Neurobiologic properties of mood disorders may have an impact on epilepsy: Should this motivate neurologists to screen for this psychiatric comorbidity in these patients?

Epilepsy and psychiatric comorbidities have a complex relation, which can be manifested by their relatively high comorbid occurrence and the existence of a bidirectional relation, whereby not only are people with epilepsy (PWE) at greater risk of developing psychiatric disorders, but patients with primary psychiatric disorders are at higher risk of developing epilepsy. The existence of common pathogenic mechanisms operant in primary psychiatric disorders and epilepsy has been postulated as one of the leading hypothesis to explain their close and very complex relation. The neurobiologic characteristics of mood disorders can be used as a model to test this hypothesis. In this manuscript, we highlight data that suggest how several neurobiologic aspects of mood disorders can facilitate the epileptogenic process in animal models and explain the increased risk of patients with primary mood disorders to develop epilepsy in general and treatment-resistant epilepsy in particular. It is our hope that the inclusion of these data in this Special Issue will motivate neurologists to screen common psychiatric comorbidities in PWE. This article is part of the Special Issue "Obstacles of Treatment of Psychiatric Comorbidities in Epilepsy"

Bidirectional relations among common psychiatric and neurologic comorbidities and epilepsy: Do they have an impact on the course of the seizure disorder?

The treatment of epilepsy is not limited to the achievement of a seizure‐free state. It must also incorporate the management of common psychiatric and neurologic comorbidities, affecting on average between 30 and 50% of patients with epilepsy, which have a significant impact on their lives at various levels, including quality of life and the prognosis of the seizure disorder. Mood and anxiety disorders are the most frequent psychiatric comorbidities, whereas stroke and migraine are among the more common neurologic comorbidities, migraine among the younger patients and stroke among the older patients. Not only do these psychiatric and neurologic comorbidities each have a bidirectional relation with epilepsy, but primary mood disorders have a bidirectional relation with these 2 neurologic disorders. Furthermore, depression and migraine have been each associated with a more severe epilepsy course, whereas depression has been associated with a more severe course of stroke and migraines. The purpose of this article is to review the clinical implications of the complex relations among epilepsy and these 3 comorbid disorders, and to identify any clinical and/or experimental evidence that may suggest that having more than one of these comorbid disorders may increase the risk of and course of epilepsy

The impact of antidepressants on seizure frequency and depressive and anxiety disorders of patients with epilepsy: Is it worth investigating?

Depression and anxiety disorders in patients with epilepsy (PWE) remain under-recognized and under-treated, despite being the most common psychiatric co-morbidities. Selective serotonin re-uptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) are considered first-line treatment for primary depression and anxiety disorders. We performed this study to investigate if SSRIs and SNRIs could affect the seizure frequency of PWE and to assess whether such effect is independent of the response of the mood and anxiety disorders to these drugs. This was a retrospective study of 100 consecutive PWE who were started on an SSRI or SNRI for the treatment of a depressive and/or anxiety disorder. Every patient underwent a psychiatric evaluation by one of the investigators using a semi-structured interview who also managed the pharmacologic treatment in all the patients. Patients were excluded if they had a diagnosis of psychogenic non-epileptic seizures or if they had undergone epilepsy surgery or the implant of the vagal nerve stimulator six months before and after the start of the antidepressant therapy. The final analysis was conducted in 84 patients. For each type of seizure, an average and maximal monthly seizure frequency during the six months preceding and following the start of psychotropic drugs was extracted from the medical records. We identified the number of patients whose seizure frequency during treatment with antidepressants: (i) shifted from a <1/month to a ≥1 seizure/month and vice-versa, (ii) increased beyond maximal/monthly baseline frequency, and (iii) patients who developed de-novo generalized tonic-clonic (GTC) seizures. None of the patients with a baseline seizure frequency 50% reduction in seizure frequency after the start of treatment with SSRIs or SNRIs. A therapeutic response to SSRIs and SNRIs was found in 73% of patients. The change in seizure frequency was independent of the improvement in psychiatric symptomatology. In this retrospective observational study, SSRIs or SNRIs did not appear to worsen seizure frequency. Also, in patients with frequent seizures, SSRIs and SNRIs may be associated with a possible decrease in seizure frequency. Furthermore, these drugs appear to yield good therapeutic response of psychiatric symptoms independently of seizure frequency. It is pivotal to replicate these data in prospective, double-blind, placebo-controlled trials. •Depression and anxiety are common co-morbidities in patients with epilepsy, which remain under-recognized and under-treated.•This study investigated the impact of SSRIs and SNRIs in the seizure frequency of patients with epilepsy.•SSRIs or SNRIs did not appear to worsen seizure frequency.•In patients with frequent seizures, SSRIs and SNRIs may be associated with a decrease in seizure frequency.•The change in seizure frequency was independent of the improvement in psychiatric symptomatology

Bidirectional relations among common psychiatric and neurologic comorbidities and epilepsy: Do they have an impact on the course of the seizure disorder?

