Publications by authors named "Sara Casciato"

51 Publications

The surgical treatment of epilepsy.

Neurol Sci 2021 Apr 2. Epub 2021 Apr 2.

Department of Neuroscience and Neurorehabilitation, Bambino Gesù Children Hospital, Rome, Italy.

In 2009, the Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE) conducted an overview about the techniques used for the pre-surgical evaluation and the surgical treatment of epilepsies. The recognition that, in selected cases, surgery can be considered the first-line approach, suggested that the experience gained by the main Italian referral centers should be pooled in order to provide a handy source of reference. In light of the progress made over these past years, some parts of that first report have accordingly been updated. The present revision aims to harmonize the general principles regulating the patient selection and the pre-surgical work-up, as well as to expand the use of epilepsy surgery, that still represents an underutilized resource, regrettably. The objective of this contribution is drawing up a methodological framework within which to integrate the experiences of each group in this complex and dynamic sector of the neurosciences.
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http://dx.doi.org/10.1007/s10072-021-05198-yDOI Listing
April 2021

Efficient automated localization of ECoG electrodes in CT images via shape analysis.

Int J Comput Assist Radiol Surg 2021 Mar 9. Epub 2021 Mar 9.

Department of Electrical Engineering and Information Technologies, Polytechnic and Basic Sciences School, University of Naples Federico II, Naples, Italy.

Purpose: People with drug-refractory epilepsy are potential candidates for surgery. In many cases, epileptogenic zone localization requires intracranial investigations, e.g., via ElectroCorticoGraphy (ECoG), which uses subdural electrodes to map eloquent areas of large cortical regions. Precise electrodes localization on cortical surface is mandatory to delineate the seizure onset zone. Simple thresholding operations performed on patients' computed tomography (CT) volumes recognize electrodes but also other metal objects (e.g., wires, stitches), which need to be manually removed. A new automated method based on shape analysis is proposed, which provides substantially improved performances in ECoG electrodes recognition.

Methods: The proposed method was retrospectively tested on 24 CT volumes of subjects with drug-refractory focal epilepsy, presenting a large number (> 1700) of round platinum electrodes. After CT volume thresholding, six geometric features of voxel clusters (volume, symmetry axes lengths, circularity and cylinder similarity) were used to recognize the actual electrodes among all metal objects via a Gaussian support vector machine (G-SVM). The proposed method was further tested on seven CT volumes from a public repository. Simultaneous recognition of depth and ECoG electrodes was also investigated on three additional CT volumes, containing penetrating depth electrodes.

Results: The G-SVM provided a 99.74% mean classification accuracy across all 24 single-patient datasets, as well as on the combined dataset. High accuracies were obtained also on the CT volumes from public repository (98.27% across all patients, 99.68% on combined dataset). An overall accuracy of 99.34% was achieved for the recognition of depth and ECoG electrodes.

Conclusions: The proposed method accomplishes automated ECoG electrodes localization with unprecedented accuracy and can be easily implemented into existing software for preoperative analysis process. The preliminary yet surprisingly good results achieved for the simultaneous depth and ECoG electrodes recognition are encouraging. Ethical approval n°NCT04479410 by "IRCCS Neuromed" (Pozzilli, Italy), 30th July 2020.
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http://dx.doi.org/10.1007/s11548-021-02325-0DOI Listing
March 2021

Very long-term seizure outcome in frontal lobe epilepsy surgery.

Epilepsy Behav 2021 Apr 20;117:107848. Epub 2021 Feb 20.

IRCCS NEUROMED, Pozzilli (IS), Italy. Electronic address:

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http://dx.doi.org/10.1016/j.yebeh.2021.107848DOI Listing
April 2021

ATP-evoked intracellular Ca transients shape the ionic permeability of human microglia from epileptic temporal cortex.

J Neuroinflammation 2021 Feb 15;18(1):44. Epub 2021 Feb 15.

IRCCS Neuromed, Pozzilli, IS, Italy.

Background: Intracellular Ca modulates several microglial activities, such as proliferation, migration, phagocytosis, and inflammatory mediator secretion. Extracellular ATP, the levels of which significantly change during epileptic seizures, activates specific receptors leading to an increase of intracellular free Ca concentration ([Ca]). Here, we aimed to functionally characterize human microglia obtained from cortices of subjects with temporal lobe epilepsy, focusing on the Ca-mediated response triggered by purinergic signaling.

Methods: Fura-2 based fluorescence microscopy was used to measure [Ca] in primary cultures of human microglial cells obtained from surgical specimens. The perforated patch-clamp technique, which preserves the cytoplasmic milieu, was used to measure ATP-evoked Ca-dependent whole-cell currents.

Results: In human microglia extracellular ATP evoked [Ca] increases depend on Ca entry from the extracellular space and on Ca mobilization from intracellular compartments. Extracellular ATP also induced a transient fivefold potentiation of the total transmembrane current, which was completely abolished when [Ca] increases were prevented by removing external Ca and using an intracellular Ca chelator. TRAM-34, a selective K3.1 blocker, significantly reduced the ATP-induced current potentiation but did not abolish it. The removal of external Cl in the presence of TRAM-34 further lowered the ATP-evoked effect. A direct comparison between the ATP-evoked mean current potentiation and mean Ca transient amplitude revealed a linear correlation. Treatment of microglial cells with LPS for 48 h did not prevent the ATP-induced Ca mobilization but completely abolished the ATP-mediated current potentiation. The absence of the Ca-evoked K current led to a less sustained ATP-evoked Ca entry, as shown by the faster Ca transient kinetics observed in LPS-treated microglia.

Conclusions: Our study confirms a functional role for K3.1 channels in human microglia, linking ATP-evoked Ca transients to changes in membrane conductance, with an inflammation-dependent mechanism, and suggests that during brain inflammation the K3.1-mediated microglial response to purinergic signaling may be reduced.
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http://dx.doi.org/10.1186/s12974-021-02096-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883449PMC
February 2021

Clinical utility of home videos for diagnosing epileptic seizures: a systematic review and practical recommendations for optimal and safe recording.

