Serum levels of inflammasome pathway factors in clinically isolated syndrome and multiple sclerosis patients: a pilot study.

Pathogenic roles of nuclear factor κB (NF-κB) pathway and NLRP3 inflammasome complex factors are involved in multiple sclerosis (MS) development. Activation of the NF-κB, NLRP3, and caspase-1 cascade results in production of proinflammatory cytokines that lead to stimulation of macrophages, lymphocytes, and glial cells. Although increased levels of inflammasome complex factors are observed in MS, contribution of inflammasome pathway to conversion from clinically isolated syndrome (CIS) to relapsing remitting MS (RRMS) has been scarcely investigated. To examine predictive value of inflammasome factors in CIS-MS conversion, levels of NLRP3, caspase-1, and NFκB are measured by ELISA in sera of age-gender matched CIS (n = 18; 8 converting, 10 non-converting) and RRMS (n = 23) patients. CIS and RRMS patients have comparable serum levels of NLRP3, caspase-1, and NFκB. Similarly, no statistically significant difference can be found among converting and non-converting CIS patients by means of inflammasome complex factor levels. Inflammasome factors are presumably overexpressed at early stages of MS. Therefore, they are unlikely to be used as biomarkers to predict CIS-MS conversion.

Adipokines in Multiple Sclerosis Patients with and without Optic Neuritis as the First Clinical Presentation.

BACKGROUND: Adipocytokines have been implied to be involved in multiple sclerosis (MS) pathogenesis. MS patients whose first clinical episode is optic neuritis (ON) have been reported to display a milder disease course. In this study, we aimed to show whether this milder disease course is related to reduced adipokine production. METHODS: A total of 55 (24 with ON as the first clinical episode) relapsing-remitting MS (RRMS) patients and 40 healthy individuals were recruited. Concentrations of adipokines were measured in sera by ELISA. RESULTS: The levels of adiponectin, leptin, resistin, monocyte chemoattractant protein-1 (MCP-1) and IL-8 were significantly higher in RRMS patients compared with healthy controls. RRMS cases starting with ON had lower expanded disability status scale scores. Serum adiponectin, leptin, resistin and MCP-1 levels were significantly lower in MS patients, whose first clinical episode was ON. CONCLUSIONS: MS patients with ON as the first manifestation display both lower disability scores and reduced serum adipokine levels implying that adipocytokine production is associated with MS progression. Exact mechanisms of this association in MS patients with first episode ON need to be further studied.

Efficacy of peripheral lidocaine application (neural therapy) in the treatment of neurogenic detrusor overactivity in multiple sclerosis patients.

AIMS: Many agents and treatments are used in the treatment of neurogenic detrusor overactivity (NDO) in MS patients, but no study has been conducted on the use of peripheric lidocaine (neural therapy-NT) on MS patients. We evaluated the effects of local administration of lidocaine on NDO in Multiple Sclerosis (MS) patients. METHODS: For each patient local anesthetic lidocaine was injected at each session. Sessions were held once a week for 5 weeks. At each session, Th 10-L1, urogenital segment intradermal injections, Frankenhauser, and sacral epidural injections were given. The patients had clinical and urodynamic assessment 1 month before and 3, 9, and 12 months after NT. In addition, multiple sclerosis quality of life inventory (MSQL-54) and bladder control scale (BLCS) was performed for patients. RESULTS: Twenty-eight patients were included in the study (8 males, 20 females). The patients' average age was 31.7 ± 8.1 years. The injection therapy significantly improved volume at first involuntary bladder contraction (FCV), maximal detrusor pression during filling (P det. max.), maximal cystometric bladder capacity (MCC) after 3 months. Also, the MSQL-54 and BLCS scores were improved with treatment. However, these improvements reached a maximum 3 months after treatment, but from the 9 month a regression was seen in the parameters, and after 12 months the findings were seen to be slightly above their basal levels. CONCLUSIONS: These results suggest that NDO treatment in MS patients could be an effective treatment which is easy and has very few side effects, and is cost effective.

Changes in serum albumin levels and neutrophil-lymphocyte ratio in patients with convulsive status epilepticus.

