Hippocampal activations obtained during language fMRI tasks: A complementary tool for predicting postoperative memory prognosis.

In medial temporal lobe epilepsy (MTLE), the benefits of surgery must be balanced against the risk of post-operative memory decline. Prediction of postoperative outcomes based on functional magnetic resonance imaging (fMRI) tasks is increasingly common but remains uncertain. The aim of this retrospective study was to determine whether hippocampal activations elicited by fMRI language tasks could enhance or refine memory fMRI in MTLE patients candidates to surgery. Forty-six patients were included: 30 right and 16 left MTLE, mostly with hippocampal sclerosis. Preoperative assessment included neuropsychological tests and fMRI with language (syntactic verbal fluency) and memory tasks (encoding, delayed, and immediate recognition of images of objects). Thirty patients underwent surgery and had neuropsychological evaluations one year after surgery. Worsening was defined as a degradation of more than 10 % in postoperative forgetting scores compared to preoperative scores in verbal, non-verbal and global memory. Memory fMRI had the best sensitivity with hippocampal activations obtained in 95 % of patients, versus 65 % with language fMRI. Considering the patients who elicited an hippocampal activation, language fMRI led to 80 %, 65 % and 85 % of correct predictions for respectively global, verbal and non verbal memory (versus 71 %, 64 % and 68 % with memory fMRI). Memory and language fMRI predictions outperformed those made by neuropsychological tests. In summary, language fMRI was less sensitive than memory fMRI to elicit hippocampal activations but when it did, the proportion of correct memory predictions was better. Moreover, it proved to be an independent predictive factor regardless of the side of the epileptic focus. Given the ease of setting up a language task in fMRI, we recommend the systematic combination of memory and language tasks to predict the post-operative memory outcome of MTLE patients undergoing epilepsy surgery.

Resective surgery for mesial temporal lobe epilepsy associated with hippocampal sclerosis in patients over 50 years: a case-control study.

BACKGROUND: Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE/HS) is the most common cause of drug-resistant focal seizures and surgical resection is the primary treatment option, with seizure-free rates ranging from 60 to 80%. However, data on postsurgical seizure outcomes in patients ≥ 50 years of age are limited. This study aimed to assess the efficacy and safety of surgery in this age group compared to younger patients. METHODS: We performed a retrospective analysis of data from resective surgeries conducted in patients with MTLE/HS between 1990 and 2022. We focused on patients aged ≥ 50 years and compared the surgical safety and efficacy variables between this group and a control group of patients aged < 50 years through a case-control study. RESULTS: Among the 450 MTLE/HS patients who underwent surgery during the inclusion period, 61 (13.6%) were aged ≥ 50 years and matched with 183 younger patients, totaling 244 study participants. The two groups had similar characteristics. At the last follow-up (median 5.7 years), Engel I outcomes were achieved in 80.3% of the older patients and 81.4% of the younger patients, with no significant difference (p = 0.85). Postoperative cognitive and psychiatric outcomes did not differ between the groups. Major complication rates were also comparable, at 3.3% in the older group and 2.7% in the younger group (p = 0.83). The extratemporal ictal abnormalities observed on video-EEG were the only variable that demonstrated a significant association with an unfavorable seizure outcome in the older group (OR 9.3, 95% CI [1.8-47.6], p = 0.005). CONCLUSIONS: This study provides grade 3 evidence that resective surgery for MTLE/HS patients aged ≥ 50 years is as effective and safe as it is for younger patients, and thus should be considered as the primary treatment option for drug-resistant cases.

Cognitive effect of antiseizure medications in medial temporal lobe epilepsy.

BACKGROUND AND PURPOSE: The specific effects of antiseizure medications (ASMs) on cognition are a rich field of study, with many ongoing questions. The aim of this study was to evaluate these effects in a homogeneous group of patients with epilepsy to guide clinicians to choose the most appropriate medications. METHODS: We retrospectively identified 287 refractory patients with medial temporal lobe epilepsy associated with hippocampal sclerosis. Scores measuring general cognition (global, verbal and performance IQ), working memory, episodic memory, executive functions, and language abilities were correlated with ASM type, number, dosage and generation (old vs. new). We also assessed non-modifiable factors affecting cognition, such as demographics and epilepsy-related factors. RESULTS: Key parameters were total number of ASMs and specific medications, especially topiramate (TPM) and sodium valproate (VPA). Four cognitive profiles of the ASMs were identified: (i) drugs with an overall detrimental effect on cognition (TPM, VPA); (ii) drugs with negative effects on specific areas: verbal memory and language skills (carbamazepine), and language functions (zonisamide); (iii) drugs affecting a single function in a specific and limited area: visual denomination (oxcarbazepine, lacosamide); and (iv) drugs without documented cognitive side effects. Non-modifiable factors such as age at testing, age at seizure onset, and history of febrile seizures also influenced cognition and were notably influenced by total number of ASMs. CONCLUSION: We conclude that ASMs significantly impact cognition. Key parameters were total number of ASMs and specific medications, especially TPM and VPA. These results should lead to a reduction in the number of drugs received and the avoidance of medications with unfavorable cognitive profiles.