Neurol Sci 2021 Apr 20;42(4):1301-1309. Epub 2021 Jan 20.

IRCSS NEUROMED, Pozzilli, IS, Italy.

Background: The aim of the present systematic revision is to analyze existing published reports about the use of home-videos recordings (HVRs) to support physicians in the differential diagnosis of paroxysmal seizure-like episodes (PSLE). We also developed practical recommendations in order to ensure adequate quality standards and safety advice for HVRs.

Material And Methods: A comprehensive search of PubMed, Medline, Scopus, and Google Scholar was performed, and results were included up to July 2020. All studies concerning the use of HVRs as a diagnostic tool for patients presenting PSLE were included.

Results: Seventeen studies satisfied all inclusion and exclusion criteria and were considered for the review. A consistent boost in diagnostic and clinical decision-making was reported across all studies in the literature. One study found that HVRs decreased the stress level in many families and improved their quality of life. Training in performing good-quality videos is necessary and increases the diagnostic value of HVRs.

Conclusions: HVRs can be of diagnostic value in epilepsy diagnosis and management. HVRs are low cost, widespread, and may provide great support for neurologists. It is important to train patients and caregivers in performing good quality videos to optimize this useful tool and to guarantee safety standards during the recording.
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http://dx.doi.org/10.1007/s10072-021-05040-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815499PMC
April 2021

Temporal lobe epilepsy surgery in children and adults: A multicenter study.

Epilepsia 2021 01 1;62(1):128-142. Epub 2020 Dec 1.

"C. Munari" Epilepsy Surgery Center, Niguarda Hospital, Milan, Italy.

Objective: To assess seizure and cognitive outcomes and their predictors in children (<16 years at surgery) and adults undergoing temporal lobe epilepsy (TLE) surgery in eight Italian centers.

Methods: This is a retrospective multicenter study. We performed a descriptive analysis and subsequently carried out multivariable mixed-effect models corrected for multiple comparisons.

Results: We analyzed data from 511 patients (114 children) and observed significant differences in several clinical features between adults and children. The possibility of achieving Engel class IA outcome and discontinuing antiepileptic drugs (AEDs) at last follow-up (FU) was significantly higher in children (P = .006 and < .0001). However, percentages of children and adults in Engel class I at last FU (mean ± SD, 45.9 ± 17 months in children; 45.9 ± 20.6 months in adults) did not differ significantly. We identified different predictors of seizure outcome in children vs adults and at short- vs long-term FU. The only variables consistently associated with class I outcome over time were postoperative electroencephalography (EEG) in adults (abnormal, improved,odds ratio [OR] = 0.414, P = .023, Q = 0.046 vs normal, at 2-year FU and abnormal, improved, OR = 0.301, P = .001, Q = 0.002 vs normal, at last FU) and the completeness of resection of temporal magnetic resonance (MR) abnormalities other than hippocampal sclerosis in children (OR = 7.93, P = .001, Q = 0.003, at 2-year FU and OR = 45.03, P < .0001, Q < 0.0001, at last FU). Cognitive outcome was best predicted by preoperative performances in either age group.

Significance: Clinical differences between adult and pediatric patients undergoing TLE surgery are reflected in differences in long-term outcomes and predictors of failures. Children are more likely to achieve sustained seizure freedom and withdraw AEDs after TLE surgery. Earlier referral should be encouraged as it can improve surgical outcome.
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http://dx.doi.org/10.1111/epi.16772DOI Listing
January 2021

Seizures in autoimmune encephalitis: Findings from an EEG pooled analysis.

Seizure 2020 Dec 31;83:160-168. Epub 2020 Oct 31.

Epilepsy Unit, Department of Human Neurosciences, "Sapienza" University of Rome, Rome, Italy. Electronic address:

Purpose: Seizures are common in autoimmune encephalitis (AE), and an extensive work-up is required to exclude alternative etiologies. The aim of our study was to identify possible clinical/EEG peculiarities suggesting the immune-mediated origin of late-onset seizures.

Methods: Thirty patients diagnosed with AE (19 men, median age 68 years, 18 seronegative) were included. Overall 212 video-electroencephalographic (EEG) and 31 24-h ambulatory EEG (AEEG) recordings were retrospectively reviewed. Posterior dominant rhythm, interictal epileptiform discharges (IEDs), clinical (CSs) and subclinical seizures (SCSs) were analyzed.

Results: Six-hundred-nineteen ictal events were recorded in 19/30 subjects, mostly (568/619) during AE acute stage. Among ten patients with CSs other than faciobrachial dystonic seizures, 7 showed prominent autonomic and emotional manifestations. SCSs were detected in 11 subjects, mainly via AEEG (260/287 SCSs vs 150/332 CSs, p < 0.001). Eight patients presented seizures during hyperventilation. IEDs, documented in 21 cases, were bilateral in 14 and focal temporal in 13. Multiple ictal EEG patterns were detected in 9/19 patients, 6 of whom had both CSs and SCSs, bilateral asynchronous seizures and ictal activities arising from temporal and extra-temporal regions. No correlation was found between the lateralization of MRI alterations and that of EEG findings.

Conclusion: Our study confirms that adult-onset, high frequency focal seizures with prominent autonomic and emotional manifestations should be investigated for AE. Multiple ictal EEG patterns could represent a 'red flag', reflecting a widespread neuronal excitability related to the underlying immune-mediated process. Finally, our work enhances the crucial role of long-lasting EEG monitoring in revealing subclinical and relapsing seizures.
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http://dx.doi.org/10.1016/j.seizure.2020.10.019DOI Listing
December 2020

New-onset anosmia and taste distortion: see beyond COVID-19.

Neurol Sci 2020 12 14;41(12):3405-3407. Epub 2020 Oct 14.

IRCCS NEUROMED, Pozzilli, (IS), Italy.