AIM: Inflammation may be involved in the ictogenesis and development of some partial epilepsies. Serum albumin levels and the neutrophil-lymphocyte ratio (NLR) are markers of inflammation. The aim of this study was to investigate the ability of serum albumin levels and NLR to predict inflammation in patients with convulsive status epilepticus (CSE). METHODS: This retrospective study was conducted on 58 patients who were diagnosed with CSE and control group comprised of 58 healthy individuals. Albumin levels and NLR were evaluated during both the acute and subacute periods of CSE. RESULTS: The average serum albumin levels were 3.27 ± 0.62 g/dL during the acute period and 3.4 ± 0.67 g/dL in the subacute period in the patient group and 3.92 ± 0.52 g/dL in the control group. Neutrophil counts were higher in patients in the acute phase of CSE, but lymphocyte counts were lower compared to the control group and the subacute phase. The average NLR values were 4.83 ± 5.1 in the acute period, 3.07 ± 3.02 during the subacute period and 1.98 ± 0.42 in the control group. Serum albumin and NLR levels were significantly different between the patients in the subacute and acute periods of CSE and the control group (p < 0.05). There were significant negative correlational relationships between serum albumin and NLR levels (p < 0.05). CONCLUSION: We found serum albumin levels were significantly lower and the NLR was significantly higher in the acute period of CSE. Neutrophil-mediated inflammation may be important in the aetiopathogenesis of CSE.

Clinical, Demographic, and Radiological Characteristics of Patients Demonstrating Antibodies Against Myelin Oligodendrocyte Glycoprotein

Background: Optic neuritis, myelitis, and neuromyelitis optica spectrum disorder (NMOSD) have been associated with antibodies against myelin oligodendrocyte glycoprotein-immunoglobulin G (anti-MOG-IgG). Furthermore, patients with radiological and demographic features atypical for multiple sclerosis (MS) with optic neuritis and myelitis also demonstrate antibodies against aquaporin-4 and anti-MOG-IgG. However, data on the diagnosis, treatment, follow-up, and prognosis in patients with anti-MOG-IgG are limited. Aims: To evaluate the clinical, radiological, and demographic characteristics of patients with anti-MOG-IgG. Study Design: Multicenter, retrospective, observational study. Methods: Patients with blood samples demonstrating anti-MOG-IgG that had been evaluated at the Neuroimmunology laboratory at Ondokuz Mayis University's Faculty of Medicine were included in the study. Results: Of the 104 patients with anti-MOG-IgG, 56.7% were women and 43.3% were men. Approximately 2.4% of the patients were diagnosed with MS, 15.8% with acute disseminated encephalomyelitis (ADEM), 39.4% with NMOSD, 31.3% with isolated optic neuritis, and 11.1% with isolated myelitis. Approximately 53.1% of patients with spinal involvement at clinical onset demonstrated a clinical course of NMOSD. Thereafter, 8.8% of these patients demonstrated a clinical course similar to MS and ADEM, and 28.1% demonstrated a clinical course of isolated myelitis. The response to acute attack treatment was lower and the disability was higher in patients aged > 40 years than patients aged < 40 years at clinical onset. Oligoclonal band was detected in 15.5% of the patients. Conclusion: For patients with NMOSD and without anti-NMO antibodies, the diagnosis is supported by the presence of anti-MOG-IgG. Furthermore, advanced age at clinical onset, Expanded Disability Status Scale (EDSS) score at clinical onset, spinal cord involvement, and number of attacks may be negative prognostic factors in patients with anti-MOG-IgG.

The Effect of Lidocaine on the Experimental Model of Streptozotocin-Induced Alzheimer's Disease.

Introduction: Alzheimer's disease (AD) is a neurodegenerative disease caused by the accumulation of amyloid plaques in the cerebral cortex and hippocampus. In this study, the effects of local anesthetic lidocaine on neurodegeneration markers and memory were investigated for the first time in streptozotocin-induced rat AD model. Methods: Streptozotocin (STZ) was administered intracerebroventricularly (ICV) into Wistar rats to develop AD model. For lidocaine group (n=14), lidocaine (5 mg/kg) was administered intraperitoneally (IP) in addition to STZ injection. Control group animals (n=9) were treated with saline for 21 days. Morris Water Maze (MWM) test was performed to evaluate memory after the injections were completed. Also, the serum levels of TAR DNA-binding protein-43 (TDP-43), amyloid precursor protein (APP), ß-secretase 1, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), response element binding protein (CREB), c-FOS were measured using ELISA test and compared between groups. Results: Lidocaine group animals showed lower escape latency and time in quadrant scores in MWM inferring better memory performance. Furthermore, lidocaine administration caused a significant decline in TDP-43 levels. However, the expression of APP and ß-secretase were significantly higher in AD and lidocaine groups compared to control group. Moreover, lidocaine group markedly had higher serum NGF, BDNF, CREB, and c-FOS levels compared to those in the AD group. Conclusion: In addition to neuroprotective effects in STZ-induced AD model, Lidocaine also appears to improve memory. This effect might be associated with increased levels of several growth factors and associated intracellular molecules. The therapeutic role of lidocaine in the pathophysiology of AD should be studied in the future.

