New stimulation procedures for language mapping in stereo-EEG.

OBJECTIVE: Cortical intracerebral electrical stimulation is an important tool for language mapping in the presurgical work-up of patients with drug-resistant focal epilepsy. Language mapping with stereo-electroencephalography (EEG) is usually performed by high-frequency stimulations (HFS: 50 Hz), whereas low-frequency stimulations (LFS: 1 Hz) are usually considered useful for primary cortices mapping. Little is known in literature about "intermediate" frequencies (IFS: 6-15 Hz). Our objective is to explore the clinical usefulness of IFS in language mapping and identify factors, beyond the electrical parameters, that impact the mapping. METHODS: We studied 23 patients submitted to stereo-EEG for presurgical evaluation. Language mapping was performed in the anterior, posterior and/or basal language region of the dominant hemisphere for language. We included all contact positions within these regions stimulated by HFS (50 Hz, 5 s, 1-3 mA) and IFS (6-15 Hz, 15 s, 5 mA). We compared the capability of both stimulation methods to induce a language deficit without afterdischarges (ADs), and we analyzed factors related to clinical examination, region, and stimulation technique by multivariate analysis. RESULTS: A total of 211 stimulations (98 HFS, 113 IFS) in 70 cortical sites within the anterior (84 stimulations), posterior (137), and basal language region (60) were included. IFS induced more frequently language deficits not associated to AD compared to HFS (37.1% vs 25.7%, p = .0043), whereas HFS provoked more diffuse AD (34.7% vs 15.0%, p = .001). Investigating multiple language functions increased the probability of revealing a deficit (odds ratio [OR] 3.16, p = .0016), independently of the stimulation method. SIGNIFICANCE: IFS are valuable for language mapping, thereby improving the probability of inducing a clinical deficit not accompanied by an AD. The completeness of the clinical examination independently affects the sensitivity of the mapping. IFS are a new tool with potential usefulness for the cortical mapping of other associative cortical regions.

Language lateralization mapping (reversibly) masked by non-dominant focal epilepsy: a case report.

Language lateralization in patients with focal epilepsy frequently diverges from the left-lateralized pattern that prevails in healthy right-handed people, but the mechanistic explanations are still a matter of debate. Here, we debate the complex interaction between focal epilepsy, language lateralization, and functional neuroimaging techniques by introducing the case of a right-handed patient with unaware focal seizures preceded by aphasia, in whom video-EEG and PET examination suggested the presence of focal cortical dysplasia in the right superior temporal gyrus, despite a normal structural MRI. The functional MRI for language was inconclusive, and the neuropsychological evaluation showed mild deficits in language functions. A bilateral stereo-EEG was proposed confirming the right superior temporal gyrus origin of seizures, revealing how ictal aphasia emerged only once seizures propagated to the left superior temporal gyrus and confirming, by cortical mapping, the left lateralization of the posterior language region. Stereo-EEG-guided radiofrequency thermocoagulations of the (right) focal cortical dysplasia not only reduced seizure frequency but led to the normalization of the neuropsychological assessment and the "restoring" of a classical left-lateralized functional MRI pattern of language. This representative case demonstrates that epileptiform activity in the superior temporal gyrus can interfere with the functioning of the contralateral homologous cortex and its associated network. In the case of presurgical evaluation in patients with epilepsy, this interference effect must be carefully taken into consideration. The multimodal language lateralization assessment reported for this patient further suggests the sensitivity of different explorations to this interference effect. Finally, the neuropsychological and functional MRI changes after thermocoagulations provide unique cues on the network pathophysiology of focal cortical dysplasia and the role of diverse techniques in indexing language lateralization in complex scenarios.

Towards a common language in neurosurgical outcome evaluation: the NEON (NEurosurgical Outcome Network) proposal.

BACKGROUND: The aim of this study was to achieve a consensus on the minimum set of outcome measures and predictors to be used in the neurosurgical practice and on the timing of outcome assessment. METHODS: A consensus building approach was employed. All neurosurgical departments in Lombardy (Italy) were invited to participate by the Carlo Besta Neurologic Institute IRCCS Foundation. Three workshops were organized during which a multidisciplinary group called Neurosurgical Outcome Network (NEON) was created and the methodology to select outcome measures, predictors, and timing of outcome assessment was established. Eight working groups were created for the different neurosurgical diseases (neuro-oncological, skull base, vascular, traumatic, spinal, peripheral nervous system, malformation, functional) and 8 workshops were organized to identify the outcome measures and predictors specific for each of the neurosurgical diseases based on the experts' clinical practice and the existing literature. RESULTS: A total of 20 neurosurgical departments participated in this study. Specific outcome measures, predictors and the timing of outcome assessment were identified for each of the 8 neurosurgical diseases. Moreover, a list of variables common to all pathologies were identified by the NEON group as further data to be collected. CONCLUSIONS: A consensus on the minimum set of outcome measures and predictors and the timing of outcome assessments for 8 neurosurgical diseases was achieved by a group of neurosurgeons of the Lombardy region, called NEON. These sets could be used in future studies for a more homogeneous data collection and as a starting point to reach further agreement also at national and international level.