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http://dx.doi.org/10.1007/s10072-020-04825-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556587PMC
December 2020

Effects of eslicarbazepine as add-on therapy on sleep architecture in temporal lobe epilepsy: results from "Esleep" study.

Sleep Med 2020 11 15;75:287-293. Epub 2020 Jul 15.

IRCCS Neuromed Istituto Neurologico Mediterraneo Sleep Medicine Center Via Atinense 18 Pozzilli IS, Italy.

Rationale: Studies looking at the effect of antiseizure medications (ASMs) on the sleep microstructure of subjects with epilepsy are scarce. This study aims to evaluate the impact of eslicarbazepine (ESL) as add-on therapy on the sleep microstructure in temporal lobe epilepsy (TLE).

Methods: Twelve patients affected by TLE were recruited to undergo overnight polysomnography and a subjective evaluation of nocturnal sleep utilizing the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence through the Epworth Sleepiness Scale (ESS) before and after three months of treatment with ESL as add-on therapy. Ten healthy controls (HC) matched for age, sex and BMI were recruited. Scoring and analysis of sleep macrostructure and cyclic alternating pattern (CAP) parameters were performed.

Results: Ten patients completed the study. The comparison between patients in basal condition (T0) and HC showed a significant lower sleep efficiency (p = 0.049), REM percentage (p = 0.002), higher REM latency (p = 0.02), N2 (p = 0.001) and WASO (p = 0.01). Regarding CAP, patients at T0 showed higher CAP rate in N1 (p = 0.01), lower A1 (%) (p = 0.03), higher A3 (%) (p = 0.01), higher mean duration of A (p = 0.02) and A3 (p = 0.006), A3 index (p = 0.02) than HC. ESL did not induce any significant changes in nocturnal macrostructural polysomnographic variables and PSQI scores. Furthermore, the ESS score showed no modification after treatment. Lower CAP rate in N3 (p = 0.02), phase A2 index (p = 0.02) average number of CAP cycle per sequences and mean duration of CAP sequences (both p = 0.02) was evident after ESL. A trend toward significance was evident for the decrease of CAP rate in N1 (p = 0.09) and N2 (p = 0.09), and for the increase of B phase mean duration (p = 0.07).

Conclusion: We found significant improvement in sleep continuity as measured by CAP after ESL. These findings suggest that ESL may positively modulate sleep fragmentation in patients with TLE, and hence enhance sleep quality. Our results suggest a favourable sleep profile with the use of ESL.
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http://dx.doi.org/10.1016/j.sleep.2020.06.033DOI Listing
November 2020

Focal Cortical Dysplasia IIIa in Hippocampal Sclerosis-Associated Epilepsy: Anatomo-Electro-Clinical Profile and Surgical Results From a Multicentric Retrospective Study.

Neurosurgery 2021 01;88(2):384-393

Department of Neuroscience and Neurorehabilitation, Bambino Gesù Children Hospital, Rome, Italy.

Background: Hippocampal sclerosis (HS) may be associated with focal cortical dysplasia IIIa (FCD IIIa) in patients undergoing surgery for temporal lobe epilepsy (TLE).

Objective: To investigate whether the anatomo-electro-clinical profile and surgical outcome in patients with HS-related TLE are affected by coexisting FCD IIIa.

Methods: A total of 220 patients, operated in 5 centers, with at least 24 mo follow-up (FU), were retrospectively studied. Preliminary univariate and subsequent multivariate analyses were performed to investigate possible associations between several potential presurgical, surgical, and postsurgical predictors and different variables (Engel's class I and Engel's class Ia, co-occurrence of FCD IIIa).

Results: At last available postoperative control (FU: range 24-95 mo, median 47 mo), 182 (82.7%) patients were classified as Engel's class I and 142 (64.5%) as Engel's class Ia. At multivariate analysis, extension of neocortical resection and postoperative electroencephalogram were significantly associated with Engel's class I, whereas length of FU had a significant impact on class Ia in the whole cohort and in isolated HS (iHS) patients, but not in the FCD IIIa group. No differences emerged in the anatomo-electro-clinical profile and surgical results between patients with FCD IIIa and with iHS.

Conclusion: Coexistence of FCD IIIa did not confer a distinct anatomo-electro-clinical profile to patients with HS-related epilepsy. Postoperative seizure outcome was similar in FCD IIIa and iHS cases. These findings indicate limited clinical relevance of FCD IIIa in HS-related epilepsy and might be useful for refining future FCD classifications. Further studies are needed to clarify the correlation of class Ia outcome with the duration of FU.
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http://dx.doi.org/10.1093/neuros/nyaa369DOI Listing
January 2021

A European questionnaire survey on epilepsy monitoring units' current practice for postoperative psychogenic nonepileptic seizures' detection.

Epilepsy Behav 2020 11 31;112:107355. Epub 2020 Jul 31.

Department of Clinical Neurosciences, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.

Background: In cases undergoing epilepsy surgery, postoperative psychogenic nonepileptic seizures (PNES) may be underdiagnosed complicating the assessment of postsurgical seizures' outcome and the clinical management. We conducted a survey to investigate the current practices in the European epilepsy monitoring units (EMUs) and the data that EMUs could provide to retrospectively detect cases with postoperative PNES and to assess the feasibility of a subsequent postoperative PNES research project for cases with postoperative PNES.

Methods: We developed and distributed a questionnaire survey to 57 EMUs. Questions addressed the number of patients undergoing epilepsy surgery, the performance of systematic preoperative and postoperative psychiatric evaluation, the recording of sexual or other abuse, the follow-up period of patients undergoing epilepsy surgery, the performance of video-electroencephalogram (EEG) and postoperative psychiatric assessment in suspected postoperative cases with PNES, the existence of electronic databases to allow extraction of cases with postoperative PNES, the data that these bases could provide, and EMUs' interest to participate in a retrospective postoperative PNES project.

