but of normal thickness. We suggest that nodule formation may be the result of a dual mechanism: (i) failure of a stop signal in the germinal periventricular region leading to cell overproduction; and (ii) early transformation of radial glial cells into astrocytes resulting in defective neuronal migration. The intrinsic interictal epileptiform activity of nodules may be due to an impaired intranodular GABAergic system.

Pattern of epithelial cell proliferation in colorectal mucosa of normal subjects and of patients with adenomatous polyps or cancer of the large bowel.

Microautoradiography has been largely used to characterize the proliferative activity of colorectal mucosa. We used this technique in a large series of patients with polyps or cancer of the large bowel and in normal controls with the following objectives: (a) to define the normal pattern of cell replication in different tracts of the large bowel; (b) to compare the proliferative activity of colonic crypts in patients with colorectal cancer or polyps with that of controls; (c) to evaluate replicative activity of colorectal mucosa in the close vicinity and at distance from a neoplastic mass. Specimens of colorectal mucosa were taken during endoscopy (controls and polyps) or at surgery (cancer). During histological examination each intestinal hemicrypt was divided into five equal longitudinal compartments from the base to the surface and the labeled cells in each compartment were counted. In controls, total labeling index (ratio of labeled to total cells) and labeling index per crypt compartment showed only minor differences between the various large bowel tracts. Total labeling index tended to be higher in patients with polyps or cancer than in controls (13.5 +/- 0.4 and 12.5 +/- 0.4, respectively, versus 11.3 +/- 0.5). Labeling index per crypt compartment in the most superficial portions of the crypt (compartments 3 to 5) was significantly higher in the two groups of patients with tumors than in controls. This was particularly evident in the fifth compartment (the most superficial), in which labeled cells were observed in 15.8% (three subjects out of 19) of controls but in 71% (15 out of 21) and 87.5% (14 out of 16) of polyp and cancer patients, respectively. In patients with colorectal cancer there were not significant differences of cell proliferation between mucosal samples taken at various distances from the tumor margin; however, increased cell replication, especially in the most superficial portions of the crypt, has been observed. In conclusion, a significant upwards expansion of the proliferative zone of intestinal glands has been observed in patients with either polyps or cancer of the large bowel. In particular, labeling of the fifth compartment seems to possess the highest discriminatory power between subjects with or without intestinal neoplasms. Hyperproliferation of the entire colonic mucosa seems to be a common feature in patients with colorectal cancer.

A Novel MGC4607/CCM2 Gene Mutation Associated with Cerebral Spinal and Cutaneous Cavernous Angiomas.

Cerebral cavernous malformations (CCMs) are vascular abnormalities that may cause seizures, headaches, intracerebral hemorrhages, and focal neurological deficits; they can also be clinically silent and occur as a sporadic or an autosomal dominant condition. Three genes have been identified as causing familial CCM: KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3, mapping, respectively, on chromosomes 7q, 7p, and 3q. Here, we report an Italian family affected by CCM due to a MGC4607 gene mutation, on exon 4. All the affected subjects suffered from seizures, and some of them underwent surgery for removal of a cavernous angioma. Brain MRI showed multiple lesions consistent with CCMs in all patients. Spinal and cutaneous cavernous angiomas were present too. This report underlines the need for a careful interdisciplinarity among neurologists, neuroradiologists, neurosurgeons, geneticists, ophthalmologists, and dermatologists for a total evaluation of the different manifestations of familial CCM. This points out that only referral centers are organized to offer a multidisciplinary management of this disease.

Stereo-electroencephalography methodology: advantages and limits.

Since January 1990, 70 patients with medically intractable partial epilepsy underwent a stereo-EEG investigation in our center. We first described technical requirements, and gave an overview of the variety of the explored cerebral regions and implantation patterns realized, pointing out the low rate of morbidity (1.4%). The three-dimensional epileptogenic zone thus defined led to a tailored individualized surgical excision in 60 patients, while 9 are waiting for surgery and the remaining 1 has been excluded (1.4%). Conceptual and technical aspects of the stereo-EEG methodology were discussed in order to underline its peculiarities in the field of "depth recordings", and more generally among the broader group of "invasive" procedures.

Cajal-Retzius cell density as marker of type of focal cortical dysplasia.

Cajal-Retzius cells, identified using calretinin antiserum, were studied in layer I (LI) of adult human temporal cortex from epileptic patients with Taylor's focal cortical dysplasia and architectural dysplasia, in comparison with normal cortex. Both types of dysplasia showed LI hypercellularity, but only in architectural dysplasia was the density of Cajal-Retzius cells significantly increased. A subset of Cajal-Retzius cells were reelin immunoreactive, but none were GABA positive. These findings suggest that differences in the persistence of Cajal-Retzius cells, which probably reflect different types of alteration during brain development, can assist in characterizing different forms of cortical dysplasia.

Immunocytochemical investigation on dysplastic human tissue from epileptic patients.

