Neuropsychology of epilepsy surgery and theory-based practice: an opinion review.

The present review attempts to discuss how some of the central concepts from the Lurian corpus of theories are relevant to the modern neuropsychology of epilepsy and epilepsy surgery. Through the lenses of the main Lurian concepts (such as the qualitative syndrome analysis), we discuss the barriers to clinical reasoning imposed by quadrant-based views of the brain, or even atheoretical, statistically-based and data-driven approaches. We further advice towards a systemic view inspired by Luria's clinical work and theorizing, given their importance towards our clinical practice, by contrasting it to the modular views when appropriate. Luria provided theory-guided methods of assessment and rehabilitation of higher cortical functions. Although his work did not specifically address epilepsy, his theory and clinical approaches actually apply to the whole neuropathology spectrum and accounting for the whole panorama of neurocognition. This holistic and systemic approach to the brain is consistent with the network approach of the neuroimaging era. As to epilepsy, the logic of cognitive functions organized into complex functional systems, contrary to modular views of the brain, heralds current knowledge of epilepsy as a network disease, as well as the concept of the functional deficit zone.

A presente revisão tenta discutir como alguns dos conceitos centrais do corpus de teorias lurianas são relevantes para a moderna neuropsicologia da epilepsia e cirurgia da epilepsia. Através das lentes dos principais conceitos lurianos (como a análise qualitativa de síndromes), discutimos as barreiras ao raciocínio clínico impostas por visões do cérebro baseadas em quadrantes, ou mesmo abordagens ateóricas, baseadas em estatísticas e orientadas por dados. Aconselhamos ainda uma visão sistêmica inspirada na clínica e na teorização de Luria, dada sua importância para nossa prática clínica, contrastando-a com as visões modulares quando apropriado. Luria forneceu métodos teóricos de avaliação e reabilitação de funções corticais superiores. Embora seu trabalho não abordasse especificamente a epilepsia, sua teoria e abordagens clínicas na verdade se aplicam a todo o espectro da neuropatologia e respondem por todo o panorama da neurocognição. Essa abordagem holística e sistêmica do cérebro é consistente com a abordagem de rede da era da neuroimagem. Quanto à epilepsia, a lógica das funções cognitivas organizadas em sistemas funcionais complexos, ao contrário das visões modulares do cérebro, anuncia o conhecimento atual da epilepsia como uma doença em rede, bem como o conceito de zona de déficit funcional.

Cognitive Impairment in MRI-Negative Epilepsy: Relationship between Neurophysiological and Neuropsychological Measures.

BACKGROUND: Epileptic patients frequently encounter cognitive impairment. Functions that are mostly affected involve memory, attention, and executive function; however, this is mainly dependent on the location of the epileptic activity. The aim of the present study is to assess cognitive functions in MRI-negative epilepsy patients by means of neurophysiological and neuropsychological measures, as well as study the concept of transient cognitive impairment in patients with epileptiform discharges during EEG acquisition. METHODS: The patients were enrolled from an outpatient Epilepsy/Clinical Neurophysiology clinic over a time period of 6 months. The study sample comprised 20 MRI-negative epilepsy patients (mean age ± standard deviation (SD), 30.3 ± 12.56 years; age range, 16-60 years; average disease duration, 13.95 years) and 10 age-matched controls (mean age ± SD, 24.22 ± 15.39 years), who were also education-matched (p > 0.05). Patients with epileptogenic lesions were excluded from the study. Informed consent was obtained from all subjects involved in the study. Auditory ERPs and the cognitive screening tool EpiTrack were administered to all subjects. RESULTS: Latencies of P300 and slow waves were prolonged in patients compared to controls (p < 0.05). The ASM load and patients' performance in the EpiTrack maze subtest were the most significant predictors of P300 latency. A decline in the memory, attention, and speed of information processing was observed in patients with cryptogenic epilepsy compared to age-matched controls, as reflected by P300 latency and EpiTrack scores.

