scispace - formally typeset
Search or ask a question

Showing papers by "Lino Nobili published in 2014"


Journal ArticleDOI
TL;DR: This work aimed at identifying biomarkers of the epileptogenic zone (EZ) based on computer‐assisted inspection of intracranial electroencephalography (EEG) with a direct impact on postsurgical outcome.
Abstract: Summary Objective In one third of patients with a diagnosis of pharmacoresistant focal epilepsy who are candidates for therapeutic surgery, cerebral areas responsible for seizure generation can be defined exclusively with invasive intracranial recordings. A correct presurgical identification of the epileptogenic zone (EZ) with intracranial electrodes has a direct impact on postsurgical outcome. We aimed at identifying biomarkers of the EZ based on computer-assisted inspection of intracranial electroencephalography (EEG). Methods Computer-driven intracranial EEG analysis in the domains of time, frequency, and space was retrospectively applied to a population of 10 patients with focal epilepsy to detect EZ electrophysiologic markers. Next, a prospective study was performed on 14 surgery candidate patients. The stereo-EEG computer-assisted analysis of EZ boundaries performed blind from patients data was compared to that defined with the traditional visual inspection completed by neurophysiologists. Results In the retrospective study, the EZ was characterized by the combined detection of three biomarkers observed at seizure onset: (1) fast activity at 80–120 Hz associated with (2) very slow transient polarizing shift and (3) voltage depression (flattening). Correlations between these indexes were calculated for each seizure. In the prospective study, the quantified analysis based on the three biomarkers confirmed a complete overlap between leads within the EZ identified by expert clinicians. In 2 of 14 patients the proposed biomarkers partially identified the EZ. Significance Our findings demonstrate and validate with a prospective unbiased study the use of three neurophysiologic intracranial EEG parameters as excellent biomarkers of ictogenesis and as reliable indicators of EZ boundaries.

89 citations


Journal ArticleDOI
TL;DR: The results support the notion that wakefulness and sleep are not mutually exclusive states, but rather part of a continuum resulting from the complex interaction between diffuse neuromodulatory systems and intrinsic properties of the different thalamocortical modules.

85 citations


Journal ArticleDOI
TL;DR: Studies on the relationships between genes, arousal regulatory mechanisms, and epileptogenesis, using both clinical and experimental models of NFLE might provide key insights in the interrelationship between sleep and epilepsy.
Abstract: Nocturnal frontal lobe epilepsy (NFLE) is a syndrome of heterogeneous etiology, characterized by the occurrence of sleep-related seizures with different complexity and duration. Genetic, lesional, and cryptogenetic NFLE forms have been described. NFLE is generally considered a benign clinical entity, although severe, drug-resistant forms do exist. A significant proportion of sleep-related complex motor seizures, hardly distinguishable from NFLE, originate outside the frontal lobe. Moreover, the distinction of NFLE from the non-rapid eye movement arousal parasomnias may be challenging. A correct diagnosis of NFLE should be based on a diagnostic approach that includes the anamnestic, video-polysomnographic, morphological, and genetic aspects. Studies on the relationships between genes, arousal regulatory mechanisms, and epileptogenesis, using both clinical and experimental models of NFLE might provide key insights in the interrelationship between sleep and epilepsy.

