Nikolaos Vlaikidis

Depression and anxiety in epilepsy: the association with demographic and seizure-related variables

BackgroundDepression and anxiety are common psychiatric symptoms in patients with epilepsy, exerting a profound negative effect on health-related quality of life. Several issues, however, pertaining to their association with psychosocial, seizure-related and medication factors, remain controversial. Accordingly, the present study was designed to investigate the association of interictal mood disorders with various demographic and seizure-related variables in patients with newly-diagnosed and chronic epilepsy.MethodsWe investigated 201 patients with epilepsy (51.2% males, mean age 33.2 ± 10.0 years, range 16–60) with a mean disease duration of 13.9 ± 9.5 years. Depression and anxiety were assessed in the interictal state with the Beck Depression Inventory, 21-item version (BDI-21) and the state and trait subscales of the State-Trait Anxiety Inventory (STAI-S and STAI-T), respectively. The association of mood disorders with various variables was investigated with simple and multiple linear regression analyses.ResultsHigh seizure frequency and symptomatic focal epilepsy (SFE) were independent determinants of depression, together accounting for 12.4% of the variation of the BDI-21. The STAI-S index was significantly associated with the type of epilepsy syndrome (SFE). Finally, high seizure frequency, SFE and female gender were independent determinants of trait anxiety accounting for 14.7% of the variation of the STAI-T.ConclusionOur results confirm the prevailing view that depression and anxiety are common psychological disorders in epileptics. It is additionally concluded that female gender, high seizure frequency and a symptomatic epilepsy syndrome are independent risk factors for the development of anxiety and/or depression.

Transcranial magnetic stimulation (TMS) modulates epileptiform discharges in patients with frontal lobe epilepsy: a preliminary EEG-TMS study.

BACKGROUND TMS is being increasingly used as a noninvasive brain stimulation technique for the therapeutic management of partial epilepsies. However, the acute effects of TMS on epileptiform discharges (EDs, i.e. interictal epileptiform activity and subclinical electrographic seizure patterns) remain unexplored. OBJECTIVE To investigate whether TMS can modulate EDs in partial epilepsy. METHODS In Experiment Set 1, the safety of the TMS protocol was investigated in 10 well-controlled by anti-epileptic drugs (AEDs) epileptic patients. In Experiment Set 2, the effects of TMS on EDs were studied in three subjects with intractable frontal lobe epilepsies, characterized by particularly frequent EDs. TMS was applied over the electrographic focus with a circular and a figure of eight coil while recording EEG with a 60-channel TMS-compatible EEG system. The effectiveness of TMS in aborting EDs was investigated using survival analysis and brain connectivity analysis. RESULTS The TMS protocol was well-tolerated. TMS was an effective method to abort EDs even when adjusting for its latency with respect to ED onset (CMH test, p < 0.0001). While the effective brain connectivity around the epileptic focus increased significantly during EDs (p < 0.01), with TMS administration the increase was not statistically significant. CONCLUSION TMS can modulate EDs in patients with epileptogenic foci in the cortical convexity and is associated with reversal of ED-induced changes in brain connectivity.

Autologous stem-cell transplantation in malignant multiple sclerosis: a case with a favorable long-term outcome.

Malignant multiple sclerosis (MS) is a rare but clinically important subtype of MS characterized by the rapid development of significant disability in the early stages of the disease process. These patients are refractory to conventional immunomodulatory agents and the mainstay of their treatment is plasmapheresis or immunosuppression with mitoxantrone, cyclophosphamide, cladribine or, lately, bone marrow transplantation. We report on the case of a 17-year old patient with malignant MS who was treated with high-dose chemotherapy plus anti-thymocyte globulin followed by autologous stem cell transplantation. This intervention resulted in an impressive and long-lasting clinical and radiological response. It is concluded that intensive immunosuppression followed by autologous stem cell transplantation is a viable therapeutic option in patients with malignant MS unresponsive to conventional forms of treatment. Multiple Sclerosis 2008; 17 : 278—283. http://msj.sagepub.com

Increased plasma homocysteine levels in patients with multiple sclerosis and depression

BackgroundThe aim of the study was to assess the plasma levels of homocysteine in patients with multiple sclerosis (MS) and to investigate whether an association with depression exists.MethodsPlasma homocysteine (Hcy), vitamin B12 and plasma folate were measured in 65 moderately disabled patients with relapsing/remitting MS (RR-MS) and 60 healthy controls. All subjects were assessed with the Beck Depression Inventory (BDI).ResultsHcy levels were significantly increased in MS patients compared to controls (13.5 ± 4.7 μmol/l vs 8.5 ± 3.1, p < 0.001). A significant correlation was found between Hcy levels and BDI scores (Pearson r = 0.3025, p < 0.05). Plasma Hcy was not related to Extended Disability Status Scale (EDSS) score, age, disease duration or vitamin B12 and folate.ConclusionModerately disabled MS patients with elevated Hcy levels are particularly prone to develop depressive symptomatology. Further study is warranted in order to elucidate the prognostic and therapeutic implications of this novel finding.

