Cognition in adult patients with newly diagnosed non-lesional temporal lobe epilepsy.

OBJECTIVE: To evaluate whether cognitive performance is affected in newly diagnosed temporal lobe epilepsy (TLE) and to determine the most vulnerable cognitive domains. METHODS: In this baseline longitudinal study, differences in memory and non-memory cognitive functions were assessed using comprehensive neuropsychological test batteries in 21 adult patients with newly diagnosed non-lesional TLE and individually matched controls. In addition, the analyses included ratings of self-perceived emotional status. RESULTS: The patients performed more poorly than the control group regarding delayed visual memory (p = 0.013) and executive function tasks related to switching (Trail Making Test and verbal fluency shifting; p = 0.025 and p = 0.03, respectively). We found no differences in verbal learning and memory, attention/working memory/processing speed, and other executive functions. SIGNIFICANCE: Our results show that patients with TLE often have specific cognitive deficits at time of diagnosis, even in the absence of structural brain abnormalities. This supports the hypothesis that memory dysfunction is linked to an underlying pathology rather than to the effect of recurrent seizures, long-term use of anti-seizure medication, or other epilepsy-related factors. As certain executive functions are affected at an early stage, the pathology may involve brain regions beyond the temporal lobe and may comprise larger brain networks. These results indicate the need for greater awareness of cognition at the time of diagnosis of TLE and before initiation of treatment, and integration of neuropsychological assessment into early routine clinical care.

Episodic Memory Dysfunction and Effective Connectivity in Adult Patients With Newly Diagnosed Nonlesional Temporal Lobe Epilepsy.

OBJECTIVE: Epilepsy is associated with both changes in brain connectivity and memory function, usually studied in the chronic patients. The aim of this study was to explore the presence of connectivity alterations measured by EEG in the parietofrontal network in patients with temporal lobe epilepsy (TLE), and to examine episodic memory, at the time point of diagnosis. METHODS: The parietofrontal network of newly diagnosed patients with TLE (N = 21) was assessed through electroencephalography (EEG) effective connectivity and compared with that of matched controls (N = 21). Furthermore, we assessed phenomenological aspects of episodic memory in both groups. Association between effective connectivity and episodic memory were assessed through correlation. RESULTS: Patients with TLE displayed decreased episodic (p ≤ 0.001, t = -5.18) memory scores compared with controls at the time point of diagnosis. The patients showed a decreased right parietofrontal connectivity (p = 0.03, F = 4.94) compared with controls, and significantly weaker connectivity in their right compared with their left hemisphere (p = 0.008, t = -2.93). There were no significant associations between effective connectivity and episodic memory scores. CONCLUSIONS: We found changes in both memory function and connectivity at the time point of diagnosis, supporting the notion that TLE involves complex memory functions and brain networks beyond the seizure focus to strongly interconnected brain regions, already early in the disease course. Whether the observed connectivity changes can be interpreted as functionally important to the alterations in memory function, it remains speculative.

Evaluation of long-term antiepileptic drug use in patients with temporal lobe epilepsy: Assessment of risk factors for drug resistance and polypharmacy.

PURPOSE: To evaluate risk factors for drug resistance and polypharmacy in patients with temporal lobe epilepsy. METHODS: Patients with temporal lobe epilepsy, treated for more than 5 years, completed questionnaires on antiepileptic drug use and effect. Logistic regression models were used for analysis of risk factors. RESULTS: Of 135 patients included in the study, 65% were classified as drug resistant and 41% identified as using polypharmacy. Poor effects associated with first-choice antiepileptic drug were reported by 59% of the patients, and 70% reported poor effects of second-line treatment. The most frequently used first-generation antiepileptic drugs had a similar mean effect to those of second-generation. Univariate regression analyses showed a significant association between drug resistance and mesial temporal sclerosis, seizure onset below 18 years, and lack of family history of epilepsy. However, multivariate regression analysis showed no association with any demographic or clinical features. Unsuccessful treatment with the first antiepileptic drug increased the risk of drug resistance by 18 times, and the risk of poor effect from the second antiepileptic drug by 9 times. Disease duration was associated with annual risk for drug resistance of 7% and for polypharmacy of 5%. CONCLUSIONS: A poor effect from initial pharmacotherapy is the only early risk factor for drug resistance found in this study. Long disease duration increases the risk of drug resistance and polypharmacy. Second-generation antiepileptic drugs provide no additional effect for poor responders to first-generation drugs.