Distinctive neuropsychological profiles of lateral temporal lobe epilepsy.

OBJECTIVE: Lateral temporal lobe epilepsies (LTLE) are poorly characterized heterogeneous epilepsies. As the lateral temporal lobe supports distinct functions, we hypothesized that neuropsychological profiles could differ according to the localization of the seizure focus within the lateral temporal lobe. METHODS: We retrospectively examined the neuropsychological characteristics of 74 consecutive patients with refractory LTLE assessed in the context of a presurgical investigation at the Pitié-Salpêtrière Hospital in Paris between 1998 and 2018. Precise localization of the epileptic focus was correlated with scores on tests of intelligence (Global, Verbal and Performance IQ), working memory, episodic memory (verbal and visual learning and forgetting), executive functions, and language abilities. RESULTS: We demonstrated an impact of the localization of the epileptic focus within the lateral temporal lobe with worse learning and/or executive performances depicted in the infero-basal and pure pole LTLE groups and greater language difficulties in the posterior LTLE group, Antiepileptic drugs had a greater effect than parameters related to the epilepsy itself as the lesion or the disease duration, and finally as in medial TLE, the age, education, and sex influenced some cognitive performances. CONCLUSION: Our findings show that the lateral temporal neocortex is also part of the neural substrate for memory processing and executive functions and suggest that this involvement could be related to functions devoted to specific subregions of the temporal lobe (i.e., temporal pole, inferior and basal regions) that support language and semantic processing.

Cognitive impairment in temporal lobe epilepsy: contributions of lesion, localization and lateralization.

BACKGROUND: Cognitive impairment is an important comorbidity of refractory temporal lobe epilepsy (TLE). We aimed to explore the impact of (i) specific lesions, such as dysembryoplastic neuroepithelial tumor (DNET), dysplasia, or hippocampal sclerosis, (ii) focus localization (medial versus lateral) and (iii) focus lateralization (right versus left) on the neuropsychological profile of refractory TLE adult patients. METHODS: We examined the neuropsychological characteristics of 312 adults with refractory TLE: 100 patients without hippocampal sclerosis (HS) and 212 with HS. Scores on tests of intelligence (Global IQ, Verbal IQ and Performance IQ), working memory, episodic memory (verbal and visual learning and forgetting), executive functions and language abilities were analyzed. RESULTS: Three main factors influenced the neuropsychological profile of refractory TLE patients: (i) the lesion, patients with HS obtaining poorer cognitive performances than patients without HS and specifically DNET patients performing better than patients with HS, (ii) the focus side, that seems only relevant for verbal memory abilities which are affected in left but not right TLE patients and (iii) the localization of seizure focus, patients with medial TLE exhibiting lower memory performances than patients with lateral TLE. CONCLUSION: Lesion, localization and lateralization are major contributors of the cognitive impairment depicted in TLE. Hippocampal sclerosis appears as the main contributor.

Evaluation of psychomotor functions in patients with drug-resistant epilepsy.

PURPOSE: This study aimed to describe and analyze psychomotor functions in patients with drug-resistant epilepsy and identify factors associated with psychomotor deficits. METHODS: We performed a prospective case-control study comparing psychomotor skill performances in 40 adult patients and 80 healthy individuals between October 2017 and March 2018. Psychomotor functions were examined in both patients and controls using a full set of specific tests (Rey-Osterrieth complex figure test, Zazzo's cancelation task, Piaget-Head test, and paired images test). Potential risk factors for psychomotor deficit were assessed in the patient group using a multivariate analysis. RESULTS: The two groups did not differ in age, sex, dominant hand, and level of education. Compared with the control group, patients with drug-resistant epilepsy showed worse performance on global psychomotor functions and, more selectively, in assessments exploring perceptual organization and visuospatial memory, laterality awareness, sustained attention, concentration, visual scanning, inhibition, and impulsivity. In the patient group, psychomotor deficits were associated with the severity of epilepsy (epileptic encephalopathy, high seizure frequency, heavy antiepileptic medication). CONCLUSION: Psychomotor deficits could therefore be systematically detected in patients with drug-resistant epilepsy in order to provide psychomotor therapy and improve quality of life.