Neuropsychology of epilepsy surgery and theory-based practice: an opinion review / Neuropsicologia da cirurgia de epilepsia e prática teórica: uma revisão de opinião

Abstract The present review attempts to discuss how some of the central concepts from the Lurian corpus of theories are relevant to the modern neuropsychology of epilepsy and epilepsy surgery. Through the lenses of the main Lurian concepts (such as the qualitative syndrome analysis), we discuss the barriers to clinical reasoning imposed by quadrant-based views of the brain, or even atheoretical, statistically-based and data-driven approaches. We further advice towards a systemic view inspired by Luria's clinical work and theorizing, given their importance towards our clinical practice, by contrasting it to the modular views when appropriate. Luria provided theory-guided methods of assessment and rehabilitation of higher cortical functions. Although his work did not specifically address epilepsy, his theory and clinical approaches actually apply to the whole neuropathology spectrum and accounting for the whole panorama of neurocognition. This holistic and systemic approach to the brain is consistent with the network approach of the neuroimaging era. As to epilepsy, the logic of cognitive functions organized into complex functional systems, contrary to modular views of the brain, heralds current knowledge of epilepsy as a network disease, as well as the concept of the functional deficit zone.

Resumo A presente revisão tenta discutir como alguns dos conceitos centrais do corpus de teorias lurianas são relevantes para a moderna neuropsicologia da epilepsia e cirurgia da epilepsia. Através das lentes dos principais conceitos lurianos (como a análise qualitativa de síndromes), discutimos as barreiras ao raciocínio clínico impostas por visões do cérebro baseadas em quadrantes, ou mesmo abordagens ateóricas, baseadas em estatísticas e orientadas por dados. Aconselhamos ainda uma visão sistêmica inspirada na clínica e na teorização de Luria, dada sua importância para nossa prática clínica, contrastando-a com as visões modulares quando apropriado. Luria forneceu métodos teóricos de avaliação e reabilitação de funções corticais superiores. Embora seu trabalho não abordasse especificamente a epilepsia, sua teoria e abordagens clínicas na verdade se aplicam a todo o espectro da neuropatologia e respondem por todo o panorama da neurocognição. Essa abordagem holística e sistêmica do cérebro é consistente com a abordagem de rede da era da neuroimagem. Quanto à epilepsia, a lógica das funções cognitivas organizadas em sistemas funcionais complexos, ao contrário das visões modulares do cérebro, anuncia o conhecimento atual da epilepsia como uma doença em rede, bem como o conceito de zona de déficit funcional.

Cognitive Neurorehabilitation in Epilepsy Patients via Virtual Reality Environments: Systematic Review.

OBJECTIVE: Epilepsy patients could possibly benefit from the remuneration observed in the use of virtual reality (VR) and virtual environments (VEs), especially in cognitive difficulties associated with visuospatial navigation (memory, attention, and processing speed). AIM: Research questions under consideration in the present systematic review are associated to VEs' efficiency as a cognitive rehabilitation practice in epilepsy and the particular VR methods indicated for epilepsy patients. To meet criteria, studies included participants suffering from any form of epilepsy and a methodological design with a structured rehabilitation program/model. Data were collected online, using academic databases. RESULTS: Fourteen studies were included in the literature review and 6 in the statistical analysis. ROBINS-I protocol was implemented to assess the risk of bias. An inverse variance analysis (random effects) of pooled estimates of differences was implemented, in the form of continuous data. Despite the heterogeneity of the studies, all of them agree on the beneficial aspects of VR and VEs in cognitive rehabilitation in relation to visuospatial memory, attention, and information processing speed. CONCLUSION: We suggest that patients suffering from epilepsy may benefit from the use of VR cognitive rehabilitation interventions, concerning visuospatial memory, attention, and information processing speed. However, further investigation is needed in order to gain a better understanding of the mechanisms involved in cognitive rehabilitation via VEs and establish efficient and dynamic rehabilitation protocols.