The treatment of epilepsy is not limited to the achievement of a seizure-free state. It must also incorporate the management of common psychiatric and neurologic comorbidities, affecting on average between 30 and 50% of patients with epilepsy, which have a significant impact on their lives at various levels, including quality of life and the prognosis of the seizure disorder. Mood and anxiety disorders are the most frequent psychiatric comorbidities, whereas stroke and migraine are among the more common neurologic comorbidities, migraine among the younger patients and stroke among the older patients. Not only do these psychiatric and neurologic comorbidities each have a bidirectional relation with epilepsy, but primary mood disorders have a bidirectional relation with these 2 neurologic disorders. Furthermore, depression and migraine have been each associated with a more severe epilepsy course, whereas depression has been associated with a more severe course of stroke and migraines. The purpose of this article is to review the clinical implications of the complex relations among epilepsy and these 3 comorbid disorders, and to identify any clinical and/or experimental evidence that may suggest that having more than one of these comorbid disorders may increase the risk of and course of epilepsy

Magnetic Resonance–Guided Laser Interstitial Thermal Therapy for Mesial Temporal Epilepsy: A Case Series Analysis of Outcomes and Complications at 2-Year Follow-Up

Laser interstitial thermal therapy (LITT) presents an important new minimally invasive tool in the management of drug-resistant mesial temporal epilepsy (MTE). However, because of its relative novelty, not much is known about long-term seizure freedom rates. The objective of this study was to evaluate the postsurgical seizure outcome following LITT after a minimum follow-up period of 2 years. Medical records of all patients who underwent LITT for MTE from 2013 to 2018 at our comprehensive epilepsy center under a single surgeon were retrospectively reviewed. Data related to demographics, presurgical evaluations, and seizure outcome were compared between seizure-free (SF) and non–seizure-free (NSF) patients. In all, 26 patients were identified with at least 2 years of follow-up. Mean age was 43.8 years ± 11.6 years, and 46.2% were female. After a mean follow-up time of 42.9 months (range, 24.3–58.8 months), 61.5% (16/26) were free of disabling seizures, and 26.9% (7/26) had only rare disabling seizures. Whereas seizure-freedom rates between patients with and without mesial temporal sclerosis (MTS) were not statistically different (68% vs. 43%, P = 0.23), NSF patients without MTS had a shorter median time to first seizure than did NSF patients with MTS (0.55 month vs. 10 months, log-rank test P = 0.007). Postoperative complications occurred in 2 patients (7.7%), consisting of 1 permanent and 1 transient homonymous hemianopia. LITT appears to be a safe and effective initial surgical option for treatment-resistant MTE. Among patients who have seizures after treatment, those without MTS appear to have seizures earlier than those with MTS

Long-term seizure and psychiatric outcomes following laser ablation of mesial temporal structures

Postsurgical seizure outcome following laser interstitial thermal therapy (LiTT) for the management of drug-resistant mesial temporal lobe epilepsy (MTLE) has been limited to 2 years. Furthermore, its impact on presurgical mood and anxiety disorders has not been investigated. The objectives of this study were (1) to identify seizure outcome changes over a period ranging from 18 to 81 months; (2) to investigate the seizure-free rate in the last follow-up year; (3) to identify the variables associated with seizure freedom; and (4) to identify the impact of LiTT on presurgical mood and anxiety disorders. Medical records of all patients who underwent LiTT for MTLE from 2013 to 2019 at the University of Miami Comprehensive Epilepsy Center were retrospectively reviewed. Demographic, epilepsy-related, cognitive, psychiatric, and LiTT-related data were compared between seizure-free (Engel Class I) and non-seizure-free (Engel Class II + III + IV) patients. Statistical analyses included univariate and multivariate stepwise logistic regression analyses. Forty-eight patients (mean age = 43 ± 14.2 years, range = 21-78) were followed for a mean period of 50 ± 20.7 months (range = 18-81); 29 (60.4%) achieved an Engel Class I outcome, whereas 11 (22.9%) had one to three seizures/year. Seizure-freedom rate decreased from 77.8% to 50% among patients with 24- and >61-month follow-up periods, respectively. In the last follow-up year, 83% of all patients were seizure-free. Seizure freedom was associated with having mesial temporal sclerosis (MTS), no presurgical focal to bilateral tonic-clonic seizures, and no psychopathology in the last follow-up year. Presurgical mood and/or anxiety disorder were identified in 30 patients (62.5%) and remitted after LiTT in 19 (62%). LiTT appears to be a safe and effective surgical option for treatment-resistant MTLE, particularly among patients with MTS. Remission of presurgical mood and anxiety disorders can also result from LiTT

Cognitive outcomes following laser interstitial therapy for mesiotemporal epilepsies

ObjectiveTo provide a review of cognitive outcomes across a full neuropsychological profile in patients who underwent laser interstitial thermal therapy (LiTT) for mesiotemporal epilepsy (mTLE).MethodsWe examined cognitive outcomes following LiTT for mTLE by reviewing a consecutive series of 26 patients who underwent dominant or nondominant hemisphere procedures. Each patient's pre- and postsurgical performance was examined for clinically significant change (>1SD improvement or decline on standardized scores), with a neuropsychologic battery that included measures of language, memory, executive functioning, and processing speed.ResultsPresurgical performance was largely consistent with previous research, where patients suffering from dominant hemisphere epilepsies demonstrated deficits in verbal learning and memory, whereas patients with nondominant hemisphere scored lower on visually mediated tests. Case-by-case review comparing presurgical to postsurgical scores revealed clinically significant improvement in both dominant and nondominant patients in learning and memory and other aspects of cognition such as processing speed and executive functioning. Of the few patients who did experience clinically significant decline following LiTT, a greater proportion had undergone dominant hemisphere procedures.ConclusionsCompared with the outcome literature of dominant open anterior temporal lobectomies (ATLs), where postsurgical decline has been documented in up to 40%–60% of cases, our LiTT case series exhibited a much lower incidence of postoperative language or verbal memory decline. Moreover, promising rates of postoperative improvements were also observed across multiple cognitive domains. Future studies exploring cognitive outcomes following LiTT should include comprehensive neuropsychological findings, rather than only select domains, as clinically significant change can occur in areas other than those typically associated with mesiotemporal structures