Intermediate stimulation frequencies for language mapping using Stereo-EEG.

OBJECTIVE: Identification of eloquent cortices is a prerequisite for the surgical plan but may be challenging, in particular for language areas (LAs), considering the complexity of language function and organization. Electrical intracerebral stimulations (ES) during Stereo-electroencephalography are an essential tool in the localization of LAs and high frequency ES (HFS, 50 Hz) are current gold standard. Low frequencies (1 Hz) are not effective. We aim to investigate different ES frequencies for establishing their utility in localizing LAs. METHODS: We implemented an observational and prospective study evaluating frequencies lower than 50 and higher than 1 Hz; indicated as "intermediate" frequencies (IFS) performed at 6, 9 and 12 Hz and lasting 15 seconds. We included ten patients and carried out a standardized protocol comparing IFS to HFS. RESULTS: Eighty-six ES were carried out in LAs, positive for a language interference in 61.6% without noteworthy difference between IFS and HFS. Among these, 53.3% IFS vs 21.7% HFS yielded no after-discharge. CONCLUSIONS: IFS were similarly effective as HFS, with lower incidence of ADs. Their longer duration facilitated more accurate clinical testing. SIGNIFICANCE: Our results are promising, suggesting that IFS can be useful in the study of LAs.

Patient-reported outcome and cognitive measures to be used in vascular and brain tumor surgery: proposal for a minimum set.

BACKGROUND: The standardization of outcome measures is needed for comparing studies and using common measures in clinical practice. We aimed to identify cognitive and patient-reported outcomes and timing of assessment for glioma, meningioma, and vascular surgery. METHOD: A consensus study was conducted. Participants selected cognitive and patient-reported measures among a list of instruments identified through a literature search. RESULTS: Seventeen cognitive tests for the glioma and meningioma's evaluation, 8 for the vascular diseases, and one questionnaire on quality of life and one on emotional distress were identified. The timing of outcome assessment selected was before surgery, at discharge, and after 3 and 12 months for glioma; before surgery and after 3 months for meningioma; before surgery, at discharge, and after 6 months for vascular diseases. CONCLUSION: The identification of common outcome measures is the first step toward a shared data collection improving the quality and comparability of future studies.

Surgery for tuberous sclerosis complex-related epilepsy: Risk factors for an unfavorable seizure outcome.

PURPOSE: This study aimed to identify risk factors of postoperative seizure outcome in a consecutive cohort of patients operated on for TSC-related focal epilepsy, by evaluating several presurgical and surgical variables, including also MRI-visible brain abnormalities other than cortical tubers. METHODS: This retrospective study included 51 patients surgically treated for drug-resistant focal epilepsy with a histological diagnosis of cortical tuber and followed for at least 12 months postoperatively. We investigated the association between several potentially explanatory variables and seizure outcome by univariate and multivariate analysis in the whole cohort and in the subgroups of patients with single and multiple tubers, respectively. RESULTS: The median postoperative follow-up was 115 months (IQR 63-168) and 54.9% of patients were in Engel's class I at final control. In the whole cohort, variables independently associated with an unfavorable seizure outcome (Engel's classes II-IV) were: preoperative non-focal interictal EEG (RR 5, CI 2.46-6.39), presence of sub-ependymal nodules (SEN) (RR 3.53, CI 1.71-4.56) and seizure onset before the first year of age (RR 3.56, CI 0.91-6.89). Non-focal interictal EEG was independently associated with an unfavorable outcome also in the subgroup of patients with multiple tubers (RR 4.34, CI 2.23-5.37), while the presence of SEN (p=0.0221) and of extra-central nervous system lesions (p= 0.0152) predicted an unfavorable seizure outcome in patients with a single tuber. CONCLUSION: Surgery represents an effective option for seizure control in patients with TSC-related epilepsy. The identification of preoperative risk factors for seizure outcome could be helpful for optimizing patients' selection for surgery and pre-surgical counseling.

Investigating visuo-spatial neglect and visual extinction during intracranial electrical stimulations: The role of the right inferior parietal cortex.

