Event-related causality in stereo-EEG discriminates syntactic processing of noun phrases and verb phrases.

Objective.Syntax involves complex neurobiological mechanisms, which are difficult to disentangle for multiple reasons. Using a protocol able to separate syntactic information from sound information we investigated the neural causal connections evoked by the processing of homophonous phrases, i.e. with the same acoustic information but with different syntactic content. These could be either verb phrases (VP) or noun phrases.Approach. We used event-related causality from stereo-electroencephalographic recordings in ten epileptic patients in multiple cortical and subcortical areas, including language areas and their homologous in the non-dominant hemisphere. The recordings were made while the subjects were listening to the homophonous phrases.Main results.We identified the different networks involved in the processing of these syntactic operations (faster in the dominant hemisphere) showing that VPs engage a wider cortical and subcortical network. We also present a proof-of-concept for the decoding of the syntactic category of a perceived phrase based on causality measures.Significance. Our findings help unravel the neural correlates of syntactic elaboration and show how a decoding based on multiple cortical and subcortical areas could contribute to the development of speech prostheses for speech impairment mitigation.

Hemispheric surgery for severe epilepsy in early childhood: a case series.

Hemispheric surgery is an effective and cost-effective option for hemispheric epilepsy. Data specifically focusing on very early infancy are scant. In our study, we report the results of hemispheric surgery in children under three years of age, along with clinical, neuroradiological and EEG features, from two Italian epilepsy surgery centres. After reviewing our epilepsy surgery databases (2008-2018), we identified 14 patients (seven males) submitted to hemispheric surgery, under three years (range: 2-29 months), with a follow-up of at least 12 months. No deaths occurred, and surgical complications were observed in 3/17 procedures. At final follow-up visit (mean: 30.8 months; range: 12-90), 10/14 patients (71.4%) achieved Engel Class I (eight Class 1A, one Class 1B, and one Class 1C). Antiepileptic drugs were completely discontinued in three and reduced in eight, thus a significant decrease in drug regimen after surgery was achieved in 11/14 patients (78.6%). Before surgery, severe developmental delay was present in 10 patients, moderate in two and mild in two. At the last follow-up visit, the degree of developmental delay changed from severe to moderate in five patients, remained unchanged in six cases (four severe and two moderate), and changed from mild to moderate in two following surgery. In many cases, hemispheric surgery in children under three years is effective in achieving seizure freedom or reducing seizure frequency, with the possibility of simplifying complex drug regimens. Moreover, it appears to be a safe and well tolerated procedure, leading to improvement in cognition and posture.

High gamma response tracks different syntactic structures in homophonous phrases.

Syntax is a species-specific component of human language combining a finite set of words in a potentially infinite number of sentences. Since words are by definition expressed by sound, factoring out syntactic information is normally impossible. Here, we circumvented this problem in a novel way by designing phrases with exactly the same acoustic content but different syntactic structures depending on the other words they occur with. In particular, we used phrases merging an article with a noun yielding a Noun Phrase (NP) or a clitic with a verb yielding a Verb Phrase (VP). We performed stereo-electroencephalographic (SEEG) recordings in epileptic patients. We measured a different electrophysiological correlates of verb phrases vs. noun phrases in multiple cortical areas in both hemispheres, including language areas and their homologous in the non-dominant hemisphere. The high gamma band activity (150-300 Hz frequency), which plays a crucial role in inter-regional cortical communications, showed a significant difference during the presentation of the homophonous phrases, depending on whether the phrase was a verb phrase or a noun phrase. Our findings contribute to the ultimate goal of a complete neural decoding of linguistic structures from the brain.

Clinical features of sleep-related hypermotor epilepsy in relation to the seizure-onset zone: A review of 135 surgically treated cases.

