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Schretlen DJ, Finley JCA, Del Bene VA, Varvaris M. The Ubiquity of Cognitive Impairment in Human Illness: a Systematic Review of Meta-Analyses. Arch Clin Neuropsychol 2025; 40:863-877. [PMID: 39667720 DOI: 10.1093/arclin/acae113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 11/18/2024] [Accepted: 11/23/2024] [Indexed: 12/14/2024] Open
Abstract
OBJECTIVE Cognitive dysfunction occurs in many neurological, psychiatric, and other health conditions. This review aimed to characterize the breadth and degree of cognitive morbidity associated with varied health conditions. METHOD We systematically reviewed Medline, EMBASE, and Cochrane databases for meta-analyses of cognitive dysfunction associated with any health condition. Meta-analyses were eligible if they reviewed studies that compared patients with health conditions to healthy controls on cognitive testing and provided effect sizes. RESULTS We found 91 meta-analyses for 94 health conditions. Among >800,297 participants, healthy controls out-performed clinical participants in every condition on cognitive testing. Mean effect sizes ranged from -2.02 to -0.00 across conditions and were ≤ -0.5 on average, denoting moderate to very severe dysfunction for 41% of them. CONCLUSIONS Cognitive dysfunction is ubiquitous in medicine. Both primary care and specialist physicians likely treat patients with cognitive dysfunction. Depending on its severity, cognitive dysfunction can affect treatment adherence, everyday functioning, quality of life, and the capacity to provide informed consent for treatment. These findings highlight the transdiagnostic nature of cognitive symptoms and the potential value of establishing collaborations between physicians and clinical neuropsychologists to integrate cognitive assessment into patient care. Even brief assessments can identify cognitive deficits that likely affect treatment adherence and functional outcomes.
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Affiliation(s)
- David J Schretlen
- Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - John-Christopher A Finley
- Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Victor A Del Bene
- Department of Neurology, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA
| | - Mark Varvaris
- Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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2
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Chafetz MD, Sweet JJ, Boone KB, Cox D, Hall V, Kirkwood MW, Lafosse JM, Merten T, Oldenburg C. Neuropsychological review of records in forensic cases: An AACN best practices paper with international perspectives. Clin Neuropsychol 2025; 39:839-869. [PMID: 39904975 DOI: 10.1080/13854046.2025.2461750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Accepted: 01/29/2025] [Indexed: 02/06/2025]
Abstract
Objective: The purpose of this American Academy of Clinical Neuropsychology (AACN) best practices paper is to provide the neuropsychological community with the fundamentals of a competent forensic review of records. Method: Narrative review addressing fundamental factors related to review of records. Examples highlighted information necessary for a forensic determination of traumatic brain injury (TBI), and the data from records that can be used to address questions regarding validity of presentation. International and intra-jurisdictional perspectives within the US were used to illustrate the necessity of adhering the review to the rules. Results: Factors identified involve ethical responsibilities, completeness in obtaining and reviewing relevant records, evaluation of credibility of the records, considerations regarding examinee self-reporting, grounding of opinions within peer-reviewed science, determination of causation in the context of litigation, and avoiding bias in reporting, as well as consideration of cultural and language factors. Different jurisdictional rules require close attention. Conclusions: Neuropsychologists need to be aware of the need for a competent review of records to obtain basic facts, maintain objectivity, and provide a context for conclusions in a neuropsychological examination report. In litigation cases, opinions based solely on review of records may be challenged for reasons that might include not having personally evaluated the plaintiff, and whether opinions meet Daubert criteria pertaining to sufficient scientific bases and facts. A thorough review in the context of examination helps deal with litigant/claimant subjectivity and malleability of self-report, and it can provide critical reasoning about other factors relevant to causation.
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Affiliation(s)
| | - Jerry J Sweet
- Department of Psychiatry & Behavioral Sciences, Endeavor Health, Evanston, IL, USA
| | | | - Darcy Cox
- Cox Neuropsychological Services, Inc., Vancouver, BC, Canada
| | - Vicki Hall
- Neuromindworks, Sutton Coldfield, West Midlands, UK
| | - Michael W Kirkwood
- Department of Physical Medicine & Rehabilitation, University of Colorado School of Medicine, Aurora, CO, USA
- Department of Rehabilitation Medicine, Children's Hospital Colorado, Aurora, CO, USA
| | - Jose M Lafosse
- Lafosse Neuropsychology, PC, San Diego, CA, USA
- Department of Psychology & Neuroscience, Regis University, Denver, CO, USA
| | - Thomas Merten
- Vivantes Klinikum im Friedrichshain, Neurology, Berlin, Germany
| | - Christian Oldenburg
- Division of Insurance Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
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3
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Amer H, Helmy H, El-Sawy E, S Ayoub M, Mounir N. Parenchymal neuro-sonological characteristics in epileptic patients and their correlation with cognitive dysfunction. ACTA EPILEPTOLOGICA 2025; 7:26. [PMID: 40259358 PMCID: PMC12010533 DOI: 10.1186/s42494-025-00212-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 03/05/2025] [Indexed: 04/23/2025] Open
Abstract
BACKGROUND Idiopathic generalized epilepsies (IGEs) are the most common syndromes within the "genetic generalized epilepsies" (GGEs). Patients with IGE often exhibit cognitive comorbidities. The primary objective of this study is to investigate the correlation between brain parenchymal sonography characteristics and cognitive impairment in IGE. METHODS This study enrolled 26 patients with IGE and 26 age- and sex-matched controls. All participants underwent comprehensive evaluations including clinical examination, electroencephalography, magnetic resonance imaging epilepsy protocol, transcranial sonography (TCS) for third and lateral ventricular diameter measurements, and cognitive assessment using the Addenbrooke's Cognitive Examination-III (ACE III). RESULTS This study found significantly lower scores in attention, memory, fluency, and total score of ACE-III in IGE patients compared to the control group (P-value = 0.011, 0.033, 0.007, and 0.001, respectively). However, no significant differences were observed between IGE patients and the control group in language and visuospatial score (P = 0.479 and 0.108, respectively). The average diameters of the third ventricle and lateral ventricle anterior horns were significantly larger in patients than in the control group (P-value 0.004, 0.009, and 0.012, respectively). CONCLUSIONS IGE patients exhibit significant cognitive impairment and notable dilatation of the third ventricle and lateral ventricles horns, which may serve as markers of brain atrophy.
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Affiliation(s)
- Hanan Amer
- Department of Neurology, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt
| | - Hanan Helmy
- Department of Neurology, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt
| | - Enji El-Sawy
- Department of Neurology, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt
| | - Maha S Ayoub
- Department of Neurology, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt
| | - Nesma Mounir
- Department of Neurology, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt.
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4
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Mameniškienė R, Puteikis K. The current state of cognitive rehabilitation for individuals with epilepsy and pathways for improvement: a multinational cross-sectional survey of epilepsy specialists. Seizure 2025; 130:4-10. [PMID: 40319522 DOI: 10.1016/j.seizure.2025.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2025] [Revised: 03/24/2025] [Accepted: 04/12/2025] [Indexed: 05/07/2025] Open
Abstract
OBJECTIVE Despite the relevance of psychosocial and cognitive issues for people with epilepsy (PWE), there remains scarce data on cognitive rehabilitation programs as a central care pathway alongside pharmacological and surgical treatment in epilepsy. We aimed to map the use, availability and characteristics of rehabilitation programs for epilepsy across different countries worldwide. METHODS We conducted a web-based survey of epilepsy specialists practicing in different countries around the world. Participants were asked to provide information on the availability, accessibility, use and methodology of cognitive rehabilitation in their country of practice. RESULTS One hundred and ten responses were received across 66 different countries: 45 respondents were from Europe, 35 - from Latin America, 14 - from the Eastern Mediterranean region, 7 - from Asia and Oceania, 8 - from Africa and 1 - from North America. Most participants were neurologists and/or epileptologists (96, 87 %) practicing in university hospitals (69, 63 %) and caring for adult patients (85, 77 %). Any rehabilitation measures for PWE were reported as generally available by 75 (68 %) respondents. For cognitive rehabilitation, this was reported by 40 (36 %) specialists with an average service accessibility of 5.4 ± 2.5 out of 10. When available, cognitive rehabilitation is primarily used in patients with cognitive complaints (38, 81 %), mood complaints or comorbid psychiatric disorders (27, 57 %). While individual sessions predominate (29, 62 %), cognitive rehabilitation programs are heterogeneous in form - compensatory (10, 21 %), restitution (12, 26 %) techniques, internal (12, 26 %) and external (12, 26 %) strategies are used alongside psychoeducation (15, 32 %) and psychological counselling (16, 34 %) without clear predominance of either approach. In 13 (32.5 %) cases, cognitive rehabilitation was supported by national standards of practice or state legislature. CONCLUSIONS Cognitive rehabilitation programs for PWE are generally less available than other forms of rehabilitation across the world. New evidence-based procedure development and harmonization is required to promote establishment and effective use of these services.
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Affiliation(s)
- Rūta Mameniškienė
- Clinic of Neurology and Neurosurgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
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5
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Garcia-Ramos C, Struck AF, Nair VA, Prabhakaran V, Imhoff-Smith TP, Adluru N, Almane DN, Jones JE, Hermann BP. The network neuropsychology of juvenile myoclonic epilepsy. Cortex 2025; 185:20-30. [PMID: 39946996 PMCID: PMC11993346 DOI: 10.1016/j.cortex.2024.12.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 12/03/2024] [Accepted: 12/20/2024] [Indexed: 02/27/2025]
Abstract
Unknown in the clinical neuropsychology of Juvenile Myoclonic Epilepsy (JME) is the impact of the disorder on the nature of the relationships of specific cognitive abilities among themselves including their patterns of integration, segregation, and topographical organization-that is, the network neuropsychology of JME remains to be addressed. Examined here is the status of cognitive networks in JME and whether similar network alterations are present in the unaffected siblings of patients with this genetic generalized epilepsy. Participants included 78 with JME (mean age = 19.8 ± 3.7 yrs), 19 unaffected siblings (mean age = 15.9 ± 3.3 yrs) and 43 unrelated controls (mean age = 20.2 ± 3.2 yrs), all administered a comprehensive clinical neuropsychological battery from which 15 metrics served as nodes for graph theory analyses. Calculated were global metric indices (i.e., normalized global efficiency, normalized average clustering coefficient, modularity) and landmark "hubs" by calculating betweenness centrality. Salient JME network findings included: 1) significantly greater intercorrelation of test measures (i.e., increased positive manifold), 2) significantly lower segregation (i.e., normalized average clustering coefficient) but similar network efficiency (i.e., normalized global efficiency), and 3) significantly lower strength of the division of the cognitive modules in the network (i.e., modularity index). Regarding the topographical structure of identified cognitive networks (i.e., their community structure), unaffected siblings and unrelated controls demonstrated three cognitive modules (speed/executive function, perceptual, language) while JME demonstrated two modules-one of which was undifferentiated and "g-like", and speed/executive function. Overall, JME is associated with less segregation of cognitive subsystems (i.e., modules) indicating less specialization in cognitive processes, abnormalities in the interrelationships of psychometric measures as well as the general configuration of their resulting cognitive networks (fewer in number and atypical in content and structure) which appear to be contributing to their generally poorer cognitive status compared to controls. Unaffected siblings show some penetrance of these atypical network features.
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Affiliation(s)
- Camille Garcia-Ramos
- Department of Neurology, University of Wisconsin-Madison, Madison, WI 53726, USA.
| | - Aaron F Struck
- Department of Neurology, University of Wisconsin-Madison, Madison, WI 53726, USA; Department of Neurology, William S Middleton Veterans Administration Hospital, Madison, WI 53705, USA
| | - Veena A Nair
- Department of Radiology, University of Wisconsin-Madison, Madison, WI 53726, USA
| | - Vivek Prabhakaran
- Department of Radiology, University of Wisconsin-Madison, Madison, WI 53726, USA
| | | | - Nagesh Adluru
- Department of Radiology, University of Wisconsin-Madison, Madison, WI 53726, USA; Waisman Center, University of Wisconsin Madison, Madison, WI, USA
| | - Dace N Almane
- Department of Neurology, University of Wisconsin-Madison, Madison, WI 53726, USA
| | - Jana E Jones
- Department of Neurology, University of Wisconsin-Madison, Madison, WI 53726, USA
| | - Bruce P Hermann
- Department of Neurology, University of Wisconsin-Madison, Madison, WI 53726, USA
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Patrikelis P, Loukopoulou E, Masoura E, Folia V, Kiosseoglou G, Messinis L, Malefaki S, Lucci G, Kimiskidis V. Autobiographical memory impairment in genetic generalized epilepsies: neurocognitive and pathophysiological determinants. ARQUIVOS DE NEURO-PSIQUIATRIA 2025; 83:1-10. [PMID: 40132998 DOI: 10.1055/s-0045-1804923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/27/2025]
Abstract
The neuropsychological breakdowns of autobiographical memory (AM) in adults suffering from genetic generalized epilepsy (GGE) are far from being understood and largely neglected.We aimed at identifying AM impairments in GGE by analyzing neurocognitive deficits in illness-related variables possibly affecting AM.Patients with GGE were compared to healthy controls (HCs), through semistructured interviews on AM, as well as neuropsychological measures to identify potential determinants of AM impairment.A single GGE group was formed by including patients with juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and epilepsy with generalized tonic-clonic seizures alone (EGTCA). Both GGE patients and HCs were tested for differential impairments in autobiographical episodic memory (AEM) and/or autobiographical semantic memory (ASEM), as well as other episodic- and/or semantic-memory and executive-function domains.The GGE patients exhibited overall impairment in autobiographical episodic and semantic information retrieval compared to HCs, both regarding childhood and the recent past. Furthermore, GGE patients demonstrated significantly poorer performance in immediate and delayed episodic recall, visuospatial working memory, visuoperceptual organization, face recognition memory, and verbal-executive functions compared to HCs. A distinct visuoperceptual involvement in retrieving childhood autobiographical episodic and semantic information has emerged, suggesting a potential connection between the latter AM systems and visual cognition.