Epilepsy and the "dark" literature of the Greek novelist Demosthenes Voutyras: an outstanding epileptic personality / Epilepsia e a literatura "sombria" do romancista grego Demosthenes Voutyras: uma personalidade epilética notável

Abstract Background The role of temporal lobe epilepsy (TLE) in determining personality traits and neurobehavioral symptoms, collectively known as the interictal behavioral syndrome (also known as Geschwind syndrome or "Gastaut-Geschwind syndrome"), as well as the syndrome's association with the particular artistic expression of many epileptic litterateurs are well known in neurology and psychiatry. A deepening of emotionality along with a serious, highly ethical, and spiritual behavior have been described as positive personality changes among patients with chronic mesial-TLE. Objectives Our narrative-based clinical hypothesis aims at contributing to the ongoing debate on the association between TLE and artistic expression, as well as the latter's supposed implication for epileptology in general and the neuropsychology of epilepsy in particular. Methods Through an analysis of the biography, language, and literary work of Greek novelist Demosthenes Voutyras, we hypothesize that his mystical and dark writing style could be attributed to medial temporal interictal dynamics. Conclusions We suggest that the psycholiterary profile of Voutyras is consistent with the idiosyncratic characteristics of the temporal lobe personality, while a non-dominant temporal lobe contribution has been proposed.

Resumo Antecedentes O papel da epilepsia do lobo temporal (ELT) na determinação de traços de personalidade e sintomas neurocomportamentais, coletivamente conhecidos como síndrome comportamental interictal (também conhecida como síndrome de Geschwind ou "síndrome de Gastaut-Geschwind"), bem como a associação da síndrome com o expressão de muitos literatos epilépticos são bem conhecidos em neurologia e psiquiatria. Um aprofundamento da emotividade juntamente com um comportamento sério, altamente ético e espiritual tem sido descrito como mudanças positivas de personalidade em pacientes com ELT mesial crônica. Objetivos A nossa hipótese clínica narrativa visa contribuir para o debate em curso sobre a associação entre ELT e a expressão artística, bem como a suposta implicação desta última para a epilepsia em geral e a neuropsicologia da epilepsia em particular. Métodos Através de uma análise da biografia, linguagem e obra literária do romancista grego Demóstenes Voutyras, levantamos a hipótese de que seu estilo de escrita místico e sombrio poderia ser atribuído à dinâmica interictal temporal medial. Conclusões Sugerimos que o perfil psicoliterário de Voutyras é consistente com as características idiossincráticas da personalidade do lobo temporal, enquanto uma contribuição do lobo temporal não dominante foi proposta.

Epilepsy and the "dark" literature of the Greek novelist Demosthenes Voutyras: an outstanding epileptic personality.

BACKGROUND: The role of temporal lobe epilepsy (TLE) in determining personality traits and neurobehavioral symptoms, collectively known as the interictal behavioral syndrome (also known as Geschwind syndrome or "Gastaut-Geschwind syndrome"), as well as the syndrome's association with the particular artistic expression of many epileptic litterateurs are well known in neurology and psychiatry. A deepening of emotionality along with a serious, highly ethical, and spiritual behavior have been described as positive personality changes among patients with chronic mesial-TLE. OBJECTIVES: Our narrative-based clinical hypothesis aims at contributing to the ongoing debate on the association between TLE and artistic expression, as well as the latter's supposed implication for epileptology in general and the neuropsychology of epilepsy in particular. METHODS: Through an analysis of the biography, language, and literary work of Greek novelist Demosthenes Voutyras, we hypothesize that his mystical and dark writing style could be attributed to medial temporal interictal dynamics. CONCLUSIONS: We suggest that the psycholiterary profile of Voutyras is consistent with the idiosyncratic characteristics of the temporal lobe personality, while a non-dominant temporal lobe contribution has been proposed.

ANTECEDENTES: O papel da epilepsia do lobo temporal (ELT) na determinação de traços de personalidade e sintomas neurocomportamentais, coletivamente conhecidos como síndrome comportamental interictal (também conhecida como síndrome de Geschwind ou "síndrome de Gastaut-Geschwind"), bem como a associação da síndrome com o expressão de muitos literatos epilépticos são bem conhecidos em neurologia e psiquiatria. Um aprofundamento da emotividade juntamente com um comportamento sério, altamente ético e espiritual tem sido descrito como mudanças positivas de personalidade em pacientes com ELT mesial crônica. OBJETIVOS: A nossa hipótese clínica narrativa visa contribuir para o debate em curso sobre a associação entre ELT e a expressão artística, bem como a suposta implicação desta última para a epilepsia em geral e a neuropsicologia da epilepsia em particular. MéTODOS: Através de uma análise da biografia, linguagem e obra literária do romancista grego Demóstenes Voutyras, levantamos a hipótese de que seu estilo de escrita místico e sombrio poderia ser atribuído à dinâmica interictal temporal medial. CONCLUSõES: Sugerimos que o perfil psicoliterário de Voutyras é consistente com as características idiossincráticas da personalidade do lobo temporal, enquanto uma contribuição do lobo temporal não dominante foi proposta.