OBJECTIVES: Sleep-related hypermotor epilepsy (SHE), formerly nocturnal frontal lobe epilepsy, is characterized by abrupt and typically sleep-related seizures with motor patterns of variable complexity and duration. They seizures arise more frequently in the frontal lobe than in the extrafrontal regions but identifying the seizure onset-zone (SOZ) may be challenging. In this study, we aimed to describe the clinical features of both frontal and extrafrontal SHE, focusing on ictal semiologic patterns in order to increase diagnostic accuracy. METHODS: We retrospectively analyzed the clinical features of patients with drug-resistant SHE seen in our center for epilepsy surgery. Patients were divided into frontal and extrafrontal SHE (temporal, operculoinsular, and posterior SHE). We classified seizure semiology according to four semiology patterns (SPs): elementary motor signs (SP1), unnatural hypermotor movements (SP2), integrated hypermotor movements (SP3), and gestural behaviors with high emotional content (SP4). Early nonmotor manifestations were also assessed. RESULTS: Our case series consisted of 91 frontal SHE and 44 extrafrontal SHE cases. Frontal and extrafrontal SHE shared many features such as young age at onset, high seizure-frequency rate, high rate of scalp electroencephalography (EEG) and magnetic resonance imaging (MRI) abnormalities, similar histopathologic substrates, and good postsurgical outcome. Within the frontal lobe, SPs were organized in a posteroanterior gradient (SP1-4) with respect to the SOZ. In temporal SHE, SP1 was rare and SP3-4 frequent, whereas in operculoinsular and posterior SHE, SP4 was absent. Nonmotor manifestations were frequent (70%) and some could provide valuable localizing information. SIGNIFICANCE: Our study shows that the presence of certain SP and nonmotor manifestations may provide helpful information to localize seizure onset in patients with SHE.

Outcome after hemispherotomy in patients with intractable epilepsy: Comparison of techniques in the Italian experience.

OBJECTIVE: The objective of the study was to evaluate clinical characteristics and outcome of hemispherotomy in children and adolescents with hemispheric refractory epilepsy in an Italian cohort of patients. METHODS: We retrospectively evaluated the clinical course and outcome of 92 patients with refractory epilepsy who underwent hemispherotomy in three Italian epilepsy centers between 2006 and 2016. Three different approaches for hemispherotomy were used: parasagittal, modified parasagittal, and lateral. RESULTS: Mean age at epilepsy onset was 1.8 ±â€¯2.51 years, and mean duration of epilepsy prior to surgery was 7.4 ±â€¯5.6 years. Mean age at surgery was 9.2 ±â€¯8.0 years. After a mean follow-up of 2.81 ±â€¯2.4 years, 66 of 90 patients (two lost from follow-up, 73.3%) were seizure-free (Engel class I). The etiology of epilepsy was related to acquired lesions (encephalomalacia or gliosis) in 44 patients (47.8%), congenital malformations (cortical dysplasia, hemimegalencephaly, other cortical malformations) in 38 (41.3%), and progressive conditions (Rasmussen or Sturge-Weber syndrome) in 10 patients (10.9%). Regarding seizure outcome, we could not identify statistically significant differences between vertical and lateral approaches (p = 0.154). Seizure outcome was not statistically different in patients with congenital vs acquired or progressive etiologies (p = 0.43). Acute postoperative seizures (APOS) correlated with poor outcome (p < 0.05). On multivariate analysis, presurgical focal to bilateral tonic-clonic seizures (Odds Ratio (OR) = 3.63, 95% Confidence Interval (CI): 1.86-15.20, p = 0.048) independently predicted seizure recurrence. Twenty-one patients (22.8%) exhibited postoperative complications, with no unexpected and persistent neurological deficit. More than 50% of the patients completely tapered drugs. SIGNIFICANCE: Our data confirm hemispherotomy to be a safe and effective procedure in patients with drug resistant epilepsies due to hemispheric lesions. Presurgical focal to bilateral tonic-clonic seizures are the strongest predictor of seizure recurrence after surgery, independently from the type of hemispherotomy.

Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis.

BACKGROUND: Half of patients who have resective brain surgery for drug-resistant epilepsy have recurrent postoperative seizures. Although several single predictors of seizure outcome have been identified, no validated method incorporates a patient's complex clinical characteristics into an instrument to predict an individual's post-surgery seizure outcome. METHODS: We developed nomograms to predict complete freedom from seizures and Engel score of 1 (eventual freedom from seizures allowing for some initial postoperative seizures, or seizures occurring only with physiological stress such as drug withdrawal) at 2 years and 5 years after surgery on the basis of sex, seizure frequency, secondary seizure generalisation, type of surgery, pathological cause, age at epilepsy onset, age at surgery, epilepsy duration at time of surgery, and surgical side. We designed the models from a development cohort of patients who had resective surgery at the Cleveland Clinic (Cleveland, OH, USA) between 1996 and 2011. We then tested the nomograms in an external validation cohort operated on over a similar period in four epilepsy surgery centres, in Brazil, France, Italy, and the USA. We assessed performance of the nomogram by calculating concordance statistics and assessing the calibration of predicted freedom from seizures with the reported freedom from seizures and Engel score of 1. FINDINGS: The development cohort included 846 patients and the validation cohort included 604 patients. Variables included in the nomograms were sex, seizure frequency, secondary seizure generalisation, type of surgery, and pathological cause. In the development cohort, the baseline risk of complete freedom from seizures was 0·57 at 2 years and 0·40 at 5 years. The baseline risk of Engel score of 1 was 0·69 at 2 years and 0·62 at 5 years. In the validation cohort, the models had a concordance statistic of 0·60 for complete freedom from seizures and 0·61 for Engel score of 1. Calibration curves showed adequate calibration (judged by eye) of predicted and reported freedom from seizures, throughout the range of seizure outcomes. INTERPRETATION: If validated in prospective cohorts, these nomograms could be used to predict seizure outcomes in patients who have been judged eligible for epilepsy surgery. FUNDING: Cleveland Clinic Epilepsy Center.