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Affiliation(s)
- Panayiotis Patrikelis
- Aristotle University of Thessaloniki, School of Psychology, Laboratory of Neuropsychology and Behavioral Neuroscience, Thessaloniki, Greece
| | - Eleni Loukopoulou
- Aristotle University of Thessaloniki, School of Psychology, Laboratory of Neuropsychology and Behavioral Neuroscience, Thessaloniki, Greece
| | - Elvira Masoura
- Aristotle University of Thessaloniki, School of Psychology, Laboratory of Neuropsychology and Behavioral Neuroscience, Thessaloniki, Greece
| | - Vasiliki Folia
- Aristotle University of Thessaloniki, School of Psychology, Laboratory of Neuropsychology and Behavioral Neuroscience, Thessaloniki, Greece
| | - Grigoris Kiosseoglou
- Aristotle University of Thessaloniki, School of Psychology, Laboratory of Neuropsychology and Behavioral Neuroscience, Thessaloniki, Greece
| | - Lambros Messinis
- Aristotle University of Thessaloniki, School of Psychology, Laboratory of Neuropsychology and Behavioral Neuroscience, Thessaloniki, Greece
- University Hospital of Patras, School of Medicine, Neuropsychology Section, Department of Psychiatry, Patras, Greece
| | - Sonia Malefaki
- Università degli Studi Guglielmo Marconi, Dipartimento di Tecnologie, Comunicazione e Società, Roma, Italy
| | - Giuliana Lucci
- Aristotle University of Thessaloniki, School of Medicine, American Hellenic Educational Progressive Association (AHEPA) University Hospital, First Department of Neurology, Thessaloniki, Greece
| | - Vasileios Kimiskidis
- Università degli Studi Guglielmo Marconi, Dipartimento di Tecnologie, Comunicazione e Società, Roma, Italy
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Neshige S, Aoki S, Ohno N, Nonaka M, Yamada H, Takebayashi Y, Ishibashi H, Shishido T, Agari D, Yamazaki Y, Iida K, Maruyama H. Interictal head-turning sign in patients with idiopathic generalized epilepsy during initial medical interview: A matched multicenter study. Epilepsy Behav 2024; 160:110039. [PMID: 39395295 DOI: 10.1016/j.yebeh.2024.110039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 09/01/2024] [Accepted: 09/02/2024] [Indexed: 10/14/2024]
Abstract
BACKGROUND Utilizing interictal manifestations for the diagnosis of epilepsy is challenging. We investigated whether an interictal "head-turning sign," typically indicative of dependence on others observed in Alzheimer's disease, can act as a behavioral marker of idiopathic generalized epilepsy. METHODS This multicenter study examined 579 consecutive patients, with a mean age of 36.8 ± 20.4 years, who did not have an intellectual disability and had their first outpatient visit for epilepsy evaluation between 2019 and 2023. Patients were categorized into IGE, non-IGE epilepsy, non-epileptic, and psychiatric conditions based on their ultimate diagnostic outcomes to identify difference of the occurrence of the head-turning sign among them. Additionally, we extracted data from patients under the age of 40, specifically adolescents and young adults (AYA). Then we used propensity score matching to confirm the reproducibility of observed differences and to identify associated factors within the AYA age group. RESULTS The occurrence of the head-turning sign was significantly more prevalent in the IGE group compared to the non-IGE group (20.4 % vs. 2.2 %; P<0.0001) and non-epileptic group (20.4 % vs. 8.3 %; P=0.033). Following the matching, the head-turning sign was still evident in IGE relative to non-IGE patients (14.6 % vs. 4.5; P=0.004), yielding a 94 % specificity for IGE. IGE diagnosis (P<0.0001), myoclonic seizure (P<0.0001), being visited by a parent (P=0.017), and comorbidity with headache (P=0.021) were significantly associated with the head-turning sign. Multivariate analysis revealed that IGE (odds ratio: OR=2.80, P=0.028), attending with a parent (OR=2.92, P=0.029), and comorbidity with headache (OR=4.06, P=0.016) were independently associated with the head-turning sign. CONCLUSIONS We confirmed a substantial association between the interictal "head-turning sign" and IGE. This unique sign may reflect a tendency towards dependence on others in IGE, and may serve as a promising diagnostic auxiliary marker for identifying IGE in the AYA age group.
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Affiliation(s)
- Shuichiro Neshige
- Department of Clinical Neuroscience and Therapeutics, Hiroshima University, Graduate School of Biomedical and Health Sciences, Japan; Epilepsy Center, Hiroshima University Hospital, Japan.
| | - Shiro Aoki
- Department of Clinical Neuroscience and Therapeutics, Hiroshima University, Graduate School of Biomedical and Health Sciences, Japan
| | - Narumi Ohno
- Department of Clinical Neuroscience and Therapeutics, Hiroshima University, Graduate School of Biomedical and Health Sciences, Japan; Epilepsy Center, Hiroshima University Hospital, Japan
| | - Megumi Nonaka
- Department of Clinical Neuroscience and Therapeutics, Hiroshima University, Graduate School of Biomedical and Health Sciences, Japan
| | - Hidetada Yamada
- Department of Clinical Neuroscience and Therapeutics, Hiroshima University, Graduate School of Biomedical and Health Sciences, Japan
| | - Yoshiko Takebayashi
- Department of Clinical Neuroscience and Therapeutics, Hiroshima University, Graduate School of Biomedical and Health Sciences, Japan
| | - Haruka Ishibashi
- Department of Clinical Neuroscience and Therapeutics, Hiroshima University, Graduate School of Biomedical and Health Sciences, Japan
| | - Takeo Shishido
- Department of Neurology, Hiroshima City Asa Citizens Hospital, Japan
| | - Dai Agari
- Department of Neurology, Hiroshima City Hiroshima Citizens Hospital, Japan
| | - Yu Yamazaki
- Department of Clinical Neuroscience and Therapeutics, Hiroshima University, Graduate School of Biomedical and Health Sciences, Japan
| | - Koji Iida
- Epilepsy Center, Hiroshima University Hospital, Japan
| | - Hirofumi Maruyama
- Department of Clinical Neuroscience and Therapeutics, Hiroshima University, Graduate School of Biomedical and Health Sciences, Japan; Epilepsy Center, Hiroshima University Hospital, Japan
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8
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Ashjazadeh N, Namjoo-Moghadam A, Mani A, Doostmohammadi N, Bayat M, Salehi MS, Rafiei E, Rostamihosseinkhani M, Khani-Robati A, Hooshmandi E. Comparison of executive function in idiopathic generalized epilepsy versus temporal lobe epilepsy. Neurocase 2024; 30:167-173. [PMID: 39611753 DOI: 10.1080/13554794.2024.2436160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 11/25/2024] [Indexed: 11/30/2024]
Abstract
Executive function (EF) deficits are common in epilepsy and impact quality of life. This study compares EF in idiopathic generalized epilepsy (IGE) and temporal lobe epilepsy (TLE) patients to healthy controls. Fifty-six IGE patients, 56 TLE patients, and 60 controls (matched by age) completed cognitive tests assessing attention, memory, learning, and verbal fluency. Both epilepsy groups performed worse than controls, with TLE patients showing significantly poorer verbal learning and memory compared to IGE patients. These findings suggest that TLE patients have more severe EF impairments, likely due to focal temporal lobe dysfunction and disruptions in EF networks.
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Affiliation(s)
- Nahid Ashjazadeh
- Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Namjoo-Moghadam
- Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Arash Mani
- Research Center for Psychiatry and Behavior Science, Hafez Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Neda Doostmohammadi
- Shiraz Neuroscience Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahnaz Bayat
- Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Saied Salehi
- Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Elahe Rafiei
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | | | - Etrat Hooshmandi
- Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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Faiman I, Young AH, Shotbolt P. Cognitive correlates of psychopathology in functional/dissociative seizures and non-lesional epilepsy: An exploratory study. Epilepsy Behav 2024; 159:109952. [PMID: 39121755 DOI: 10.1016/j.yebeh.2024.109952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 07/12/2024] [Accepted: 07/14/2024] [Indexed: 08/12/2024]
Abstract
OBJECTIVE To explore the relationship between cognitive functioning and psychopathological features in Functional/Dissociative Seizures (FDS), and test whether this differs from that observed in epilepsy. METHODS We recruited a cross-sectional sample of adults (age > 18) with a diagnosis of non-lesional epilepsy or FDS between January 2021 and July 2022 (n = 73). Participants completed a series of psychiatric questionnaires and neuropsychological measures. Spearman's Correlation Coefficient was computed between each of the psychiatric and cognitive measures in each group. Fisher's Z test of significance for independent correlation coefficients then tested the significance of the difference between correlation coefficients for the two groups. RESULTS There were no group differences in neuropsychological test scores. However, people with FDS reported higher seizure severity, depression levels, number of medically unexplained somatic symptoms, and exposure to traumatic events compared to epilepsy. Results of the Fisher's Z-test revealed significant differences in correlation coefficients between groups in two instances. First, in the association between the number of traumatic experiences and cognitive switching (z = 2.77, p = 0.006); the number of traumatic experiences were positively associated with cognitive switching in epilepsy but showed a non-significant negative trend in FDS. Secondly, in the association between vocabulary abilities and the number of medically unexplained symptoms (z = -2.71; p = 0.007); higher vocabulary ability was associated with fewer somatic symptoms in epilepsy, while no such correlation was observed in FDS. SIGNIFICANCE This study provides preliminary evidence for the complex interplay between cognitive functioning and psychopathology in FDS and epilepsy. Neurocognitive functioning such as vocabulary abilities or attentional switching may play a role in the expression or maintenance of pathological features of FDS.
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Affiliation(s)
- Irene Faiman
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, Camberwell, London SE5 8AB, United Kingdom.
| | - Allan H Young
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, Camberwell, London SE5 8AB, United Kingdom; South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Monks Orchard Road, Beckenham, Kent BR3 3BX, United Kingdom.
| | - Paul Shotbolt
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, Camberwell, London SE5 8AB, United Kingdom.
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Phillips KHT, Patterson K, Butler CR, Woodberry E, Ralph MAL, Cope TE. Does epilepsy differentially affect different types of memory? Seizure 2024; 121:217-225. [PMID: 39243667 DOI: 10.1016/j.seizure.2024.08.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 08/23/2024] [Indexed: 09/09/2024] Open
Abstract
Despite the recognition that epilepsy can substantially disrupt memory, there are few published accounts of whether and how this disruption varies across different types of memory and/or different types of epilepsy. This review explores four main questions: (1) Are working, episodic and semantic memory differentially affected by epilepsy? (2) Do various types of epilepsy, and their treatment, have different, specifiable effects on memory? (3) Are the usual forms of neuropsychological assessments of memory - many or most designed for other conditions - appropriate for patients with epilepsy? (4) How can research on epilepsy contribute to our understanding of the neuroscience of memory? We conclude that widespread and multifactorial problems are seen in working memory in all patient groups, while patients with temporal lobe epilepsy seem particularly prone to episodic memory deficit, and those with frontal lobe epilepsy to executive function deficits that may in turn impair semantic control. Currently, it is difficult to make individual patient predictions about likely memory deficits based on seizure aetiology and type, but it is possible to guide and tailor neuropsychological assessments in an individualised way. We make recommendations for future directions in validating and optimising neuropsychological assessments, and consider how to approach effective shared decision making about the pros and cons of seizure treatment strategies, especially at crucial educational stages such as adolescence.
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Affiliation(s)
| | - Karalyn Patterson
- Cambridge University Hospitals, Cambridge, UK; MRC Cognition and Brain Sciences Unit, Cambridge, UK
| | | | | | - Matthew A Lambon Ralph
- Cambridge University Hospitals, Cambridge, UK; MRC Cognition and Brain Sciences Unit, Cambridge, UK
| | - Thomas E Cope
- Cambridge University Hospitals, Cambridge, UK; MRC Cognition and Brain Sciences Unit, Cambridge, UK
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11
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Yu YM, Jin GH, Zhong C, Qian H, Wang L, Zhan F. Exploring the role of interleukin-6 receptor blockade in epilepsy and associated neuropsychiatric conditions through a mendelian randomization study. World J Psychiatry 2024; 14:1244-1253. [PMID: 39165549 PMCID: PMC11331385 DOI: 10.5498/wjp.v14.i8.1244] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 07/05/2024] [Accepted: 07/11/2024] [Indexed: 08/12/2024] Open
Abstract
BACKGROUND The interplay between inflammation, immune dysregulation, and the onset of neurological disorders, including epilepsy, has become increasingly recognized. Interleukin (IL)-6, a pro-inflammatory cytokine, is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients. The role of IL-6 receptor (IL6R) blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes. AIM To explore the potential of IL6R blockade in reducing the risk of epilepsy and investigate whether this pathway might also influence associated psychiatric and neuropsychiatric conditions due to neuroinflammation. METHODS Mendelian randomization (MR) analysis employing single nucleotide polymorphisms (SNPs) in the vicinity of the IL6R gene (total individuals = 408225) was used to evaluate the putative causal relationship between IL6R blockade and epilepsy (total cases/controls = 12891/312803), focal epilepsy (cases/controls = 7526/399290), and generalized epilepsy (cases/controls = 1413/399287). SNP weights were determined by their effect on C-reactive protein (CRP) levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects. To address potential outlier and pleiotropic influences, sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions. RESULTS The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk [inverse variance weighting: Odds ratio (OR): 0.827; 95% confidence interval (CI): 0.685-1.000; P = 0.05]. Subtype analysis showed variability, with no significant effect observed in generalized, focal, or specific childhood and juvenile epilepsy forms. Beyond the primary inflammatory marker CRP, the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy, hinting at possible links to neuroinflammation, psychiatric symptoms, and associated mental disorders. CONCLUSION The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence, likely mediated via complex neuroinflammatory pathways. These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy. The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.
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Affiliation(s)
- Yan-Mei Yu
- Department of Pediatrics, The First People's Hospital of Chuzhou, Chuzhou 239001, Anhui Province, China
| | - Gui-Hong Jin
- Department of Pediatrics, The First People's Hospital of Chuzhou, Chuzhou 239001, Anhui Province, China
| | - Chong Zhong
- Department of Pediatrics, The First People's Hospital of Chuzhou, Chuzhou 239001, Anhui Province, China
| | - Hao Qian
- Department of Pediatrics, The First People's Hospital of Chuzhou, Chuzhou 239001, Anhui Province, China
| | - Lei Wang
- Department of Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325000, Zhejiang Province, China
| | - Feng Zhan
- Department of Pediatrics, The First People's Hospital of Chuzhou, Chuzhou 239001, Anhui Province, China
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12
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Struck AF, Garcia-Ramos C, Nair VA, Prabhakaran V, Dabbs K, Conant LL, Binder JR, Loring D, Meyerand M, Hermann BP. The relevance of Spearman's g for epilepsy. Brain Commun 2024; 6:fcae176. [PMID: 38883806 PMCID: PMC11179110 DOI: 10.1093/braincomms/fcae176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 04/18/2024] [Accepted: 06/10/2024] [Indexed: 06/18/2024] Open
Abstract
Whilst the concept of a general mental factor known as 'g' has been of longstanding interest, for unknown reasons, it has never been interrogated in epilepsy despite the 100+ year empirical history of the neuropsychology of epilepsy. This investigation seeks to identify g within a comprehensive neuropsychological data set and compare participants with temporal lobe epilepsy to controls, characterize the discriminatory power of g compared with domain-specific cognitive metrics, explore the association of g with clinical epilepsy and sociodemographic variables and identify the structural and network properties associated with g in epilepsy. Participants included 110 temporal lobe epilepsy patients and 79 healthy controls between the ages of 19 and 60. Participants underwent neuropsychological assessment, clinical interview and structural and functional imaging. Cognitive data were subjected to factor analysis to identify g and compare the group of patients with control participants. The relative power of g compared with domain-specific tests was interrogated, clinical and sociodemographic variables were examined for their relationship with g, and structural and functional images were assessed using traditional regional volumetrics, cortical surface features and network analytics. Findings indicate (i) significantly (P < 0.005) lower g in patients compared with controls; (ii) g is at least as powerful as individual cognitive domain-specific metrics and other analytic approaches to discriminating patients from control participants; (iii) lower g was associated with earlier age of onset and medication use, greater number of antiseizure medications and longer epilepsy duration (Ps < 0.04); and lower parental and personal education and greater neighbourhood deprivation (Ps < 0.012); and (iv) amongst patients, lower g was linked to decreased total intracranial volume (P = 0.019), age and intracranial volume adjusted total tissue volume (P = 0.019) and age and intracranial volume adjusted total corpus callosum volume (P = 0.012)-particularly posterior, mid-posterior and anterior (Ps < 0.022) regions. Cortical vertex analyses showed lower g to be associated specifically with decreased gyrification in bilateral medial orbitofrontal regions. Network analysis of resting-state data with focus on the participation coefficient showed g to be associated with the superior parietal network. Spearman's g is reduced in patients, has considerable discriminatory power compared with domain-specific metrics and is linked to a multiplex of factors related to brain (size, connectivity and frontoparietal networks), environment (familial and personal education and neighbourhood disadvantage) and disease (epilepsy onset, treatment and duration). Greater attention to contemporary models of human cognition is warranted in order to advance the neuropsychology of epilepsy.
