E-learning as valuable caregivers' support for people with dementia - A systematic review.

BACKGROUND: Present demographic trends show a considerable rise in elderly populations with aging disorders, such as dementia. The current article focused on the exploitation of e-learning as an informal support for caregivers of people with dementia and considered its benefits and limitations to provide proper and relevant care for this target group of people as well as maintain the quality of life of their caregivers. METHODS: The methodology of this study is based on a literature review of accessible peer-review articles from three recognized databases: Web of Science, Scopus, and PubMed. The findings of the selected studies were compared and evaluated. RESULTS: The findings showed that e-learning educational programs/courses helped caregivers feel more confident about dementia care, reduced their perceived stress and enhanced their feelings of empathy, understanding and concern. CONCLUSIONS: The findings of this study reveal that the exploitation of e-learning as a support tool, especially for informal caregivers, in the management of dementia may be a promising method, but its implementation requires professional training of informal caregivers in the use of this technology. More evidence-based studies are needed on this topic.

Encephalitis with anti-NMDA receptor antibodies: paraneoplastic or non-paraneoplastic?

We report the case of an encephalitis patient with anti-N-methyl-D-aspartate receptor (NMDAR) antibody positivity. Anti-NMDAR encephalitis is a relatively rare autoimmune disease. In our patient, the diagnosis of anti-NMDAR encephalitis was established as late as several months after the first manifestations of the condition. Further development demonstrated that the patient probably suffered from a paraneoplastic form of the disease, although the presence of an underlying tumour was not detected by the available imaging methods at the time of diagnosis. The case is a rarity since the disease usually affects females, and only 5% of adult male patients have a paraneoplastic aetiology.

Peripheral endothelial dysfunction as a marker of cardiovascular risk in physically healthy patients with schizophrenia and related psychoses: a matched case control study.

OBJECTIVES: Our aim was to assess endothelial function in physically healthy patients with schizophrenia and related psychoses and to compare the results with healthy controls. Endothelial dysfunction was shown to predict future cardiovascular events in general population so we assumed to find a higher prevalence of endothelial dysfunction in patients with psychosis, as their cardiovascular morbidity is markedly higher than in general population, and to confirm the referred correlation with the traditional cardiovascular (CV) risk factors. DESIGN: We assessed the traditional CV risk factors and endothelial function using non-invasive peripheral arterial tonometry (EndoPAT2000) in 50 stabilized and medicated schizophrenic patients (aged between 18 and 50 years) without any history of cardiovascular diseases and compared the results with 50 age-matched healthy controls. SETTING: Psychiatric Clinic, University Hospital, Hradec Kralove and 2nd Department of Internal Medicine, General University Hospital, Prague, Czech Republic RESULTS: There was no difference in relative hyperaemia index as an endothelial function measure between patients and controls (2.19±0.68 vs. 1.98±0.57, p=NS) and there were also no correlations between reactive hyperaemia index and the traditional CV risk factors, illness duration or psychotic symptoms. On the other hand, the two study groups differed significantly in almost all traditional CV risk factors.

New portable device for an examination of visual cognitive evoked potentials might extend their diagnostic applications in psychiatry.

Despite positive prior results obtained by using event-related potentials (ERPs) in psychiatric patients, they are not routinely used in the clinical setting. This may in part be due to problems regarding a lack of transportable equipment availability. It can be difficult for these patients to repeatedly visit electrophysiological laboratories. To address this issue, we propose using a new, fully portable device for visually evoked potentials (VEP) and cognitive function assessment, that can be used for quick examinations (https://www.veppeak.com). Our device, called "VEPpeak", is built into a headset with a color LED visual stimulator. It weighs 390 g and is connected to a notebook (PC) with evaluation software via USB. In this pilot study, we verified the device's usability in 31 patients with schizophrenia. We used the oddball paradigm with the recognition of colors for the P300 wave and choice reaction time evaluation. The examination lasted only about ten minutes. The results indicated good reproducibility of large cognitive potentials (P300) with prolonged P300 latencies and reduced amplitudes in patients compared to 15 control subjects. The P300 latency and reaction time prolongation in patients correlated with their age and the sedative effect of the pharmacotherapy.