Epilepsies associated with focal cortical dysplasias (FCDs).

Focal cortical dysplasias (FCDs) are increasingly recognized as one of the most common causes of pharmaco-resistant epilepsies. FCDs were recently divided into various clinico-pathological subtypes due to distinct imaging, electrophysiological, and outcome characteristics. In this review, we will overview the international consensus classification of FCDs in light of more recently reported clinical, electrical, imaging and functional observations, and will also address areas of ongoing debate. In addition, we will summarize our current knowledge on pathobiology and epileptogenicity of FCDs as well as its underlying molecular and cellular mechanisms. The clinical (electroencephalographic, imaging, and functional) characteristics of major FCD subtypes and their implications on the presurgical evaluation and surgical management will be discussed in light of studies describing these characteristics and postoperative seizure outcomes in patients with medically intractable focal epilepsy due to histopathologically confirmed FCDs.

Surgery for temporal lobe epilepsy in children: relevance of presurgical evaluation and analysis of outcome.

OBJECT: The authors' goal in this paper was to retrospectively evaluate the relevance of the presurgical workup and the postoperative outcome in children (< 15 years) who undergo surgery for temporal lobe epilepsy (TLE). METHODS: The authors performed a retrospective analysis of 68 patients (43 boys and 25 girls) who underwent resection for TLE between 2001 and 2010 at a single center and had a minimum postoperative follow-up of 12 months. Presurgical investigations included full clinical evaluation, interictal electroencephalography (EEG), and MRI in all cases; cognitive evaluation in patients older than 5 years; scalp video-EEG in 46 patients; and invasive EEG in 3 patients. Clinical evaluation included a careful assessment of ictal semiology (based on anamnestic reports or video-EEG review), with particular attention to early signs and/or symptoms suggestive of temporal lobe origin of the seizure. Microsurgical resections were performed within the anatomical limits of the temporal lobe, and surgical specimens were processed for histological examination. Postoperative assessment of seizure outcome (Engel classification system) and cognitive performance was conducted at regular intervals. The effect on postoperative seizure outcome (good = Engel Class I; poor = Engel Classes II-IV) of several presurgical and surgical variables was investigated by bivariate statistical analysis. RESULTS: All patients had at least 1 early sign or symptom suggesting a temporal lobe origin of their seizures. Lateralized interictal or ictal EEG abnormalities were seen in all patients, and they were localized to the temporal lobe in 45 patients. In all cases MRI demonstrated a structural abnormality. Surgery consisted of a tailored anterior temporal lobectomy in 64 patients and a neocortical lesionectomy in 4 patients. Postoperatively, 58 patients (85%) were in Engel Class I. Variables significantly associated with a poor outcome were preoperative sensory motor deficit (p = 0.019), mental retardation (p = 0.003), MRI abnormalities extending outside the temporal lobe (p = 0.0018), history of generalized seizures (p = 0.01) or status epilepticus (p = 0.008), unremarkable histology (p = 0.001), seizures immediately postoperatively (p = 0.00001), and ipsilateral epileptiform activity on postoperative EEG (p = 0.005). At postoperative neuropsychological assessment, the percentage of patients with a pathological score at the final visit invariably decreased compared with that at the preoperative evaluation in all considered cognitive domains. CONCLUSIONS: Among the study population, a surgical selection based on a noninvasive evaluation was possible in most patients. The invaluable information resulting from the rigorous noninvasive electroclinical and neuroimaging evaluation can lead to excellent surgical results without the use of invasive, time-consuming, and expensive diagnostic tools. The potential reduction of invasiveness-related risks, complexity, and costs of presurgical investigations should hopefully allow for an increase in the number of children with TLE who will receive surgery, particularly in centers with limited technological resources.