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Affiliation(s)
- Aaron F Struck
- Department of Neurology, University of Wisconsin–Madison, Madison, WI 53726, USA
- Department of Neurology, William S. Middleton Veterans Administration Hospital, Madison, WI 53705, USA
| | - Camille Garcia-Ramos
- Department of Neurology, University of Wisconsin–Madison, Madison, WI 53726, USA
| | - Veena A Nair
- Department of Radiology, University of Wisconsin–Madison, Madison, WI 53726, USA
| | - Vivek Prabhakaran
- Department of Radiology, University of Wisconsin–Madison, Madison, WI 53726, USA
| | - Kevin Dabbs
- Department of Neurology, University of Wisconsin–Madison, Madison, WI 53726, USA
| | - Lisa L Conant
- Department of Neurology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Jeffrey R Binder
- Department of Neurology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - David Loring
- Department of Neurology and Pediatrics, Emory University, Atlanta, GA 30322, USA
| | - Mary Meyerand
- Department of Medical Physics, Wisconsin-Madison, Madison, WI 53726, USA
| | - Bruce P Hermann
- Department of Neurology, University of Wisconsin–Madison, Madison, WI 53726, USA
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13
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Paramonova AI, Lysova KD, Timechko EE, Senchenko GV, Sapronova MR, Dmitrenko DV. Cognitive impairment in childhood-onset epilepsy. EPILEPSY AND PAROXYSMAL CONDITIONS 2024; 16:54-68. [DOI: 10.17749/2077-8333/epi.par.con.2024.176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
In pediatric practice, epilepsy holds one of the leading places among neurological pathologies. Along with seizures, a child's intellectual impairment lowering quality of life plays a crucial role in social disintegration. Cognitive impairments occuring in idiopathic generalized epilepsies (IGE) and self-limited epilepsy with centrotemporal spikes (SeLECTS) considered benign have been widely investigated. However, available data suggest that such disorders result in multiple persistent alterations in the cognitive sphere. In this case, features of the epilepsy etiopathogenesis account for disease early onset and profoundly remodeled structures involved in the implementation of cognitive functions. Current review is aimed to summarizing data regarding developmental mechanisms and range of cognitive impairment in IGE and SeLECTS.
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Affiliation(s)
| | - K. D. Lysova
- Voino-Yasenetsky Krasnoyarsk State Medical University
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14
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Joplin S, Gascoigne M, Barton B, Webster R, Gill D, Lawson J, Mandalis A, Sabaz M, McLean S, Gonzalez L, Smith ML, Lah S. Repeat testing enhances long-term verbal memory in children with epilepsy. Child Neuropsychol 2024; 30:425-443. [PMID: 37144751 DOI: 10.1080/09297049.2023.2205633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 04/14/2023] [Indexed: 05/06/2023]
Abstract
To (i) determine whether accelerated long-term forgetting (ALF) can be found using standardized verbal memory test materials in children with genetic generalized epilepsy (GGE) and temporal lobe epilepsy (TLE), and (ii) to establish whether ALF is impacted by executive skills and repeat testing over long delays. One hundred and twenty-three children aged 8 to 16, (28 with GGE, 23 with TLE, and 72 typically developing; TD) completed a battery of standardized tests assessing executive functioning and memory for two stories. Stories were recalled immediately and after a 30-min delay. To examine whether repeat testing impacts long-term forgetting, one story was tested via free recall at 1-day and 2-weeks, and the other at 2-weeks only. Recognition was then tested for both stories at 2-weeks. Children with epilepsy recalled fewer story details, both immediately and after 30-min relative to TD children. Compared to TD children, the GGE group, but not the TLE group, showed ALF, having significantly poorer recall of the story tested only at the longest delay. Poor executive skills were significantly correlated with ALF for children with epilepsy. Standard story memory materials can detect ALF in children with epilepsy when administered over long delays. Our findings suggest that (i) ALF is related to poor executive skills in children with epilepsy, and (ii) repeated testing may ameliorate ALF in some children.
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Affiliation(s)
- Samantha Joplin
- School of Psychology, The University of Sydney, Camperdown, NSW, Australia
| | - Michael Gascoigne
- School of Psychology and Translational Health Research Institute, Western Sydney University, Sydney, NSW, Australia
| | - Belinda Barton
- Faculty of Health, Discipline of Psychology, Southern Cross University, Coffs Harbour, NSW, Australia
| | - Richard Webster
- TY Nelson Department of Neurology, Kids Neuroscience Centre, The Children's Hospital at Westmead, Westmead, NSW, Australia
| | - Deepak Gill
- TY Nelson Department of Neurology, Kids Neuroscience Centre, The Children's Hospital at Westmead, Westmead, NSW, Australia
| | - John Lawson
- Department of Neurology SCHN, School of Women and Children's Health, UNSW, Randwick, NSW, Australia
| | - Anna Mandalis
- Department of Psychology, Sydney Children's Hospital, Randwick, NSW, Australia
| | - Mark Sabaz
- Department of Psychology, Sydney Children's Hospital, Randwick, NSW, Australia
| | - Samantha McLean
- TY Nelson Department of Neurology, The Children's Hospital at Westmead, Sydney, NSW, Australia
| | - Linda Gonzalez
- Brain and Mind, Murdoch Children's Research Institute, Melbourne, VIC, Australia
| | - Mary-Lou Smith
- Department of Psychology, University of Toronto Mississauga and Neurosciences and Mental Health Program, The Hospital for Sick Children, Toronto, ON, Canada
| | - Suncica Lah
- School of Psychology, The University of Sydney, Camperdown, NSW, Australia
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15
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Puteikis K, Wolf P, Mameniškienė R. Longer-term verbal and visual memory patterns in patients with temporal lobe and genetic generalized epilepsies. Epilepsia Open 2023; 8:1279-1287. [PMID: 37381720 PMCID: PMC10690666 DOI: 10.1002/epi4.12779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 06/24/2023] [Indexed: 06/30/2023] Open
Abstract
OBJECTIVE To compare forgetting patterns between patients with temporal lobe (TLE) and generalized (GGE) epilepsies and to assess whether recall is associated with epileptic activity. METHODS Thirty-three patients with TLE (13 left, 17 right, and 3 nonlateralized TLE), 42 patients with GGE, and 57 healthy controls (HCs) were asked to recall words, verbal story material, and the Rey-Osterrieth complex figure at two delays. Accelerated long-term forgetting (ALF) was defined by group performance comparable to HCs at 30 min and worse recall than HCs after 4 weeks. ALF was assessed by comparing raw test scores in a two-way repeated measures analysis of variance (ANOVA) adjusted for the learning capacity. RESULTS Compared to HCs, patients with R-TLE remembered fewer items of the word list after 30 min as well as after 4 weeks. Patients with L-TLE and GGE had comparable learning-adjusted performance to HCs at the 30 min delay but scored less after 4 weeks (group by delay interaction F(3, 124) = 3.2, P = 0.026,η p 2 = 0.07). The epilepsy group (patients with TLE and GGE combined) performed as well as HCs at 30 min but worse after 4 weeks irrespective of experienced seizures during the 4-week delay or interictal bilateral (TLE) or generalized (GGE) activity before the study. We noted no statistically significant differences between patient and HC verbal story (group by delay interaction F(3, 124) = 0.7, P = 0.570,η p 2 = 0.02) or complex figure (F(3, 124) = 0.8, P = 0.488,η p 2 = 0.02) recall. SIGNIFICANCE Our data support verbal and visual memory impairment in both TLE and GGE with different performances between these groups in the task of word recall. We suggest the presence of ALF in patients with GGE and left TLE after adjusting for learning capacity. We could not confirm the influence of epileptic activity on long-term forgetting patterns. Future studies are required to better define domain-specific differences in memory impairment in TLE and GGE.
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Affiliation(s)
| | - Peter Wolf
- Center for NeurologyVilnius UniversityVilniusLithuania
- Danish Epilepsy Center FiladelfiaDianalundDenmark
- Postgraduation Program of Medical SciencesSanta Catarina Federal UniversityFlorianópolisBrazil
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16
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Oyegbile-Chidi T, Harvey D, Dunn D, Jones J, Byars A, Fastenau P, Austin J, Hermann B. The Impact of Sociodemographic Disadvantage on Cognitive Outcomes in Children With Newly Diagnosed Seizures and Their Unaffected Siblings Over 36 Months. Pediatr Neurol 2023; 148:178-188. [PMID: 37742443 PMCID: PMC11972614 DOI: 10.1016/j.pediatrneurol.2023.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 07/25/2023] [Accepted: 08/19/2023] [Indexed: 09/26/2023]
Abstract
BACKGROUND Accumulating evidence indicates that children with newly diagnosed epilepsy have comorbidities including cognitive challenges. Research investigating comorbidities has focused on clinical epilepsy characteristics and neurobiological/genetic correlates. The role that sociodemographic disadvantage (SD) may play has received less attention. We investigated the role of SD in cognitive status in youth with newly diagnosed epilepsy over a follow-up of 36 months to determine the degree, extent, and duration of the role of disadvantage. METHODS A total of 289 children (six to 16 years) within six weeks of their first seizure along with 167 siblings underwent comprehensive neuropsychological assessments (intelligence, language, memory, executive function, processing speed, and academic achievement) at baseline, 18 months later, and at 36 months from baseline. Baseline demographic information (race, caregivers education, household income, and parental marital status), clinical epilepsy characteristics (e.g., age of onset), and magnetic resonance imaging (MRI) and electroencephalographic (EEG) information was collected. RESULTS An SD index was computed for each family and categorized into four groups by level of disadvantage. In children and siblings, the least disadvantaged group exhibited the highest Full-Scale IQ, neuropsychological factor scores, and academic performances, whereas the most disadvantaged showed the polar opposite with the worst performances across all tests. Findings remained stable and significant over 36 months. Linear regression analyses indicated that disadvantage was a more constant and stable predictor of cognitive and academic performance over time compared with clinical epilepsy characteristics and MRI/EEG abnormalities. CONCLUSIONS This study indicates the strong association between SD and cognitive/academic performance in children with newly diagnosed epilepsy and their siblings is significant and predictive of three-year cognitive outcomes.
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Affiliation(s)
| | - Danielle Harvey
- Department of Public Health Sciences, University of California Davis, Sacramento, California
| | - David Dunn
- Departments of Psychiatry and Neurology, Indiana University, Indianapolis, Indiana
| | - Jana Jones
- Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Anna Byars
- Department of Pediatrics, Cincinnati Children's Hospital at the University of Cincinnati, Cincinnati, Ohio
| | - Philip Fastenau
- Department of Neurology, University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Joan Austin
- Distinguished Professor Emerita, School of Nursing, Indiana University, Indianapolis, Indiana
| | - Bruce Hermann
- Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
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17
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Puteikis K, Jakonienė A, Jasionis A, Wolf P, Mameniškienė R. Rehabilitation of cognition and psychosocial well-being - a better life with epilepsy (ReCaP-ABLE): a protocol for a randomized waitlist-controlled trial. Front Neurol 2023; 14:1273550. [PMID: 37965169 PMCID: PMC10641769 DOI: 10.3389/fneur.2023.1273550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Accepted: 10/11/2023] [Indexed: 11/16/2023] Open
Abstract
Despite advances in the understanding of cognitive dysfunction among people with epilepsy (PWE), evidence for cognitive rehabilitation in epilepsy (CoRE) remains scarce. We present the protocol of a randomized waitlist-controlled trial (ClinicalTrials.gov ID NCT05934786) of a psychological-behavioral intervention aiming to ameliorate quality of life as well as cognitive functioning in a mixed PWE sample. The study is set at Vilnius University Hospital Santaros Klinikos and will offer adult PWE six individual and two group sessions led by a certified psychologist and directed toward improving memory, attention, self-regulation, mood and quality of life. The trial is expected to address major gaps in the literature by providing novel evidence on the effectiveness of CoRE in patients with genetic generalized epilepsies, the importance of epilepsy-specific factors for the response to CoRE, the impact of CoRE on long-term memory as well as its maintenance effects.
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Affiliation(s)
| | - Asta Jakonienė
- Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Arminas Jasionis
- Center for Neurology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Peter Wolf
- Center for Neurology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
- Danish Epilepsy Center Filadelfia, Dianalund, Denmark
- Postgraduation Programme in Clinical Medicine, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - Rūta Mameniškienė
- Center for Neurology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
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18
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Jeppesen JM, Sandvei CM, Beier CP, Gesche J. Neuropsychological profile and drug treatment response in Idiopathic Generalized Epilepsy. Seizure 2023; 109:12-17. [PMID: 37178660 DOI: 10.1016/j.seizure.2023.04.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 04/26/2023] [Accepted: 04/28/2023] [Indexed: 05/15/2023] Open
Abstract
PURPOSE The endophenotype of Idiopathic Generalized Epilepsies (IGE) comprises distinct neuropsychological deficits compared to normal controls. It is unknown if the severity of features of the endophenotype correlates with resistance to anti-seizure medication. Therefore, we here studied the association of neuropsychological profiles with treatment response. METHODS We evaluated 106 Danish patients aged ≥18 and diagnosed with IGE using a neuropsychological test battery comprising tests for executive dysfunction, visual attention, episodic memory, and verbal comprehension. Tests were complemented by the Purdue Pegboard test. Patients with suspected ongoing psychogenic non-epileptic seizures were excluded. RESULTS At testing, 72 patients were seizure free, and 34 patients had recent seizures despite anti-seizure medication. As compared to age corrected Danish normative values, IGE patients showed significant impairments in semantic fluency and performed significantly worse in the Purdue Pegboard test. The vocabulary subtest of the WAIS-IV suggested lower verbal comprehension in IGE patients. We found no signs of memory impairment. Comparisons between results of the test battery, drug resistance, and the different IGE subsyndromes revealed consistent null-associations in various predefined and exploratory univariate and multivariate analyses. CONCLUSION We here found and confirmed the distinct neuropsychological profile comprising impaired executive functions, reduced psychomotor speed, and normal memory previously described in juvenile myoclonic epilepsy. This profile was, however, not restricted to juvenile myoclonic epilepsy but equally affected all IGE patients. The neuropsychological deficits were not significantly associated with drug treatment outcome.
