Impact of Polytherapy on Memory Functioning in Patients With Drug-Resistant Epilepsy: The Role of Attention and Executive Functions.

OBJECTIVE: The aim was to examine the effect of polytherapy (i.e., the number of administered anti-seizure medications (ASMs)) on memory, and whether the interaction between the number of ASMs and attentional/executive functioning affect presurgical memory functioning and postsurgical memory changes in patients with drug-resistant epilepsy. METHODS: Two studies were carried out. Study 1 consisted of a presurgical assessment of 125 adult patients, in which attention/executive function (EpiTrack screening tool) and memory were assessed (cross-sectional study). Of them, 72 patients underwent a second postsurgical evaluation, in which memory was assessed (Study 2). Patients were distributed into groups based on EpiTrack performance and number of ASMs. RESULTS: The interaction between the number of ASMs and the attentional/executive functioning significantly affected presurgical memory, with patients with impaired EpiTrack performance taking three-four ASMs having poorer scores than patients with intact EpiTrack performance taking three-four ASMs (for all, p < .0001). This interaction also affected postsurgical memory changes, with patients with impaired Epitrack performance taking three-four ASMs having higher postsurgical decline than those with intact Epitrack performance taking three-four ASMs (for all, p < .005). No differences were found in patients taking two ASMs. Furthermore, the number of ASMs was associated with presurgical memory performance and postsurgical memory changes only in patients with impaired EpiTrack performance (for all, p < .05). CONCLUSIONS: Our findings underline the utility of EpiTrack, together with the clinical information on the number of prescribed ASMs, to corroborate the impact of polytherapy on memory and to optimize the prediction of postsurgical memory changes.

Risk and Protective Factors Associated with Drug Use in Healthcare Professionals: A Systematic Review.

Healthcare professionals are exposed to stressful situations that may favor substance use vulnerability. This systematic review aims to synthesize the risk and protective factors associated with use, abuse, and dependence of alcohol, tobacco, psychoactive drugs, and cannabis in healthcare professionals. Following PRISMA recommendations, a systematic search was performed in PsycINFO, Web of Science, PubMed/MEDLINE, Embase, Scopus, and Cochrane Library. The search yielded 1523 studies, of which 19 were selected. The identified risk factors were demographic factors (i.e. male gender, and single/divorced marital status), psychopathological factors, social factors, positive attitudes toward drugs, unhealthy lifestyle habits, the COVID-19 pandemic, and the coexistence of the use of several substances. The protective factors were demographic factors (i.e. ethnicity and having dependent children), healthy lifestyle habits, and workplace anti-drug policies (i.e. restriction of tobacco use). These findings highlight the need for preventive actions against drug use in healthcare professionals to improve their health and reduce the possible negative impact on their healthcare practice. Knowledge of modifiable risk and protective factors allows their incorporation as components in preventive actions, and non-modifiable factors (e.g. demographic variables) may contribute to the detection of groups of greater vulnerability to propose selective prevention actions in this population.

[Effects of cannabis use on attention and memory in adolescent population: a systematic review.] / Efectos del consumo de cannabis en la atención y la memoria en población adolescente: una revisión sistemática.

OBJECTIVE: Cannabis is an illegal drug whose use has increased in recent years, especially among adolescents. Despite its popularity, its use and abuse brings with it health consequences, being greater if consumption occurs in the adolescent stage, since the brain is in full development. The objective of this systematic review was to determine the effects of cannabis use on cognitive functions of attention and memory in adolescent population. METHODS: A systematic review of the literature was carried out in the main search portals (Pubmed, Web of Science, SciELO, Cochrane) referring to the last 10 years, following the PRISMA criteria. The systematic search strategy was carried out in the period from March to May 2021, applying the PICO method and the PEDro scale to guarantee the methodological quality of the included studies. RESULTS: Both attention and memory are affected by cannabis use; however, memory functions improve with abstinence, not being so for attention. Memory deficits are an indicator of therapeutic abandonment of addiction treatment. In relation to psychosocial interventions aimed at improving memory, the contingency management, educational interventions and motivational interviewing have not been shown to be effective on the effects of substances. Working memory training offers positive results, although not clinically significant. Finally, memory deficits are an indicator of therapeutic abandonment of pharmacological treatment for cannabis addiction. Therefore, research is needed aimed both at reducing the side effects of drugs on memory processes and at establishing to what extent memory deficits associated with cannabis use can facilitate therapeutic abandonment. CONCLUSIONS: More research is necessary, considering the dual consumption of cannabis-tobacco and the effects that both substances may have jointly and separately on attention and memory processes.

