Treatment of relapsing multiple sclerosis - recommendations of the Croatian Neurological Society.

Untreated multiple sclerosis (MS) irretrievably leads to severe neurological impairment. In European health care systems, patient access to disease modifying therapies (DMT) is often confined to more advanced stages of the disease because of restrictions in reimbursement. A discrepancy in access to DMTs is evident between West and East European countries. In order to improve access to DMTs for people with MS (pwMS) living in Croatia, the Croatian Neurological Society issued new recommendations for the treatment of relapsing MS. The aim of this article is to present these recommendations. The recommendations for platform therapies are to start DMT as soon as the diagnosis is made. If poor prognostic criteria are present (≥9 T2 or FLAIR lesions on the initial brain and spinal cord magnetic resonance imaging [MRI] or ≥3 T1 lesions with postcontrast enhancement on the initial brain and spinal cord MRI or Expanded Disability Status Scale after treatment of the initial relapse ≥3), high-efficacy DMT should be initiated. If pwMS experience ≥1 relapse or ≥3 new T2 lesions while on platform therapies, they should be switched to high-efficacy DMT. Further efforts should be made to enable early and unrestricted access to high-efficacy DMT with a freedom of choice of an appropriate therapy for expert physicians and pwMS. The improvement of access to DMT achieved by the implementation of national treatment guidelines in Croatia can serve as an example to national neurological societies from other Eastern European countries to persuade payers to enable early and unrestricted treatment of pwMS.

Psychometric Properties of the Pittsburgh Sleep Quality Index (PSQI) in Patients with Multiple Sclerosis: Factor Structure, Reliability, Correlates, and Discrimination.

Sleep disturbances and poor sleep are a common complaint in the population with multiple sclerosis (MS) disease. The most commonly reported scale is the Pittsburgh Sleep Quality Index (PSQI), measuring seven components of sleep quality. Yet, till today, the PSQI instrument has not been validated in people with multiple sclerosis (pwMS). The objective of our study was to add precision in sleep quality assessment by investigating the psychometric properties of PSQI (factor structure, reliability, validity based on relations with other variables, cut-off scores) in pwMS. The cross-sectional study included data on a total of 87 patients with MS and 216 control subjects. Demographic information, education level, and MS-related variables were ascertained. Psychometric properties were examined by estimating the validity, including factor structure, metric invariance, and relations with other MS- and non-MS-related variables, reliability, and discrimination ability of the PSQI. The Croatian version of the PSQI had a two-factor structure which demonstrated loading and partial intercept invariance between pwMS and the control group. The global score and both subscales had high internal consistencies (McDonald's omega and Cronbach's alpha coefficients) in pwMS and showed expected relations with demographic and MS-related variables. PwMS differed significantly in the PSQI global score from the control groups, although receiver operating characteristics (ROC) curve analysis did not indicate a clear cut-off point. The PSQI is a reliable and valid scale and can be applied in clinical settings for assessing sleep quality in pwMS.

Validation of the fatigue severity scale in Croatian population of patients with multiple sclerosis disease: Factor structure, internal consistency, and correlates.

BACKGROUND: Fatigue is a common symptom in people with multiple sclerosis (MS) and is evaluated and monitored with self-report questionnaires. The objective of this study was to determine the psychometric properties of the Croatian version of the Fatigue Severity Scale (FSS) in people with MS. MATERIAL AND METHODS: This is a retrospective cohort study conducted as an online survey from December 16, 2020, until January 13, 2021. A total of 179 people with MS and 999 control subjects completed FSS and self-administered questionnaires capturing information of demographic, education level, disease-related variables (duration of the disease, MS type, the expanded disability status scale (EDSS), and Multiple Sclerosis Impact Scale-29 (MSIS-29). Psychometric properties were examined by estimating the validity, reliability, and factor structure of the FSS scale in people with MS. RESULTS: The Croatian version of the FSS had excellent internal consistency (Cronbach's α value 0.93). Factor analysis demonstrated a unidimensional structure. The concurrent validity of the FSS appeared to be satisfactory due to the significant differences between people with MS and control subjects (p < .05). The correlations between FSS and MSIS-29 physical (r = 0.60) and psychological (r = 0.50) subscale results confirmed the convergent validity of the FSS scale. Results also indicated that the best cut-off score is between 4 and 5 with a relatively high sensitivity and specificity. CONCLUSIONS: The Croatian version of FSS was shown to have excellent psychometric properties in people with MS and can be used in the research and clinical settings evaluating fatigue in people with MS in Croatia.