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.

Stereoelectroencephalography in the presurgical evaluation of focal epilepsy in infancy and early childhood.

OBJECT: The authors report on the use of stereoelectroencephalography (stereo-EEG) in the presurgical electroclinical evaluation of infants and very young children with focal drug-resistant epilepsy. METHODS: Fifteen patients (9 girls and 6 boys, mean age 34.1 ± 7.3 months, range 21-45 months), potentially candidates to receive surgical treatment for their focal drug-resistant epilepsy, were evaluated using stereo-EEG recording for a detailed definition of the epileptogenic zone. Stereoelectroencephalography was indicated because neuroradiological (brain MRI) and video-EEG data failed to adequately localize the epileptogenic zone. Stereotactic placement of multicontact intracerebral electrodes was preceded by the acquisition of all pertinent anatomical information from structural and functional MRI and from brain angiography, enabling the accurate targeting of desired structures through avascular trajectories. Stereoelectroencephalography monitoring attempted to record habitual seizures; electrical stimulations were performed to induce seizures and for the functional mapping of eloquent areas. Stereoelectroencephalography-guided microsurgery, when indicated, pointed to removal of the epileptogenic zone and seizure control. RESULTS: Brain MRI revealed an anatomical lesion in 13 patients (lobar in 2 cases, multilobar or hemispheric in 11 cases) and was unremarkable in 2 patients. One patient underwent 2 stereo-EEG studies. The arrangement of the intracerebral electrodes was unilateral in all but 1 case. One patient died the day following electrode placement due to massive brain edema and profound hyponatremia of undetermined cause. In 8 cases intracerebral electrical stimulations allowed mapping of functionally critical areas; in 3 other cases that received purposeful placement of electrodes in presumably eloquent areas, no functional response was obtained. Of the 14 patients who completed stereo-EEG monitoring, 1 was excluded from surgery for multifocality of seizures and 13 underwent operations. Postoperatively, 2 patients exhibited an anticipated, permanent motor deficit, 3 experienced a transient motor deficit, and 2 experienced transient worsening of a preexisting motor deficit. Three patients developed a permanent homonymous hemianopia after posterior resections. Histological analysis revealed cortical malformations in 10 cases. Of the 10 patients with a postoperative follow-up of at least 12 months, 6 (60%) were seizure-free (Engel Class Ia), 2 (20%) experienced a significant reduction of seizures (Engel Class II), and 2 (20%) were unchanged (Engel Class IV). CONCLUSIONS: The present study indicates that stereo-EEG plays a prominent role in the presurgical evaluation of focal epilepsies also in the first years of life and that it may offer a surgical option in particularly complex cases that would have scarcely benefitted from further medical treatment. Results of stereo-EEG-guided resective surgery were excellent, with 80% of patients exhibiting a substantial improvement in seizures. In consideration of the potentially life-threatening risks of major intracranial surgery in this specific age group, the authors recommend reserving stereo-EEG evaluations for infants with realistic chances of benefiting from surgery.

Dissociated wake-like and sleep-like electro-cortical activity during sleep.

Sleep is traditionally considered a global process involving the whole brain. However, recent studies have shown that sleep depth is not evenly distributed within the brain. Sleep disorders, such as sleepwalking, also suggest that EEG features of sleep and wakefulness might be simultaneously present in different cerebral regions. In order to probe the coexistence of dissociated (wake-like and sleep-like) electrophysiological behaviors within the sleeping brain, we analyzed intracerebral electroencephalographic activity drawn from sleep recordings of five patients with pharmacoresistant focal epilepsy without sleep disturbances, who underwent pre-surgical intracerebral electroencephalographic investigation. We applied spectral and wavelet transform analysis techniques to electroencephalographic data recorded from scalp and intracerebral electrodes localized within the Motor cortex (Mc) and the dorso-lateral Prefrontal cortex (dlPFc). The Mc showed frequent Local Activations (lasting from 5 to more than 60s) characterized by an abrupt interruption of the sleep electroencephalographic slow waves pattern and by the appearance of a wake-like electroencephalographic high frequency pattern (alpha and/or beta rhythm). Local activations in the Mc were paralleled by a deepening of sleep in other regions, as expressed by the concomitant increase of slow waves in the dlPFc and scalp electroencephalographic recordings. These results suggest that human sleep can be characterized by the coexistence of wake-like and sleep-like electroencephalographic patterns in different cortical areas, supporting the hypothesis that unusual phenomena, such as NREM parasomnias, could result from an imbalance of these two states.