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Affiliation(s)
| | | | - Christoph P Beier
- Department of Neurology, Odense University Hospital, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; OPEN - Open Patient Data Explorative Network, Odense, Denmark.
| | - Joanna Gesche
- Department of Neurology, Odense University Hospital, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
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19
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Javurkova A, Zivnustka M, Brezinova T, Raudenska J, Zarubova J, Marusic P. Neurocognitive profile in patients with idiopathic generalized epilepsies: Differences between patients, their biological siblings, and healthy controls. Epilepsy Behav 2023; 142:109204. [PMID: 37086591 DOI: 10.1016/j.yebeh.2023.109204] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 03/25/2023] [Accepted: 03/26/2023] [Indexed: 04/24/2023]
Abstract
BACKGROUND Idiopathic generalized epilepsy (IGE) is one of the most common epilepsies and is believed to have a strong genetic origin. Patients with IGE present largely heterogeneous neurocognitive profiles and might show some neurocognitive impairments. Furthermore, IGE siblings may demonstrate worse results in neuropsychological tests as well. In our study, we aimed to map the neurocognitive profile both in patients with IGE and the siblings. We also sought to establish a neurocognitive profile for each IGE syndrome. METHODS The research sample included 110 subjects (IGE n = 46, biological siblings BS n = 16, and healthy controls n = 48) examined. Subjects were neuropsychologically examined in domains of intelligence, attention, memory, executive, and motor functions. The data obtained from the examination were statistically processed to determine whether and how IGE patients (including distinct syndromes) and the siblings differed neurocognitively from healthy controls (adjusted z-scores by age, education, and gender, and composite z-scores of cognitive domains). Data on anti-seizure medication, including defined daily doses, were obtained and included in the analysis. RESULTS IGE patients and their biological siblings performed significantly worse in most of the neuropsychological tests than healthy controls. The neurocognitive profile of composite z-scores showed that IGE and biological siblings had equally significantly impaired performance in executive functions. IGE group also demonstrated impaired composite attention and motor function scores. The profile of individual IGE syndromes showed that JAE, JME, and EGTCS had significantly worse performance in composite execution score and motor function score. JAE presented significantly worse performance in intelligence and attention. JME exhibited significantly worse composite score in the attention domain. Anti-seizure medication, depression, and quality of life were unrelated to cognitive performance in IGE group. The level of depression significantly predicted the overall value of quality of life in patients with IGE, while cognitive domains, sociodemographic, and clinical factors were unrelated. CONCLUSION Our study highlights the importance to consider the neurocognitive profile of IGE patients that can lead to difficulties in their education, acceptance, and management of coping strategies. Cognitive difficulties of IGE siblings could support a hypothesis that these impairments emerge from heritable traits.
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Affiliation(s)
- A Javurkova
- Department of Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic; Department of Nursing, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
| | - M Zivnustka
- Department of Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
| | - T Brezinova
- Department of Clinical Neuropsychology, University of Groningen, Netherlands.
| | - J Raudenska
- Department of Nursing, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
| | - J Zarubova
- Department of Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
| | - P Marusic
- Department of Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
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Daker LI, Sayed SS, Abdelghaffar M, Hamed AH, Aboelnor MI, El-Khatib MES. Could thalamic biochemical changes correlate to cognitive impairment in idiopathic generalized epilepsy? THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2023. [DOI: 10.1186/s41983-023-00638-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/17/2023] Open
Abstract
Abstract
Background
The thalamus is crucial in the development of idiopathic generalized epilepsy (IGE), which could lead to cognitive dysfunctions, according to data from neuropsychology and advanced neuroimaging investigations. This research aimed to measure the metabolic changes in the thalamus and to assess if could be contributed to cognitive impairment in IGE patients. Thirty IGE patients and thirty healthy volunteers with matched ages, genders, and educational levels participated in this cross-sectional case–control research. The IGE patients and controls were evaluated neuropsychologically using Intelligence Quotient (IQ) to assess general cognitive ability, Digit span for attention, Wechsler memory scale (WMS) for verbal memory, cube drawing test for visuospatial memory, Trail making test for executive functions, and Controlled Oral Word Association test (COWAT) for verbal fluency and quantitative multi-voxel MR spectroscopy (MRS) measurements of N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), NAA/Cr, NAA/Cho and Cho/Cr ratios at 1.5 T scanner. The voxels were located over the right and left thalamus.
Results
The IGE patients showed worse cognitive performance in IQ, attention, executive function, and verbal and visuospatial memory domains compared to the controls. The IGE patients exhibited a significantly decrease NAA in the right thalamus (p = 0.004) and a lower NAA/Cr ratio in the left thalamus (p = 0.01). the mean thalamus NAA level exhibited a positive correlation with CDT (r = 0.45, p = P = 0.01), and WMS-R (r = 0.39, p = 0.03) and a negative correlation with trail-making A test (r = 0.42, P = 0.01).
Conclusions
it was concluded that IGE patients exhibited poor cognition which could be attributed to thalamic neurometabolic changes due to impaired thalamic cortical circuits.
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Dharan AL, Bowden SC, Peterson A, Lai A, Seneviratne U, Dabscheck G, Nurse E, Loughman A, Parsons N, D'Souza WJ. A cross-sectional investigation of cognition and epileptiform discharges in juvenile absence epilepsy. Epilepsia 2023; 64:742-753. [PMID: 36625418 DOI: 10.1111/epi.17505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 12/21/2022] [Accepted: 01/06/2023] [Indexed: 01/11/2023]
Abstract
OBJECTIVES Despite the prevalence of cognitive symptoms in the idiopathic generalized epilepsies (IGEs), cognitive dysfunction in juvenile absence epilepsy (JAE), a common yet understudied IGE subtype, remains poorly understood. This descriptive study provides a novel, comprehensive characterization of cognitive functioning in a JAE sample and examines the relationship between cognition and 24-h epileptiform discharge load. METHOD Forty-four individuals diagnosed with JAE underwent cognitive assessment using Woodcock Johnson III Test of Cognitive Abilities with concurrent 24-h ambulatory EEG monitoring. Generalized epileptiform discharges of any length, and prolonged generalized discharges ≥3 s were quantified across wakefulness and sleep. The relationship between standardized cognitive scores and epileptiform discharges was assessed through regression models. RESULTS Cognitive performances in overall intellectual ability, acquired comprehension-knowledge, processing speed, long-term memory storage and retrieval, and executive processes were 0.63-1.07 standard deviation (SD) units lower in the JAE group compared to the population reference mean, adjusted for educational attainment. Prolonged discharges (≥3 s) were recorded in 20 patients (47.6%) from 42 available electroencephalography (EEG) studies and were largely unreported. Duration and number of prolonged discharges were associated with reduced processing speed and long-term memory storage and retrieval. SIGNIFICANCE Cognitive dysfunction is seen in patients with JAE across various cognitive abilities, including those representing more stable processes like general intellect. During 24-h EEG, prolonged epileptiform discharges are common yet underreported in JAE despite treatment, and they show moderate effects on cognitive abilities. If epileptiform burden is a modifiable predictor of cognitive dysfunction, therapeutic interventions should consider quantitative 24-h EEG with routine neuropsychological screening. The growing recognition of the spectrum of neuropsychological comorbidities of IGE highlights the value of multidisciplinary approaches to explore the causes and consequences of cognitive deficits in epilepsy.
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Affiliation(s)
- Anita L Dharan
- Melbourne School of Psychological Sciences, The University of Melbourne, Melbourne, Victoria, Australia
| | - Stephen C Bowden
- Melbourne School of Psychological Sciences, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Neuroscience, St. Vincent's Hospital, The University of Melbourne, Melbourne, Victoria, Australia
| | - Andre Peterson
- Department of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria, Australia
| | - Alan Lai
- Department of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria, Australia
| | - Udaya Seneviratne
- Department of Neuroscience, St. Vincent's Hospital, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Neuroscience, Monash Medical Centre Clayton, Melbourne, Victoria, Australia
| | - Gabriel Dabscheck
- Department of Neurology, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia
- Neurosciences, Murdoch Childrens Research Institute, Parkville, Victoria, Australia
| | - Ewan Nurse
- Seer Medical Inc Research, Melbourne, Victoria, Australia
| | - Amy Loughman
- Food & Mood Centre, Institute of Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Victoria, Australia
| | - Nicholas Parsons
- Deakin University, Cognitive Neuroscience Unit, School of Psychology, Melbourne, Victoria, Australia
| | - Wendyl J D'Souza
- Department of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria, Australia
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22
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Heerwig C, Möller H, Brückner K. Neuropsychology of epilepsy in old age – English Version. ZEITSCHRIFT FÜR EPILEPTOLOGIE 2022. [DOI: 10.1007/s10309-022-00479-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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23
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Patrikelis P, Giovagnoli AR, Messinis L, Fasilis T, Malefaki S, Verentzioti A, Stefanatou M, Alexoudi A, Korfias S, Mitsikostas DD, Kimiskidis V, Gatzonis S. Understanding frontal lobe function in epilepsy: Juvenile myoclonic epilepsy vs. frontal lobe epilepsy. Epilepsy Behav 2022; 134:108850. [PMID: 35933958 DOI: 10.1016/j.yebeh.2022.108850] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 06/27/2022] [Accepted: 07/08/2022] [Indexed: 11/16/2022]
Abstract
AIM To compare neuropsychological function in juvenile myoclonic epilepsy (JME) and frontal lobe epilepsy (FLE) since frontal circuitry is involved in both conditions. By drawing on previously theory-guided hypotheses and findings, a particular emphasis is placed on the way different cognitive-pathophysiological mechanisms act upon to produce frontal dysfunction in JME (frontal-executive and attention-related problems: vigilance, reaction times, processing speed, and response inhibition) and in FLE (reflecting the coproduct of the functional deficit zone), respectively. METHODS A total of 16 patients with JME, 34 patients with FLE, and 48 normal controls, all matched for age and education, were administered a comprehensive battery of tests to assess frontal-executive functions, as well as attention, memory, and learning domains. Participants did not take medications other than antiepileptics or have a psychiatric history. RESULTS Patients with FLE overall showed worse neuropsychological performance compared to both JME and HCs. With respect to JME, patients with FLE did significantly worse in measures of verbal and nonverbal executive function, short-term-, and long-term- auditory-verbal memory and learning, immediate and delayed episodic recall, visual attention and motor function, visuo-motor coordination and psychomotor speed, speed of visual information processing, and vocabulary. Patients with JME performed significantly worse compared to FLE only in associative semantic processing, while the former outperformed all groups in vocabulary, visuomotor coordination, and psychomotor speed. CONCLUSION We suggest that selective impairments of visual- and mostly auditory-speed of information processing, vigilance, and response inhibition may represent a salient neuropsychological feature in JME. These findings suggest the existence of an aberrantly working executive-attention system, secondary to pathological reticulo-thalamo-cortical dynamics. Contrariwise, cortically (frontal and extra-frontal) and subcortically induced malfunction in FLE is determined by the functional deficit zone i.e., the ensemble of cortical and subcortical areas that are functionally abnormal between seizures.
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Affiliation(s)
- Panayiotis Patrikelis
- 1st Department of Neurosurgery, National & Kapodistrian University of Athens, Greece; Laboratory of Cognitive Neuroscience, Department of Psychology, Aristotle University of Thessaloniki, Greece.
| | - Anna-Rita Giovagnoli
- Laboratory of Cognitive Behavioral Neurology, Neurology and Neuropathology Unit, Department of Diagnostics and Technology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
| | - Lambros Messinis
- Laboratory of Cognitive Neuroscience, Department of Psychology, Aristotle University of Thessaloniki, Greece
| | - Theodoros Fasilis
- 1st Department of Neurosurgery, National & Kapodistrian University of Athens, Greece
| | - Sonia Malefaki
- Department of Mechanical Engineering and Aeronautics, University of Patras School of Engineering, Rio Patras, Greece
| | - Anastasia Verentzioti
- 1st Department of Neurosurgery, National & Kapodistrian University of Athens, Greece
| | - Maria Stefanatou
- 1st Department of Neurosurgery, National & Kapodistrian University of Athens, Greece
| | - Athanasia Alexoudi
- 1st Department of Neurosurgery, National & Kapodistrian University of Athens, Greece
| | - Stefanos Korfias
- 1st Department of Neurosurgery, National & Kapodistrian University of Athens, Greece
| | - Dimos D Mitsikostas
- 1st Neurology Department, Aeginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
| | - Vasileios Kimiskidis
- 1st Department of Neurology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Stylianos Gatzonis
- 1st Department of Neurosurgery, National & Kapodistrian University of Athens, Greece
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24
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Lehner J, Frueh JS, Datta AN. Sleep quality and architecture in Idiopathic generalized epilepsy: A systematic review and meta-analysis. Sleep Med Rev 2022; 65:101689. [PMID: 36037570 DOI: 10.1016/j.smrv.2022.101689] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 08/07/2022] [Accepted: 08/09/2022] [Indexed: 11/16/2022]
Abstract
Idiopathic generalized epilepsies are a group of sleep related epilepsy syndromes with sleep deprivation as a strong trigger for seizures and increased spike-wave activity during sleep and transition to sleep. Neuropsychological deficits are common in Idiopathic generalized epilepsy patients. Learning and memory processes are closely linked to sleep. Therefore, this systematic review and meta-analysis investigates the evidence of sleep disturbances in Idiopathic generalized epilepsy patients. A search of the databases EMBASE, Medline and Scopus identified 22 studies comparing polysomnographic parameters and scores of sleep questionnaires between Idiopathic generalized epilepsy patients and healthy controls. Random effect univariate meta-analyses revealed reduced sleep efficiency, total sleep time, proportion of N2 stage and prolonged REM onset latency in Idiopathic generalized epilepsy patients. Self-assessed sleep quality of patients measured by the Pittsburgh sleep quality index was lower in two thirds of reporting studies. Considering the influence on behavioral issues, cognitive performance and quality of life, the revealed alteration in sleep architecture and lower subjective sleep quality emphasizes the importance of screening for sleep disturbances in the medical care of patients with Idiopathic generalized epilepsy.
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Affiliation(s)
- Julia Lehner
- Department of Pediatric Neurology and Developmental Medicine, University Children's Hospital Basel UKBB, Basel, Switzerland
| | - Julia S Frueh
- Department of Pediatric Neurology, Boston Children's Hospital, Boston, MA, United States of America
| | - Alexandre N Datta
- Department of Pediatric Neurology and Developmental Medicine, University Children's Hospital Basel UKBB, Basel, Switzerland.