79 citations


Journal ArticleDOI
TL;DR: SEEG-guided RF-THC proved to be a safe and effective option in a small case-series of NH-related focal epilepsy, strictly dependent on findings of intracerebral recording by SEEG, which can define the role of the NH in the generation of the ictal discharge.
Abstract: Objective To retrospectively evaluate seizure outcome in a case-series of patients with nodular heterotopy (NH)-related epilepsy treated by stereo-EEG (SEEG)-guided radio-frequency thermocoagulation (RF-THC) of the NH. Methods Five patients (three male, age 5–33 years) with drug-resistant focal epilepsy presented a single NH at brain MRI. Following video-EEG monitoring, patients underwent SEEG recording to better identify the epileptogenic zone. All patients received RF-THC of the NH, using contiguous contacts of the electrodes employed for recording. The contacts for RF-THC lesions were chosen according to anatomical (intranodular position) and electrical (intranodular ictal low-voltage fast activity) criteria. Results At SEEG recordings, ictal discharge originated from the NH alone in three cases and from the NH and ipsilateral hippocampus in one case. In the remaining case, different sites of ictal onset, including the NH, were identified within the left frontal lobe. No adverse effects related to the RF-THC procedures were observed, apart from a habitual seizure that occurred during coagulation in one patient. Postprocedural sustained seizure freedom was detected in four cases (mean follow-up 33.5 months). In the case with left frontal multifocal ictal activity, RF-THC of the NH provided no benefit on seizures, and the patient is seizure-free after left frontal lobe resection. Conclusions SEEG-guided RF-THC proved to be a safe and effective option in our small case-series of NH-related focal epilepsy. The indications to this treatment were strictly dependent on findings of intracerebral recording by SEEG, which can define the role of the NH in the generation of the ictal discharge.

68 citations


Journal ArticleDOI
TL;DR: Accurate analysis of the chronology of ictal semiology and electrophysiological features, viewed in the context of the complete electroclinical pattern, provides a topographical orientation for posterior cortex epilepsy and, together with the presence of a lesion detectable on imaging, may improve the rate of surgical success of posterior cortical epilepsy at paediatric age.
Abstract: Past surgical series have emphasized the diagnostic complexity of posterior cortex epilepsy. Available data are sparse, especially in children, and most published series report a high number of surgical failures and post-operative neurological deficits. In this article, we present a paediatric cohort of 62 children who underwent surgery for drug resistant posterior cortex epilepsy before the age of 16 years with a mean post-operative follow-up of 6.94 years (range: 2-16). Mean age at epilepsy onset was 3.2 years and 28 children (45%) had onset before 1 year of age. The mean age at surgery was 7.9 years (range: 1-16). Daily seizures were present in 63% of children. MRI was positive in 58 cases (93.5%) and invasive stereo-EEG was judged mandatory in 24/62 (39%) of patients. Surgery was confined to the parietal lobe in 11 children, the occipital lobe in 8, the occipito-parietal region in four, the occipito-temporal region in 18, and involved both the temporal and parietal lobes in the remaining 21. Following surgery, 53 subjects (85.5%) remained seizure-free and among those who underwent a SEEG procedure, 75% achieved seizure freedom. Focal cortical dysplasia was the most frequent histopathological diagnosis (50%), followed by tumoural (24%) and gliotic lesions (14.5%). An older age at epilepsy onset, the presence of a rather restricted epileptogenic area, and a complete resection of the epileptogenic zone were predictive of a favourable surgical outcome. These results demonstrate that a good surgical outcome is possible in children with drug resistant posterior cortex epilepsy. Accurate analysis of the chronology of ictal semiology and electrophysiological features, viewed in the context of the complete electroclinical pattern, provides a topographical orientation for posterior cortex epilepsy and, together with the presence of a lesion detectable on imaging, may improve the rate of surgical success of posterior cortex epilepsy at paediatric age.

42 citations


Journal ArticleDOI
TL;DR: A growing body of evidence showing how electrophysiological features of sleep and wakefulness are coexisting across diffuse brain areas in pathological and physiological sleep as well as during state transitions (sleep onset and awakenings) is discussed.
Abstract: Sleep and waking have been traditionally considered global behavioural states regulated by subcortical neuromodulatory circuits in a top-down fashion. Over the last years, we have been experiencing a paradigm shift towards a view that both wake and sleep are in essence local processes. Here we review recent clinical and basic research works supporting this view by taking advantage of stereotactic electroencephalography (Stereo-EEG, SEEG) recordings performed in epileptic patients. Specifically, we will discuss a growing body of evidence showing how electrophysiological features of sleep and wakefulness are coexisting across diffuse brain areas in pathological and physiological sleep as well as during state transitions (sleep onset and awakenings). Finally, we will discuss their implication for sleep medicine to extent that, reconsidering the classical definition of wakefulness and sleep as separate and mutually exclusive states may offer new insight for the understanding of parasomnias and other dissociated states.