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.

Emotions induced by intracerebral electrical stimulation of the temporal lobe.

PURPOSE: To assess the quality and frequency of emotions induced by intracerebral electrical stimulation of the temporal lobe. METHODS: Behavioral responses were obtained by electrical stimulation in 74 patients undergoing presurgical video-stereo-EEG monitoring for drug-resistant epilepsy. Intracerebral electrical stimulation was performed by delivering trains of electrical stimuli of alternating polarity; the intensity could vary from 0.2 to 3 mA. Stimulation frequency was 1 Hz or 50 Hz. Nine hundred thirty-eight stimulation procedures were performed. RESULTS: Seventy-nine emotional responses (ERs) were obtained (8.4%). Of these, 67 were "fear responses." Sad feelings were evoked 3 times, happy-pleasant feelings 9 times. Anger and disgust were never observed. The following variables affected the incidence of ER: (a) Anatomical site of stimulation. ERs (always fear) were maximal at the amygdala (12%) and minimal for lateral neocortical stimulation (3%, p < 0.01). (b) Pathology. Stimulation of a temporal lobe with hippocampal sclerosis was associated with a lower frequency of ERs compared with stimulation of a temporal lobe with no evidence of atrophy in the medial temporal structures. (c) Stimulation frequency. ERs were 12% at 50 Hz versus 6.0% at 1 Hz (p < 0.01). (d) Gender. In women fear responses were 16% compared with 3% in men (p < 0.01). There were no gender differences when analyzing nonemotional responses. CONCLUSIONS: These data confirm the role of the medial temporal lobe region in the expression of emotions, especially fear-related behaviors. Fear was observed more frequently in the absence of medial temporal sclerosis, supporting the hypothesis that emotional behaviors induced by stimulation are positive phenomena, strictly related to the physiological function of these regions. Further investigations should address why women express fear behaviors more frequently than men.

Focal cortical resection in malformations of cortical development.

Malformations of cortical development may be associated with drug-resistant partial epilepsy suitable for surgical therapy. From the anatomopathological point of view, this categorisation has been used in reference to a wide range of alterations of the cortical mantle. Focal cortical dysplasias represent the main group of malformations of cortical development, but there are also other types of alterations, such as heterotopias, double cortex or polymicrogyria. Defining candidacy for surgical therapy and tailored resection requires thorough pre-surgical evaluation so that the approach will be individualised for each patient. We present our series of 126 patients with malformation of cortical development selected from 321 consecutively operated patients. Within this group encompassing different types of malformation of cortical development, including periventricular heterotopia (nine patients), polymicrogyria (three patients), hemimegalencephaly (one patient) and subcortical band heterotopia (one patient), the largest group was 81 individuals with focal cortical dysplasia. For this last group, we propose a simplified classification defining 42 architectural dysplasias, 12 cytoarchitectural dysplasias and 27 Taylor's focal cortical dysplasias. In addition, at routine neuropathological investigation, the only morphological alteration shown by 31 patients was diffuse neuronal heterotopia. All patients underwent scalp EEG and video-EEG, and 75 patients (59.5%) also underwent stereo-EEG. Magnetic resonance imaging and stereotactic stereoscopic angiography represented the indispensable premises for further studies, in particular stereo-EEG, and for planning surgery and tailoring resection. Magnetic resonance imaging was unhelpful in 17 out of 81 patients with focal cortical dysplasia and in seven out of 31 with neuronal heterotopia, while signal alterations were present in all other cases. Common characteristics corresponding to clinical-histopathological homogeneous subgroups were found within the focal cortical dysplasia group. In patients with architectural dysplasia, the epileptogenic zone was mainly in the temporal lobe and there was a lower seizure frequency than in patients with Taylor's focal cortical dysplasia. Patients with Taylor's type had an epileptogenic zone that was mainly extra-temporal, and a distinctive interictal stereo-EEG. The best outcome was observed in patients with Taylor's type dysplasia: 69% seizure-free (Engel class Ia) after at least 1 year of follow-up, compared with 45% of cytoarchitectural dysplasia and 49% of architectural dysplasia patients.