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25
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School performance and psychiatric comorbidity in juvenile absence epilepsy and juvenile myoclonic epilepsy: a Danish population-based cohort study. J Neurol 2022; 269:4997-5007. [PMID: 35595971 DOI: 10.1007/s00415-022-11147-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 04/17/2022] [Accepted: 04/18/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND We aimed to determine school performance and psychiatric comorbidity in juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and generalized tonic-clonic seizures (GTCS) alone. METHODS All children (< 18 years) fulfilled International League Against Epilepsy criteria after review of their medical records. Control groups were the pediatric background population or children with non-neurological chronic disease. Outcomes were on school performance and psychiatric comorbidity. We compared mean grade point averages using linear regression and estimated hazard ratios using Cox regression in the remaining analyses. We adjusted for the child's sex, age, and year of birth; and parental highest education, receipt of cash benefits or early retirement. RESULTS We included 92 JAE, 190 JME, 27 GTCS alone, 15,084 non-neurological chronic disease controls, and population controls. JAE had two times increased hazard for special needs education compared with age-matched population controls (hazard ratio 2.2, 95% CI = 1.1‒4.6, p = 0.03); this was not seen in JME. Compared with population controls, both JAE and JME had lower grade point average in secondary and high school (JME: 9th grade: - 0.5 points, 95% CI = -0.9 to -0.06, p = 0.03; high school: - 0.6 points, 95% CI = -1.3 to -0.1, p = 0.04), and 8% fewer JME and 15% fewer JAE attended high school. Both JME and JAE had higher hazard for redeeming sleep medication compared with non-neurological chronic disease; additionally, JAE had increased hazard for ADHD medicine redemptions. CONCLUSIONS Both JAE and JME had marginally poorer school performance; performance seemed worse in JAE than in JME. Both JAE and JME had increased use of sleep medication.
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26
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Rodriguez-Cruces R, Royer J, Larivière S, Bassett DS, Caciagli L, Bernhardt BC. Multimodal connectome biomarkers of cognitive and affective dysfunction in the common epilepsies. Netw Neurosci 2022; 6:320-338. [PMID: 35733426 PMCID: PMC9208009 DOI: 10.1162/netn_a_00237] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 02/02/2022] [Indexed: 11/05/2022] Open
Abstract
Epilepsy is one of the most common chronic neurological conditions, traditionally defined as a disorder of recurrent seizures. Cognitive and affective dysfunction are increasingly recognized as core disease dimensions and can affect patient well-being, sometimes more than the seizures themselves. Connectome-based approaches hold immense promise for revealing mechanisms that contribute to dysfunction and to identify biomarkers. Our review discusses emerging multimodal neuroimaging and connectomics studies that highlight network substrates of cognitive/affective dysfunction in the common epilepsies. We first discuss work in drug-resistant epilepsy syndromes, that is, temporal lobe epilepsy, related to mesiotemporal sclerosis (TLE), and extratemporal epilepsy (ETE), related to malformations of cortical development. While these are traditionally conceptualized as ‘focal’ epilepsies, many patients present with broad structural and functional anomalies. Moreover, the extent of distributed changes contributes to difficulties in multiple cognitive domains as well as affective-behavioral challenges. We also review work in idiopathic generalized epilepsy (IGE), a subset of generalized epilepsy syndromes that involve subcortico-cortical circuits. Overall, neuroimaging and network neuroscience studies point to both shared and syndrome-specific connectome signatures of dysfunction across TLE, ETE, and IGE. Lastly, we point to current gaps in the literature and formulate recommendations for future research. Epilepsy is increasingly recognized as a network disorder characterized by recurrent seizures as well as broad-ranging cognitive difficulties and affective dysfunction. Our manuscript reviews recent literature highlighting brain network substrates of cognitive and affective dysfunction in common epilepsy syndromes, namely temporal lobe epilepsy secondary to mesiotemporal sclerosis, extratemporal epilepsy secondary to malformations of cortical development, and idiopathic generalized epilepsy syndromes arising from subcortico-cortical pathophysiology. We discuss prior work that has indicated both shared and distinct brain network signatures of cognitive and affective dysfunction across the epilepsy spectrum, improves our knowledge of structure-function links and interindividual heterogeneity, and ultimately aids screening and monitoring of therapeutic strategies.
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Affiliation(s)
- Raul Rodriguez-Cruces
- McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
| | - Jessica Royer
- McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
| | - Sara Larivière
- McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
| | - Dani S. Bassett
- Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
- Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, Pennsylvania 19104 USA
- Department of Electrical and Systems Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104 USA
- Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 USA
- Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 USA
| | - Lorenzo Caciagli
- Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
- Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London WC1N 3BG, United Kingdom
| | - Boris C. Bernhardt
- McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
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27
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Vorderwülbecke BJ, Wandschneider B, Weber Y, Holtkamp M. Genetic generalized epilepsies in adults - challenging assumptions and dogmas. Nat Rev Neurol 2022; 18:71-83. [PMID: 34837042 DOI: 10.1038/s41582-021-00583-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/19/2021] [Indexed: 01/16/2023]
Abstract
Genetic generalized epilepsy (GGE) syndromes start during childhood or adolescence, and four commonly persist into adulthood, making up 15-20% of all cases of epilepsy in adults. These four GGE syndromes are childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy and epilepsy with generalized tonic-clonic seizures alone. However, in ~20% of patients with GGE, characteristics of more than one syndrome are present. Novel insights into the genetic aetiology, comorbidities and prognosis of the GGE syndromes have emerged and challenge traditional concepts about these conditions. Evidence has shown that the mode of inheritance in GGE is mostly polygenic. Neuropsychological and imaging studies indicate similar abnormalities in unaffected relatives of patients with GGE, supporting the concept that underlying alterations in bilateral frontothalamocortical networks are genetically determined. Contrary to popular belief, first-line anti-seizure medication often fails to provide seizure freedom in combination with good tolerability. Nevertheless, long-term follow-up studies have shown that with advancing age, many patients can discontinue their anti-seizure medication without seizure relapses. Several outcome predictors have been identified, but prognosis across the syndromes is more homogeneous than previously assumed. Overall, overlap in pathophysiology, seizure types, treatment responses and outcomes support the idea that GGEs are not separate nosological entities but represent a neurobiological continuum.
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Affiliation(s)
- Bernd J Vorderwülbecke
- Epilepsy-Center Berlin-Brandenburg, Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- EEG and Epilepsy Unit, University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Britta Wandschneider
- Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK
- Department of Neurology, The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Yvonne Weber
- Department of Epileptology and Neurology, University of Aachen, Aachen, Germany
- Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
| | - Martin Holtkamp
- Epilepsy-Center Berlin-Brandenburg, Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
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28
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Baggio M, Toffoli L, Da Rold M, Duma GM, Mento G, Morao V, Danieli A, Bonanni P. Neuropsychological and behavioral profiles of self-limited epileptic syndromes of childhood: a cross-syndrome comparison. Child Neuropsychol 2022; 28:878-902. [PMID: 35086426 DOI: 10.1080/09297049.2022.2028754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Childhood epilepsy with centro-temporal spikes (CECTS), Childhood absence epilepsy (CAE) and Panayiotopoulos syndrome (PS) are some of the most common pediatric epileptic syndromes. Despite the relatively benign (self-limited) course of epilepsy, current evidence suggests that these conditions are associated with an increased risk of neuropsychological and behavioral comorbidities. This study provides a cross-epileptic syndromes' comparison reporting on the cognitive and behavioral profile of a cohort of 32 children with CECTS (n = 14), CAE (n = 10) and PS (n = 8), aged 6 to 15 years old. Frequent, although often subclinical cognitive difficulties involving attention, executive functions and academic abilities were found in children with CECTS and CAE, and to a lesser extent in PS. Internalizing symptoms (particularly anxiety) were more common in the PS group compared to CECTS and CAE based on parental reports. Correlational analysis revealed a significant correlation between phonemic fluency and seizure-free interval at the time of evaluation, suggesting a beneficial effect of epilepsy remission on this executive function measure in all the three groups. These results add to existing literature providing further detail on neuropsychological and behavioral peculiarities of children with CECTS, CAE, and PS. Moreover, the need for neuropsychological assessment as part of the standard childhood epilepsy evaluation is stressed. The results are discussed in the context of the current literature, highlighting areas of consensus and controversies related to the clinical management of these epileptic syndromes as well as directions for future research.
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Affiliation(s)
- Martina Baggio
- Epilepsy and Clinical Neurophysiology Unit, Irccs "E. Medea," Conegliano, Treviso, Italy
| | - Lisa Toffoli
- Epilepsy and Clinical Neurophysiology Unit, Irccs "E. Medea," Conegliano, Treviso, Italy.,Department of General Psychology, University of Padova, Italy
| | - Martina Da Rold
- Epilepsy and Clinical Neurophysiology Unit, Irccs "E. Medea," Conegliano, Treviso, Italy
| | - Gian Marco Duma
- Epilepsy and Clinical Neurophysiology Unit, Irccs "E. Medea," Conegliano, Treviso, Italy.,Department of General Psychology, University of Padova, Italy
| | - Giovanni Mento
- Epilepsy and Clinical Neurophysiology Unit, Irccs "E. Medea," Conegliano, Treviso, Italy.,Padova Neuroscience Center (PNC), University of Padova, Italy
| | - Veronica Morao
- Epilepsy and Clinical Neurophysiology Unit, Irccs "E. Medea," Conegliano, Treviso, Italy
| | - Alberto Danieli
- Epilepsy and Clinical Neurophysiology Unit, Irccs "E. Medea," Conegliano, Treviso, Italy
| | - Paolo Bonanni
- Epilepsy and Clinical Neurophysiology Unit, Irccs "E. Medea," Conegliano, Treviso, Italy
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29
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Puteikis K, Wolf P, Mameniškienė R. Accelerated long-term forgetting in adult patients with genetic generalized epilepsy. Epilepsia 2021; 63:474-482. [PMID: 34893974 DOI: 10.1111/epi.17144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 11/24/2021] [Accepted: 11/29/2021] [Indexed: 10/19/2022]
Abstract
OBJECTIVE Accelerated long-term forgetting (ALF) has been demonstrated among children but not adults with genetic generalized epilepsy (GGE). We investigated (1) how forgetting patterns of verbal and visuospatial material differ between patients with GGE and healthy controls (HCs) and (2) whether ALF is associated with ictal or interictal epileptic activity. METHODS Forty-two patients with GGE (39, 92.9% experiencing seizures) were compared to 57 HCs in word, logical story, and Rey-Osterrieth complex figure recall tasks by testing after intervals of 30 min and 4 weeks. Ambulatory electroencephalography (EEG) was performed before testing to detect generalized epileptic activity, and patients were asked to document the number of seizures during the 4-week interval. RESULTS A two-way repeated measures ANOVA indicated that individuals with GGE have different forgetting patterns in comparison to HCs in tasks of word (delay by group interaction F1.5, 142.5 = 4.5, p = .02, η p 2 = .04) and figure (F2, 194 = 15.9, p < .001, η p 2 = .14) but not story (F1.6 151.1 = .5, p = .58, η p 2 = .005) recall. Last learning trial-adjusted scores of word recall were comparable between HCs and patients with epilepsy (PWEs) at 30 min (p = .21) but not at 4 weeks (p = .006). Individuals with GGE performed worse than HCs in figure recall at 30 min and 4 weeks (p < .001), with lower performance after the 4-week interval present only among seizure-positive and EEG-positive individuals (p < .001) during subgroup analysis. Performance on memory tests was unrelated to overall seizure frequency, the number of antiseizure drugs used, and epilepsy duration. SIGNIFICANCE Our study supports the presence of ALF in a task of word recall among adult patients with GGE. The pattern of forgetting visuospatial information suggests greater forgetting of material before the first delay and ongoing deficits among PWEs with epileptic activity. Future studies should confirm our findings and investigate the functional or pathological mechanisms of memory dysfunction in GGE.
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Affiliation(s)
| | - Peter Wolf
- Center for Neurology, Vilnius University, Vilnius, Lithuania.,Danish Epilepsy Center Filadelfia, Dianalund, Denmark.,Postgraduation Program of Medical Sciences, Santa Catarina Federal University, Florianópolis, Brazil
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30
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Hermann BP, Struck AF, Busch RM, Reyes A, Kaestner E, McDonald CR. Neurobehavioural comorbidities of epilepsy: towards a network-based precision taxonomy. Nat Rev Neurol 2021; 17:731-746. [PMID: 34552218 PMCID: PMC8900353 DOI: 10.1038/s41582-021-00555-z] [Citation(s) in RCA: 86] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2021] [Indexed: 02/06/2023]
Abstract
Cognitive and behavioural comorbidities are prevalent in childhood and adult epilepsies and impose a substantial human and economic burden. Over the past century, the classic approach to understanding the aetiology and course of these comorbidities has been through the prism of the medical taxonomy of epilepsy, including its causes, course, characteristics and syndromes. Although this 'lesion model' has long served as the organizing paradigm for the field, substantial challenges to this model have accumulated from diverse sources, including neuroimaging, neuropathology, neuropsychology and network science. Advances in patient stratification and phenotyping point towards a new taxonomy for the cognitive and behavioural comorbidities of epilepsy, which reflects the heterogeneity of their clinical presentation and raises the possibility of a precision medicine approach. As we discuss in this Review, these advances are informing the development of a revised aetiological paradigm that incorporates sophisticated neurobiological measures, genomics, comorbid disease, diversity and adversity, and resilience factors. We describe modifiable risk factors that could guide early identification, treatment and, ultimately, prevention of cognitive and broader neurobehavioural comorbidities in epilepsy and propose a road map to guide future research.
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Affiliation(s)
- Bruce P. Hermann
- Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.,
| | - Aaron F. Struck
- Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.,William S. Middleton Veterans Administration Hospital, Madison, WI, USA
| | - Robyn M. Busch
- Epilepsy Center and Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.,Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Anny Reyes
- Department of Psychiatry and Center for Multimodal Imaging and Genetics, University of California, San Diego, San Diego, CA, USA
| | - Erik Kaestner
- Department of Psychiatry and Center for Multimodal Imaging and Genetics, University of California, San Diego, San Diego, CA, USA
| | - Carrie R. McDonald
- Department of Psychiatry and Center for Multimodal Imaging and Genetics, University of California, San Diego, San Diego, CA, USA
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31
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Chen Y, Fallon N, Kreilkamp BAK, Denby C, Bracewell M, Das K, Pegg E, Mohanraj R, Marson AG, Keller SS. Probabilistic mapping of thalamic nuclei and thalamocortical functional connectivity in idiopathic generalised epilepsy. Hum Brain Mapp 2021; 42:5648-5664. [PMID: 34432348 PMCID: PMC8559489 DOI: 10.1002/hbm.25644] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 08/04/2021] [Accepted: 08/16/2021] [Indexed: 02/06/2023] Open
Abstract
It is well established that abnormal thalamocortical systems play an important role in the generation and maintenance of primary generalised seizures. However, it is currently unknown which thalamic nuclei and how nuclear‐specific thalamocortical functional connectivity are differentially impacted in patients with medically refractory and non‐refractory idiopathic generalised epilepsy (IGE). In the present study, we performed structural and resting‐state functional magnetic resonance imaging (MRI) in patients with refractory and non‐refractory IGE, segmented the thalamus into constituent nuclear regions using a probabilistic MRI segmentation method and determined thalamocortical functional connectivity using seed‐to‐voxel connectivity analyses. We report significant volume reduction of the left and right anterior thalamic nuclei only in patients with refractory IGE. Compared to healthy controls, patients with refractory and non‐refractory IGE had significant alterations of functional connectivity between the centromedian nucleus and cortex, but only patients with refractory IGE had altered cortical connectivity with the ventral lateral nuclear group. Patients with refractory IGE had significantly increased functional connectivity between the left and right ventral lateral posterior nuclei and cortical regions compared to patients with non‐refractory IGE. Cortical effects were predominantly located in the frontal lobe. Atrophy of the anterior thalamic nuclei and resting‐state functional hyperconnectivity between ventral lateral nuclei and cerebral cortex may be imaging markers of pharmacoresistance in patients with IGE. These structural and functional abnormalities fit well with the known importance of thalamocortical systems in the generation and maintenance of primary generalised seizures, and the increasing recognition of the importance of limbic pathways in IGE.