OBJETIVO: El cannabis es una droga ilegal cuyo consumo se ha visto incrementado en los últimos años, especialmente en población adolescente. A pesar de su popularidad, su uso y abuso trae consigo consecuencias para la salud, siendo mayores si el consumo se produce en la etapa adolescente, ya que el cerebro se encuentra en pleno desarrollo. El objetivo de esta revisión sistemática fue determinar los efectos del consumo de cannabis en las funciones cognitivas de atención y memoria en población adolescente. METODOS: Se llevó a cabo una revisión sistemática de la literatura en los principales portales de búsqueda (Pubmed, Web of Science, SciELO, Cochrane) referida a los últimos diez años, siguiendo los criterios PRISMA. La estrategia de búsqueda sistemática se realizó en el periodo de tiempo comprendido entre los meses de marzo a mayo de 2021, aplicándose el método PICO y la escala PEDro para garantizar la calidad metodológica de los estudios incluidos. RESULTADOS: Tanto la atención como la memoria se ven afectadas por el consumo de cannabis; sin embargo, la memoria mejora su funcionamiento con la abstinencia, no ocurriendo lo mismo con la atención. Los déficits de memoria son un indicador de abandono terapéutico del tratamiento para la adicción. En relación con las intervenciones psicosociales orientadas a la mejora de la memoria, tanto el manejo de contingencias como las intervenciones educativas y la entrevista motivacional no se han mostrado efectivas sobre los efectos de las sustancias. El entrenamiento en la memoria de trabajo ofrece resultados positivos, aunque clínicamente no significativos. Finalmente, los déficits de memoria son un indicador de abandono terapéutico del tratamiento farmacológico para la adicción al cannabis, por lo que se precisa investigación orientada tanto a reducir los efectos secundarios de los fármacos sobre los procesos mnésicos como a establecer en qué medida los déficits de memoria asociados al consumo de cannabis pueden facilitar el abandono terapéutico. CONCLUSIONES: Se precisa mayor investigación, considerando el consumo dual de cannabis-tabaco y los efectos que ambas sustancias pueden tener, conjuntamente y por separado, sobre los procesos de atención y memoria.

Clinical utility of Epitrack for differentiating profiles and patterns of post-surgical change in memory and quality of life in patients with drug-resistant epilepsy.

PURPOSE: To assess whether performance in attention and executive functions evaluated with the Epitrack screening tool before surgery can differentiate memory and quality of life (QOL) profiles, and detect different post-surgical change patterns in these variables in patients with epilepsy. METHODS: This is a longitudinal study. Seventy-seven patients with drug-resistant epilepsy (mean age = 37.91) underwent a neuropsychological assessment before and one year after surgery. Epitrack, a screening tool that exclusively evaluates attention and executive functioning, was administered in the pre-surgical assessment, and verbal and visual memory and QOL were assessed before and after surgery. RESULTS: Patients with impaired Epitrack performance had poorer verbal and visual memory than those with intact Epitrack performance, regardless of the time point (for all, p < 0.0001). They also showed a post-surgical decline in immediate verbal recall (p = 0.04) and discriminability (p = 0.001). Patients with intact Epitrack performance did not exhibit this decline. Epitrack total score significantly contributed to 13 and 11% of the variance of post-surgical changes in immediate verbal recall and discriminability, respectively. Epitrack groups did not differ in QOL profiles or changes, but post-surgical immediate verbal recall improvements were related to post-surgical QOL improvements. CONCLUSION: Our findings underline the utility of Epitrack screening tool to detect different patterns of verbal and visual memory dysfunction, as well as to predict post-surgical verbal memory decline in patients with drug-resistant epilepsy. Patients with lower pre-surgical Epitrack scores appear to be at increased risk for post-surgical memory decline.

Hippocampal Shape Is Associated with Memory Deficits in Temporal Lobe Epilepsy.