Use of follow-on fingolimod for multiple sclerosis: Analysis of effectiveness and patient reported outcomes in a real-world clinical setting.

BACKGROUND: Follow-on disease modifying therapies (FO-DMTs) do not always require Phase III studies. There are concerns that cheaper FO-DMTs are only used to reduce healthcare costs. However, the well-being of people with MS (pwMS) should be a priority. We aimed to evaluate the efficacy, safety and treatment satisfaction of one of the FO- Fingolimod (FTY) used in Turkey with the approval of Turkish Ministry of Health. METHODS: PwMS under FTY were recruited from 13 centers and real-world data and answers of satisfaction and adherence statements of pwMS on FTY treatment were analyzed. RESULTS: Data of 239 pwMS were obtained. The duration of FTY treatment was 2.5 ± 0.8 (1-4) years in pwMS who were included in the study and whose treatment continued for at least one year. Significant decreases in annual relapse rate (p < 0.001), Expanded Disability Status Scale (p < 0.001) and neuroimaging findings (p < 0.001) were observed. While 64% of the patients were satisfied and 71.5% were found to adherent with this FO-FTY. CONCLUSION: This multicenter retrospective study found that the efficacy, safety and treatment adherence of a prescribed FO-FTY were consistent with the results of real-world studies. Studies including real-world data may provide guidance to address issues related to FO-FTY use.

Serum prolidase activity and oxidative status in patients with diabetic neuropathy.

We found no data in the literature related to oxidative stress index (OSI), total oxidative status (TOS) and prolidase activity in patients with diabetic neuropathy (DN). In this study, we aimed to evaluate the oxidative status of DN patients via measurement of TOS and serum total antioxidant status (TAS) and estimation of OSI using new automated methods. Thirty-eight healthy participants, 40 diabetic patients without neuropathy, and 39 patients with DN were included. Electrophysiological and neurological examinations were performed. The activity of prolidase and levels of TOS and TAS were determined in the serum of patients. The level of TAS was lower, while the levels of TOS and OSI, and activity of prolidase were higher in both DN and diabetic control groups compared with the healthy subjects (p < 0.05). Prolidase activity was found to be higher in the DN group than in the diabetic control group (p = 0.001). In conclusion, the presence of high TOS and OSI levels together with low levels of TAS in diabetic patients with or without neuropathy may support a role of oxidative stress in the pathogenesis of diabetes mellitus. In addition, increased serum prolidase activity in DN may be interpreted as evidence of increased collagen turnover.

Relationship between optical coherence tomography angiography and visual evoked potential in patients with multiple sclerosis.

PURPOSE: This study aimed to identify an easy-to-apply biomarker by correlating visual evoked potential (VEP) with optical coherence tomography angiography (OCTA) results in multiple sclerosis (MS). METHODS: Our study was planned prospectively. Patients with MS were divided into two groups, VEP prolonged group 1 and VEP normal group 2. Age-matched and gender-matched healthy individuals (group 3) were included as the control group. Vascular density (VD) of the optic nerve head (ONH) and radial peripapillary capillaries (RPCs) were measured and recorded by OCTA. The optic nerve damage of patients was measured and recorded with a VEP device. RESULTS: Thirty-two eyes were included in group 1, 50 eyes were included in group 2, and 51 healthy eyes were included in group 3. In terms of visual acuity, group 1 was significantly lower than the other groups (P < 0.001). Regardless of the prolongation of p100 latency in patients with MS, whole image, inside disc ONH VD and in the same sectors in RPC VD were found to be significantly lower than the control group (P < 0.05). Retinal nerve fiber layer thickness was found to be significantly lower in group 1 than in group 2 and group 3 (P < 0.05). There was a significant correlation between low ONH VD and RPC VD and prolonged VEP P100 (P < 0.05). CONCLUSION: VEP measurements can be correlated with OCTA measurements in patients with MS and can be used as a biomarker to determine the degree of optic nerve damage.

The Turkish experience of COVID-19 infection in people with NMOSD and MOGAD: A milder course?