Both visuo-spatial neglect and visual extinction may occur following right-brain damage. So far, studies on brain-damaged patients have not provided definite evidence about which lesion patterns may lead to the association or dissociation of these deficits. This study was set out to address this issue using Intracranial Electrical Stimulation (IES) in a group of nine patients affected by refractory epilepsy. Cerebral regions associated with visuo-spatial neglect and visual extinction were stimulated, including the right frontal, temporal, and posterior parietal areas. During IES, patients with intracranial implantation involving at least one of these cortical regions were administered with a manual line bisection task (N = 9) to assess visuo-spatial neglect, and a computerized task (N = 8) assessing visual extinction. Results showed that parietal IES induced a rightward bias at the manual bisection task, together with a general improvement in reaction times at bilateral and unilateral visual stimuli detection at the extinction task. The occurrence of visual extinction did not vary across stimulations. By adopting a complementary approach to anatomo-clinical correlation studies, our work corroborates the notion that lesions to the right inferior parietal lobule play a pivotal role in the pathogenesis of visuo-spatial neglect. Importantly, our results also suggest that temporarily interfering with the activity of this region is not sufficient per se to generate visual extinction, which instead may involve a broader and/or different network, possibly extending beyond the cerebral regions considered here, posing important theoretical and clinical implications.

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.

Mini-Mental State Pediatric Examination (MMSPE) standardization and normative data on Italian children aged 36 to 72 months.

The MMSE (Mini-Mental State Examination), which is broadly used as a cognitive screening test for adults, has been successfully adapted and standardized for children of different nationalities. In the Italian clinical settings, the Mini-Mental State Pediatric Examination (MMSPE) is being more and more used as cognitive screening tool for children. However, the Italian norms for the MMSPE are available for the school age only. The current study was aimed at providing clinicians with the Italian normative data of the MMSPE for preschool age. Here, we therefore adapted the MMSE to the preschool age. The MMSPE for preschoolers assesses spatial and temporal orientation, verbal and visual memory, reading prerequisites, numerical knowledge, praxis, body representation, and executive functions through 16 items in a short period of time. It was administered to 305 Italian children aged 36 to 72 months. A Generalized Linear Model was fitted to explore predictors' effects on the MMSPE total score. Raw scores were adjusted for critical variables (child's age and parental mean education) and the 5th percentile cut-offs were obtained. With this study, we extended the Italian normative data of the MMSPE, formerly available for school age only, to preschool age population.

Tailored multilobar disconnective epilepsy surgery in the posterior quadrant.

OBJECTIVE: Surgical treatment of drug-resistant epilepsy originating from the posterior quadrant (PQ) of the brain often requires large multilobar resections, and disconnective techniques have been advocated to limit the risks associated with extensive tissue removal. Few previous studies have described a tailored temporoparietooccipital (TPO) disconnective approach; only small series with short postoperative follow-ups have been reported. The aim of the present study was to present a tailored approach to multilobar PQ disconnections (MPQDs) for epilepsy and to provide details about selection of patients, presurgical investigations, surgical technique, treatment safety profile, and seizure and cognitive outcome in a large, single-center series of patients with a long-term follow-up. METHODS: In this retrospective longitudinal study, the authors searched their prospectively collected database for patients who underwent MPQD for drug-resistant epilepsy in the period of 2005-2017. Tailored MPQDs were a posteriori grouped as follows: type I (classic full TPO disconnection), type II (partial TPO disconnection), type III (full temporooccipital [TO] disconnection), and type IV (partial TO disconnection), according to the disconnection plane in the occipitoparietal area. A bivariate statistical analysis was carried out to identify possible predictors of seizure outcome (Engel class I vs classes II-IV) among several presurgical, surgical, and postsurgical variables. Preoperative and postoperative cognitive profiles were also collected and evaluated. RESULTS: Forty-two consecutive patients (29 males, 24 children) met the inclusion criteria. According to the presurgical evaluation (including stereo-electroencephalography in 13 cases), 12 (28.6%), 24 (57.1%), 2 (4.8%), and 4 (9.5%) patients received a type I, II, III, or IV MPQD, respectively. After a mean follow-up of 80.6 months, 76.2% patients were in Engel class I at last contact; at 6 months and 2 and 5 years postoperatively, Engel class I was recorded in 80.9%, 74.5%, and 73.5% of cases, respectively. Factors significantly associated with seizure freedom were the occipital pattern of seizure semiology and the absence of bilateral interictal epileptiform abnormalities at the EEG (p = 0.02). Severe complications occurred in 4.8% of the patients. The available neuropsychological data revealed postsurgical improvement in verbal domains, whereas nonunivocal outcomes were recorded in the other functions. CONCLUSIONS: The presented data indicate that the use of careful anatomo-electro-clinical criteria in the presurgical evaluation allows for customizing the extent of surgical disconnections in PQ epilepsies, with excellent results on seizures and an acceptable safety profile.