Understanding frontal lobe function in epilepsy: Juvenile myoclonic epilepsy vs. frontal lobe epilepsy.

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.

Paternal age and specific neurological soft signs as reliable and valid neurobiological markers for the diagnosis of patients with schizophrenia.

Advanced parental age at delivery and neurological soft signs (NSS) constitute risk factors for schizophrenia. The aim of the current study was to develop a neurobiological diagnostic index by combining them, and without the contribution of clinical symptomatology. The study sample included 133 patients suffering from schizophrenia according to DSM-IV-TR (77 males and 56 females; aged 33.55 ± 11.22 years old) and 122 normal controls (66 males and 56 females; aged 32.89 ± 9.91 years old). The assessment included the Neurological Evaluation Scale (NES), and a number of scales assessing the clinical symptoms and adverse effects. The statistical analysis included exploratory t-test, Pearson Correlation coefficient (R) and Discriminant Function Analysis (DFA). Exploratory t-tests and Pearson's R suggested that sex, parental age and NSS constitute independent components. On the basis of DFA results, the Psychotic Neurological Index was developed. At the cut-off PNI score of 8.5, sensitivity was equal to 94.74 and specificity to 93.44. The current is probably the first study to report on an easily obtainable diagnostic neurobiological marker with identifiable properties which is absolutely independent from the clinical manifestations and could serve in distinguishing between patients with schizophrenia and healthy controls with high efficacy.

Neurological adverse events post allogeneic hematopoietic cell transplantation: major determinants of morbidity and mortality.

BACKGROUND: Despite advances in the field, diagnosis and management of the wide spectrum of neurological events post allogeneic hematopoietic cell transplantation (alloHCT) remain challenging. Therefore, we investigated their incidence, diagnosis, management and long-term prognosis in alloHCT recipients. METHODS: We retrospectively recorded data from consecutive alloHCT recipients with or without neurological complications in our center. RESULTS: Among 758 alloHCT recipients, 127 (16.8%) presented with neurological complications. Complications developed in central nervous system (89.7%) during the late post-transplant period. Neurological adverse events included a wide spectrum of infectious and non-infectious etiologies. With a median follow-up of 11.4 months, incidence of chronic graft-versus-host disease (GVHD) was 52.8%, relapse mortality 48.6%, transplant-related mortality 39.1% and 5-year overall survival (OS) 25.8% in patients with neurological complications. Timing of appearance of neurological complications, early or late, was associated only with acute and chronic graft-versus-host-disease/GVHD. Independent pre-transplant risk factors of neurological complications in the multivariate model were unrelated or alternative donors, ALL diagnosis and non-myeloablative conditioning. In multivariate analysis of post-alloHCT events, favorable OS was independently associated with resolution of neurological syndromes, absence of chronic GVHD and sibling transplantation. In our cohort, 10-year OS was significantly lower in patients with neurological complications and independently associated with acute and chronic GVHD, relapse, fungal and bacterial infections and neurological complications. CONCLUSIONS: Our large study with long-term follow-up highlights the wide spectrum of neurological complications in alloHCT. Accurate recognition is required for adequate management, a major determinant of survival. Thus, long-term increased awareness and collaboration between expert physicians is warranted.

Lacosamide as a first-line treatment option in focal epilepsy: a cost-utility analysis for the Greek healthcare system.