In this report we describe three patients with developmental cortical abnormalities (generally referred as cortical dysplasia), revealed by MRI and operated on for intractable epilepsy. Tissue, removed for strictly therapeutic reasons, was defined as the epileptogenic area by electroclinical data and stereo EEG (SEEG) recordings. Tissue samples were processed initially for histology, and selected sections were further processed for immunocytochemical investigation in order to determine whether the region of cortical dysplasia was co-extensive with the epileptogenic area. In two patients with nodular heterotopia, disorganized aggregates of neurons (as revealed by neuronal cytoskeletal markers) were found within the nodules. Both pyramidal and local circuit neurons were present in the nodules, but no reactive gliosis was present. When nodules reached the cortex, the cortical layers were disrupted. In the patient with localized cortical dysplasia, a complete disorganization of the cortical lamination was found, and numerous neurons were also present in the white matter. Disoriented pyramidal neurons weakly labelled with cytoskeletal neuronal markers were also present but no cytomegalic cells were found. One of the patients with nodular heterotopia underwent only partial resection of both the 'epileptogenic area' and of the lesion; this patient still presents with seizures. The other patient with nodular heterotopia is seizure-free after a complete lesionectomy and excision of the epileptogenic area. The third patient, with focal cortical dysplasia, had two surgeries; she became seizure-free only after the excision of the epileptogenic area detected by SEEG recording. The present data suggest that the dysplastic areas identified by MRI should not be considered as the only place of origin of the ictal discharges. From the neuropathological point of view, the focal cortical dysplasia can be considered as a pure form of migrational disorder. However, the presence of large aggregates of neurons interspersed within the white matter, in the subcortical nodular heterotopia, suggests that a defect of neuronal migration could be associated with an exuberant production of neuroblasts and/or a disruption of mechanisms for naturally occurring cell death.

[Electroclinical manifestations elicited by intracerebral electric stimulation "shocks" in temporal lobe epilepsy]. / Manifestations électrocliniques induites par la stimulation électrique intracérébrale par "chocs" dans les épilepsies temporales.

In patients with severe drug-resistant partial epilepsy, undergoing Stereo-EEG investigations, spatial definition of the "epileptogenic area" is mainly based on spontaneous seizures recordings, but also on seizures induced by intracerebral electrical stimulation (ES). Only "trains" ES (TES, 50 pps) are currently used with this aim; "shocks" ES (SES, 1 pps) are principally applied to localize motor pathways. We have shown, during a prospective study concerning 10 temporal lobe epileptic patients, that SES could frequently induce seizures, especially when stimulation is applied in the anterior part of the Ammon's horn. Even if its efficacy seems lower than by TES, this kind of stimulation, in the majority of the cases, does reproduce isolated ictal subjective symptomatology, allowing the visualization of the progressive organisation of ictal electrical discharges, and avoids "unexpected" ("false positive"?) clinical responses.

Research perspectives in cortical dysplasia and associated epilepsies.

Our understanding of cortical alterations and related epilepsies has grown enormously in the last decade thanks to the explosion of basic information from laboratory neuroscience combined with advances in diagnostic tools, therapeutic approaches and surgical techniques. In the present paper, we briefly review the most important advances in these fields from the point of view of the clinician concerned with cortical malformation-related epilepsies. We propose that a highly effective way forward, expected not only to widen knowledge of the basic mechanisms of seizure generation, but also to improved the management of patients, would be to promote interdisciplinary research programmes on resected human cortex that involve neurosurgeons, neurologists and laboratory neuroscientists.

MNA predictive value in the follow-up of geriatric patients.

OBJECTIVE: The aim of this study is to verify, in a sample of elderly subjects admitted to long-term care, the impact of malnutrition, according to the Mini Nutritional Assessment (MNA), on mortality and on the occurrence of Adverse Clinical Events in a 3-12 months follow-up study. SUBJECTS: The survey included all patients admitted to a geriatric hospital--"Villa delle Querce", Nemi (Rome, Italy)--between January 1997 and April 2000, whose nutritional status we were able to monitor for over 3 months. The study comprised 167 elderly subjects, of which 125 women (74.9%) aged 83.3 8 years (60-95 years), and 42 men (25.1%) aged 79.6 9 years with an average follow-up period of 7.5 months. METHODS: Upon admission and at every check we evaluated each subject's cognitive functions, functional status, co-morbidity, frailty, nutritional status (anthropometric and biochemical indices; MNA). During the follow-up we recorded Adverse Clinical Events. We calculated the predictive value of MNA, we correlated variations in MNA scores with variations of nutritional parameters. RESULTS: MNA's predictive ability both upon admission and upon discharge was found to be excellent. The MNA score was found to be correlated-although not to a very high degree-with variations nutritional parameters. Even more than malnutrition, a low MNA score was found to be predictive of a greater incidence of Adverse Clinical Events during hospitalisation and of higher mortality.