Seasonal adherence to, and effectiveness of, subcutaneous interferon ß-1a administered by RebiSmart® in patients with relapsing multiple sclerosis: results of the 1-year, observational GEPAT-SMART study.

BACKGROUND: Little is known about whether tolerability and adherence to treatment can be influenced by weather and temperature conditions. The objective of this study was to assess monthly and seasonal adherence to and safety of sc IFN-ß1a (Rebif®, Merck) in relapsing-remitting multiple sclerosis (RRMS) patients using the RebiSmart® electronic autoinjector. METHODS: A multicentre, prospective observational study in Greece in adult RRMS patients with EDSS < 6, under Rebif®/RebiSmart® treatment for ≤6 weeks before enrollment. The primary endpoint was monthly, seasonal and annual adherence over 12 months (defined in text). Secondary endpoints included number of relapses, disability, adverse events. RESULTS: Sixty four patients enrolled and 47 completed all study visits (Per Protocol Set - PPS). Mean annual adherence was 97.93% ± 5.704 with no significant monthly or seasonal variations. Mean relapses in the pre- and post- treatment 12-months were 1.1 ± 0.47 and 0.2 ± 0.54 (p < 0.0001, PPS). 10 patients (22%) showed 3-month disability progression, 19 (40%) stabilization and 18 (38%) improvement. EDSS was not correlated to pre- (r = 0.024, p = 0.87) or post-treatment relapses (r = 0.022, p = 0.88). CONCLUSION: High adherence with no significant seasonal or weather variation was observed over 12 months. While the efficacy on relapses was consistent with published studies, we could not identify a relationship between relapses and disability. TRIAL REGISTRATION: Greek registry of non-interventional clinical trials ID: 200136 , date of registration: February 18th, 2013.

Observational study assessing demographic, economic and clinical factors associated with access and utilization of health care services of patients with multiple sclerosis under treatment with interferon beta-1b (EXTAVIA).

Multiple sclerosis (MS) results in an extensive use of the health care system, even within the first years of diagnosis. The effectiveness and accessibility of the health care system may affect patients' quality of life. The aim of the present study was to evaluate the health care resource use of MS patients under interferon beta-1b (EXTAVIA) treatment in Greece, the demographic or clinical factors that may affect this use and also patient satisfaction with the health care system. Structured interviews were conducted for data collection. In total, 204 patients (74.02% females, mean age (SD) 43.58 (11.42) years) were enrolled in the study. Analysis of the reported data revealed that during the previous year patients made extensive use of health services in particular neurologists (71.08% visited neurologists in public hospitals, 66.67% in private offices and 48.53% in insurance institutes) and physiotherapists. However, the majority of the patients (52.45%) chose as their treating doctor private practice neurologists, which may reflect accessibility barriers or low quality health services in the public health system. Patients seemed to be generally satisfied with the received health care, support and information on MS (84.81% were satisfied from the information provided to them). Patients' health status (as denoted by disease duration, disability status and hospitalization needs) and insurance institute were found to influence their visits to neurologists. Good adherence (up to 70.1%) to the study medication was reported. Patients' feedback on currently provided health services could direct these services towards the patients' expectations.

The STAR Study: a real-world, international, observational study of the safety and tolerability of, and adherence to, serum-free subcutaneous interferon ß-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) ß-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 ß-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 ß-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 ß-1a may help ensure a high level of adherence, which is associated with better clinical outcomes. ClinicalTrials.gov identifier: NCT01080027.

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.

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.

Impact of pregabalin treatment on pain, pain-related sleep interference and general well-being in patients with neuropathic pain: a non-interventional, multicentre, post-marketing study.

BACKGROUND 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.

Severely stressful events and dementia: a study of an elderly Greek demented population.