The dynamics of haemostatic parameters in acute psychotic patients: a one-year prospective study.

BACKGROUND: The primary goal of the present study was to replicate our previous finding of increased coagulation and thrombocytes activity in drug-naïve psychotic patients in comparison with healthy controls and ascertain whether the blood levels of thrombogenesis markers further increase over the course of a consecutive one-year antipsychotic treatment. SUBJECTS AND METHODS: We investigated the plasma levels of markers indicating activation of coagulation (D-dimers and Factor VIII) and platelets (soluble P-selectin, sP-selectin) in an antipsychotic-naive group of nineteen men and seventeen women with acute psychosis (age 28.1±8.0 years, body mass index 22.6±4.2), and thirty-seven healthy volunteers matched for age, gender and body mass index. In the patient group, we repeated these assessments after three months and again after one year of antipsychotic treatment. RESULTS: D-dimers (median 0.38 versus 0.19 mg/l; p=0.00008), factor VIII (median 141.5% versus 110%; p=0.02) and sP-selectin (median 183.6 versus 112.4 ng/ml; p=0.00005) plasma levels were significantly increased in the group of patients with acute psychosis prior to treatment compared with healthy volunteers. The plasma levels of sP-selectin varied significantly (p=0.016) in the course of the one-year antipsychotic treatment, mainly between 3 and 6 months after start of therapy. The plasma levels of D-dimers and factor VIII did not change significantly, D-dimers remained elevated in contrast to the healthy controls. CONCLUSIONS: Patients with acute psychosis had increased levels of markers of thrombogenesis in comparison to the healthy volunteers. The haemostatic parameters also remained elevated during the one-year antipsychotic treatment.

Widened retinal arteriolar and venular diameters are not an endophenotype of schizophrenia: A one-time cross-sectional study.

OBJECTIVES: Studies of schizophrenia endophenotypes may help clinicians better understand the etiopathogenesis and treatment of this mental disorder. The aim of the study was to determine if retinal arteriolar or venular abnormalities are an endophenotype of schizophrenia. DESIGN: We performed a one-time cross-sectional study. MATERIALS AND METHODS: We enlisted schizophrenic patients (n = 53) hospitalized in the Department of Psychiatry, University Hospital Hradec Kralove; their mentally healthy first-degree relatives (n = 53); and unrelated, age- and sex-matched mentally healthy controls (n = 49). We recorded all participants´ sociodemographic and, if relevant, clinical variables. Retinal imaging was carried out using a digital fundus camera (FF450 + IR). Outcomes included retinal vessel calibers measured using the software application VAMPIRE. RESULTS: The study enrolled fifty-three schizophrenic patients (average age 32.1 years; males n = 38), an equal number of healthy relatives (average age 47.3 years; males n = 18), and forty-nine unrelated healthy controls (average age 32.2 years; males n = 35). Patients with schizophrenia had significantly increased retinal arteriolar diameters when compared to unrelated healthy controls (left eye p = 0.003; right eye p = 0.011) but not when compared to healthy relatives. The sizes of the retinal venules were not significantly different among the study groups. CONCLUSIONS: Our cross-sectional findings do not support the notion that retinal microvascular anomalies are an endophenotype in schizophrenia. Longitudinal studies of this subject should be included in further research.

Risk of venous thromboembolism during treatment with antipsychotic agents.

