Showing papers by "Lino Nobili published in 2017"

Global and local complexity of intracranial EEG decreases during NREM sleep.

Abstract: Key to understanding the neuronal basis of consciousness is the characterisation of the neural signatures of changes in level of consciousness during sleep. Here we analysed three measures of dynamical complexity on spontaneous depth electrode recordings from 10 epilepsy patients during wakeful rest and different stages of sleep: (i) Lempel-Ziv complexity, which is derived from how compressible the data are; (ii) amplitude coalition entropy, which measures the variability over time of the set of channels active above a threshold; (iii) synchrony coalition entropy, which measures the variability over time of the set of synchronous channels. When computed across sets of channels that are broadly distributed across multiple brain regions, all 3 measures decreased substantially in all participants during early-night non-rapid eye movement (NREM) sleep. This decrease was partially reversed during late-night NREM sleep, while the measures scored similar to wakeful rest during rapid eye movement (REM) sleep. This global pattern was in almost all cases mirrored at the local level by groups of channels located in a single region. In testing for differences between regions, we found elevated signal complexity in the frontal lobe. These differences could not be attributed solely to changes in spectral power between conditions. Our results provide further evidence that the level of consciousness correlates with neural dynamical complexity.

Stereo-EEG: Diagnostic and therapeutic tool for periventricular nodular heterotopia epilepsies.

Abstract: SummaryObjective Periventricular nodular heterotopias (PNHs) are malformations of cortical development related to neuronal migration disorders, frequently associated with drug-resistant epilepsy (DRE). Stereo-electroencephalography (SEEG) is considered a very effective step of the presurgical evaluation, providing the recognition of the epileptogenic zone (EZ). At the same time, via the intracerebral electrodes it is possible to perform radiofrequency thermocoagulation (SEEG-guided RF-TC) with the aim of ablating and/or disrupting the EZ. The purpose of this study was to evaluate both the relationships between PNH and the EZ, and the efficacy of SEEG-guided RF-TC. Methods Twenty patients with DRE related to PNHs were studied. Inclusion criteria were the following: (1) patients with epilepsy and PNHs (unilateral or bilateral, single or multiple nodules) diagnosed on brain magnetic resonance imaging (MRI); (2) SEEG recordings available as part of the presurgical investigations, with at least one intracerebral electrode inside the heterotopia; (3) complete surgical workup with SEEG-guided RF-TC and/or with traditional neurosurgery, with a follow-up of at least 12 months. Results Complex and heterogenic epileptic networks were found in these patients. SEEG-guided RF-TC both into the nodules and/or the cortex was efficacious in the 76% of patients. Single or multiple, unilateral or bilateral PNHs are the most suitable for this procedure, whereas patients with PNHs associated with complex cortical malformations obtained excellent outcome only with traditional resective surgery. Significance Each patient had a specific epileptogenic network, independent from the number, size, or location of nodules and from the cortical malformation associated with. SEEG-guided RF-TC appears as a new and very effective diagnostic and therapeutic approach for DRE related to PNHs.

Modular co-organization of functional connectivity and scale-free dynamics in the human brain.

Abstract: Scale-free neuronal dynamics and interareal correlations are emergent characteristics of spontaneous brain activity. How such dynamics and the anatomical patterns of neuronal connectivity are mutually related in brain networks has, however, remained unclear. We addressed this relationship by quantifying the network colocalization of scale-free neuronal activity-both neuronal avalanches and long-range temporal correlations (LRTCs)-and functional connectivity (FC) by means of intracranial and noninvasive human resting-state electrophysiological recordings. We found frequency-specific colocalization of scale-free dynamics and FC so that the interareal couplings of LRTCs and the propagation of neuronal avalanches were most pronounced in the predominant pathways of FC. Several control analyses and the frequency specificity of network colocalization showed that the results were not trivial by-products of either brain dynamics or our analysis approach. Crucially, scale-free neuronal dynamics and connectivity also had colocalized modular structures at multiple levels of network organization, suggesting that modules of FC would be endowed with partially independent dynamic states. These findings thus suggest that FC and scale-free dynamics-hence, putatively, neuronal criticality as well-coemerge in a hierarchically modular structure in which the modules are characterized by dense connectivity, avalanche propagation, and shared dynamic states.