Results: Twenty EMUs completed the questionnaire sheet. The number of patients operated every year/per center is 26.7 ( ± 19.1), and systematic preoperative and postoperative psychiatric evaluation is performed in 75% and 50% of the EMUs accordingly. Sexual or other abuse is systematically recorded in one-third of the centers, and the mean follow-up period after epilepsy surgery is 10.5 ± 7.5 years. In suspected postoperative PNES, video-EEG is performed in 85% and psychiatric assessment in 95% of the centers. An electronic database to allow extraction of patients with PNES after epilepsy surgery is used in 75% of the EMUs, and all EMUs that sent the sheet completed expressed their interest to participate in a retrospective postoperative PNES project.

Conclusion: Postoperative PNES is an underestimated and not well-studied entity. This is a European survey to assess the type of data that the EMUs surgical cohorts could provide to retrospectively detect postoperative PNES. In cases with suspected PNES, most EMUs perform video-EEG and psychiatric assessment, and most EMUs use an electronic database to allow extraction of patients developing PNES.
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http://dx.doi.org/10.1016/j.yebeh.2020.107355DOI Listing
November 2020

The diagnosis of epilepsy in the COVID-19 era: Dealing with revolution in clinical practice.

Epilepsy Behav 2020 10 18;111:107305. Epub 2020 Jul 18.

IRCCS NEUROMED, Pozzilli, IS, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.yebeh.2020.107305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368156PMC
October 2020

Ictal Asystole in Drug-Resistant Focal Epilepsy: Two Decades of Experience from an Epilepsy Monitoring Unit.

Brain Sci 2020 Jul 12;10(7). Epub 2020 Jul 12.

IRCCS NEUROMED, 86077 Pozzilli (IS), Italy.

Background: Ictal asystole (IA) is a rare event observed in people with epilepsy (PwE). Clinical and IA video-electroencephalographic findings may be helpful in screening for high-risk subjects. From all PwE undergoing video-EEG for presurgical evaluation between 2000 and 2019, we retrospectively selected those with at least one IA (R-R interval of ≥3 s during a seizure). IA was detected in eight out of 1088 (0.73%) subjects (mean age: 30 years; mean epilepsy duration: 9.6 years). Four out of them had a history of atonic falls. No patients had cardiac risk factors or cardiovascular diseases. Seizure onset was temporal ( = 5), temporo-parietal ( = 1) or frontal ( = 2), left-sided and right-sided in five and two patients, respectively. In one case a bilateral temporal independent seizure onset was recorded. IA was recorded in 11 out of 18 seizures. Mean IA duration was 13 s while mean IA latency from seizure onset was 26.7 s. Symptoms related to IA were observed in all seizures. IA is a rare and self-limiting event often observed during video-EG in patients with a history of atonic loss of consciousness and/or tardive falls in the course of a typical seizure.
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http://dx.doi.org/10.3390/brainsci10070443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408581PMC
July 2020

Valproate impact and sex-dependent seizure remission in patients with idiopathic generalized epilepsy.

J Neurol Sci 2020 08 30;415:116940. Epub 2020 May 30.

Epilepsy Unit, Department of Human Neurosciences, Policlinico Umberto I, "Sapienza" University, Rome, Italy. Electronic address:

Background: Idiopathic Generalized Epilepsy (IGE) management has become increasingly challenging due to the restricted use of Valproate (VPA) in females. The aim of the study was to assess possible differences in terms of seizure outcome between men and women suffering from IGE.

Methods: A cohort of IGE patients (age range: 13-50 years) followed from 1980 to 2018 were included. Their medical history was retrospectively reviewed to investigate possible factors influencing seizure outcome. Seizure Remission (SR) was defined as the absence of any seizure type over 18 months prior to the last medical observation. The primary outcome was to evaluate sex differences in terms of SR at last observation. A multivariable logistic regression model was elaborated using SR as dependent variable.

Results: Three-hundred and sixty patients were included, 204 (56.7%) of whom were women. The median age at the end of follow-up was 30. At last medical observation, fewer women were receiving VPA compared with men (females 39.7% vs males 79.5%, p < .001). Overall SR was 70.6%. SR was significantly different according to sex (females 62.3% vs males 81.4%, p < .001). Multivariable logistic regression model showed that female sex (Odds Ratios [OR] = 0.52, 95% Confidence Interval [CI] = 0.29-0.94; p = .03), VPA treatment at last observation (OR = 0.44, 95% CI = 0.25-0.76; p = .003) and epilepsy syndrome (p < .001) were the factors independently associated with SR.

Conclusions: Recent modifications in VPA prescribing patterns may have determined a worse seizure control among IGE female patients. Comparative clinical trials assessing the best therapeutic options for women with childbearing potential are urgently needed.
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http://dx.doi.org/10.1016/j.jns.2020.116940DOI Listing
August 2020

Antidepressant effect of vagal nerve stimulation in epilepsy patients: a systematic review.

Neurol Sci 2020 Nov 10;41(11):3075-3084. Epub 2020 Jun 10.

Epilepsy Surgery Center, IRCCS NEUROMED, Via Atinense 18, 86170, Pozzilli (IS), Italy.

Background: Vagal nerve stimulation (VNS) is an effective palliative therapy in drug-resistant epileptic patients and is also approved as a therapy for treatment-resistant depression. Depression is a frequent comorbidity in epilepsy and it affects the quality of life of patients more than the seizure frequency itself. The aim of this systematic review is to analyze the available literature about the VNS effect on depressive symptoms in epileptic patients.

Material And Methods: A comprehensive search of PubMed, Medline, Scopus, and Google Scholar was performed, and results were included up to January 2020. All studies concerning depressive symptom assessment in epileptic patients treated with VNS were included.

Results: Nine studies were included because they fulfilled inclusion criteria. Six out of nine papers reported a positive effect of VNS on depressive symptoms. Eight out of nine studies did not find any correlation between seizure reduction and depressive symptom amelioration, as induced by VNS. Clinical scales for depression, drug regimens, and age of patients were broadly different among the examined studies.