The evidence to date on the relation between the risk of venous thromboembolic disease (VTE) and antipsychotic agents derives primarily from observational and case history studies. While an increased risk of VTE has been associated with first-generation low-potency antipsychotic agents, particularly clozapine, there appears to be a growing number of reports on the occurrence of this adverse reaction during the use of second-generation antipsychotics, such as risperidone and olanzapine. The highest risk of pathological blood clotting emerges during the first 3 months after initiation of treatment with the product. Potential etiopathogenetic factors leading to VTE during treatment with antipsychotic agents include sedation, obesity, elevation of antiphospholipid antibodies, increased platelet activation and aggregation, hyperhomocysteinemia, and hyperprolactinemia. Diagnoses of schizophrenia and/or bipolar affective disorder, as well as hospitalization or stress with sympathetic activation and elevation of catecholamine levels, have been reported as known prothrombogenic factors. The present article contains the new version of the guideline for the prevention of VTE in psychiatric patients with limited mobility. Further prospective studies are necessary to elucidate the biological mechanisms of the relations between antipsychotic agents and VTE.

Lactic acidosis in medical ICU - the role of diabetes mellitus and metformin.

OBJECTIVES: To evaluate the significance of diabetes mellitus and metformin in patients admitted to medical ICU with lactic acidosis. METHODS: All the patients admitted to medical ICU with serum lactic acid exceeding 5 mmol/L and pH<7.35 were enrolled into analysis. The impact of diabetes mellitus and metformin treatment on ICU presence of lactic acidosis and its mortality was evaluated. The metabolic parameters were compared with respect to the presence of diabetes mellitus and metformin application. RESULTS: Lactic acidosis was detected in 69 (4%) out of 1,755 admitted patients, 44 were nondiabetic and 25 had diabetes mellitus, 11 of them treated with metformin. No significant impact of diabetes mellitus or metformin application on presence of lactic acidosis and its mortality was detected. In nondiabetic subjects mortality was associated with eGFR and the presence of acute renal failure while in diabetic patients with sepsis. Acute renal failure was detected in 9 out of 11 patients on metformin. Three patients died due to sepsis, however only 1 out of 6 due to another cause if renal replacement therapy was started soon after admission. The acidosis was more expressed in diabetic subjects mainly in patients taking metformin. It might be attributed to the more pronounced acute renal failure in diabetic patients. CONCLUSION: The presence of diabetes mellitus and metformin application is not associated with the presence of lactic acidosis in medical ICU and its mortality. The prognosis of acute renal failure of patients on metformin is good if the subjects with sepsis are excluded.

The prevalence of cardiometabolic risk factors and the ten-year risk of fatal cardiovascular events in patients with schizophrenia and related psychotic disorders.

BACKGROUND: People suffering from schizophrenia have a significantly shorter lifespan compared to the general population. The majority of deaths are caused by physical diseases, including cardiovascular events. The aim of this cross-sectional study was to predict the risk of premature cardiovascular mortality and assess the prevalence of cardiometabolic risk factors in a sample of Czech patients with schizophrenia and related psychoses. SUBJECTS AND METHODS: We reviewed data from 129 subjects treated in an outpatient clinic that specialised in psychoses. The main collected variables included basic physical parameters (height, weight, waist circumference, blood pressure), smoking habits, laboratory data (glucose level, serum lipid level) and an electrocardiograph (ECG). We calculated the ten-year risk of fatal cardiovascular events using the Systematic Coronary Risk Evaluation (SCORE) chart. RESULTS: The most prevalent risk factors were being overweight (70% of patients had a BMI over 25), dyslipidaemia (70% of patients) and smoking (43% of patients). According to the SCORE diagram, there was a high risk of fatal cardiovascular events over a ten-year period in 10% of the study group. The percentage was even higher (24%) when the latest European guidelines for cardiovascular disease prevention were used to calculate the risk. CONCLUSIONS: Our outcomes indicate even higher cardiometabolic morbidity rates in patients with psychoses than those referenced in the literature.

An electrophysiological study of visual processing in spinocerebellar ataxia type 2 (SCA2).