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Affiliation(s)
- Yachin Chen
- Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,The Walton Centre NHS Foundation Trust, Liverpool, UK
| | - Nicholas Fallon
- Department of Psychology, University of Liverpool, Liverpool, UK
| | - Barbara A K Kreilkamp
- Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,Department of Neurology, University Medicine Göttingen, Göttingen, Germany
| | | | - Martyn Bracewell
- The Walton Centre NHS Foundation Trust, Liverpool, UK.,Schools of Medical Sciences and Psychology, Bangor University, Bangor, UK
| | - Kumar Das
- The Walton Centre NHS Foundation Trust, Liverpool, UK
| | - Emily Pegg
- Department of Neurology, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK.,Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, UK
| | - Rajiv Mohanraj
- Department of Neurology, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK.,Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, UK
| | - Anthony G Marson
- Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,The Walton Centre NHS Foundation Trust, Liverpool, UK
| | - Simon S Keller
- Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,The Walton Centre NHS Foundation Trust, Liverpool, UK
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Seneviratne U, Cook M, D'Souza W. Brainwaves beyond diagnosis: Wider applications of electroencephalography in idiopathic generalized epilepsy. Epilepsia 2021; 63:22-41. [PMID: 34755907 DOI: 10.1111/epi.17119] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 10/22/2021] [Accepted: 10/25/2021] [Indexed: 11/30/2022]
Abstract
Electroencephalography (EEG) has long been used as a versatile and noninvasive diagnostic tool in epilepsy. With the advent of digital EEG, more advanced applications of EEG have emerged. Compared with technologically advanced practice in focal epilepsies, the utilization of EEG in idiopathic generalized epilepsy (IGE) has been lagging, often restricted to a simple diagnostic tool. In this narrative review, we provide an overview of broader applications of EEG beyond this narrow scope, discussing how the current clinical and research applications of EEG may potentially be extended to IGE. The current literature, although limited, suggests that EEG can be used in syndromic classification, guiding antiseizure medication therapy, predicting prognosis, unraveling biorhythms, and investigating functional brain connectivity of IGE. We emphasize the need for longer recordings, particularly 24-h ambulatory EEG, to capture discharges reflecting circadian and sleep-wake cycle-associated variations for wider EEG applications in IGE. Finally, we highlight the challenges and limitations of the current body of literature and suggest future directions to encourage and enhance more extensive applications of this potent tool.
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Affiliation(s)
- Udaya Seneviratne
- Department of Neuroscience, St. Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia.,Department of Neuroscience, Monash Medical Centre, Melbourne, Victoria, Australia
| | - Mark Cook
- Department of Neuroscience, St. Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia
| | - Wendyl D'Souza
- Department of Neuroscience, St. Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia
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Guerrero-Molina MP, Rodriguez-López C, Panadés-de Oliveira L, Uriarte-Pérez de Urabayen D, Garzo-Caldas N, García-Cena CE, Saiz-Díaz RA, Benito-León J, Gonzalez de la Aleja J. Antisaccades and memory-guided saccades in genetic generalized epilepsy and temporal lobe epilepsy. Epilepsy Behav 2021; 123:108236. [PMID: 34419714 DOI: 10.1016/j.yebeh.2021.108236] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 07/22/2021] [Accepted: 07/24/2021] [Indexed: 11/15/2022]
Abstract
OBJECTIVE Oculomotor tasks can be used to measure volitional control of behavior sensitive to frontal dysfunction. This study aimed to examine the saccadic eye movement in Genetic Generalized Epilepsy (GGE) which could correlate with the abnormality of the frontal lobe or the thalamo-frontal network. METHODS Twenty-one patients with GGE were compared with 22 patients with Temporal Lobe Epilepsy (TLE) and 39 healthy controls. Visual-guided saccades, Antisaccades, and Memory-guided saccades as oculomotor tasks were performed using a novel gaze-tracker designed for clinical practice use. RESULTS Patients with epilepsy (either GEE or TLE) had similar latency, accuracy, and velocity in visual-guided saccades and memory-guided saccades. Patients with epilepsy had similar latencies and correct antisaccade number. However, healthy volunteers, matched by age, had faster responses and more accurate results than patients with epilepsy. CONCLUSIONS Our investigations did not reveal differences between TLE and GGE patients' groups in visually guided saccades, antisaccades, and memory-guided saccades, thus suggesting that the frontal cortical mechanisms responsible for them are not explicitly impaired in patients with GGE.
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Affiliation(s)
| | | | | | | | | | - Cecilia E García-Cena
- Centre for Automation and Robotics, Universidad Politécnica de Madrid, 28012 Madrid, Spain.
| | - Rosa A Saiz-Díaz
- 12th of October University Hospital, Avenida Córdoba S/N, 28041 Madrid, Spain
| | - Julián Benito-León
- 12th of October University Hospital, Avenida Córdoba S/N, 28041 Madrid, Spain
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Sager G, Vatansever Z, Batu U, Çağ Y, Akin Y. Neuropsychiatric comorbidities in genetic/idiopathic generalized epilepsies and their effects on psychosocial outcomes. Epilepsy Behav 2021; 124:108339. [PMID: 34600282 DOI: 10.1016/j.yebeh.2021.108339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 09/08/2021] [Accepted: 09/12/2021] [Indexed: 11/18/2022]
Abstract
INTRODUCTION Idiopathic/genetic generalized epilepsy (GGE) accounts for 15-20% of all epilepsy cases. Neuropsychiatric comorbidities and disorders, such as attention-deficit hyperactivity disorder (ADHD), academic failure, and poor social competence, are present at a higher rate in patients with epilepsy compared with the general population. In this study, we aimed to determine the frequency of neuropsychiatric comorbidities in GGE subgroups, and to reveal the risk factors in the patient group with neuropsychiatric comorbidities. MATERIAL AND METHOD This hospital-based, cross-sectional study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Patients with seizure-controlled GGE were invited to a semi-structured interview at the hospital. Variables [photosensitivity, valproic acid (VPA) resistance, timing of the neuropsychiatric comorbidities Attention deficit and hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and low academic performance), seizure control, and timing of the antiepileptic treatment] were statistically analyzed and evaluated in terms of their association with GGE subgroups [Generalized tonic-clonic seizures alone (EGTGS), juvenile myoclonic epilepsy (JME), and juvenile absence epilepsy (JAE)], RESULTS: Total 101 patients with GGE were included in the study and the mean age was 13.94 ± 1.66 years. A total of 12.9% (n = 13) of the patients had EGTGS, 49.5% (n = 50) had JME, and 37.6% (n = 38) had JAE. VPA resistance, photosensitivity, and the presence of neuropsychiatric symptoms before the starting of epilepsy were found to be risk factors in the GGE group with neuropsychiatric comorbidities compared with the group without neuropsychiatric comorbidities (p < 0.001). The subgroups of GGE did not show any relationship with psychiatric disorders, including ADHD, ODD, and low academic performance (neuropsychiatric comorbidities) (p > 0.005). No correlation was found between seizure control and decline in neuropsychiatric symptoms (p > 0.05). CONCLUSION In this study, the onset of psychiatric symptoms prior to the onset of epilepsy, photosensitivity, and VPA resistance were the most important factors affecting neuropsychiatric comorbidities. The JME, JAE, and EGTCS subgroups, early initiation of antiepileptic treatment, and seizure control were found to have no effect on poor psychosocial outcome and neuropsychiatric comorbidities.
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Affiliation(s)
- Gunes Sager
- Department of Pediatric Neurology, Kartal Dr. Lutfi Kirdar City Hospital, Istanbul, Turkey.
| | - Zeynep Vatansever
- Department of Child and Adolescent Psychiatry Dr. Lutfi Kirdar City Hospital, Istanbul, Turkey
| | - Utku Batu
- Department of Pediatrics, Van Education and Research Hospital, Van, Turkey
| | - Yakup Çağ
- Department of Pediatrics, Kartal Dr. Lutfi Kirdar City Hospital, Istanbul, Turkey
| | - Yasemin Akin
- Department of Pediatrics, Kartal Dr. Lutfi Kirdar City Hospital, Istanbul, Turkey
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Executive Functions and Attention in Childhood Epilepsies: A Neuropsychological Hallmark of Dysfunction? J Int Neuropsychol Soc 2021; 27:673-685. [PMID: 33183389 DOI: 10.1017/s1355617720001125] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Patients with epilepsy are at risk for several lifetime problems, in which neuropsychological impairments may represent an impacting factor. We evaluated the neuropsychological functions in children suffering from three main epilepsy categories. Further, we analyzed the longitudinal evolution of the neuropsychological profile over time. METHODS Patients undergoing neuropsychological evaluation at our Department from 2012 to 2018 were identified retrospectively. We selected patients aged 6-16 years and with at least two evaluations. Three epilepsy categories were considered: focal/structural, focal self-limited, and idiopathic generalized. Each evaluation included the same structured assessment of main neuropsychological domains. The effect of the epilepsy category, illness duration, seizure status, and medication was computed in multilevel models. RESULTS We identified 103 patients (focal self-limited = 27; focal/structural = 51; and idiopathic generalized = 25), for 233 evaluations. The majority of deficits were reported in attention and executive functions (>30% of patients); the results were dichotomized to obtain global indexes. Multilevel models showed a trend toward statistical significance of category of epilepsy on the global executive index and of illness duration on global attention index. Illness duration predicted the scores of executive and attention tasks, while category and medication predicted executive task performance. Focal/structural epilepsies mostly affected the executive domain, with deficits persisting over time. By contrast, an ameliorative effect of illness duration for attention was documented in all epilepsies. CONCLUSIONS This study offers lacking information about the evolution of deficits in time, the role of epilepsy category, and possible psychological implications for high-order cognitive skills, central in several social and academic problems.
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Moncrief GG, Aita SL, Tyson BT, Abecassis M, Roth RM, Caller TA, Schmidt SS, Jobst BC. Self-rated executive dysfunction in adults with epilepsy and effects of a cognitive-behavioral intervention (HOBSCOTCH). Epilepsy Behav 2021; 121:108042. [PMID: 34058488 DOI: 10.1016/j.yebeh.2021.108042] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 04/30/2021] [Accepted: 04/30/2021] [Indexed: 10/21/2022]
Abstract
RATIONALE Cognitive problems are common in adults with epilepsy and significantly affect their quality of life. HOBSCOTCH (HOme Based Self-management and COgnitive Training CHanges lives) was developed to teach problem-solving and compensatory memory strategies to these individuals. This study examined whether HOBSCOTCH is associated with improvement in specific aspects of subjective executive functions. METHODS Fifty-one adults, age 18-65, with epilepsy and subjective cognitive concerns were randomized to receive HOBSCOTCH (n = 31) or a care-as-usual control sample (n = 20). Participants completed the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A), as well as the Patient Health Questionnaire-9 (PHQ-9) to assess depression. Rates of elevated (i.e., T ≥ 65, impaired) BRIEF-A scores at baseline, as well as pre-post score changes for the BRIEF-A clinical scales were evaluated. Significance was set at α = 0.05, one-tailed, given our directional hypothesis. RESULTS At baseline, a considerable percentage of patients in the overall sample endorsed executive dysfunction on BRIEF-A scales: Inhibit = 28%, Shift = 51%, Emotional Control = 45%, Self-Monitor = 33%, Initiate = 35%, Working Memory = 88%, Plan/Organize = 45%, Task Monitor = 47%, Organization of Materials = 28%. Significant improvement was seen in mean T-scores for Inhibit, Shift, Initiate, and Working Memory in the treatment group, but only Working Memory improved in the control group. The control group endorsed worse task monitoring and organization of materials at baseline and follow-up. Change in depression was not observed for either group, and there was no association between changes in depression and BRIEF-A scores. CONCLUSIONS A sizeable subset of adults with epilepsy reported experiencing executive dysfunction in their everyday lives, especially for working memory. HOBSCOTCH resulted in amelioration of subjective executive functioning independent of changes in mood.
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Affiliation(s)
- Grant G Moncrief
- Neuropsychology Program, Department of Psychiatry, Geisel School of Medicine at Dartmouth, Hanover, NH, United States.
| | - Stephen L Aita
- Neuropsychology Program, Department of Psychiatry, Geisel School of Medicine at Dartmouth, Hanover, NH, United States
| | - Brad T Tyson
- EvergreenHealth Neuroscience Institute, EvergreenHealth Medical Center, Kirkland, WA, United States
| | - Maurissa Abecassis
- Neuropsychology Program, Department of Psychiatry, Geisel School of Medicine at Dartmouth, Hanover, NH, United States
| | - Robert M Roth
- Neuropsychology Program, Department of Psychiatry, Geisel School of Medicine at Dartmouth, Hanover, NH, United States
| | - Tracie A Caller
- Cheyenne Regional Medical Center, Cheyenne, WY, United States; Department of Neurology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States
| | - Samantha S Schmidt
- Department of Neurology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States
| | - Barbara C Jobst
- Department of Neurology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States
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37
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Gholami M, Nami M, Shamsi F, Jaberi KR, Kateb B, Rahimi Jaberi A. Effects of transcranial direct current stimulation on cognitive dysfunction in multiple sclerosis. Neurophysiol Clin 2021; 51:319-328. [PMID: 34088588 DOI: 10.1016/j.neucli.2021.05.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 05/22/2021] [Accepted: 05/24/2021] [Indexed: 10/21/2022] Open
Abstract
BACKGROUND Around 40%-70% of patients with multiple sclerosis (MS) may experience cognitive impairments during the course of their disease with detrimental effects on social and occupational activities. Transcranial direct current stimulation (tDCS has been investigated in pain, fatigue, and mood disorders related to MS, but to date, few studies have examined effects of tDCS on cognitive performance in MS. OBJECTIVE The current study aimed to investigate the effects of a multi-session tDCS protocol on cognitive performance and resting-state brain electrical activities in patients with MS. METHODS Twenty-four eligible MS patients were randomly assigned to real (anodal) or sham tDCS groups. Before and after 8 consecutive daily tDCS sessions over the left dorsolateral prefrontal cortex (DLPFC), patients' cognitive performance was assessed using the Cambridge Brain Sciences-Cognitive Platform (CBS-CP). Cortical electrical activity was also evaluated using quantitative electroencephalography (QEEG) analysis at baseline and after the intervention. RESULTS Compared to the sham condition, significant improvement in reasoning and executive functions of the patients in the real tDCS group was observed. Attention was also improved considerably but not statistically significantly following real tDCS. However, no significant changes in resting-state brain activities were observed after stimulation in either group. CONCLUSION Anodal tDCS over the left DLPFC appears to be a promising therapeutic option for cognitive dysfunction in patients with MS. Larger studies are required to confirm these findings and to investigate underlying neuronal mechanisms.