Conclusions: Reviewed studies strongly suggest that VNS ameliorates depressive symptoms in drug-resistant epileptic patients and that the VNS effect on depression is uncorrelated to seizure response. However, more rigorous studies addressing this issue are encouraged.
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http://dx.doi.org/10.1007/s10072-020-04479-2DOI Listing
November 2020

Doing without valproate in women of childbearing potential with idiopathic generalized epilepsy: Implications on seizure outcome.

Epilepsia 2020 01 11;61(1):107-114. Epub 2019 Dec 11.

Epilepsy Unit, Department of Human Neurosciences, Policlinico "Umberto I", "Sapienza" University, Rome, Italy.

Objective: Valproate (VPA) use in women with idiopathic generalized epilepsy (IGE) who are of reproductive age has been a matter of concern and debate, which eventually led to the recent restrictions by regulatory agencies. The aim of our study was to investigate the relationship between VPA avoidance/switch and seizure outcome in women of childbearing potential.

Methods: We retrospectively reviewed data from female patients with IGE, 13-50 years of age, followed since 1980. We evaluated the prescription habits, and the rate of VPA switch for other antiepileptic drugs (AEDs) and its prognostic implications. Seizure remission (SR) was defined as the absence of any seizure type more than 18 months before the last medical observation. The main aim of the study was to assess (a) possible changes in seizure outcome related to VPA switch for other AEDs, especially in patients planning a pregnancy; and (b) possible differences in SR based on the presence/absence of VPA at last observation.

Results: One hundred ninety-eight patients were included in the study. Overall SR at last medical observation was 62.7%. SR significantly differed between subjects taking and those not taking VPA (P < .001) at last visit. Multiple regression models showed that taking VPA at last medical observation was strongly associated with SR in both the general population (P < .001) and the juvenile myoclonic epilepsy (JME) group (P < .001). Thirty-six (70.6%) of 51 patients who switched from VPA during follow-up experienced a clinical worsening. Switching back to VPA was more frequently associated with SR at last observation (P < .001). In those patients who substituted VPA in view of a pregnancy, SR and drug burden (monotherapy vs polytherapy) differed significantly before and after the switch.

Significance: Our study suggests that VPA avoidance/switch might be associated with unsatisfactory seizure control in women with IGE who are of childbearing potential. Our findings further highlight the complexity of the therapeutic management of female patients of reproductive age.
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http://dx.doi.org/10.1111/epi.16407DOI Listing
January 2020

Epilepsy, cerebral calcifications, and gluten-related disorders: Are anti-transglutaminase 6 antibodies the missing link?

Seizure 2019 Dec 16;73:17-20. Epub 2019 Oct 16.

Regional Epilepsy Centre, Great Metropolitan Hospital "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy; Department of Medicine, Surgery and Health Sciences, Magna Græcia University, Catanzaro, Italy. Electronic address:

Purpose: Gluten-related disorders (GRDs) are a group of immune-mediated diseases often associated to neurologic manifestations. Epilepsies with cerebral calcifications, with or without coeliac disease (CD), are rare neurological disorders characterized by childhood-onset focal seizures, often refractory to antiepileptic drugs. Transglutaminase 6 antibodies (anti-TG6) have been considered a biomarker for gluten-related ataxia and neuropathy, but their prevalence in epilepsies with cerebral calcifications is unknown. The aim of this study is to evaluate anti-TG6 prevalence in patients with epilepsies and cerebral calcifications.

Method: this was a cross-sectional study conducted at five Italian epilepsy centres. The following groups were included. Group 1: nine patients with CD, posterior cerebral calcifications and epilepsy (CEC); group 2: nine patients with epilepsy and posterior cerebral calcifications, without CD; group 3: twenty patients with focal epilepsy of unknown etiology; group 4: twenty-two healthy controls (HC). All subjects were tested for serological evidence of anti-TG6 IgA and IgG. Differences among groups were analysed using χ ² test.

Results: anti-TG6 were present in 1/9 subjects (11%) of group 1, 2/9 subjects (22%) of group 2, 0/20 subjects in group 3, 3/22 (13.6%) of HC. No significant difference was found among the 4 groups.

Conclusions: Anti-TG6 do not seem to be associated to epilepsies with cerebral calcifications.
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http://dx.doi.org/10.1016/j.seizure.2019.10.012DOI Listing
December 2019

Subclinical dysphagia in task-specific mouth tremor triggered by drinking.

Clin Neurophysiol 2019 08 18;130(8):1289-1291. Epub 2019 May 18.

Unit of Neurology & Neurorehabilitation, IRCCS Neuromed, Via Atinense 18, 86077 Pozzilli, IS, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.clinph.2019.05.009DOI Listing
August 2019

HCN ion channels and accessory proteins in epilepsy: genetic analysis of a large cohort of patients and review of the literature.

Epilepsy Res 2019 07 8;153:49-58. Epub 2019 Apr 8.

Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

The Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels are highly expressed in the Central Nervous Systems, where they are responsible for the I current. Together with specific accessory proteins, these channels finely regulate neuronal excitability and discharge activity. In the last few years, a substantial body of evidence has been gathered showing that modifications of I can play an important role in the pathogenesis of epilepsy. However, the extent to which HCN dysfunction is spread among the epileptic population is still unknown. The aim of this work is to evaluate the impact of genetic mutations potentially affecting the HCN channels' activity, using a NGS approach. We screened a large cohort of patients with epilepsy of unknown etiology for mutations in HCN1, HCN2 and HCN4 and in genes coding for accessory proteins (MiRP1, Filamin A, Caveolin-3, TRIP8b, Tamalin, S-SCAM and Mint2). We confirmed the presence of specific mutations of HCN genes affecting channel function and predisposing to the development of the disease. We also found several previously unreported additional genetic variants, whose contribution to the phenotype remains to be clarified. According to these results and data from literature, alteration of HCN1 channel function seems to play a major role in epilepsy, but also dysfunctional HCN2 and HCN4 channels can predispose to the development of the disease. Our findings suggest that inclusion of the genetic screening of HCN channels in diagnostic procedures of epileptic patients should be recommended. This would help pave the way for a better understanding of the role played by I dysfunction in the pathogenesis of epilepsy.
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http://dx.doi.org/10.1016/j.eplepsyres.2019.04.004DOI Listing
July 2019

Ictal dancing-like semiology in frontal lobe epilepsy.