BACKGROUND AND AIMS: Epilepsy is the most common serious neurological disorder worldwide. Approximately 40% of patients with focal epileptic seizures remain uncontrolled with antiepileptic drug (AED) monotherapy or polytherapy. Lacosamide has been recently approved by the European Medicines Agency as monotherapy for the treatment of focal seizures. The aim of this study was to estimate the cost-effectiveness of lacosamide compared with zonisamide as first-line treatment of focal epilepsy in patients with epilepsy aged ≥ 16 years to inform clinical decision-making in Greece. METHODS: A discrete event simulation model was adapted to reflect treatment pathways and resource use within the Greek national healthcare system, as specified by clinical experts. The model captures time-varying events and patient characteristics. Clinical inputs were sourced from pivotal trials and a network meta-analysis comparing lacosamide with other AEDs. The model predicts disease progression and seizures, relevant and most common adverse events, withdrawal due to lack of efficacy or adverse events, and epilepsy-specific and all-cause mortality over a 2-year time horizon. Unit costs were retrieved from published Greek sources. Health outcomes were measured as quality-adjusted life years (QALYs); secondary outcome was the cost per seizure avoided. Robustness of the results was tested with univariate and probabilistic sensitivity analyses. RESULTS: The lacosamide treatment pathway was associated with higher costs (i.e. €1,064) and an additional 0.119 QALYs when compared with zonisamide, resulting in an incremental cost-effectiveness ratio of €8,938 per QALY gained. The sensitivity analyses demonstrated that the results are most sensitive to the efficacy and utility estimates. LIMITATIONS: There are a number of limitations which stem from the process of model adaptation and lack of local real-world evidence. CONCLUSIONS: Lacosamide is a cost-effective option at a willingness-to-pay threshold of €30,000 per QALY, representing a valuable monotherapy treatment option for patients with focal epileptic seizures in the Greek setting.

Male patient with mild cognitive impairment and extremely high P300 and Slow-wave latencies: a case report.

We present a case of a 74-year-old Greek male who suffered from paraphasias, memory and orientation problems. The patient was assessed with neuropsychometric tests, auditory event-related potentials and cerebrospinal fluid proteins and was diagnosed with mild cognitive impairment. The emphasis on the case is on the unexplained high levels of P300 and Slow wave of the auditory event-related potentials. P300 is believed to be delayed in Alzheimer's Disease (AD), however in our case it was extremely prolonged in baseline and follow-up examinations without AD being diagnosed. This might suggest that AD is a complex and multifactorial disease.

Usefulness of event-related potentials in the assessment of mild cognitive impairment.

BACKGROUND: The aim of this study was to determine if changes in latencies and amplitudes of the major waves of Auditory Event-Related Potentials (AERP), correlate with memory status of patients with mild cognitive impairment (MCI) and conversion to Alzheimer's disease (AD). 91 patients with MCI (mean +/- SD age = 66.6 +/- 5.4, MMSE score = 27.7) and 30 age-matched healthy control (AMHC) subjects (mean +/- SD age = 68.9 +/- 9.9) were studied. 54 patients were re-examined after an average period of 14(+/- 5.2) months. During this time period 5 patients converted to AD. Between-group differences in latency and amplitude of the major AERP waves (N200, P300 and Slow Wave) were determined. Within each group, correlation coefficients (CC) between these characteristics of the different AERP waves were calculated. Finally, for patients, CCs were determined among each AERP wave and their age and MMSE scores. Confirmatory factor analysis (CFA) was used to examine the underlying structure of waveforms both in the control and the patient groups. RESULTS: Latencies of all major AERP components were prolonged in patients compared to controls. Patients presented with significantly higher N200 amplitudes, but no significant differences were observed in P300 amplitudes. Significant differences between follow-up and baseline measurements were found for P300 latency (p = 0.009), N200 amplitude (p < 0.001) and P300 amplitude (p = 0.05). MMSE scores of patients did not correlate with latency or amplitude of the AERP components. Moreover, the establishment of a N200 latency cut-off value of 287 ms resulted in a sensitivity of 100% and a specificity of 91% in the prediction of MCI patients that converted to AD. CONCLUSION: Although we were not able to establish significant correlations between latencies and amplitudes of N200, P300 and SW and the patients' performance in MMSE, which is a psychometric test for classifying patients suffering from MCI, our results point out that the disorganization of the AERP waveform in MCI patients is a potential basis upon which a neurophysiologic methodology for identifying and "staging" MCI can be sought. We also found that delayed N200 latency not only identifies memory changes better than the MMSE, but also may be a potential predictor of the MCI patients who convert to AD.