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Affiliation(s)
- Mohsen Gholami
- Department of Neurology, School of Medical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Nami
- Department of Neurology, School of Medical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran; Neuroscience Center, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Panama City, Panama; Visiting Scientist, Society for Brain Mapping and Therapeutics and Brain Mapping Foundation, Los Angeles, CA, USA
| | - Fatemeh Shamsi
- Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Khojaste Rahimi Jaberi
- Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran; Students Research Committee, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Babak Kateb
- National Center for NanoBioElectoronics, Los Angeles, CA, USA; Brain Technology and Innovation Park, Los Angeles, CA, USA; Brain Mapping Foundation, Los Angeles, CA, USA; Society for Brain Mapping and Therapeutics, Los Angeles, CA, USA; Neuroscience20-G20 Summit, Los Angeles, CA, USA
| | - Abbas Rahimi Jaberi
- Department of Neurology, School of Medical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
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ELAhwal SA, El-Heneedy YAE, Bahnasy WS, Amer RAR, Rashed KH. The interictal activities load and cognitive performance of children with typical absence epilepsy. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2021. [DOI: 10.1186/s41983-021-00299-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
The description of childhood absence epilepsy (CAE) a benign self-limited generalized epilepsy has become a matter of debate. The objectives of this work were to evaluate the existence of psychiatric and cognitive impairments among patients with typical CAE and to correlate their possible relation to seizure frequency, duration of epilepsy, IISL, and valproate therapy.
Methods
The study was conducted on 19 typical CAE patients receiving valproate therapy, 11 newly diagnosed CAE patients not receiving AEDs, and 30 healthy control subjects (HCS). Participants were subjected to medical history taking, EEG monitoring, child behavior checklist (CBCL), Stanford Binet Intelligence Scale 5th edition, and computerized psychometric tests that assess cognitive domains and executive functions.
Results
The study revealed a high rate of cognitive and psychiatric dysfunctions in CAE patients. 53.3% of patients had psychiatric problems versus 16.6% in HCS. Attention deficit hyperactive disorder (ADHD) (26.6%), anxiety (16.6%), and depression (6.6%) were the most common psychiatric disorders in the patient group. Withdrawn/depressed symptoms, thought problems, social problems, and attention problems in CAE patients were significantly increased compared to HCS. At the same time, CAE patients perform worse in cognitive scales than HCS with comparable intelligent quotient (IQ) scores.
Conclusion
Cognitive and psychiatric impairments in typical CAE patients appear multifactorial in origin with epilepsy-related factors including the duration of epilepsy and interictal spike load (IISL).
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Poole BJ, Phillips NL, Stewart E, Harris IM, Lah S. Working Memory in Pediatric Epilepsy: A Systematic Review and Meta-Analysis. Neuropsychol Rev 2021; 31:569-609. [PMID: 33818735 DOI: 10.1007/s11065-021-09491-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 02/21/2021] [Indexed: 10/21/2022]
Abstract
Working memory is a multicomponent system that is supported by overlapping specialized networks in the brain. Baddeley's working memory model includes four components: the phonological loop, visuo-spatial sketchpad, the central executive, and episodic buffer. The aim of this review was to establish the gravity and pattern of working memory deficits in pediatric epilepsy. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guided electronic searches. Sixty-five studies were included in the review. Meta-analyses revealed significant impairments across each working memory component: phonological loop (g = 0.739), visuo-spatial sketchpad (g = 0.521), and central executive (g = 0.560) in children with epilepsy compared to controls. The episodic buffer was not examined. The pattern of impairments, however, differed according to the site and side of seizure focus. This suggests that working memory components are differentially vulnerable to the location of seizure focus in the developing brain.
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Affiliation(s)
- Belinda J Poole
- School of Psychology, University of Sydney, Sydney, NSW, 2006, Australia.,ARC Centre of Excellence in Cognition and its Disorders, Macquarie University, Sydney, NSW, 2109, Australia
| | - Natalie L Phillips
- School of Psychology, University of Sydney, Sydney, NSW, 2006, Australia.,ARC Centre of Excellence in Cognition and its Disorders, Macquarie University, Sydney, NSW, 2109, Australia
| | - Elizabeth Stewart
- School of Psychology, University of Sydney, Sydney, NSW, 2006, Australia.,ARC Centre of Excellence in Cognition and its Disorders, Macquarie University, Sydney, NSW, 2109, Australia
| | - Irina M Harris
- School of Psychology, University of Sydney, Sydney, NSW, 2006, Australia
| | - Suncica Lah
- School of Psychology, University of Sydney, Sydney, NSW, 2006, Australia. .,ARC Centre of Excellence in Cognition and its Disorders, Macquarie University, Sydney, NSW, 2109, Australia.
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Duma GM, Danieli A, Morao V, Da Rold M, Baggio M, Toffoli L, Zanatta A, Vettorel A, Bonanni P, Mento G. Implicit cognitive flexibility in self-limited focal epilepsy of childhood: An HD-EEG study. Epilepsy Behav 2021; 116:107747. [PMID: 33493810 DOI: 10.1016/j.yebeh.2020.107747] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 12/23/2020] [Accepted: 12/23/2020] [Indexed: 10/22/2022]
Abstract
Self-limited focal epilepsy of childhood (SFEC) is often related to mild impairments in several neuropsychological domains, including cognitive flexibility, which is generally considered a process requiring volition and attention. However, recent evidence showed that it can be implicitly adjusted exploiting simple 'stimulus-response' associations as for example, the probability of the stimulus occurrence. Here, we evaluated the capability to implicitly extract environmental patterns of regularities and use them to flexibly adjust proactive control motor control. We tested 21 children with epilepsy (total IQ > 80; 13 with Childhood epilepsy with centro-temporal spikes, 8 with Panayiotopoulos syndrome (PS); 5-13 years old) compared to a healthy age-matched control group (32 participants). We used the Dynamic Temporal Prediction (DTP) task to investigate how behavioral performance is implicitly shaped by the manipulation of the stimulus occurrence probability over time. We recorded EEG to identify neural markers to differentiate the two groups. SFEC group showed a reduction in accuracy (p = .0013) and response speed (p < .001) as well as an absence of response adjustment (p = .65) in relation to the implicit changes in stimulus probability occurrence, in comparison to the control group. The epilepsy group performance in the DTP showed a significant correlation with the phonemic fluency (r = -0.50) and the Perseverations index of the CPT test (r = 0.53). Finally, children with SFEC did not show the modulation of the contingent negative variation (CNV) evoked potential. Overall, children with SFEC showed poor implicit flexibility compared to a control group. This pattern is individually related to high-level executive function, suggesting to extend neuropsychological assessment to the implicit domain.
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Affiliation(s)
- Gian Marco Duma
- Department of General Psychology, University of Padova, Italy; Scientific Institute, IRCCS "E. Medea", Association "La Nostra Famiglia", Conegliano (TV), Italy.
| | - Alberto Danieli
- Scientific Institute, IRCCS "E. Medea", Association "La Nostra Famiglia", Conegliano (TV), Italy
| | - Veronica Morao
- Scientific Institute, IRCCS "E. Medea", Association "La Nostra Famiglia", Conegliano (TV), Italy
| | - Martina Da Rold
- Scientific Institute, IRCCS "E. Medea", Association "La Nostra Famiglia", Conegliano (TV), Italy
| | - Martina Baggio
- Scientific Institute, IRCCS "E. Medea", Association "La Nostra Famiglia", Conegliano (TV), Italy
| | - Lisa Toffoli
- Scientific Institute, IRCCS "E. Medea", Association "La Nostra Famiglia", Conegliano (TV), Italy
| | - Arianna Zanatta
- Department of Experimental-Clinical and Health Psychology, Ghent University, Belgium
| | - Airis Vettorel
- Scientific Institute, IRCCS "E. Medea", Association "La Nostra Famiglia", Conegliano (TV), Italy
| | - Paolo Bonanni
- Scientific Institute, IRCCS "E. Medea", Association "La Nostra Famiglia", Conegliano (TV), Italy
| | - Giovanni Mento
- Department of General Psychology, University of Padova, Italy; Padova Neuroscience Center (PNC), University of Padova, Italy
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Lam J, Williams M, Ashla M, Lee DJ. Cognitive outcomes following vagus nerve stimulation, responsive neurostimulation and deep brain stimulation for epilepsy: A systematic review. Epilepsy Res 2021; 172:106591. [PMID: 33711711 DOI: 10.1016/j.eplepsyres.2021.106591] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 01/25/2021] [Accepted: 02/16/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND The cognitive impacts of resective surgery for epilepsy have been well-studied. While seizure outcomes for less invasive, neuromodulatory treatments are promising, there is a paucity of data for cognitive outcomes. METHODS Medline, EMBASE, and the Cochrane Library were searched on November 2019. Inclusion criteria were studies reporting cognitive outcomes following chronic (>6 months) vagus nerve stimulation (VNS), deep brain stimulation (DBS) and responsive neurostimulation (RNS) for epilepsy in at least five patients. Studies reporting acute on-off effects of stimulation were also included. Studies were screened, extracted of data, and assessed for bias using the Joanna Briggs Institute Critical Appraisal Tools by two independent reviewers. Prospero ID: CRD42020184432. RESULTS Of 8443 studies screened, 29 studies were included. Nineteen investigated the effects of chronic stimulation (11 VNS, 6 DBS, 2 RNS): 10 (53 %) reported no change compared to preoperative baseline; 8 (42 %) reported some improvement in one or more cognitive domain; 1 (5%) reported decline. Ten investigated the effects of acute stimulation (5 VNS, 5 DBS): 3 (30 %) reported no change; 4 reported improvement (40 %); 3 (30 %) reported decline. Eight (28 %) did not report statistical analysis. CONCLUSIONS Long-term cognitive outcomes are at least stable following VNS, DBS and RNS. Acute effects of stimulation are less clear. However, data are limited by number, size, and quality. More robust evidence is needed to properly assess the cognitive effects of each of these treatments.
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Affiliation(s)
- Jordan Lam
- Department of Neurological Surgery, Keck School of Medicine of USC, Los Angeles, United States; USC Neurorestoration Center, Keck School of Medicine of USC, Los Angeles, United States
| | - Marcus Williams
- King's College London Medical School, London, United Kingdom
| | - Mark Ashla
- Department of Neurological Surgery, Keck School of Medicine of USC, Los Angeles, United States
| | - Darrin J Lee
- Department of Neurological Surgery, Keck School of Medicine of USC, Los Angeles, United States; USC Neurorestoration Center, Keck School of Medicine of USC, Los Angeles, United States.
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42
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Lam J, Cabeen RP, Tanna R, Navarro L, Heck CN, Liu CY, Lee B, Russin JR, Toga AW, Lee DJ. Gray Matter Atrophy: The Impacts of Resective Surgery and Vagus Nerve Stimulation in Drug-Resistant Epilepsy. World Neurosurg 2021; 149:e535-e545. [PMID: 33549931 DOI: 10.1016/j.wneu.2021.01.141] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 01/25/2021] [Accepted: 01/26/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND There is great concern for cognitive function after resective temporal lobe surgery for drug-resistant epilepsy. However, few studies have investigated postoperative anatomical changes, and the downstream effects of surgery are poorly understood. This study investigated volumetric changes after resective surgery and vagus nerve stimulation (VNS) for epilepsy. METHODS Preoperative and latest postoperative (mean, 28 months) structural T1 magnetic resonance imaging scans were retrospectively obtained for 43 patients: 27 temporal lobe resections (TLRs), 6 extratemporal lobe resections, and 10 VNS, undergoing surgery for drug-resistant epilepsy between 2012 and 2017. Automated volumetric analyses of predefined cortical gray matter and subcortical structures were performed. Preoperative and postoperative volumes were compared, and the effects of age, gender, operation type, resection laterality, selectivity, time since surgery, and seizure outcome on volumetric changes were analyzed. RESULTS After TLRs, there were reductions in contralateral hemispheric gray matter, temporal lobe, entorhinal cortex, parahippocampal, superior temporal, middle temporal, inferior temporal (P = 0.02), lingual, fusiform, precentral, paracentral, postcentral, pericalcarine gyri, and ipsilateral superior parietal gyrus. After VNS, there was bilateral atrophy in the thalamus, putamen, cerebellum, rostral anterior cingulate, posterior cingulate, medial orbitofrontal, paracentral, fusiform, and transverse temporal gyri. There was a significant effect of surgery type but no effect of age, gender, operation type, resection laterality, selectivity, time since surgery, and seizure outcome on contralateral hippocampal gray matter change. CONCLUSION This is the first study to demonstrate volumetric decreases in temporal and connected regions after TLRs and VNS. These results provide interesting insight into functional network changes.
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Affiliation(s)
- Jordan Lam
- USC Neurorestoration Center, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
| | - Ryan P Cabeen
- Laboratory of Neuro Imaging, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Los Angeles, California, USA
| | - Runi Tanna
- USC Neurorestoration Center, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
| | - Lauren Navarro
- USC Neurorestoration Center, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
| | - Christianne N Heck
- USC Neurorestoration Center, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
| | - Charles Y Liu
- USC Neurorestoration Center, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
| | - Brian Lee
- USC Neurorestoration Center, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
| | - Jonathan R Russin
- USC Neurorestoration Center, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
| | - Arthur W Toga
- Laboratory of Neuro Imaging, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Los Angeles, California, USA
| | - Darrin J Lee
- USC Neurorestoration Center, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
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Dilcher R, Malpas CB, Walterfang M, Kwan P, O'Brien TJ, Velakoulis D, Vivash L. Cognitive profiles in patients with epileptic and nonepileptic seizures evaluated using a brief cognitive assessment tool. Epilepsy Behav 2021; 115:107643. [PMID: 33317941 DOI: 10.1016/j.yebeh.2020.107643] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 11/16/2020] [Accepted: 11/16/2020] [Indexed: 11/15/2022]
Abstract
BACKGROUND There is a need for the development of brief tools to screen for cognitive impairments in epilepsy patients in order to prioritize and direct formal comprehensive cognitive testing. Yet, shorter cognitive screening tools are limited in their breadth of cognitive domains or have not been intensively studied on an epilepsy population. This study used a brief cognitive screening tool in order to compare cognitive profiles between patients with epilepsy and those with nonepileptic seizures. METHODS Patients admitted to the Royal Melbourne Hospital video-EEG monitoring unit between 2005 and 2017 were included. Patients were categorized according to seizure etiology (epileptic, psychogenic or other nonepileptic seizures), epilepsy syndrome (focal or generalized; temporal lobe (TLE) or extra-temporal lobe epilepsy (ETLE)), seizure frequency, and anti-seizure medications (ASMs). Attention, visuoconstructional, memory, executive, and language functioning were assessed with the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). General linear mixed models were computed to investigate cognitive profiles according to diagnostic group and other clinicodemographic variables. RESULTS 800 patients were included in the analysis (61% female and 39 % male, median age 36 years). Patients with both epileptic seizures and psychogenic seizures (n = 25) had the lowest total scores on NUCOG, followed by patients with epileptic seizures (n = 411), psychogenic seizures (n = 185), and nonepileptic seizures (n = 179, p = 0.002). Specifically, patients with epileptic seizures performed worse than those with nonepileptic seizures in the executive, language, and memory domain, and had lower language domain scores than those with psychogenic seizures. Patients with bilateral TLE had poorer performance than those with unilateral TLE, particularly for memory function. Specific ASMs and polypharmacy but not seizure frequency had a negative effect on cognition (p < 0.001). NUCOG scores did not differ between focal and generalized epilepsies, or between TLE and ETLE. CONCLUSION The NUCOG differentiated cognitive profiles in patients with uncontrolled seizures due to different etiologies. Bilateral TLE and medication adversely affected cognitive performance, and overall patients with epilepsy performed worse than those with nonepileptic seizures. These results provide further evidence for sensitivity of the NUCOG for detecting cognitive impairment in patients with seizure disorders.