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

Abstract: 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.

Sleep and Epilepsy

Abstract: This chapter outlines an interaction between sleep and epilepsy including effect of sleep on epilepsy, epilepsy on sleep, and antiepileptic medication on sleep, preceded by a brief discussion about mechanism of epilepsy and sleep. We also mention about the impact of autonomic nervous system and sleep apnea in epilepsy. Finally, we discuss about special seizure types occurring during night as well as diagnostic procedures and practical relevance to understanding the relationship between sleep and epilepsy.

Correlating Interictal Spikes with Sigma and Delta Dynamics during Non-Rapid-Eye-Movement-Sleep.

Abstract: Interictal spikes (IS) are one of the major hallmarks of epilepsy. Understanding the factors promoting or suppressing IS would increase our comprehension of epilepsy and possibly open new avenues for therapy. Sleep strongly influences epileptic activity, and the modulatory effects of the different sleep stages on IS have been studied for decades. However, several aspects are still disputed, in particular the role of sleep spindles and slow waves in the activation of IS during Non-REM sleep. Here, we correlate the rate of IS with quantitative measures derived from stereo-EEG during one Non-REM cycle in 10 patients suffering from drug-resistant epilepsy due to type 2 focal cortical dysplasia. We show that the IS rate (ISR) is positively correlated with sigma power (a surrogate for sleep-spindle density) but negatively correlated with delta power (surrogate for slow wave activity). In addition, we present two new indices for quantifying the spatial and temporal instability of sleep. We found that both instability indices are correlated with a high ISR. The main contribution of this study is to confirm the suppressive effect of stable deep sleep on IS. This result might influence future guidelines for therapy of patients suffering from epilepsy and sleep disorders.

A stereo EEG study in a patient with sleep-related hypermotor epilepsy due to DEPDC5 mutation.

Abstract: Purpose Dishevelled EGL-10 and pleckstrin domain-containing protein 5 (DEPDC5) mutations are found in a wide spectrum of focal epilepsies ranging from epilepsy caused by malformation of cortical development to non-lesional epilepsy, including sleep-related hypermotor epilepsy (SHE). A surgical approach has been anecdotally reported in patients with DEPDC5 mutations, but most of these cases had a lesional etiology. Methods We describe a stereo-EEG (SEEG) study in a patient with drug-resistant/non-lesional SHE. Patient was screened for known mutations associated with SHE. Results SEEG disclosed bilateral synchronous and independent activity prevailing on the right central-anterior cingulate cortex, without a clear spatially defined epileptogenic zone. Due to the lack of a clear epileptogenic zone, surgery was contraindicated. Years later a DEPDC5 mutation was identified. Conclusion We suggest that genetic analysis should be considered before performing SEEG study in a patient with drug resistant non-lesional SHE, in the presence of seizures in wakefulness and unclear anatomo-electroclinical correlation. If DEPDC5 mutations are identified, the presurgical evaluation should be tailored to look for MRI-negative focal cortical dysplasia and a wide epileptogenic network. The appropriate management and potential benefit of surgery for genetic non-lesional epilepsy have yet to be clarified.

Parasomnias in Children

Abstract: Parasomnias are undesirable physical events or experiences that occur during sleep. They are classified on the basis of the sleep stage during which each of the parasomnias tends to occur: NREM-related parasomnias also defined as disorders of arousal (confusional arousals, sleepwalking, sleep terrors, and sleep-related eating disorder), REM-related parasomnias (REM sleep behavior disorder, recurrent isolated sleep paralysis, and nightmare disorder), and other parasomnias (exploding head syndrome, sleep-related hallucinations, and sleep enuresis). Parasomnias include several clinical features, with different complexity of behaviors, usually associated with autonomic nervous system changes and skeletal muscle activity.