Epilepsy surgery in patients older than 50 years: Effectiveness, safety, and predictors of outcome.

PURPOSE: Surgery is an effective treatment for drug resistant focal epilepsy. Predictors of seizure outcome have been extensively addressed in the general population but similar data on older patients are still lacking. The aim of this study is to evaluate effectiveness and safety of surgery for patients over 50 years and to investigate variables associated to seizure outcome. METHODS: We performed a single center retrospective study including 50 patients over 50 years treated surgically for drug resistant focal epilepsy between 1997 and 2014. We analyzed the rate of success of seizure control, the association of several clinical variables with seizure outcome and the rate of surgery-related complications. We also investigated the impact of surgery on the patients' cognitive performances and mood profile. RESULTS: At last follow-up 78% of our patients were seizure-free, similar to patients younger than 50 years operated on in the same period (p=1). The rate of surgery-related complications was 10%, higher compared to younger patients (p<0.0001). Pre-surgical daily seizure frequency (p=0.0040) and the histological diagnosis of LEAT (p=0.0233) were associated to a poorer seizure outcome. No significant differences were evidenced between pre- and postoperative neuropsychological profiles. A slight, not statistically significant improvement of the mood profile was observed postoperatively. CONCLUSION: Our results suggest that surgery is an effective treatment option also for older epileptic patients, although it is burdened by a higher surgical risk as compared to younger patients. The availability of predictors of outcome also for these patients may be helpful for pre-surgical counseling.

Dissociation between preserved body structural description and impaired body image following a pediatric spinal trauma.

In adult patients, Spinal Cord Injury (SCI) may influence the mental Body Representation (BR). Currently, there is no evidence on the modulation of SCI on BR during early stages of cognitive development. Here, we investigated BR in a 3-year-old child with complete SCI. The patient was administered with a specific battery assessing different BR components. We found evidence for putative classical neuropsychological dissociation between a preserved topological map with impaired semantic knowledge of the body. This finding sheds new light on the impact of SCI on BR in childhood, as well as on the level of interdependence between BR's components..

Declarative long-term memory and the mesial temporal lobe: Insights from a 5-year postsurgery follow-up study on refractory temporal lobe epilepsy.

It is largely recognized that the mesial temporal lobe and its substructure support declarative long-term memory (LTM). So far, different theories have been suggested, and the organization of declarative verbal LTM in the brain is still a matter of debate. In the current study, we retrospectively selected 151 right-handed patients with temporal lobe epilepsy with and without hippocampal sclerosis, with a homogeneous (seizure-free) clinical outcome. We analyzed verbal memory performance within a normalized scores context, by means of prose recall and word paired-associate learning tasks. Patients were tested at presurgical baseline, 6months, 2 and 5years after anteromesial temporal lobe surgery, using parallel versions of the neuropsychological tests. Our main finding revealed a key involvement of the left temporal lobe and, in particular, of the left hippocampus in prose recall rather than word paired-associate task. We also confirmed that shorter duration of epilepsy, younger age, and withdrawal of antiepileptic drugs would predict a better memory outcome. When individual memory performance was taken into account, data showed that females affected by left temporal lobe epilepsy for longer duration were more at risk of presenting a clinically pathologic LTM at 5years after surgery. Taken together, these findings shed new light on verbal declarative memory in the mesial temporal lobe and on the behavioral signature of the functional reorganization after the surgical treatment of temporal lobe epilepsy.

Accounting for ethnic-cultural and linguistic diversity in neuropsychological assessment of patients with drug-resistant epilepsy: A retrospective study.