Neurol Sci 2019 Jul 4;40(7):1491-1493. Epub 2019 Feb 4.

IRCCS "NEUROMED", Pozzilli, IS, Italy.

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http://dx.doi.org/10.1007/s10072-019-3723-0DOI Listing
July 2019

Long-term seizure outcome in frontal lobe epilepsy surgery.

Epilepsy Behav 2019 01 3;90:93-98. Epub 2018 Dec 3.

IRCCS "NEUROMED", Pozzilli, IS, Italy; Department of Neurology and Psychiatry, "Sapienza" University of Rome, Italy.

Purpose: The purpose of this study was to report long-term seizure outcome in patients who underwent frontal lobe epilepsy (FLE) surgery.

Method: This retrospective study included 44 consecutive subjects who underwent resective surgery for intractable FLE at IRCCS NEUROMED (period 2001-2014), followed up for at least 2 years (mean: 8.7 years). All patients underwent noninvasive presurgical evaluation and/or invasive electroencephalography (EEG) monitoring when nonconcordant data were obtained or epileptogenic zone was hypothesized to be close to the eloquent cortex. Electroclinical, neuroimaging, surgical data, and histology were compared to seizure outcome.

Results: Mean epilepsy duration was 19 years; mean age at surgery was 31.6 years. Preoperative magnetic resonance imaging (MRI) showed a frontal lesion in 86.4 % of cases. Scalp video-electroencephalography (VEEG) monitoring detected a focal ictal onset in 90% of cases. Twenty-seven patients (61.4%) underwent invasive recordings. Resections involved dorsolateral (47.7%), medial (9%), orbital (13.6%), and rolandic (13.6%) region. Lobectomy within functional boundaries was performed in the remaining 7 cases (16%). Transient and permanent neurological deficits were observed in 2 and 3 cases, respectively. Histology revealed focal cortical dysplasia (45.5%), World Health Organization (WHO) I-II grade tumors (15.9%), gliosis (22.7%), vascular malformations (4.5%), Rasmussen encephalitis (6.8%), and normal tissue (4.5%). At last observation 68.1% of patients were in Engel's class I, 11.4% in class II, 9% in class III, and 11.4% in class IV. A favorable outcome was associated with focal ictal scalp EEG onset (p = 0.0357).

Conclusion: Surgery is a safe treatment option in drug-resistant FLE with a satisfying long-term outcome. These data highlight the importance of an appropriate selection of potential surgical candidates.
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http://dx.doi.org/10.1016/j.yebeh.2018.10.033DOI Listing
January 2019

Factors underlying the development of chronic temporal lobe epilepsy in autoimmune encephalitis.

J Neurol Sci 2019 01 30;396:102-107. Epub 2018 Oct 30.

Epilepsy Unit, Department of Neurosciences/Mental Health, "Sapienza" University, Rome, Italy. Electronic address:

Purpose: Limbic encephalitis (LE) is an autoimmune condition characterized by amnestic syndrome, psychiatric features and seizures. Early diagnosis and prompt treatment are crucial to avoid long-term sequelae, including psycho-cognitive deficits and persisting seizures. The aim of our study was to analyze the characteristics of 33 LE patients in order to identify possible prognostic factors associated with the development of chronic epilepsy.

Methods: This is a retrospective cohort study including adult patients diagnosed with LE in the period 2010-2017 and followed up for ≥12 months. Demographics, seizure semiology, EEG pattern, MRI features, CSF/serum findings were reviewed.

Results: All 33 LE patients (19 M/14F, mean age 61.2 years) presented seizures. Thirty subjects had memory deficits; 22 presented behavioural/mood disorders. Serum and/or CSF auto-antibodies were detected in 12 patients. In 31 subjects brain MRI at onset showed typical alterations involving temporal lobes. All patients received immunotherapy. At follow-up, 13/33 had developed chronic epilepsy; predisposing factors included delay in diagnosis (p = .009), low seizure frequency at onset (p = .02), absence of amnestic syndrome (p = .02) and absence/rarity of inter-ictal epileptic discharges on EEG (p = .06).

Conclusions: LE with paucisymptomatic electro-clinical presentation seemed to be associated to chronic epilepsy more than LE presenting with definite and severe "limbic syndrome".
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http://dx.doi.org/10.1016/j.jns.2018.10.026DOI Listing
January 2019

Perampanel as adjunctive therapy in highly refractory epilepsies: Real-world data from an Italian tertiary care epilepsy centre.

J Neurol Sci 2018 07 12;390:67-74. Epub 2018 Apr 12.