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Affiliation(s)
- Roxane Dilcher
- Melbourne Brain Centre, The Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia; Department of Neuroscience, Central Clinical School, Alfred Health, Monash University, Melbourne, VIC, Australia
| | - Charles B Malpas
- Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia; Department of Neuroscience, Central Clinical School, Alfred Health, Monash University, Melbourne, VIC, Australia; Clinical Outcomes Research Unit (CORe), Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, VIC, Australia
| | - Mark Walterfang
- Neuropsychiatry Unit, Royal Melbourne Hospital, Melbourne, VIC, Australia; Melbourne Neuropsychiatry Centre, University of Melbourne and North Western Mental Health, Melbourne, VIC, Australia
| | - Patrick Kwan
- Melbourne Brain Centre, The Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia; Department of Neuroscience, Central Clinical School, Alfred Health, Monash University, Melbourne, VIC, Australia
| | - Terence J O'Brien
- Melbourne Brain Centre, The Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia; Department of Neuroscience, Central Clinical School, Alfred Health, Monash University, Melbourne, VIC, Australia
| | - Dennis Velakoulis
- Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia; Neuropsychiatry Unit, Royal Melbourne Hospital, Melbourne, VIC, Australia
| | - Lucy Vivash
- Melbourne Brain Centre, The Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia; Department of Neuroscience, Central Clinical School, Alfred Health, Monash University, Melbourne, VIC, Australia.
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Patrikelis P, Lucci G, Fasilis T, Korfias S, Messinis L, Kosmidis MH, Lagogianni C, Konstantakopoulos G, Manolia S, Sakas D, Gatzonis S. Selective impairment of auditory attention processing in idiopathic generalized epilepsies: Implications for their cognitive pathophysiology. APPLIED NEUROPSYCHOLOGY-ADULT 2020; 29:1131-1140. [PMID: 33284641 DOI: 10.1080/23279095.2020.1852566] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
The neuropsychological characteristics of Idiopathic Generalized Epilepsies (IGEs) as a wide syndrome encompassing different clinical entities have been as yet not well understood. We have studied neuropsychological performance in patients suffering Juvenile Myoclonic Epilepsy (JME) and Generalized Tonic Clonic Seizures (IGE-GTCS-only) to provide indirect-cognitive evidence on the pathophysiology of IGE-related neuropsychological dysfunction. Greater arousal-related impairments were expected for the auditory modality, by drawing on previous anatomo-clinical and neuro-evolutionary accounts. We have studied neurocognitive functioning in 26 IGE patients, suffering either JME (n = 16) or IGE-GTCS-only (n = 10), and their healthy counterparts consisted of 26 (18 females) demographically matched participants. IGE patients (JME and IGE-GTCS-only) did worse with respect to HC (healthy controls) in visual- and auditory- speed of information processing (reaction time), auditory-vigilance and -response inhibition, visuo-motor coordination, visual working memory and motor speed, delayed visual recall, immediate- and delayed verbal episodic recall, lexical access and retrieval, semantic associative processing, auditory-verbal memory span and verbal learning. Although both IGE-GTCS-only and JME patients delayed episodic recall was defective, the former did significantly worse. We believe that IGE patients' neuropsychological derailments represent indirect-secondary manifestations of a primary cortical tone deregulation inherent to IGEs' pathophysiology. In particular, IGE patients' worse-dissociated performance in auditory TOVA-also seen previously in TBI and schizophrenia-may implicate a grater vulnerability of the auditory information processing system, as well as a possibly shared cognitive pathophysiological component between IGE and the above nosologies.
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Affiliation(s)
- Panayiotis Patrikelis
- Department of Neurosurgery, Epilepsy Surgery Unit, School of Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Giuliana Lucci
- Department of Technologies, Communication and Society, University of Rome G. Marconi, Rome, Italy
| | - Theodoros Fasilis
- Department of Neurosurgery, Epilepsy Surgery Unit, School of Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Stefanos Korfias
- Department of Neurosurgery, Epilepsy Surgery Unit, School of Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Lambros Messinis
- Departments of Neurology and Psychiatry, Neuropsychology Section, School of Medicine, University Hospital of Patras, Patras, Greece
| | - Mary H Kosmidis
- Department of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Christodouli Lagogianni
- Department of Neurosurgery, Epilepsy Surgery Unit, School of Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - George Konstantakopoulos
- First Department of Psychiatry, National and Kapodistrian University of Athens, Athens, Greece.,Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Stamatina Manolia
- Department of Statistics and Actuarial Science, University of Pireaus, Pireaus, Greece
| | - Damianos Sakas
- Department of Neurosurgery, Epilepsy Surgery Unit, School of Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Stylianos Gatzonis
- Department of Neurosurgery, Epilepsy Surgery Unit, School of Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, Athens, Greece
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A Review of Accelerated Long-Term Forgetting in Epilepsy. Brain Sci 2020; 10:brainsci10120945. [PMID: 33297371 PMCID: PMC7762289 DOI: 10.3390/brainsci10120945] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 11/30/2020] [Accepted: 12/03/2020] [Indexed: 11/16/2022] Open
Abstract
Accelerated long-term forgetting (ALF) is a memory disorder that manifests by a distinct pattern of normal memory for up to an hour after learning, but an increased rate of forgetting during the subsequent hours and days. The topic of ALF has gained much attention in group studies with epilepsy patients and the phenomenon has been shown to have contradictory associations with seizures, epileptiform activity, imaging data, sleep, and antiepileptic medication. The aim of this review was to explore how clinical and imaging data could help determine the topographic and physiological substrate of ALF, and what is the possible use of this information in the clinical setting. We have reviewed 51 group studies in English to provide a synthesis of the existing findings concerning ALF in epilepsy. Analysis of recently reported data among patients with temporal lobe epilepsy, transient epileptic amnesia, and generalized and extratemporal epilepsies provided further indication that ALF is likely a disorder of late memory consolidation. The spatial substrate of ALF might be located along the parts of the hippocampal-neocortical network and novel studies reveal the increasingly possible importance of damage in extrahippocampal sites. Further research is needed to explore the mechanisms of cellular impairment in ALF and to develop effective methods of care for patients with the disorder.
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Joplin S, Webster R, Gill D, Barton B, Lawson JA, Mandalis A, Sabaz M, Gascoigne M, Lah S. Accelerated long-term forgetting in children with genetic generalized epilepsy: The temporal trajectory and contribution of executive skills. Epilepsy Behav 2020; 113:107471. [PMID: 33142199 DOI: 10.1016/j.yebeh.2020.107471] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 09/01/2020] [Indexed: 11/18/2022]
Abstract
PURPOSE Long-term memory, which is critical for social and vocational functioning, is impaired in children with genetic generalized epilepsy (GGE). In this study, we examined the relationship between the temporal pattern of long-term forgetting for visual and verbal materials and executive skills in children with GGE. METHOD Thirty-two children, 17 with GGE and 25 typically developing age-matched controls completed standardized tests of short-term memory (recall after a 30-minute delay), executive skills, and experimental long-term memory tasks (one verbal and one visual) involving recall after one short (30-minute), and two long (1-day, 2-week) delays. RESULTS On the long-term visual memory task, children with GGE performed comparably with typically developing children at a 30-minute delay (p = .298), although obtained lower object placement accuracy score, at 1 day (p = .039) and at 2 weeks (p = .022) relative to typically developing children. On the verbal task, the between-group difference was not significant at any delay. In children with GGE, poorer object placement accuracy at two weeks correlated with lower visuospatial short-term memory (r = -0.624, p = .005) and verbal working memory (r = -0.448, p = .041). CONCLUSIONS This study provided several novel findings. For the first time, accelerated long-term forgetting (ALF) was found in long-term visual memory in children with GGE, despite comparable learning and recall at 30 min. Study results indicated that deficits in long-term visual memory are present after one day, increase over time, and may relate to reduced executive skills. Our findings can be used to inform our understanding of the temporal trajectory of ALF and contribution of executive skills.
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Affiliation(s)
- Samantha Joplin
- School of Psychology, The University of Sydney, NSW 2006, Australia
| | - Richard Webster
- T. Y. Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, Sydney, Australia
| | - Deepak Gill
- T. Y. Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, Sydney, Australia
| | - Belinda Barton
- Children's Hospital Education Research Institute, The Children's Hospital at Westmead, Sydney, Australia; Discipline of Paediatrics and Child Health, Faculty of Medicine, The University of Sydney, Australia
| | - John A Lawson
- Department of Neurology, Sydney Children's Hospital, Sydney, Australia
| | - Anna Mandalis
- Department of Psychology, Sydney Children's Hospital, Sydney, Australia
| | - Mark Sabaz
- Department of Psychology, Sydney Children's Hospital, Sydney, Australia
| | - Michael Gascoigne
- School of Psychology, The University of Sydney, NSW 2006, Australia; School of Psychological Sciences, Australian College of Applied Psychology, Sydney, Australia
| | - Suncica Lah
- School of Psychology, The University of Sydney, NSW 2006, Australia.
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James L, Jacobs KE, Roodenburg J. Adoption of the Cattell–Horn–Carroll Model of Cognitive Abilities by Australian Psychologists. AUSTRALIAN PSYCHOLOGIST 2020. [DOI: 10.1111/ap.12110] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Lara James
- Faculty of Education, Monash University,
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48
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Network characteristics of genetic generalized epilepsy: Are the syndromes distinct? Seizure 2020; 82:91-98. [DOI: 10.1016/j.seizure.2020.09.022] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 09/27/2020] [Accepted: 09/28/2020] [Indexed: 01/02/2023] Open
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Evaluating Executive Functions in Patients with Juvenile Myoclonic Epilepsy Using Frontal Assessment Battery. Behav Neurol 2020; 2020:8710373. [PMID: 32963634 PMCID: PMC7501547 DOI: 10.1155/2020/8710373] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 08/21/2020] [Accepted: 08/29/2020] [Indexed: 11/29/2022] Open
Abstract
Objective In this study, we aimed to evaluate the executive profile of juvenile myoclonic epilepsy (JME) patients using the Frontal Assessment Battery (FAB) as a bedside screening tool and investigate its association with seizure proximity, family history of epilepsy, and polytherapy/monotherapy with antiepileptic drugs (AEDs). Background JME patients have deficits in various aspects of executive functions. FAB has proved to be a useful tool for evaluating executive functions in clinical settings. Methods Thirty-one JME patients and 110 healthy controls (HCs) were enrolled in this study. The participants were assessed using six subsets of FAB, including conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. Results Compared to HCs, JME patients showed lower scores in conceptualization, mental flexibility, programming, sensitivity to interference, and total FAB. The number of AEDs (polytherapy versus monotherapy) and duration of time since the last seizure had no significant effect on FAB scores in JME patients. We found significant associations between disease duration and conceptualization, mental flexibility, inhibitory control, and total FAB score only in JME patients with recent seizure. Finally, receiver operating characteristic (ROC) analysis showed area under the curve (AUC) of 0.971 (95% confidence interval (CI): 0.947–0.994) for FAB total score, 0.933 for conceptualization (95% CI: 0.973-894), and 0.836 for mental flexibility (95% CI: 0.921-751). Conclusions In summary, JME patients had deficits in different aspects of executive functions. FAB is a useful clinical tool for evaluation of executive functions in JME patients.
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50
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Fonseca Wald ELA, Debeij-Van Hall MHJA, De Jong E, Aldenkamp AP, Vermeulen RJ, Vles JSH, Klinkenberg S, Hendriksen JGM. Neurocognitive and behavioural profile in Panayiotopoulos syndrome. Dev Med Child Neurol 2020; 62:985-992. [PMID: 32608507 DOI: 10.1111/dmcn.14417] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/20/2019] [Indexed: 11/30/2022]
Abstract
AIM To determine neurocognitive performance and behavioural problems in children with Panayiotopoulos syndrome. METHOD All 18 children (10 females, 8 males; mean age 4y 7mo; SD 1y 10mo) diagnosed with Panayiotopoulos syndrome at the Kempenhaeghe Epilepsy Center in the Netherlands between 2010 and 2017 were analysed retrospectively. All underwent a neuropsychological/behavioural assessment, an academic assessment, and a 24-hour electroencephalogram. RESULTS Mean full-scale IQ (93.5; range 76-123; p=0.04) and performance IQ (93.2; range 76-126; p=0.04) were within the normal range, although significantly lower compared to the normative mean. Verbal IQ (96.3; range 76-118) and processing speed (96.1; range 74-114) were not significantly lower. Simple auditory/visual reaction times, visual attention, visual-motor integration, and verbal memory were significantly lower compared to normative values. On average, patients with Panayiotopoulos syndrome were 8 months behind in arithmetic speed and 11 months behind in reading speed for the number of months in school. Behavioural questionnaires revealed significantly higher scores on reported internalizing behavioural problems. INTERPRETATION Children with Panayiotopoulos syndrome demonstrated diffuse cognitive dysfunction in full-scale IQ, performance IQ, visual attention, visual-motor integration, and verbal memory. A high incidence of internalizing behavioural problems was reported. This strongly suggests neuropsychological and behavioural comorbidity in children with Panayiotopoulos syndrome. WHAT THIS PAPER ADDS Children with Panayiotopoulos syndrome are at risk for cognitive deficits in various cognitive domains. Children with Panayiotopoulos syndrome are also prone to internalizing behavioural problems. Mild-to-severe academic underachievement was present in more than half of the children with Panayiotopoulos syndrome.
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Affiliation(s)
- Eric L A Fonseca Wald
- Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands.,Kempenhaeghe Epilepsy Center, Heeze, the Netherlands.,School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands
| | | | - Eline De Jong
- Kempenhaeghe Epilepsy Center, Heeze, the Netherlands
| | - Albert P Aldenkamp
- Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands.,Kempenhaeghe Epilepsy Center, Heeze, the Netherlands.,School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.,Department of Electrical Engineering, Eindhoven University of Technology, the Netherlands
| | - R Jeroen Vermeulen
- Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands.,School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands
| | - Johan S H Vles
- Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands.,School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands
| | - Sylvia Klinkenberg
- Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands.,School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands
| | - Jos G M Hendriksen
- Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands.,Kempenhaeghe Epilepsy Center, Heeze, the Netherlands
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