Integrated Imaginative Distention Therapy to Cope with Fatigue. DIMMI SI Study: The First Randomized Controlled Trial in Multiple Sclerosis

Abstract: Fatigue is a frequent, disabling, and difficult to treat symptom in neurological disease and in other stress-related conditions; Integrated Imaginative Distention (IID) is a therapy combining muscular and imaginative relaxation, feasible also in disabled subjects; the DIMMI SI trial was planned to evaluate IID efficacy on fatigue. The design was a parallel, randomised 1:1 (intervention:waiting list), controlled, open-label trial. Participants were persons with multiple sclerosis (pwMS), persons with insomnia (pwINS), and health professionals (HP) as conditions related to fatigue and stress. The primary outcome was the post-intervention change of fatigue; secondary outcomes were changes in insomnia, stress, and quality of life (QoL). Eight IID weekly training group sessions were delivered by a skilled psychotherapist. The study lasted 12 months. One hundred and forty-four subjects were enrolled, 48 for each condition. The mean change in Modified Fatigue Impact Scale (MFIS) score among exposed was 7.7 [95% CI 1.1, 14.4] (P = 0.023) in pwMS; 7.1 [1.9, 12.3] (P = 0.007) among pwINS, and 11.3 [4.3, 18.2] among HP (P = 0.002). At the last follow-up, the benefit was confirmed on physical fatigue for pwMS, on total fatigue for pwINS and HP. DIMMI SI is the first randomized controlled trial evaluating the efficacy of IID on fatigue. IID resulted a complementary intervention to reduce fatigue in stress-related conditions, in both health and disease status. NCT02290990ClinicalTrials.gov.

Functional Clustering approach for the analysis of Stereo-EEG activity patterns in correspondence of epileptic seizures

Abstract: In this study, a functional clustering approach is proposed and tested for the identification of brain functional networks emerging during sleep-related seizures. Stereo-EEG signals recorded in patients with Type II Focal Cortical Dysplasia (FCD type II), were analyzed. This novel approach is able to identify the network configuration changes in pre-ictal and early ictal periods, by grouping Stereo-EEG signals on the basis of the Cluster Index, after wavelet multiscale decomposition. Results showed that the proposed method is able to detect clusters of interacting leads, mainly overlapped on the Epileptogenic Zone (EZ) identified by a clinical expert, with distinctive configurations related to analyzed frequency ranges. This suggested the presence of coupling activities between the elements of the epileptic system at different frequency scales.

Measuring autonomic involvement related to seizure onset in Focal Cortical Dysplasia type II

Abstract: The research here presented aims to the investigation of the Autonomic Nervous System (ANS) and of the sympatho-vagal balance during sleep-related seizures in patients affected by Focal Cortical Dysplasia (FCD) type II. Heart Rate Variability (HRV) signal was recorded during sleep together with S-EEG (stereo EEG) acquisitions performed for pre-surgical evaluation. The sympatho-vagal balance was estimated in pre-ictal, ictal and post-ictal time, by means of parameters in the time and in the frequency domain. The results here presented are related to 10 epileptic seizures occurring during the same night in one patient. The obtained results testify a significant decrease (p < 0.005) in the RR mean value and standard deviation during the ictal and post-ictal periods in respect to the inter-ictal phase, and a significant decrease (p < 0.001) in the HF(%) power between inter-ictal and post-ictal periods. All these findings are associated to a sympathetic activation and to a vagal drive reduction. A deeper knowledge of the correlations between ANS and epilepsy can lead to better understand the causes of SUDEP (Sudden Unexpected Death in Epilepsy); can contribute to the development of methods for the detection and prediction of epileptic seizures and help to evaluate the effects of vagal nerve stimulation used in those cases in which the patient is not an ideal candidate for surgery.