BACKGROUND: COVID-19 is a multisystemic infection with variables consequences depending on individual and comorbid conditions. The course and outcomes of COVID-19 during neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are not clearly known. OBJECTIVE/METHODS: The aim of this study was to examine the features and outcomes of COVID-19 infection in NMOSD and MOGAD patients. The patients' demographic and clinical factors, disease modifying treatment (DMT) used and disease information of COVID-19 infection were recorded. Conditions leading to hospitalization and severe exposure to COVID-19 infection were also analyzed. RESULTS: The study included 63 patients from 25 centers. Thirty-two patients (50.8%) belong to AQP-4 seropositive group, 13 (20.6%) and 18 (28.6%) were in MOG-positive and double-seronegative groups, respectively. Risk factors for severe COVID-19 infection and hospitalization were advanced age, high disability level and the presence of comorbid disease. Disease severity was found to be high in double-seronegative NMOSD and low in MOGAD patients. No statistically significant effect of DMTs on disease severity and hospitalization was found. CONCLUSION: In NMOSD and MOGAD patients, advanced age, high disability and presence of comorbid disease pose risks for severe COVID-19 infection. There was no direct significant effect of DMTs for COVID-19 infection.

CSF levels of HoxB3 and YKL-40 may predict conversion from clinically isolated syndrome to relapsing remitting multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) often initiates with an acute episode of neurological disturbance, known as clinically isolated syndrome (CIS). There is an unmet need for biomarkers that differentiate patients who will convert to MS and who will remain as CIS after the first attack. METHODS: First attack serum and cerebrospinal fluid (CSF) samples of 33 CIS patients were collected and these patients were divided as those who converted to MS (CIS-MS, n=17) and those who continued as CIS (CIS-CIS, n=16) in a 3-year follow-up period. Levels of homeobox protein Hox-B3 (HoxB3) and YKL-40 were measured by ELISA in samples of CIS-CIS, CIS-MS, relapsing remitting MS (RRMS) patients (n=15) and healthy controls (n=20). RESULTS: CIS-CIS patients showed significantly reduced CSF levels of YKL-40 and increased serum/CSF levels of HoxB3 compared with CIS-MS and RRMS patients. CIS-MS and RRMS patients had comparable YKL-40 and HoxB3 level profiles. Receiver operating characteristic (ROC) curve analysis showed the highest sensitivity for CSF HoxB3 measurements in prediction of CIS-MS conversion. Kaplan-Meier analysis demonstrated that CIS patients with lower CSF HoxB3 (<3.678 ng/ml) and higher CSF YKL-40 (>654.9 ng/ml) displayed a significantly shorter time to clinically definite MS. CONCLUSION: CSF levels of HoxB3 and YKL-40 appear to predict CIS to MS conversion, especially when applied in combination. HoxB3, which is a transcription factor involved in immune cell activity, stands out as a potential candidate molecule with biomarker capacity for MS.

Low dose vincristine-induced severe polyneuropathy in a Hodgkin lymphoma patient: a case report (vincristine-induced severe polyneuropathy).

Chemotherapeutic drugs are the most common toxic agents for peripheral nerves. Vincristine is a vinca alkaloid drug that is used for the treatment of several malignancies in combination with other chemotherapeutic agents. Treatment with intravenous (IV) vincristine at doses above 5 mg leads to a dose-dependent neuropathy with sensory symptoms but higher cumulative doses at around 30 to 50 mg are needed for the development of motor symptoms. The standard maximum adult IV vincristine dose is 2 mg IV per dose given at weekly intervals. However, administration of a single 2-mg dose IV vincristine may rarely result in the development of peripheral neuropathy. Few case reports have been presented on vincristine-associated severe paralysis in patients with preexisting hereditary neuropathy like Charcot-Marie Tooth (CMT) disease, who received doses even lower than 2 mg. Herein, we reported a Hodgkin lymphoma patient who developed severe polyneuropathy after receiving 2 mg vincristine treatment and was subsequently found to carry the CMT1A duplication responsible for CMT disease.

Predictive factors for acute stress disorder and posttraumatic stress disorder after motor vehicle accidents.