OBJECTIVE: Cognitive problems, especially disturbances in episodic memory, and hippocampal sclerosis are common in temporal lobe epilepsy (TLE), but little is known about the relationship of hippocampal morphology with memory. We aimed to relate hippocampal surface-shape patterns to verbal and visual learning. METHODS: We analyzed hippocampal surface shapes on high-resolution magnetic resonance images and the Adult Memory and Information Processing Battery in 145 unilateral refractory TLE patients undergoing epilepsy surgery, a validation set of 55 unilateral refractory TLE patients, and 39 age- and sex-matched healthy volunteers. RESULTS: Both left TLE (LTLE) and right TLE (RTLE) patients had lower verbal (LTLE 44 ± 11; RTLE 45 ± 10) and visual learning (LTLE 34 ± 8, RTLE 30 ± 8) scores than healthy controls (verbal 58 ± 8, visual 39 ± 6; p < 0.001). Verbal learning was more impaired the greater the atrophy of the left superolateral hippocampal head. In contrast, visual memory was worse with greater bilateral inferomedial hippocampal atrophy. Postsurgical verbal memory decline was more common in LTLE than in RTLE (reliable change index in LTLE 27% vs RTLE 7%, p = 0.006), whereas there were no differences in postsurgical visual memory decline between those groups. Preoperative atrophy of the left hippocampal tail predicted postsurgical verbal memory decline. INTERPRETATION: Memory deficits in TLE are associated with specific morphological alterations of the hippocampus, which could help stratify TLE patients into those at high versus low risk of presurgical or postsurgical memory deficits. This knowledge could improve planning and prognosis of selective epilepsy surgery and neuropsychological counseling in TLE. ANN NEUROL 2020 ANN NEUROL 2020;88:170-182.

Epilepsy surgery beyond 50 years: Long-term seizure and cognitive outcomes.

INTRODUCTION: Surgery is a well-demonstrated effective treatment for patients with refractory epilepsy. However, there are scarce data about the efficacy in older patients. Endpoint was to evaluate the outcome of epilepsy surgery in pharmacorresistant patients operated in middle-late adulthood. METHODS: We conducted a retrospective observational study including patients who underwent a epilepsy surgery at age ≥ 50. Presurgical clinical data, type of surgery, and postsurgical seizure outcome and neurological complications, including neuropsychological assessment were analyzed. Minimum post-surgical follow-up was 1 year. RESULTS: We identified 38 patients (22 males, 17 females) out of 350 patients who underwent a resective surgery with curative intention in our Epilepsy Unit (12%). Median age at surgery was 56 years (50-69), with median epilepsy duration of 42 years (4-67). Neuroimaging showed focal epileptogenic lesions in 37 patients, mainly mesial temporal sclerosis (21). Presurgical neuropsychological evaluation was available in 38 patients: 35 had deficits, mostly in verbal or visual memory. Twenty-eight patients underwent standard temporal lobectomy with amygdalohippocampectomy, 7 lesionectomy and 4 lobectomy. Median follow-up was 4.46 years (1-9.75). A good outcome was achieved by 86.8% (28 Engel I; 5 Engel II); 5 patients were studied with SEEG, without any complications. None had postsurgical permanent neurological complications. From 22 patients with available post-surgical neuropsychological assessment, 16 scored lower than in pre-surgical one, mainly in memory domain. CONCLUSION: Surgical treatment of long-term refractory epilepsy in patients ≥50 years can be effective and safe. Post-surgical memory decline is a frequent side effect, but with a low impact in daily life.

Typical asymmetry in the hemispheric activation during an fMRI verbal comprehension paradigm is related to better performance in verbal and non-verbal tasks in patients with epilepsy.

Chronic exposure to seizures in patients with left hemisphere (LH) epileptic focus could favor higher activation in the contralateral hemisphere during language processing, but the cognitive effects of this remain unclear. This study assesses the relationship between asymmetry in hemispheric activation during language fMRI and performance in verbal and non-verbal tasks. Whereas prior studies primarily used fMRI paradigms that favor frontal lobe activation and less prominent activation of the medial or superior temporal lobes, we used a verbal comprehension paradigm previously demonstrated to activate reliably receptive language areas. Forty-seven patients with drug-resistant epilepsy candidates for surgery underwent a multidisciplinary assessment, including a comprehensive neuropsychological evaluation and an fMRI verbal comprehension paradigm. Patients were distributed in two groups depending on laterality indexes (LI): typical hemispheric asymmetry (unilateral left activation preponderance; n = 23) and atypical hemispheric asymmetry (bilateral or unilateral right preponderance; n = 24). Right-handedness and right hemisphere (RH) focus were significant predictors of typical asymmetry. Patients with typical activation pattern presented better performance intelligence quotient and verbal learning than patients with atypical hemispheric asymmetry (for all, p < 0.014). Patients with LH focus had more frequently atypical hemispheric asymmetry than patients with RH focus (p = 0.05). Specifically, they showed lower LI and this was related to worse performance in verbal and non-verbal tasks. In conclusion, an increased activation of homologous RH areas for verbal comprehension processing could imply a competition of cognitive resources in the performance of the same task, disrupting cognitive performance.