Neurology Unit, Department of Neurosciences and Mental Health, "Sapienza" University, Rome, Italy. Electronic address:

Perampanel (PER) is a selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist, licensed as adjunctive therapy in focal epilepsy and primary generalized tonic-clonic seizures (pGTCSs). We performed a retrospective study on highly refractory adult patients taking PER, with 1-year follow-up. Retention rate represented the primary outcome of our work; seizure frequency reduction (≥50%), "switch rate" and proportion of adverse events (AEs) were evaluated as secondary endpoints. Eighty-nine subjects (47 females, age range: 19-78 years) were included. Seventy-three had focal epilepsy (FE), 9 generalized epilepsy and 7 epileptic encephalopathy. All patients were highly drug-resistant (medication failures: 5-17). Retention rate was 87.6%, 63% and 51.7% at 3, 6 and 12 months. Responders were 27/89 (30.3%), with 8/27 seizure-free. The number of previous treatment failures and the concomitant use of enzyme inducers negatively influenced clinical response, whereas no correlation was documented between PER dose and outcome. Responder proportion was more satisfying in structural FE than in FE of unknown etiology (33% versus 20%), and in secondarily GTCSs than focal seizures (54% vs 28%), whereas pGTCSs showed a lower reponse rate (25%). Mild-to-moderate AEs (mainly dizziness, gait disturbances and psychiatric effects) were reported by 40% of patients; serious psychiatric AEs usually occurred in subjects with psychiatric comorbidities. Our study confirms the tolerability and effectiveness of PER in highly drug-resistant patients with different epilepsy syndromes and aetiologies.
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http://dx.doi.org/10.1016/j.jns.2018.04.017DOI Listing
July 2018

Possible autoantibody-negative limbic encephalitis after anterior temporal lobectomy for hippocampal sclerosis.

Int J Neurosci 2018 May 16;128(5):464-466. Epub 2017 Nov 16.

a IRCCS NEUROMED Pozzilli (IS) , Italy.

Purpose: Amnestic syndromes are acknowledged to be associated to bilateral hippocampal damage.

Materials And Methods: We briefly report the case of a young man who underwent anterior left temporal lobectomy for a medically refractory temporal lobe epilepsy due to hippocampal sclerosis with an excellent seizure and neuropsychological outcome. Approximately 10 years later, he presented with a subacute severe global amnesia and neuroimaging findings of a damage involving the contralateral mesial temporal lobe structures.

Results: A diagnosis of a possible autoimmune encephalitis was made.

Conclusions: Due to its peculiarities (compared with other cases of bilateral temporal lesions, the damage occurred on two distinct occasions), this case might contribute to shed light on the issue of the possible contralateral reorganization of memory processes subserved by the mesial temporal lobe structures chronically involved in epileptogenesis.
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http://dx.doi.org/10.1080/00207454.2017.1394852DOI Listing
May 2018

Switch From Originator to Equivalent Drug in the Era of Generic Antiepileptic Drugs: Study of Keppra Versus Epitiram Clinical Equivalence.

Clin Neuropharmacol 2017 Nov/Dec;40(6):239-242

Department of Neurology and Psychiatry, Neurology Unit, "Sapienza" University, Rome, Italy.

Objectives: Generic antiepileptic drugs represent a measure to maximize cost saving. Levetiracetam (LEV) is one of most commonly used and effective antiepileptic drugs. The objective of our work was to demonstrate the effectiveness and safety of overnight switch from monotherapy with Keppra (original drug) to epitiram (generic drug) at the same dose.

Methods: In our observational study, we consecutively enrolled 37 seizure-free patients with epilepsy who expressed the wish to switch to a generic drug for economic reasons. During the 6-month evaluation period, we assessed treatment efficacy, tolerability, compliance, and intersubject variability of LEV serum concentration. At each visit, clinical and neurological examination, scales, video-electroencephalogram, and blood sample analysis to evaluate LEV plasma level were performed.

Results: A total of 36 of 37 enrolled patients switched from Keppra to epitiram, which was administered at the same dose in monotherapy. Three of 36 patients dropped out during follow-up for adverse events. The other 33 subjects had neither seizures nor adverse events. No significant differences in electroencephalogram features and scale scores were revealed; the intersubject variability of LEV serum concentration did not differ significantly at follow-up evaluation (P = 0.53). All the patients expressed good clinical personal impression and continued to take epitiram. The switchback rate was 8 %.

Conclusions: The switch from Keppra to epitiram was easy and safe in our population, and epitiram can be considered as effective and tolerable as Keppra. Only a slight, non-statistically significant variability in LEV serum concentration was documented after the switch from Keppra to epitiram. Larger epileptic populations should be studied to confirm these results.
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http://dx.doi.org/10.1097/WNF.0000000000000250DOI Listing
June 2018

Facial emotion decoding in patients with Parkinson's disease.

Int J Neurosci 2018 Jan 28;128(1):71-78. Epub 2017 Aug 28.

a I.R.C.C.S. Neuromed , Pozzilli (IS) , Italy.

Purpose: In line with the growing attention on non-motor symptoms and disturbance of affective and emotional processing in Parkinson's disease, we aimed to study the different aspects of facial emotion expression evaluation in a group of Parkinson's disease without cognitive decline in treatment with common antiparkinsonian drugs, matched for sex, age and education with healthy subjects.

Materials And Methods: The study was conducted on 30 patients (13 male; mean age: 63.3 ± 6.7; mean age of disease onset: 56.5 ± 7.1; mean duration of the disease: 6.7 ± 2.6) with a diagnosis of Parkinson's disease and receiving dopaminergic therapy, as compared with 30 healthy controls. Different tasks of facial expression evaluation were used. All patients were assessed for neuropsychological and psychological profiles during optimized medication-on condition.

Results: The total number of errors in facial emotion recognition task is higher (p < 0.001) in patients than controls and it is due to errors in identifying sadness (p < 0.001), anger (p = 0.01) and fear (p < 0.001). No differences in the total amount of activation, valence and intensity ratings were found. The difference between patients and controls in emotion recognition appears to be independent by the severity of depressive symptoms.

Conclusions: The present study provides further evidence of altered non-verbal emotional information processing in Parkinson's disease patients, suggesting that nigrostriatal dopaminergic depletion leads also to emotional information processing dysfunction. The consequences of these emotional encoding disturbances in daily living and their relationship to mood and behavioural disorders remain to be clarified.
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http://dx.doi.org/10.1080/00207454.2017.1366475DOI Listing
January 2018

Ictal pain in focal non-convulsive status epilepticus.

Pract Neurol 2017 Oct 9;17(5):400-402. Epub 2017 Jun 9.

Epilepsy Unit, Department of Neurology and Psychiatry, 'Sapienza' University, Rome, Italy.