There is evidence that proneness to experience psychological distress is a risk factor for Alzheimer's disease (AD). In the present study, an attempt is made to examine the possible association between stressful events and cognitive impairment of the elderly, based on a sample of 1271 patients (500 male, 771 female) diagnosed with dementia according to the DSM-IV criteria and 140 age- and gender-matched cognitive healthy subjects. All patients were recruited from the Memory and Dementia Outpatient Clinic of the 3rd University Department of Neurology in "G. Papanikolaou" General Hospital, Thessaloniki, and examined over a period of 7 years. The majority of patients reported a history of a stressful event before the onset of dementia (n=990, 77.9%), while fewer patients reported insidious onset (n=281, 22.1%). The most frequently reported event was the announcement of a life threatening disease (n=472, 37.1%), followed by problems within the family (n=157, 12.4%), spouse death (n = 100, 7.9%), death of a sibling or other beloved person (n=77, 6.1%). Only 55% of the control subjects encountered stressful events, which is significantly different from the percentage of the study group. Our results demonstrate that a stressful event in the elderly could potentially trigger a cognitive decline.

Increased plasma homocysteine levels in patients with multiple sclerosis and depression.

BACKGROUND: The 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. METHODS: Plasma 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). RESULTS: Hcy levels were significantly increased in MS patients compared to controls (13.5 +/- 4.7 mumol/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. CONCLUSION: Moderately 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.

Auditory processing disorder and brain pathology in a preterm child with learning disabilities.

BACKGROUND: Auditory processing disorders involve deficits in the processing of information in the auditory domain that are not due to higher order language, cognitive or other related factors. PURPOSE: To evaluate the possibility of structural brain abnormalities in preterm children manifesting as auditory processing disorders. RESEARCH DESIGN: A case report of a young girl, preterm at birth, with language difficulties, learning problems at school, and additional listening problems. RESULTS: A diagnosis of a central auditory processing disorder was made on the basis of severe deficits in three nonspeech temporal tests (the frequency and duration pattern and the random gap detection tests). Her brain MRI revealed large porencephalic cysts and thinning of the corpus callosum. CONCLUSIONS: The observed auditory deficits would be compatible with a pressure effect of the cysts at a brainstem or higher level for the random gap detection test, and with the thinning of the corpus callosum for the pattern tests, the latter requiring interhemispheric transfer of information. The case highlights that preterm children with learning difficulties may suffer from an auditory processing disorder, in the presence of structural brain abnormalities that are due to birth and neonatal complications.

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

BACKGROUND: Depression 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. METHODS: We 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. RESULTS: High 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. CONCLUSION: Our 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.

The effect of valproate on silent period and corticomotor excitability.

OBJECTIVE: To investigate, by transcranial magnetic stimulation, the effects of valproate on silent period and corticomotor excitability. METHODS: thirty patients with generalized epilepsy were studied at baseline, and re-examined 4 (S1) and 25 (S2) weeks after the administration of valproate (mean dose: 1040 +/- 284 mg). Transcranial magnetic stimulation was performed with a figure of eight coil (recording, first dorsal interosseous). Threshold was measured at 1% steps. Silent period was measured using a recently described protocol. Briefly, silent periods were elicited at 5% increments from 0 to 100% maximum stimulus intensity. At each stimulus intensity, 4 silent periods were obtained and the average value of silent period duration was used to construct a stimulus/response curve of stimulus intensity versus silent period. The resulting curves were then fitted to a Boltzman function and were statistically compared. The motor-evoked potential recruitment curve was constructed under active conditions and analyzed in a similar way. RESULTS: Valproate increased threshold from 36.5 +/- 5.99% at baseline to 41.02 +/- 7.84% at S1 (p < 0.0001, paired t-test). The maximum value of the silent period curve decreased from 257.5 +/- 3.9 ms at baseline to 230.3 +/- 3.9 ms at S1 (p < 0.0001, F-test and AIC) while the other best-fit values (V(50), slope, threshold) were not significantly affected. Regarding the motor-evoked potential recruitment curve, the maximum value decreased significantly post-drug (from 0.449 +/- 0.007 to 0.392 +/- 0.009, p < 0.01, F-test and AIC test), whereas the rest of the best-fit values remained unaffected. CONCLUSION: In patients with idiopathic generalized epilepsy, valproate increases threshold and reduces the maximum values of the silent period curve and the motor-evoked potential recruitment curve. These findings probably reflect valproate's effects on voltage-dependent Na(+) channels, as well as an activation of GABA(A) receptors.