Antiepileptic drug reduction and increased risk of stimulation-evoked focal to bilateral tonic-clonic seizure during cortical stimulation in patients with focal epilepsy.

INTRODUCTION: Stimulation-evoked focal to bilateral tonic-clonic seizure (FBTCS) can be a stressful and possibly harmful adverse event for patients during cortical stimulation (CS). We evaluated if drug load reduction of antiepileptic drugs (AEDs) during CS increases the risk of stimulation-evoked FBTCS. MATERIAL AND METHODS: In this retrospective cohort study, we searched our local database for patients with drug-resistant epilepsy who underwent invasive video-EEG monitoring and CS in the University Hospital la Fe Valencia from January 2006 to November 2016. The AED drug load was calculated with the defined daily dose. We applied a uni- and multivariate logistic regression model to estimate the risk of stimulation-evoked FBTCS and evaluate possible influencing factors. Furthermore, we compared patients whose AEDs were completely withdrawn with those whose AEDs were not. RESULTS: Fifty-eight patients met the inclusion criteria and were included in the analysis. Stimulating 3806 electrode contact pairs, 152 seizures were evoked in 28 patients (48.3%). Ten seizures (6.6%) in seven patients (12.1%) evolved to FBTCS. In the univariate and multivariate analysis, a 10% reduction in drug load was associated with an increase of the odds ratio (OR) of stimulation-evoked FBTCS by 1.9 (95%-CI 1.2, 4.0, p-value=0.04) and 1.9 (95%-CI 1.2, 4.6, p-value=0.04), respectively. In patients, whose AEDs were completely withdrawn the OR of FBTCS increased by 9.1 (95%CI 1.7, 69.9, p-value=0.01) compared with patients whose AEDs were not completely withdrawn. No other factor (implantation type, maximum stimulus intensity, number of stimulated contacts, history of FBTCS, age, gender, or epilepsy type) appears to have a significant effect on the risk of stimulation-evoked FBTCS. CONCLUSIONS: The overall risk of stimulation-evoked FBTCS during CS is relatively low. However, a stronger reduction and, especially, a complete withdrawal of AEDs are associated with an increased risk of stimulation-evoked FBTCS.

Age at surgery as a predictor of cognitive improvements in patients with drug-resistant temporal epilepsy.

Temporal lobe epilepsy (TLE) surgery is an effective procedure that can produce cognitive changes. However, the prognostic factors related with cognitive outcomes need to be better understood. The aim of the present study is to know if age at surgery is a reliable predictor of verbal memory competence and considering factors such as: hemisphere; type of surgery; pre-surgical seizure frequency; and epilepsy duration. Sixty-one typically dominant patients with drug-resistant TLE (34 with left TLE [L-TLE] and 27 with right TLE [R-TLE]) underwent a neuropsychological assessment before and a year after surgery. Results showed that R-TLE patients had better evolution in short- and long-term verbal memory and naming than L-TLE patients (for all, p >.04). L-TLE patients also more frequently showed a strong and reliable decline in these functions than R-TLE patients. No effects for gender or type of surgery were found. From a multivariate approach, patients with improvements in verbal competence underwent surgery at earlier ages and suffered epilepsy for less time (for all, p <0.4). The relevance of age at surgery was confirmed as a predictor of long-term verbal memory changes, although the frequency of partial seizures also explains, at least partially, these changes. In addition, the frequency of partial seizures explains short-term verbal memory changes. These results emphasize the importance of early intervention, independently of the resected hemisphere, in order to minimize the cognitive side-effects of epilepsy treatment, as well the need to consider cognitive functions as related processes and network dependent.