Concurrent mood and anxiety disorders are associated with pharmacoresistant seizures in patients with MTLE

Nogueira, Mateus Henrique; Yasuda, Clarissa Lin; Coan, Ana Carolina; Kanner, Andrés M.; Cendes, Fernando

doi:10.1111/epi.13781

Cited by 84 publications

(72 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our cohort, the odds ratio of pharmacoresistance with co‐occurrence of anxiety and depressive symptoms was 7.7, in accordance with a recent report of an odds ratio of 6.1 for refractoriness when patients presented a psychiatric disorder (including depression, anxiety, and schizophrenia) . These results are consistent with our recent temporal lobe epilepsy analyses, as the odds ratio of pharmacoresistance with concurrent anxiety and mood disorders was 4.4, reinforcing the hypothesis of common neurobiological mechanisms between epilepsy and psychiatric disorders . Although the natural idea is that pharmacoresistant seizures cause anxiety and depression, both animal models and population‐based studies have provided evidence of a more bidirectional relationship between psychiatric disorders and epilepsy.…”

Section: Discussionsupporting

confidence: 92%

Anxiety and depression symptoms disrupt resting state connectivity in patients with genetic generalized epilepsies

et al. 2019

Self Cite

View full text Add to dashboard Cite

Summary Objective To analyze the lifetime trajectories in genetic generalized epilepsies (GGEs) and investigate the impact of symptoms of anxiety and depression on resting state functional connectivity (FC). Methods Seventy‐four GGE patients were classified according to the pharmacological response as seizure‐free (12 patients), pharmacoresistant (PhR; 14 patients), and fluctuating (FL; 48 patients). Fifty‐four subjects completed both the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), and 38 also underwent 3‐T resting state functional magnetic resonance imaging. These 38 patients were subdivided into a positive group (13 patients with concurrent symptoms of depression and anxiety) and a negative group (21 asymptomatic patients and four with mild anxiety or depression symptoms). For FC analysis of resting state networks, we matched 38 healthy asymptomatic volunteers and used the UF2C toolbox running on MATLAB2017/SPM12. Results The PhR group presented shorter duration of epilepsy (P = 0.016) and follow‐up (P < 0.001) compared to the FL group. The PhR group showed higher levels (median = 20) on the BAI and BDI. Myoclonic seizures were the most difficult to control, as 50% of subjects persisted with them at last appointment, compared to generalized tonic–clonic seizures and absence seizures (<40%). Patients with concurrent anxiety and depression symptoms were 7.7 times more likely to exhibit pharmacoresistant seizures, although an increase of 1 year of epilepsy duration was associated with a decrease in the odds of presenting pharmacoresistance by a factor of 0.9. Overall, FC was altered between default mode network (DMN) and visuospatial/dorsal attention. However, only the positive group displayed abnormal FC between DMN and left executive control network, and between salience and visuospatial/dorsal attention. Significance Our findings may help clinicians to have a better understanding of GGE clinical course and increase attention to the potential relationship of psychopathologies and brain connectivity.

show abstract

Section: Discussionsupporting

confidence: 92%

Anxiety and depression symptoms disrupt resting state connectivity in patients with genetic generalized epilepsies

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has been established long time ago that depression is a better indicator of quality of life than seizure frequency itself (36). It is now becoming evident that depression is also associated with poor response to the antiepileptic drug treatment (37,38), poor outcome after epilepsy surgery (39,40), increased seizure severity (41), increased risk of injury (42) and premature mortality (43). Future studies need to clarify whether early identification and prompt treatment of psychiatric comorbidities can have an impact on the prognosis of the epilepsy or whether they just represent indicators of poor prognosis.…”

Section: Psychiatric Comorbidities As a Poor Prognostic Marker In Adumentioning

confidence: 99%

Common psychiatric comorbidities in epilepsy: How big of a problem is it?