30 citations


Journal ArticleDOI
TL;DR: A retrospective analysis of a case series of 955 patients operated on for drug-resistant focal epilepsy from 1997 to 2009 found that SRE can frequently originate outside the frontal lobe and a favorable surgical outcome is achieved in three-fourths of cases independently from the location of the EZ.

23 citations


Journal ArticleDOI
TL;DR: The present findings support the crucial role of hippocampal slow EEG frequencies during sleep in the memory consolidation processes and suggest that slow frequency rhythms are a fundamental characteristic of human hippocampal EEG during both sleep and wakefulness, and are related to the consolidation of different types of memories.
Abstract: The hypothesis that sleep is instrumental in the process of memory consolidation is currently largely accepted. Hippocampal formation is involved in the acquisition of declarative memories and particularly of spatial memories. Nevertheless, although largely investigated in rodents, the relations between spatial memory and hippocampal EEG activity have been scarcely studied in humans. Aimed to evaluate the effects of spatial learning on human hippocampal sleep EEG activity, we recorded hippocampal Stereo-EEG (SEEG) in a group of refractory epilepsy patients undergoing presurgical clinical evaluation, after a training on a spatial navigation task. We observed that hippocampal high-delta (2-4 Hz range) activity increases during the first NREM episode after learning compared to the baseline night. Moreover, the amount of hippocampal NREM high-delta power was correlated with task performance at retest. The effect involved only the hippocampal EEG frequencies inasmuch no differences were observed at the neocortical electrodes and in the traditional polysomnographic measures. The present findings support the crucial role of hippocampal slow EEG frequencies during sleep in the memory consolidation processes. More generally, together with previous results, they suggest that slow frequency rhythms are a fundamental characteristic of human hippocampal EEG during both sleep and wakefulness, and are related to the consolidation of different types of memories.

22 citations


Journal ArticleDOI
TL;DR: This ‘catalogue of knowledge and skills’ for sleep medicine is proposed as a template for developing more standardized curricula across Europe, serving not only physicians with a medical speciality degree, but also PhD and MSc health professionals such as clinical psychologists and scientists, technologists and nurses.
Abstract: Summmary: Sleep medicine is evolving globally into a medical subspeciality in its own right, and in parallel, behavioural sleep medicine and sleep technology are expanding rapidly. Educational programmes are being implemented at different levels in many European countries. However, these programmes would benefit from a common, interdisciplinary curriculum. This 'catalogue of knowledge and skills' for sleep medicine is proposed, therefore, as a template for developing more standardized curricula across Europe. The Board and The Sleep Medicine Committee of the European Sleep Research Society (ESRS) have compiled the catalogue based on textbooks, standard of practice publications, systematic reviews and professional experience, validated subsequently by an online survey completed by 110 delegates specialized in sleep medicine from different European countries. The catalogue comprises 10 chapters covering physiology, pathology, diagnostic and treatment procedures to societal and organizational aspects of sleep medicine. Required levels of knowledge and skills are defined, as is a proposed workload of 60 points according to the European Credit Transfer System (ECTS). The catalogue is intended to be a basis for sleep medicine education, for sleep medicine courses and for sleep medicine examinations, serving not only physicians with a medical speciality degree, but also PhD and MSc health professionals such as clinical psychologists and scientists, technologists and nurses, all of whom may be involved professionally in sleep medicine. In the future, the catalogue will be revised in accordance with advances in the field of sleep medicine. Copyright © 2014 European Sleep Research Society 232 April 2014 10.1111/jsr.12095 Catalogue for sleep medicine Catalogue for sleep medicine © 2013 European Sleep Research Society.