Reports of visual functional impairment in spinocerebellar ataxia type 2 (SCA2) have been studied previously using pattern reversal visually evoked potentials (VEPs) with contradictory results. To provide additional evidence to this area, visual functions were studied using VEPs and event-related potentials (ERPs) in a group of ten patients with genetically verified SCA2. The electrophysiological examination included pattern reversal and motion-onset VEPs as well as visually driven oddball ERPs with an evaluation of a target and a pre-attentive response. In six patients, we found abnormal visual/cognitive processing that differed from normal values in latency, but not in the amplitude of the dominant VEP/ERP peaks. Among the VEPs/ERPs used, the motion-onset VEPs exhibited the highest sensitivity and showed a strong Spearman correlation to SCA2 duration (from r = 0.82 to r = 0.90, p < 0.001) and clinical state assessed by Brief Ataxia Rating Scale (from r = 0.71 (p = 0.022) to r = 0.80 (p < 0.001)). None of the VEP/ERP latencies showed a correlation to the triplet repeats of the SCA2 gene. In three patients, we did not find any visual/cognitive pathology, and one subject showed only a single subtle prolongation of the VEP peak. The observed visual/cognitive deficit was related to the subjects' clinical state and the illness duration, but no relationship to the genetic marker of SCA2 was found. From the VEP/ERP types used, the motion-onset VEPs seems to be the most promising candidate for clinical state monitoring rather than a tool for early diagnostic use.

Markers of thrombogenesis are activated in unmedicated patients with acute psychosis: a matched case control study.

BACKGROUND: Antipsychotic treatment has been repeatedly found to be associated with an increased risk for venous thromboembolism in schizophrenia. The extent to which the propensity for venous thromboembolism is linked to antipsychotic medication alone or psychosis itself is unclear. The objective of this study was to determine whether markers of thrombogenesis are increased in psychotic patients who have not yet been treated with antipsychotic medication. METHODS: We investigated the plasma levels of markers indicating activation of coagulation (D-dimers and Factor VIII) and platelets (soluble P-selectin, sP-selectin) in an antipsychotic-naive group of fourteen men and eleven women with acute psychosis (age 29.1 ± 8.3 years, body mass index 23.6 ± 4.7), and twenty-five healthy volunteers were matched for age, gender and body mass index. RESULTS: D-dimers (median 0.38 versus 0.19 mg/l, mean 1.12 ± 2.38 versus 0.28 ± 0.3 mg/l; P = 0.003) and sP-selectin (median 204.1 versus 112.4 ng/ml, mean 209.9 ± 124 versus 124.1 ± 32; P = 0.0005) plasma levels were significantly increased in the group of patients with acute psychosis as compared with healthy volunteers. We found a trend (median 148% versus 110%, mean 160 ± 72.5 versus 123 ± 62.5; P = 0.062) of increased plasma levels of factor VIII in psychotic patients as compared with healthy volunteers. CONCLUSIONS: The results suggest that at least a part of venous thromboembolic events in patients with acute psychosis may be induced by pathogenic mechanisms related to psychosis rather than by antipsychotic treatment. Finding an exact cause for venous thromboembolism in psychotic patients is necessary for its effective treatment and prevention.

Cognitive changes in spinocerebellar ataxia type 2.