Salpekar

Mula

2019

Epilepsy & Behavior

View full text Add to dashboard Cite

Psychiatric illness and epilepsy commonly co-occur in adults and in children and adolescents. Theories of comorbidity are complex, but recurring associations between the conditions suggest overlap that is more than simple co-occurrence. Common underlying pathophysiology may imply that epilepsy itself may constituently include psychiatric symptoms. Conditions such as depression or cognitive difficulties commonly occur and in some cases, are considered to be associated with specific epilepsy characteristics such as localization or seizure type. Regardless of etiologic attributions to psychiatric comorbidity, it is clear today that treatment for epilepsy needs to target psychiatric illness. In many cases, quality-of-life improvements depend more upon addressing psychiatric symptoms than seizures themselves.

show abstract

“…These so-called mesial temporal lobe epilepsies (mTLEs) cannot be cured, and the currently available pharmacological options cause significant unwanted side effects and are ineffective in up to onethird of the patients (Kwan and Brodie, 2000;Engel et al, 2012). These patients continue to experience seizures, and, in many cases, their seizures increase in frequency and are associated with significant cognitive decline and psychiatric disorders (Aldenkamp and Arends, 2004;Lin et al, 2012;Nogueira et al, 2017). The focal nature of mTLE opens the opportunity for direct therapeutic options including surgery, local radiation, and deep brain stimulation.…”

Section: Introductionmentioning

confidence: 99%

Long-Term, Targeted Delivery of GDNF from Encapsulated Cells Is Neuroprotective and Reduces Seizures in the Pilocarpine Model of Epilepsy

et al. 2019

View full text Add to dashboard Cite

Neurotrophic factors are candidates for treating epilepsy, but their development has been hampered by difficulties in achieving stable and targeted delivery of efficacious concentrations within the desired brain region. We have developed an encapsulated cell technology that overcomes these obstacles by providing a targeted, continuous, de novo synthesized source of high levels of neurotrophic molecules from human clonal ARPE-19 cells encapsulated into hollow fiber membranes. Here we illustrate the potential of this approach for delivering glial cell line-derived neurotrophic factor (GDNF) directly to the hippocampus of epileptic rats. In vivo studies demonstrated that bilateral intrahippocampal implants continued to secrete GDNF that produced high hippocampal GDNF tissue levels in a long-term manner. Identical implants robustly reduced seizure frequency in the pilocarpine model. Seizures were reduced rapidly, and this effect increased in magnitude over 3 months, ultimately leading to a reduction of seizures by 93%. This effect persisted even after device removal, suggesting potential disease-modifying benefits. Importantly, seizure reduction was associated with normalized changes in anxiety and improved cognitive performance. Immunohistochemical analyses revealed that the neurological benefits of GDNF were associated with the normalization of anatomical alterations accompanying chronic epilepsy, including hippocampal atrophy, cell degeneration, loss of parvalbumin-positive interneurons, and abnormal neurogenesis. These effects were associated with the activation of GDNF receptors. All in all, these results support the concept that the implantation of encapsulated GDNF-secreting cells can deliver GDNF in a sustained, targeted, and efficacious manner, paving the way for continuing preclinical evaluation and eventual clinical translation of this approach for epilepsy.Epilepsy is one of the most common neurological conditions, affecting millions of individuals of all ages. These patients experience debilitating seizures that frequently increase over time and can associate with significant cognitive decline and psychiatric disorders that are generally poorly controlled by pharmacotherapy. We have developed a clinically validated, implantable cell encapsulation system that delivers high and consistent levels of GDNF directly to the brain. In epileptic animals, this system produced a progressive and permanent reduction (Ͼ90%) in seizure frequency. These benefits were accompanied by improvements in cognitive and anxiolytic behavior and the normalization of changes in CNS anatomy that underlie chronic epilepsy. Together, these data suggest a novel means of tackling the frequently intractable neurological consequences of this devastating disorder.

show abstract

Concurrent mood and anxiety disorders are associated with pharmacoresistant seizures in patients with MTLE

Cited by 84 publications

References 37 publications

Anxiety and depression symptoms disrupt resting state connectivity in patients with genetic generalized epilepsies

Anxiety and depression symptoms disrupt resting state connectivity in patients with genetic generalized epilepsies

Common psychiatric comorbidities in epilepsy: How big of a problem is it?

Long-Term, Targeted Delivery of GDNF from Encapsulated Cells Is Neuroprotective and Reduces Seizures in the Pilocarpine Model of Epilepsy

Contact Info

Product

Resources

About