Is polysomnography screening effective for stroke prevention

Abstract: Stroke ranks as the second most common cause of death worldwide and the leading cause of adult disability [1]. Thus, identification and treatment of modifiable risk factors represent the most effective approach to diminish stroke-related burden. A recent meta-analysis supports existing evidence that obstructive sleep apnea (OSA) represents an independent stroke predictor, showing that cerebrovascular risk increases with OSA severity [2]. Another meta-analysis revealed a high prevalence of sleep-disordered breathing (SDB) in patients with stroke or transient ischemic attack (TIA) (63% of patients with an apnea– hypopnea index more than 10/h); SDB was primarily obstructive in nature (OSA), with only 7% of patients having primarily central apneas [3]. Moreover, SDB seems to be similarly prevalent in stroke and TIA patients, indicating that SDB probably represents a preexisting condition. OSA has been also associated with poor outcomes among patients with stroke, including higher mortality and recurrent vascular events, worse functional status, and longer hospitalization duration [4]. Thus, screening and intervention in OSA patients represent a relevant issue not only for prevention of stroke recurrence but, probably, to facilitate poststroke recovery as well. The mechanisms underlying the relationship between OSA and stroke are not fully established. Recurrent OSA events lead to different acute adverse consequences: brain arousal, intrathoracic pressure changes, and intermittent episodes of hypoxemia. These events activate pathways such as oxidative stress, sympathetic activation, inflammation, hypercoagulability, endothelial dysfunction, and metabolic dysregulation that, in turn, predispose OSA patients to other main risk factors for stroke: hypertension, atherosclerosis, and atrial fibrillation (AF) [5]. In particular, OSA represents the most common condition associated with resistant hypertension [6]. Moreover, current literature reports a strong association between OSA and AF, with a prevalence of AF in patients with OSA of approximately 5%, which is higher than the prevalence of AF in the general population (1–2%). Conversely, the prevalence of OSA among AF patients ranges between 21% and just over 80% [7]. A retrospective study showed that in a group of AF patients, the occurrence of first-time stroke was more common in patients with OSA compared with patients without; this association remained significant after accounting for cardiovascular risk factors [8]. Besides these long-standing mechanisms, sleep apnea could act as a precipitating, acute factor, favoring a cardioembolic cerebrovascular ischemic event in patients with patent foramen ovale (PFO). Indeed, a study conducted in 335 patients with mild stroke or TIA found that the association of sleep apnea events with right to left shunt increases the risk of wake-up stroke, suggesting that OSA might provoke paradoxical embolism [9]. Even though studies analyzing the prevalence of SDB in different stroke etiologies obtained discordant results, a recent work revealed a strong association between OSA and cardioembolic stroke [10]. Interestingly, Lipford et al. [10] found that the association between OSA and cardioembolic stroke remains even after adjustment for the presence of known AF. This finding may be explained by a high rate of occult paroxysmal AF in this population but, alternatively, OSA may lead to stroke through mechanisms independent of cardiac arrhythmias. One of this could be represented by a PFO-mediated paradoxic embolism. Although OSA affects 24% of middle-aged men and 9% of women [11], as many as 70–80% of them are neither diagnosed nor treated [12]. Considering the high prevalence of OSA and its role as an independent risk factor for stroke, the American Heart Association/American Stroke Association (AHA/ASA) recently included recommendations on diagnosis and treatment of SDB for the primary prevention of Stroke (Class IIb; Level of Evidence C) [13]. Recently, a low level of accuracy for the diagnosis of OSA of different clinical prediction algorithms against PSG has been highlighted [14]. For instance, the high number of potential false-negative results using different questionnaires compared to PSG limits their use as instruments to diagnose individual patients with OSA (for the AHI ≥5 cutoff: Berlin Questionnaire sensitivity was 0.76 and specificity was 0.45; Epworth Sleepiness Scale sensitivity was 0.27–0.72 and specificity was 0.50–0.76; STOP-BANG questionnaire sensitivity was 0.93 and specificity was 0.36). For these reasons, the recent guidelines of the American Academy of Sleep Medicine recommend that clinical tools, questionnaires, and prediction algorithms not be used to diagnose OSA in adults, in the absence of polysomnography (PSG) or home sleep apnea testing [14]. Thus, an integration of hypnological anamnesis together with a physical examination