OBJECTIVES: Cognitive disorders and dementia occur in 19 to 42% of patients with spinocerebellar ataxia type 2 (SCA2). Neuropsychological tests can reveal executive dysfunction, impaired visual and verbal memory, tongue and speech impairment, attention disorders and impaired verbal fluency. METHODS: We performed psychiatric and neuropsychological examinations in 12 patients diagnosed with genetically confirmed SCA2 and 12 healthy volunteers matching the patients in age, gender, and length of education. The level of motor impairment was determined using the brief ataxia rating scale (BARS). The neuropsychological examination focused on testing executive functions, short-term visual and verbal memory, attention, psychomotor tempo, visual motor coordination, learning ability and comprehension ability. The tests were divided into two subgroups according to the difficulty of motor tasks. The cognitive abilities composite score (CACS) was determined by calculating the arithmetic mean of T scores of the respective tests. RESULTS: Patients with SCA2 had significantly lower CACSs (p=0.00005) compared to the healthy volunteers. Patients exhibited impaired performance in both difficult and simple motor tests. The severity of cognitive impairment was related to the age at the onset of the disease (p=0.002) but not to the duration or to the overall BARS score. CONCLUSIONS: Compared to healthy volunteers, patients with SCA2 exhibited significantly worse cognitive performance in all areas tested, including the tests of simple motor tasks. Moreover, the cognitive performance of patients worsened as the difficulty of the motor tasks increased.

Dopamine Receptor Partial Agonists: Do They Differ in Their Clinical Efficacy?

Dopamine receptor partial agonists (DRPAs; aripiprazole, brexpiprazole, and cariprazine) constitute a novel class of antipsychotics. Although they share a similar mechanism of action, DRPAs differ in their pharmacodynamics, pharmacokinetics, drug interactions, or safety and tolerability. The antipsychotic efficacy of all three drugs was established in several placebo-controlled randomized trials (RCTs) in schizophrenia, both acute phase and relapse prevention. In addition, each of the DRPA agents has been tested in other psychiatric disorders, including bipolar disorder or major depression. However, a few studies have examined their comparative clinical efficacy. There are no head-to-head comparisons between aripiprazole, brexpiprazole, or cariprazine. In two acute schizophrenia RCTs of cariprazine and brexpiprazole, aripiprazole was used as an indirect comparator to control for study sensitivity. To assess potential differences in the efficacy of DRPAs, we reviewed data from controlled trials, systematic reviews, and meta-analyses. Our results showed that the acute antipsychotic effects of DRPAs, as measured by the number needed to treat, are comparable. The three agents were superior to placebo in acute treatment, and cariprazine was found to be effective in the reduction of primary negative symptoms of schizophrenia. In the therapy of bipolar disorder, aripiprazole and cariprazine showed antimanic efficacy, cariprazine was also effective in the management of bipolar depression, and aripiprazole was effective for relapse prevention. The addon administration of aripiprazole or brexpiprazole reduced symptoms of major depression. Aripiprazole can control acute agitation associated with psychosis or bipolar disorder; brexpiprazole showed the potential to manage agitation in dementia patients. Aripiprazole has also established evidence of efficacy in children and adolescents and other conditions: OCD, tic disorders, and autism spectrum disorder. Our review of published data suggests that in terms of clinical efficacy, DRPAs are a heterogeneous group, with each drug possessing its own therapeutic benefits.

Impairment of Executive Functions Associated With Lower D-Serine Serum Levels in Patients With Schizophrenia.

A core symptom that is frequently linked with dysregulation of glutamatergic neurotransmission in regard to schizophrenia is impairment or damage of executive functioning as a component of cognitive deficiency. The amino acid D-serine plays the role of an endogenous coagonist at the glutamatergic N-methyl-D-aspartate (NMDA) receptor glycine modulatory site. Considerably reduced serum levels of D-serine were found in patients suffering from schizophrenia compared with healthy control participants. An increase in D-serine led to augmented cognitive functionality in patients suffering from schizophrenia who were undergoing clinical trials and given the treatment of first- and second-generation antipsychotics. The study proposed the hypothesis that the D-serine blood serum levels may be linked with the extent of executive functionality in those suffering from the mental illness in question. For the purpose of examining executive function in such patients, the Rey-Osterrieth Complex Figure, Trail Making, and Wisconsin Card Sorting tests were applied (n = 50). High-performance liquid chromatography was used to gauge the total serine and D-serine levels. The extent of damage was examined through neuropsychological tests and was found to be considerably linked to D-serine serum level and the D-serine/total serine ratio (p < 0.05) in the sample being considered. A lower average serum level of D-serine and lower D-serine/total serine ratio were observed in participants with the worst performance compared with those displaying the best performance-this was true when the patients were split into quartile groups based on their results (p < 0.05). The findings of modified D-serine serum levels and the D-serine/total serine ratio linked to the extent of damage in executive functioning indicate that serine metabolism that is coresponsible for NMDA receptor dysfunction has been changed.