We report an adult with acute unilateral pain as isolated manifestation of acute symptomatic focal non-convulsive status epilepticus. Pain is rarely a manifestation of epileptic seizures. Traditionally, painful seizures have been thought to originate in either the parietal or temporal lobes, but their localising value is debatable. Recent functional neuroimaging studies and electrophysiological findings obtained by using intracerebral recordings have shown the involvement of the insular cortex along with several other brain structures in the processing of painful inputs, comprising a more widespread anatomo-functional network. Despite their rarity as a distinct clinical entity, especially in adults, painful somatosensory seizures can be disabling and misdiagnosis or delayed diagnosis is common; it is therefore essential to consider epilepsy as a possible cause of paroxysmal pain to ensure proper assessment and appropriate treatment.
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http://dx.doi.org/10.1136/practneurol-2017-001623DOI Listing
October 2017

Severe and rapidly-progressive Lafora disease associated with NHLRC1 mutation: a case report.

Int J Neurosci 2017 Dec 12;127(12):1150-1153. Epub 2017 Jun 12.

a IRCCS "NEUROMED" , Pozzilli (IS) , Italy.

Lafora disease (LD), also known as progressive myoclonic epilepsy-2 (EPM2), is a rare, fatal autosomal recessive disorder typically starting during adolescence in otherwise neurologically normal individuals. It is clinically characterized by insidious of progressive neurological features including seizures, action myoclonus, visual hallucination, ataxia and dementia. Mutations in the laforin (EPM2A) gene on chromosome 6q24 or in the malin gene (NHLRC1) on chromosome 6p22 are responsible of LD phenotype. Diagnostic workup includes genetic analysis as well as axillary skin biopsy with evidence of typical periodic acid-Schiff (PAS)-positive polyglucosan inclusion bodies (Lafora bodies) in the apocrine glands and/or in the eccrine duct. Usually, genotype-phenotype correlations do not reveal substantial differences between patients carrying EPM2A and NHLRC1 mutations, but a few specific NHLRC1 mutations appear to correlate with a late onset and slow progressing LD. We report a case of LD due to compound heterozygote NHLRC1 mutation in an adolescent presenting with severe and atypical electro-clinical features, mimicking an autoimmune encephalopathy, and a rapidly progressive clinical course.
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http://dx.doi.org/10.1080/00207454.2017.1337012DOI Listing
December 2017

Temporal pole abnormalities detected by 3 T MRI in temporal lobe epilepsy due to hippocampal sclerosis: No influence on seizure outcome after surgery.

Seizure 2017 May 12;48:74-78. Epub 2017 Apr 12.

IRCCS "NEUROMED", Pozzilli (IS), Italy. Electronic address:

Purpose: To assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) detected by using 3 Tesla MRI in the preoperative workup in patients with temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS) who underwent surgery.

Methods: We studied 78 consecutive patients with TLE-HS who underwent surgery and were followed up for at least 2 years. Based on findings of pre-surgical 3 Tesla MRI, patients were subdivided in subgroups according to the presence of TB or TA. Subgroups were compared on demographic, clinical, neuropsychological data and seizure outcome.

Results: TB was found in 39 (50%) patients, while TA was found in 32 (41%) patients, always ipsilateral to HS, with a considerable degree of overlap (69%) between TB and TA (p=0.01). Patients with temporopolar abnormalities did not significantly differ from those without TB or TA with regard to sex, age, age of epilepsy onset, duration of epilepsy, history of febrile convulsions or birth complications, side of surgery, seizure frequency at surgery, presence of GTCSs, and, in particular, seizure outcome. On the other hand, TB patients show a less frequent family history of epilepsy (p<.05) while age at epilepsy onset showed a trend to be lower in the TB group (p=.09). Patients with temporopolar atrophy did not significantly differ from those without TA on any variable, except for age at epilepsy onset, which was significantly lower for the TA group (p<.05). History of birth complications and longer duration of epilepsy also showed a trend to be associated with TA (p=.08). Multivariate analysis corroborated the association between temporopolar abnormalities and absence of family history of epilepsy and history of birth complications.

Conclusions: High-field 3 T MRI in the preoperative workup for epilepsy surgery confirms that temporopolar abnormalities are frequent findings in TLE-HS patients and may be helpful to lateralize the epileptogenic zone. Their presence did not influence seizure outcome.
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http://dx.doi.org/10.1016/j.seizure.2017.04.006DOI Listing
May 2017

Coexistence of childhood absence epilepsy and benign epilepsy with centrotemporal spikes: A case series.

Eur J Paediatr Neurol 2017 May 14;21(3):570-575. Epub 2017 Feb 14.

IRCCS "NEUROMED", Pozzilli, IS, Italy.

Aim: Childhood absence epilepsy (CAE) and benign childhood epilepsy with centrotemporal spikes (BECTS) are the most common forms of childhood epilepsy. Recent studies in animal models suggest that the two phenotypes may represent a neurobiological continuum. Although the coexistence of CAE and BECTS has been reported, this issue remains controversial. The purpose of this study was to analyse the electro-clinical characteristics of a group of children with contemporary or subsequent features of absence seizures and focal seizures consistent with BECTS.

Material And Methods: A systematic record review from 8 epilepsy centres was used to identify 11 subjects, 5 females and 6 males, with electro-clinical documented consecutive or contemporary coexistence of CAE and BECTS.

Results: Patient's age ranged between 7.8 and 17.3 years. Four out of 11 patients presented concomitant features of both syndromes, whereas the remaining 7 experienced the two syndromes at different times.

Conclusions: Although CAE and BECTS are clearly defined syndromes and considered very different in terms of their pathophysiology, they share some features (such as similar age of onset, overall good prognosis), and can occur in the same patient. The long term prognosis of these patients seems to be good with an excellent response to anticonvulsant therapy.
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http://dx.doi.org/10.1016/j.ejpn.2017.02.002DOI Listing
May 2017