BACKGROUND: Since traffic accidents are more common in developing countries than in developed countries, we aimed to investigate the association of several factors with the development and persistence of posttraumatic stress disorder (PTSD) after traffic accidents. SAMPLING AND METHODS: In the study,95 participants with injuries from traffic accidents were evaluated at 4 different times: in the beginning, and after 3, 6 and 12 months. RESULTS: During the first evaluation, 41.1% (39) of our participants had acute stress disorder (ASD). It was found that lower perceived social support (OR = 0.0908, 95% CI = 0.834-0.989, p = 0.027) and higher peritraumatic dissociative experience scores (OR = 1.332, 95% CI = 1.170-1.516, p < 0.001) were significant predictors of ASD. In the evaluations after 3, 6 and 12 months after the accident, we found PTSD affected 29.8, 23.1 and 17.9% of the participants, respectively. Although limitations at work and in social life after a traffic accident were not related to PTSD at 3 months (OR = 122.43, 95% CI = 0.000, p = 0.999) or at 6 months (OR = 63.438, 95% CI = 0.529-76.059, p = 0.089), limitations at work and in social life were predictors of PTSD at 12 months (OR = 155.514, 95% CI = 2.321-104.22, p = 0.019). CONCLUSIONS: The persistence of PTSD at the 12-month evaluation is related to ASD, limitations in work and social life, and lower social support scores. In developing countries like Turkey, long-term PTSD is commonly seen after traffic accidents.

Apolipoprotein E genotype in patients with cerebrovascular diseases and its effect on the disease outcome.

A total of 100 hospitalized stroke patients and 30 healthy controls were included in a study aiming to determine the predictive role of ApoE genotype polymorphism for stroke outcome in the Turkish population. The most frequent ApoE genotype was epsilon3/3 reflecting Asian population polymorphic distribution. ApoE polymorphism in the Eastern Turkish population was found to be independent of stroke type, OSCP subtypes of infarction, localization of hemorrhage, severity of carotid artery stenosis, and resultant stroke outcome. Distinct polymorphic results in populations from nearby regions suggest a multifactorial pathogenesis and presence of very complex genetic factors in the development of stroke and stroke outcome.

Association of apolipoprotein E genotype and cerebrovascular disease risk factors in a Turkish population.

The purpose of the present study was to investigate the predictive role of apolipoprotein E genotypes for stroke-related risk factors in the Turkish population. Among 100 stroke patients and 30 healthy subjects included in the study, most frequent Apo E genotype was epsilon3/3, compatible with polymorphic distribution of Asian population. VLDL and triglyceride levels in epsilon2/4(+) subjects were higher than in epsilon2/4(-) patients. HDL and homocysteine levels were higher in epsilon4/4 (+) subjects than in epsilon4/4 (-) stroke patients. These results suggest that ApoE polymorphism in this population was not associated with any other demographic or clinical variables except for lipid profiles and homocysteine levels.

[The prevalence of dementia three months after stroke and its risk factors]. / Inme sonrasi demans: sikligi ve risk faktörleri.

OBJECTIVE: The aim of this study was to determine the prevalence of post-stroke dementia (PSD) and its possible clinical and sociodemographic risk factors 3 months after the index stroke episode. METHODS: Among 147 patients who were hospitalized in the inpatient neurology clinic of Dicle University Faculty of Medicine with a diagnosis of stroke, 106 that met the inclusion criteria were included in the study 3 months after the index stroke. All patients underwent a detailed systemic and neurological examination, as well as a clinical interview in an effort to determine the sociodemographic features, and both vascular and non-vascular risk factors of stroke. Routine laboratory examinations and cranial imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) were also conducted. The functional, clinical, and cognitive status of the patients were evaluated at the time of hospitalization and 3 months later with the Barthel Index, NIH Stroke Scale (NIHSS), and Mini Mental State Examination (MMSE), respectively. RESULTS: Of the 106 patients included in the study, 32 (30.2%) were diagnosed with PSD. Multivariate analyses revealed that increased age, presence of atrial fibrillation, multiple brain lesions, and cognitive and functional status during hospitalization predicted the development of PSD in this group of patients. CONCLUSION: The results corroborate previous findings that PSD is a common complication of stroke. Early recognition and treatment of PSD risk factors will definitely diminish the burden of stroke on society and help to improve patient quality of life.

Prevalence of and risk factors for cognitive impairment in patients with relapsing-remitting multiple sclerosis: Multi-center, controlled trial.