Information Processing Speed Assessed with Letter Digit Substitution Test in Croatian Sample of Multiple Sclerosis Patients.

Cognitive impairment is a common complaint in people with multiple sclerosis (pwMS). The study objective was to determine the psychometric properties of the letter digit substitution test (LDST) that measures information processing speed and to investigate the impact of relevant predictors of LDST achievement in pwMS. The design was cross-sectional. The study included 87 pwMS and 154 control subjects. The validity of LDST was examined, and a hierarchical regression model was used to explore relevant predictors of LDST success. The LDST had excellent construct validity, as expressed by differences between pwMS and control subjects. Convergent validity of the LDST was supported by a significant moderate correlation with the expanded disability status scale (EDSS) (ρ = -0.36; p < 0.05) and a significantly strong correlation with the multiple sclerosis impact scale (MSIS-29) physical subscale (r = -0.64; p < 0.01). The LDTS score well differentiated the pwMS considering age, education, EDSS, disease duration, comorbidity, and medication therapy. Using the LDST as a criterion variable in pwMS results showed consistent evidence for the age, education, and EDSS impact on LDST performance. The best cut-off score of ≤35 discriminated the control and MS group. LDST proved to be a valid test for assessing information processing speed in pwMS.

DEPRESSION AND FATIGUE ARE DUE TO OBSTRUCTIVE SLEEP APNEA IN MULTIPLE SCLEROSIS.

To our knowledge, there is no study investigating whether fatigue and depression as the most commonly reported symptoms in multiple sclerosis (MS) and obstructive sleep apnea (OSA) patients have arisen from primary mechanisms of MS or from secondary associated conditions such as OSA in MS patients. The aim of our survey study was to determine whether depression and fatigue in MS patients were associated with clinical features of OSA or with MS. We conducted a self-administered survey using four validated questionnaires (STOP-BANG, Epworth Sleepiness Scale, Fatigue Severity Scale and The Center for Epidemiologic Studies Depression Scale-Revised) in 28 consecutive outpatients with proven MS. The prevalence of MS patients at an increased risk of OSA was 29% and age was positively correlated with this risk (p=0.019). None of the clinical features of MS patients (subtype, disability status, disease duration, modifying therapy, other medication) was correlated with depression and fatigue. On the contrary, excessive daytime sleepiness as a hallmark of OSA was significantly and positively associated with the level of depressive symptoms (p=0.004) and level of fatigue (p=0.015). Also, depression was significantly and positively correlated with the increased risk of OSA (p=0.015) and age of MS patients (p=0.016). Finally, a significant positive correlation was found between fatigue severity and level of depressive symptoms (p=0.003). OSA is a common disorder in MS patients. The clinical features and risk factors for OSA in MS patients are associated with the two most commonly reported symptoms of depression and fatigue, thus supporting the hypothesis that both symptoms are due to a secondary condition in MS.

Psychometric Properties of the HADS Measure of Anxiety and Depression Among Multiple Sclerosis Patients in Croatia.

Depression and anxiety are common complaints in patients with multiple sclerosis (MS). The study objective was to investigate the factor structure, internal consistency, and correlates of the Croatian version of the Hospital Anxiety and Depression Scale (HADS) in patients with MS. A total of 179 patients with MS and 999 controls were included in the online survey. All subjects completed the HADS and self-administered questionnaires capturing information of demographic, education level, disease-related variables, and the Multiple Sclerosis Impact Scale-29 (MSIS-29). Psychometric properties were examined by estimating the validity, reliability, and factor structure of the HADS in patients with MS. The two HADS subscales (anxiety and depression) had excellent internal consistencies (Cronbach's α value 0.82-0.83), and factor analysis confirmed a two-factor structure. The convergent validity of the HADS subscales appeared to be good due to the significant correlations between HADS and MSIS-29. Receiver operating characteristic (ROC) analysis indicates that the HADS subscales have a significant diagnostic validity for group differentiation. Hierarchical regression analysis using MSIS-29 subscales as criterion variables showed consistent evidence for the incremental validity of the HADS. The HADS is a reliable and valid self-assessment scale in patients with MS and is suggested to be used in clinical monitoring of the psychiatric and psychological status of patients with MS.