16 citations



Journal ArticleDOI
TL;DR: Auditory aura may be a symptom suggesting an extra-frontal epileptogenic zone, and 11 out of 165 nocturnal frontal lobe epilepsy patients reported an auditory aura as initial ictal symptom.

Journal ArticleDOI
TL;DR: 2 children with mucopolysaccharidosis who were referred for significant sleep disturbance are described and long term video-EEG monitoring demonstrated sleep-related hypermotor seizures consistent with NFLE.
Abstract: Nocturnal frontal lobe epilepsy (NFLE) is an epileptic syndrome that is primarily characterized by seizures with motor signs occurring almost exclusively during sleep. We describe 2 children with mucopolysaccharidosis (MPS) who were referred for significant sleep disturbance. Long term video-EEG monitoring (LT-VEEGM) demonstrated sleep-related hypermotor seizures consistent with NFLE. No case of sleep-related hypermotor seizures has ever been reported to date in MPS. However, differential diagnosis with parasomnias has been previously discussed. The high frequency of frontal lobe seizures causes sleep fragmentation, which may result in sleep disturbances observed in at least a small percentage of MPS patients. We suggest monitoring individuals with MPS using periodic LT-VEEGM, particularly when sleep disorder is present. Moreover, our cases confirm that NFLE in lysosomal storage diseases may occur, and this finding extends the etiologic spectrum of NFLE.

Book ChapterDOI
01 Jan 2014
TL;DR: Management and prevention of sleep-related accidents should be a priority for the public, labor, governments, and industries and scientific data on potentially useful countermeasures are needed.
Abstract: Sleep deprivation affects performance outcomes across a wide range of cognitive domains. Sleepiness and fatigue, caused by sleep loss, extended work and wakefulness, circadian misalignment, and sleep disorders are major causes of workplace human errors, incidents, and accidents. Car crashes related to falling asleep represent up to 20 % of all traffic accidents in industrial societies and are known to be more likely to cause death and severe injury. Sleep-related accidents are substantial in terms of personal injury, of property damage, lost productivity, and death. Management and prevention of sleep-related accidents should be a priority for the public, labor, governments, and industries. Scientific data on potentially useful countermeasures are needed.

Book ChapterDOI
01 Jan 2014
TL;DR: The average amount of sleep reported by middle age subjects seems to have decreased by about 1 h per night in the last half century, and due to the increasing misalignment between biological and social time there is a risk of developing a "social jet-lag" and becoming a “chronically sleep deprived” society with adverse effects on safety, health, psychological well-being, and productivity.
Abstract: Nowadays there seems to be a growing attention to encouraging healthy lifestyles. Sleep is a key indicator of health-related habits. Sleep disturbances are considered important risk factors for several medical illnesses. On the other hand, in the last years there has been a widespread growth in services, available regardless of time or day organization (24/7 service) and a diffuse increase in the utilization, both in work and private lives, of modern information and communication technology, generally ignoring the importance of a regular sleep organization. The average amount of sleep reported by middle age subjects seems to have decreased by about 1 h per night in the last half century. Due to the increasing misalignment between biological and social time there is a risk of developing a “social jet-lag” and becoming a “chronically sleep deprived” society with adverse effects on safety, health, psychological well-being, and productivity.


Journal ArticleDOI
TL;DR: In this article, the effects on the subject's sleep cycle, alertness, and performance of the sleep phase shift due to working at times of the day when sleep propensity is high were quantified and model mathematically.
Abstract: Aims: To quantify and model mathematically the effects on the subjectssleepwake cycle, alertness, and performance of the sleep phase shift due to working at times of the day when sleep propensity is high. Methodologi es: Thirty-seven police officers working on a fast counterclockwise schedule, filled for 25 consecutive days a self -administered questionnaire about the previous night sleep, subjective fatigue, sleep attacks, errors. For each subject, the hom eostatic process was computed according to the BorbEly -Achermann model. Night sleep decreased progressively during the shift schedule, with effects on sleep pressure Original ResearchArticle