Neuropsychological assessment is critical in both diagnosis and prognosis of patients with epilepsy. Beyond electrophysiological and anatomical alterations, other factors including different ethnic-cultural and linguistic backgrounds might affect neuropsychological performance. Only a few studies considered migration and acculturation effects and they typically concerned nonclinical samples. The current study aimed at investigating the influence of ethnic background and time spent in Italy on a full neuropsychological battery administered to both Italian and foreign-born patients and at providing a brief interview for obtaining relevant information on each patient's transcultural and language-related history. Clinical reports from 43 foreign-born patients with drug-resistant epilepsy were collected from the archives of Milan Niguarda Hospital. Epileptogenic zone, age, education, profession, illness duration, seizure frequency, handedness, and gender were considered in selecting 43 Italian controls. Ethnicity (Italian/foreign-born) and years spent in Italy were analyzed as main predictors on 21 neuropsychological scales by means of General(ized) Linear Models. An additional analysis studied two composite scores of overall verbal and nonverbal abilities. Ethnicity significantly affected the following: the verbal overall score, Verbal Fluency, Naming, Token-test, Digit Span, Attentional Matrices, Trail-Making-Test, Line-Orientation-Test, and Raven matrices; no effects were found on the nonverbal overall score, Word Pairs Learning, Episodic Memory, reading accuracy, visual span, Bells test, Rey Figure, and face memory and recognition. No significant effects of years spent in Italy emerged. While years spent in Italy does not predict neuropsychological performance, linguistic background had a strong impact on it. With respect to Italian-speaking patients, those who were foreign-born showed large task-related variability, with an especially low performance on language-related tests. Hence, language tests should not be considered as valid measures of neuropsychological impairment in this population, not even in foreign-born patients with good Italian fluency. Clinicians should consider such asymmetries in order to improve the accuracy of neuropsychological assessment of foreign-born patients.

Drug-resistant parietal epilepsy: polymorphic ictal semiology does not preclude good post-surgical outcome.

We investigated the anatomo-electro-clinical features and clinical outcome of surgical resections strictly confined to the parietal lobe in 40 consecutive patients who received surgery for pharmacoresistant seizures. The population was subcategorized into a paediatric (11 subjects; mean age at surgery: 7.2+/-3.7 years) and an adult group (29 patients; mean age at surgery: 30+/-10.8 years). The paediatric group more frequently exhibited personal antecedents, neurological impairment, high seizure frequency, and dysplastic lesions. Nonetheless, compared with adults, children had better outcome and more frequently reached definitive drug discontinuation after surgery. After a mean follow-up of 9.4 years (range: 3.1-16.7), 30 subjects (75%) were classified as Engel Class I. The presence of multiple types of aura in the same patient, as well as a high incidence of secondary generalization, represented a characteristic feature of parietal seizures and did not correlate negatively with surgical outcome. A total resection of the epileptogenic zone and a localizing/regional interictal EEG were statistically significant predictive factors of outcome. Intracerebral investigation, performed in 55% of cases, contributed to complete tailored resections of the epileptogenic area and determination of prognosis. Frequent subjective manifestations of parietal lobe seizures, such as vertiginous, cephalic and visual-moving sensations, underscore their potential misdiagnosis as non-epileptic events.

Overview of presurgical assessment and surgical treatment of epilepsy from the Italian League Against Epilepsy.

The Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE) presents an overview of the techniques and methodologies of presurgical evaluation and of the surgical treatment of epilepsies. This overview is the result of the experience developed in the past years in the major Italian centers where programs of epilepsy surgery have been established, and it has the aim of offering a quick and easy reference tool for those involved in the treatment of patients with epilepsy. The sharing of different experiences has the additional aim of conforming and disseminating the employed techniques as well as the methods of selection and evaluation of patients. The synthetic coverage of the main issues concerning the presurgical workup and the available surgical options will hopefully provide a framework that may integrate and develop the contributions of every single center, in one of the more complex, challenging, and dynamic areas of neurological sciences.

Ambiguous emotion recognition in temporal lobe epilepsy: the role of expression intensity.

The lateralization of emotion processing is currently debated and may be further explored by examining facial expression recognition (FER) impairments in temporal lobe epilepsy (TLE). Furthermore, there is also debate in the literature whether FER deficits in individuals with TLE are more pronounced in the right than in the left hemisphere. Individuals with TLE were tested with an FER task designed to be more sensitive than those classically used to shed light on this issue. A total of 25 right- and 32 left-TLE patients, candidates for surgery, along with controls, underwent an FER task composed of stimuli shown not only at full-blown intensities (100 %), but also morphed to lower-intensity display levels (35 %, 50 %, and 75 %). The results showed that, as compared to controls, right-TLE patients showed deficits in the recognition of all emotional categories. Furthermore, when considering valence, right-TLE patients were impaired only in negative emotion recognition, but no deficits for positive emotions were highlighted in left-TLE patients. Finally, only the right-TLE patients' impairment was found to be related to the age of epilepsy onset. Our work demonstrates that the FER deficits in TLE span multiple emotional categories and show manifestations dependent on the laterality of the epileptic focus. Taken together, our findings provide the strongest evidence for the right-hemisphere model, but they also partially support the valence model. We suggest that current models are not exhaustive at explaining emotional-processing cerebral control, and further that multistep models should be developed.