Regression of Asymmetric Upper Extremity Tremor After Liver Transplantation in a Patient With Hepatic Encephalopathy: Case Report.

Hepatic encephalopathy (HE) is a brain dysfunction caused by liver failure. Clinically, it can manifests as a wide spectrum of neurological or psychiatric abnormalities. This report presents a case of a 43-year-old male with HE and asymmetric kinetic, postural and resting tremor of upper extremities. Magnetic resonance imaging (MRI) of the brain showed signal abnormalities in numerous areas. The patient underwent liver transplantation and six months after normalization of liver function, tremor as well as brain MRI abnormalities almost completely regressed. This case re-port presents the asymmetric and reversible kinetic, postural and resting tremor of upper extremities as part of the spectrum of neurological abnormalities in HE.

Correlation analysis of visual analogue scale and measures of walking ability in multiple sclerosis patients.

Walking limitation assessment in multiple sclerosis patients (MSPs) is a demanding task, especially in the clinical setting. The aim of this study is to correlate the visual analogue scale (VAS), a simple method for measuring subjective experience, with measures of walking ability used in clinical research of MS. The study included 82 ambulatory MSPs who have resided in the local community. The applied measures of walking ability were the following: the single-item and patient-rated Walking Ability Visual Analogue Scale (WA-VAS), the Expanded Disability Status Scale (EDSS), the 25-foot walk test (25FWT), the Six Spot Step Test (SSST), the 2 min timed walk (2 min TW), the Multiple Sclerosis Walking Scale-12 (MSWS-12), and step activity monitor accelerometer (SAM) during 7 day period. The SAM analysis included the average daily step count, the average steps/min of the highest 1 min of a day, and the average steps/min of the highest continuous 60 min of a day. The WA-VAS scores significantly and strongly correlated with EDSS (ρ = 0.679, P < 0.001), 25FWT (ρ = 0.606, P < 0.001), SSST (ρ = 0.729, P < 0.001), 2 min TW (ρ = -0.643, P < 0.001), MSWS-12 (ρ = 0.746, P < 0.001), average daily step count (ρ = -0.507, P < 0.001), average steps/min of the highest 1 min of a day (ρ = -0.544, P < 0.001), and average steps/min of the highest continuous 60 min of a day (ρ = -0.473, P < 0.001). Correlations between WA-VAS and measures of walking ability used in clinical research of MS were satisfactory. The results obtained in this research indicate that the WA-VAS could be an instrument for simple measurement of walking limitations in MSPs in the clinical setting.

Role of NMO-IgG in distinguishing the type of optic neuritis.

PURPOSE: To emphasize the importance of neuromyelitis optica (NMO)-immunoglobulin G (IgG) antibodies testing in patients with typical optic neuritis (ON) refractory to steroid treatment. METHODS: Two patients were evaluated with ON refractory to steroid therapy and poor visual acuity; they were tested for NMO-IgG antibodies. RESULTS: Brain magnetic resonance imaging was normal in both patients. The serum and cerebrospinal fluid were positive for NMO-IgG antibodies. Magnetic resonance imaging of the cervical and thoracic spine revealed lesions longer than three vertebral segments and the diagnosis of NMO was confirmed. Treatment with plasma exchange and immunosuppressive therapy resulted in marked improvement of visual acuity. This improvement was sustained. CONCLUSIONS: The testing for NMO-IgG antibodies is important for distinguishing ON in NMO from multiple sclerosis in cases of ON refractory to steroid treatment. These cases suggest that testing for NMO-IgG antibodies should be performed in comparative trials on a larger series.

Responsiveness of walking-based outcome measures after multiple sclerosis relapses following steroid pulses.