Multiple sclerosis and immune system biomarkers: Novel comparison in glatiramer acetate and interferon beta-1a-treated patient groups.

BACKGROUND: Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS). T cells and B lymphocytes are involved in the development of this disease. METHODS: The following biomarkers were determined in peripheral blood in 28 patients treated with glatiramer acetate (GA) and 21 patients treated with interferon beta 1-a (IFN): IL-10, BAFF, Mx1, IgG, IgG1, IgG2, IgG3 and IgG4 (at baseline and after 6 months of treatment). All participants had confirmed MS diagnosis. OBJECTIVES: The primary objective is to assess a percentual change of biomarkers after 6 months since the first-line treatment initiation with GA or IFN. The secondary objective is to explore correlations between the baseline biomarkers' values (levels). RESULTS: A positive trend was observed in the increase in IL-10 concentration by 30.33 % (IFN) and by 15.65 % (GA). In the IFN group, we observed a statistically significant increase in the BAFF protein concentration by 29.9% (P < 0.001). We found that Mx1 protein levels did not change with the administration of GA, which can be explained by the different mechanisms of action of GA. The serum levels of IgG immunoglobulins and both IgG1 and IgG4 subclasses in both groups of patients were increased. Thus, our data were in accordance with the generally accepted assumption that both IFN and GA are capable of modulating the B cell system. CONCLUSIONS: Our results suggest that treatment with IFN and GA has a more pronounced influence on the B cell system of MS.

The role of the immune system and the biomarker CD3 + CD4 + CD45RA-CD62L- in the pathophysiology of migraine.

The role of the immune system as an integral component of the inflammatory response in the pathophysiology of migraine remains unclear. The aim of this study was to evaluate the differences in immune system parameters (acquired immunity parameters) in patients with episodic migraine (EM) and in healthy controls. In EM patients, we aimed to determine whether the changes found in peripheral blood parameters were related to migraine severity according to the standardised MIDAS and HIT-6 tests. Forty-nine patients with EM and 50 healthy controls were included in this study. The authors compared different lymphocyte parameters obtained by multicolor flow cytometry in the EM and control groups by performing statistical tests. The relationship between the changes in peripheral blood parameters and migraine severity in EM patients was investigated using correlation and regression analysis. EM patients showed higher values than healthy controls, especially in nine parameters: relative count of lymphocytes, relative and absolute counts of CD3 T cells, relative and absolute counts of CD8 suppressor cytotoxic T cells, relative and absolute counts of CD4 + TEMRA (terminally differentiated helper T lymphocytes), absolute count of CD8 naïve T cells, and absolute count of CD19 switched memory B cells. Among the lymphocyte parameters, CD4 + TEM (effector memory helper T lymphocytes) and CD8 + TEMRA (terminally differentiated cytotoxic T lymphocytes) were statistically significantly associated with HIT-6. Patients with a CD4 + TEM value below 15 had a high probability (90%) that the HIT-6 value would be higher than 60. The results of this study show that EM patients have changes in immune system parameters measured in the peripheral blood. Changes in the abundance of CD4 + TEM could be used as a biomarker for disease severity.

Four cases of venous thromboembolism associated with olanzapine.