BACKGROUND: Cognitive impairment (CI) is a common problem in multiple sclerosis (MS), may occur either in early or late phase of the disease, and impairs quality of life. OBJECTIVES: This study aimed to determine the prevalence of CI and related risk factors in relapsing-remitting MS (RRMS) patients in Turkey. METHODS: The present cross-sectional, multi-center, and nationally representative study included RRMS patients. Sociodemographic characteristics, cognitive functions and additional outcomes were compared between patients with and without CI. RESULTS: The analyses included 487 RRMS patients. According to the BRB-N battery results, CI prevalence was 53.7%. There was a negative significant correlation of BRB-N subtests with age, disease duration, and EDSS and MSNQ-patient rated scores. On the logistic regression analysis, increased age, living in village/rural area, high income level, and high EDSS score were significant increasing risk factors in the development of CI. CONCLUSIONS: This is the first national cognitive data obtained from MS in Turkey, which is a country between Europe and Asia and thus has characteristics of both continents. The similarity of the results of the present study obtained from Turkey to the Western-based data indicates that CI is universal in MS and the main factors affecting CI have not changed.

Coexisting subarachnoid hemorrhage and subdural hematoma mimicking acute anterolateral myocardial infarction.

Ischemic electrocardiographic changes, elevations in cardiac-specific markers such as troponin and creatinine phosphokinase MB, segmental wall motion abnormalities, and myocardial dysfunction may occur after central nervous system events such as subarachnoid hemorrhage, subdural hematoma, and ischemic stroke. The pathophysiology remains unclear, but a catecholamine-induced neurocardiogenic injury has been mentioned as a causative factor. We reported a case of coexisting subarachnoid hemorrhage and subdural hematoma with ischemic electrocardiography changes, increases in cardiac-specific enzymes, and a regional wall motion abnormality despite normal epicardial coronary arteries. It is very important to differentiate neurogenic stunned myocardium from myocardial dysfunction caused by coronary artery disease in patients with intracranial hemorrhages for appropriately managing the treatment of cases.

Effect of rivastigmine on regional cerebral blood flow in Alzheimer's disease.

Cholinesterase inhibitors improve or stabilize cognitive impairment in patients with Alzheimer's disease (AD). The purpose of this study was to detect brain perfusion changes and the effects of rivastigmine, an acetylcholinesterase inhibitor on single photon emission computed tomography (SPECT) before and after treatment. Fifteen patients who fulfilled the clinical criteria for probable AD of mild to moderate severity, as put forth by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association, and as specified by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were included in the study. A control group of 15 healthy individuals from the same age and education range was included in the study. Before treatment was begun, Mini Mental State Examination (MMSE) tests were performed on all patients to evaluate cognitive function. All patients underwent baseline SPECT for evaluation of 25 different brain regions. Rivastigmine 3 mg/d was given for the first 4 wk of treatment; the dosage was then increased to 6 mg/d. The MMSE and SPECT were repeated 6 mo after the start of treatment. SPECT findings revealed that rivastigmine did not significantly affect brain perfusion in AD cases except in the inferior frontal lobe, despite stabilization and improvement noted in MMSE scores during treatment. Rivastigmine treatment of patients with AD did not significantly change brain perfusion as seen on SPECT, except in the inferior frontal lobe, but cognitive performance was stabilized or improved during the treatment course. These findings suggest the need for additional, larger studies to investigate the effects of acetylcholinesterase inhibitors on regional cerebral blood flow.

Testing patient-reported outcome measurement equivalence in multinational clinical trials: An exemplar using the 12-item Multiple Sclerosis Walking Scale.

BACKGROUND: Although multinational clinical trials frequently use patient-reported outcomes to measure efficacy, measurement equivalence across cultures and languages, a scientific requirement, is rarely tested. Clinically accessible accounts are rare; exemplars are needed. OBJECTIVE: To develop and test a Turkish version of the Multiple Sclerosis Walking Scale (MSWS-12v2) as a clinical exemplar for examining measurement equivalence. METHODS: The MSWS-12v2 Turkish (MSWS-12v2T) was developed using recognised methods for linguistic equivalence. Rasch measurement theory was used to examine measurement performance (multiple tests of targeting, scale performance, and person measurement) and measurement equivalence (differential item functioning). UK data (n = 3310) were used for comparisons and differential item functioning testing. RESULTS: One hundred and twenty-four people from two Turkish centres completed the MSWS-12v2T. Rasch measurement theory evidence supported MSWS-12v2T as reliable (person separation = 0.96) and valid (thresholds ordered; no concerning item misfit, bias, or person misfit). However, four items demonstrated significantly different performance between UK and Turkish samples. These item differences significantly affected scores (person measurements) at the group-level (p < 0.001). Individual person differences were less pronounced. CONCLUSIONS: Linguistic equivalence does not guarantee measurement equivalence; independent testing is required. Rasch measurement theory enables sophisticated and unique examinations of cross-cultural measurement equivalence and we recommend this be tested routinely in pivotal multiple sclerosis clinical trials.