Impact of Pregabalin Treatment on Pain, Pain-Related Sleep Interference and General Well-Being in Patients with Neuropathic Pain

AbstractBackground and Objectives: Numerous controlled clinical trials have demonstrated the safety and efficacy of pregabalin in the treatment of neuropathic pain. The objectives of the present study were to assess the impact of pregabalin under real-world conditions on pain, pain-related sleep interference and general well-being, and to assess the tolerability and safety of pregabalin in patients diagnosed with neuropathic pain of central or peripheral origin. Methods: This was a non-interventional, multicentre study in which pregabalin was administered for 8 weeks, at the therapeutic dosages of 150–600 mg/day, to patients with a diagnosis of neuropathic pain. Pain intensity and pain-related sleep interference were measured using 11-point numerical rating scales, while well-being was assessed by documenting how often emotions associated with anxiety or depression were felt over the past week. Patient and Clinician Global Impression of Change (PGIC and CGIC) were assessed at the final visit. Results: In the 668 patients included in the full analysis set, there were significant (p< 0.0001) reductions in mean pain and pain-related sleep interference scores of 4.16 and 4.02, respectively. Indicators of general well-being showed improvement from baseline to final visit. The majority of patients were rated as ‘much improved’ (43.7% and 36.7%) or ‘very much improved’ (24.0% and 26.2%) on CGIC and PGIC scores, respectively. Discontinuation because of lack of efficacy occurred in 0.7% of 691 patients in the safety analysis set while discontinuation because of adverse events occurred in 5.1% of this population; 76.4% continued treatment after the study ended. Conclusion: Significant reductions in pain and pain-related sleep interference, combined with reductions in feelings of anxiety and depression, suggest that pregabalin under real-world conditions improves the overall health and well-being of patients with neuropathic pain.

The STAR Study: A Real-World, International, Observational Study of the Safety and Tolerability of, and Adherence to, Serum-Free Subcutaneous Interferon β-1a in Patients With Relapsing Multiple Sclerosis

BACKGROUND Adverse reactions, particularly injection site reactions (ISRs), are common reasons for nonadherence to injectable multiple sclerosis (MS) treatments. Adherence to MS treatment is important to ensure good treatment outcomes. OBJECTIVE The aim of this study was to assess the local tolerability of subcutaneous (SC) serum-free interferon (IFN) β-1a in patients with relapsing MS over 1 year in a real-life, international setting. The study also assessed safety, disease activity, and adherence. METHODS This was a prospective, international, multicenter, observational study of 251 patients with relapsing-remitting MS treated with SC serum-free IFN β-1a 44 μg or 22 μg 3 times weekly for 12 months or until early discontinuation. The primary end point was the proportion of patients with ISRs. Secondary end points included proportion of patients with adverse events (AEs); annualized relapse rate (ARR); proportion of patients remaining relapse-free; and adherence to treatment. RESULTS During the observation period, 27.5% (69 of 251) of patients experienced nonserious ISRs, which was consistent with the incidence reported in clinical studies. Five patients discontinued treatment and 2 patients suspended treatment because of ISRs. Mean age was 35.8 years; patients were predominantly white (94.8%), and two thirds (66.1%) were female. The overall incidence of AEs was 63.7% (160 of 251), and overall safety and tolerability were assessed as excellent, very good, or good in >85% of patients. More than 70% of patients remained relapse-free, and the mean ARR was 0.4. More than 90% of patients had very good or good adherence to treatment; a significantly greater proportion of these were relapse-free at 12 months compared with those with fair or poor adherence (77.6% vs 50.0%; P = 0.0107), and their ARR was significantly lower (0.3 vs 0.9; P = 0.0055). Patients with fair or poor adherence had 4.6 times higher odds of experiencing a relapse than those with very good or good adherence. CONCLUSIONS The incidence of ISRs and the overall safety profile in this observational study, in an international population in a real-life setting, confirm the good local tolerability of SC serum-free IFN β-1a reported in clinical studies. The association between good adherence and a lower ARR underlines the importance of good adherence. The good local and general tolerability of SC IFN β-1a may help ensure a high level of adherence, which is associated with better clinical outcomes. ClinicalTrials.gov identifier: NCT01080027.

Apathy, cognitive dysfunction and impaired social cognition in a patient with bilateral thalamic infarction.

We describe the case of a patient with bilateral thalamic lesions due to brain infarcts in the paramedian thalamic artery territories. The patient demonstrated symptoms of apathy (e.g., loss of initiative and interest in others, poor motivation, flattened affect). Neuropsychological assessment 3 and 5 years post-infarct revealed severe deficits in verbal and non-verbal immediate and delayed memory, attention, and executive functioning, with minimal improvement over time. Also, he demonstrated difficulties in social cognition (i.e., perception of facial expressions of others and of sarcasm). These findings are discussed and interpreted in light of current theories regarding the neurobiological substrate of apathy.