AIMS: Psychiatric disorders and treatment with conventional antipsychotic medications have been associated with venous thromboembolism, but only a few data on recent antipsychotics such as olanzapine are available. METHODS: We describe four subjects treated with olanzapine who developed venous thromboembolism, and were hospitalized at the University Hospital in Hradec Kralove during the period 2004-2006. RESULTS: We found a combination of several clinical and laboratory risk factors in our patients. CONCLUSIONS: A cohort study or case-control studies are needed to better elucidate the possible role of olanzapine in etiopathogenesis of venous thromboembolism.

Repeated occurrence of clozapine-induced myocarditis in a patient with schizoaffective disorder and comorbid Parkinson's disease.

Myocarditis is a rare but life threatening adverse effect of clozapine. Some symptoms of myocarditis--elevated temperature, tachycardia and fatigue--appear commonly during the onset of treatment with clozapine and during the dose titration. We present a case of a patient with concurrent schizoaffective disorder and Parkinson's disease, who twice developed clozapine-induced myocarditis. All symptoms disappeared after the discontinuation of the drug. Early diagnosis, discontinuation of clozapine and supportive therapy of myocarditis lower the risk of a fatal outcome.

Venous Thromboembolism as an Adverse Effect During Treatment With Olanzapine: A Case Series.

Objective: Venous thromboembolism (VTE) is a serious multifactorial disorder. Patients with severe mental illness have a higher risk of developing the condition compared to the general population. Methods: We observed 10 cases of VTE in patients with mental illness who were treated with the antipsychotic drug olanzapine. The diagnosis of VTE was made at the University Hospital Hradec Kralove (UH HK) from 2004 to 2013. VTE was objectively determined by imaging techniques (duplex ultrasonography, CT angiography) and laboratory tests (D-dimer). The average age was 46 years. The clinical manifestation of VTE was deep vein thrombosis in nine cases, including one case of simultaneous pulmonary embolism and one case of a concurrent ischemic cerebrovascular accident (iCVA). None of our patients had a history of malignant disease, trauma, or surgery. Results: Apart from antipsychotic medication, all the patients had clinical or laboratory risk factors for VTE. The most frequent clinical risk factors were obesity (n = 7) and smoking (n = 6). The most frequent laboratory risk factors were increased levels of FVIII (n = 4), mild hyperhomocysteinemia (n = 3), and factor V Leiden mutation (n = 2). VTE developed within 3 months after antipsychotic drug initiation in three patients and within 6 months in three patients. Conclusion: Olanzapine can be considered a precipitating factor for VTE formation. When olanzapine is administered, we need to monitor for clinical signs and symptoms of VTE, especially when other risk factors are present.

CD4+/CD45RO+: A Potential Biomarker of the Clinical Response to Glatiramer Acetate.

Background: Glatiramer acetate (GA) is an effective treatment for the earliest stages of multiple sclerosis (MS)-clinically isolated syndrome (CIS) or clinically definite MS (CDMS). Objective: This study aims to determine the differences in the lymphocyte population (at baseline and the course of five years) between confirmed sustained progression (CSP) and non-CSP groups and to identify potential biomarkers among these parameters that can predict a positive response to the treatment. Methods: Twelve male and 60 female patients were included in the study. Peripheral blood samples were collected before and five years after treatment with GA. The authors compared lymphocyte parameters between the CSP and non-CSP groups by statistical analyses. Univariate and penalized logistic regression models were fitted to identify the best lymphocyte parameters at baseline and their combination for potential biomarkers. Subsequently, the ROC analysis was used to identify cut-offs for selected parameters. Results: The parameter CD4+/CD45RO+ was identified as the best single potential biomarker, demonstrating the ability to identify patients with CSP. Moreover, a combination of four lymphocyte parameters at baseline, relative lymphocyte counts, CD3+/CD69+, CD4+/CD45RO+, and CD4+/CD45RA+ab, was identified as a potential composite biomarker. This combination explains 23% of the variability in CSP, which is better than the best univariate parameter when compared to CD4+/CD45RO+ at baseline. Conclusions: The results suggest that other biomarkers can help monitor the conditions of patients and predict a favourable outcome.