BACKGROUND: The aim of this study was to examine the impact of intravenous methylprednisolone therapy (IVMP) on the recovery of walking ability in patients experiencing multiple sclerosis (MS) relapses, to compare the responsiveness of walking-based measures, and to estimate the impact of different walking-based measures responsiveness on clinical trials. MATERIAL/METHODS: The study included 49 consecutive patients with relapsing-remitting MS who received Solu-Medrol 1000 mg/day over 3 days for relapse with difficulties in walking. The following walking-based measures were administered before and a month after IVMP: the Multiple Sclerosis Walking Scale-12 (MSWS-12), the Expanded Disability Status Scale (EDSS), the 2-minute timed walk (2-minTW), the 25-foot walk test (25FWT), the Six Spot Step Test (SSST). All patients had worn the step activity monitor accelerometer (SAM) 1 week prior to IVMP was applied and wore it again the fourth week upon the corticosteroid therapy was completed. The SAM analysis utilized the average daily step count and data regarding frequency and intensity of walking over a continuous time interval. We examined: (1) the impact of IVMP on the recovery of walking ability; (2) the responsiveness of each walking-based measure; (3) the relative responsiveness of competing walking-based measures; and (4) the impact of different walking-based measures responsiveness on clinical trials. RESULTS: All walking-based measures showed significant improvement of walking ability 1 month after the IVMP. The most responsive were MSWS-12 and EDSS. Different responsiveness implied a greater than 6-fold impact on sample size estimates. CONCLUSIONS: All applied walking-based measures showed significant improvement of walking ability 1 month after the IVMP. Responsiveness of various walking-based measures notably differ, thus affecting sample size calculations.

Risk factors and outcome differences between ischemic and hemorrhagic stroke.

The aim of the study was to justify the hypothesis that risk factors do not differ between ischemic and hemorrhagic stroke. This retrospective study included 1066 stroke patients. The prevalence of risk factors and hospital-based survival were compared between patients with ischemic and hemorrhagic stroke. Data were retrieved from patient records. Statistical analysis was done by use of chi2-test and t-test for dependent samples. The group of hemorrhagic stroke consisted of 70 (47.9%) female and 76 (52.1%) male patients. The group of ischemic stroke included 450 (48.9%) female and 470 (51.1%) male patients. Ischemic stroke patients had a higher prevalence of hypertension (79% vs. 72%), atherosclerotic diseases (50% vs. 34%) and atrial fibrillation (15.5% vs. 4.2%), and were statistically significantly older (72.5 +/-10.4 vs. 65.7 +/- 12.8) than those with hemorrhagic stroke, however, fatal outcome was more common in the latter (26% vs. 17%). In conclusion, data analysis pointed to differences between hemorrhagic and ischemic stroke according to both risk factors and stroke outcome.

[Study of quality of life in patients with multiple sclerosis]. / Kvaliteta zivota u oboljelih s multiplom sklerozom.

INTRODUCTION: Multiple sclerosis (MS) is a neurological impairment mostly affecting younger adults substantially decreasing their working and living abilities. Different rating scales to determine disabilities are being used: EDSS, NRS, and CAMBS. The objective of this study was to assess the quality of life in MS patients, with reference to the disease itself and its treatment, comparing patients with MS and a matching healthy control group. METHODS AND SUBJECTS: Subjects were divided into two groups, a group of patients with MS and a control group of healthy subjects. There were 37 MS patients, 25 women and 12 men. Control group consisted of 51 subjects, 39 women and 12 men. There was no statistically significant sex difference. The mean age of the MS patients was 45.9 +/- 12.4 years, and of control group 42.4 +/- 10.3 years; yielding no statistically significant difference. The severity of impairment in MS patients according to EDSS scale was 3 to 3.5. The quality of life determined by the prediction and criterion variables was studied in both MS patients groups and control group. All variables were graded on a 1 to 5 scale. On statistical data processing chi2 test and t-test were used. RESULTS AND DISCUSSION: Predictors referring to family history, sexual life, social life, satisfaction with education, job, social environment, religious life, housing status, financial status and present family life did not differ between the MS and control group. MS patients were less satisfied with their place in society, their state of health and ways of spending their free time. The decrease of satisfaction correlated with the areas generally known to be directly or indirectly affected by MS. As to the criterion variable of 'satisfaction with former way of life' no significant differences were found, since the disease did not affect previous life achievements. MS patients were less satisfied with their status in society, their state of health and ways of spending their free time. Changes occurred as a consequence of substantial life changes caused by the disease, results of treatments and circumstances in which the patients lives. Results obtained indicated that patients were aware of their disease, lower quality of life that limited their daily activities and future plans. Answers referring to the state of health, social status, and sexual activities did not show any statistically significant difference between the groups of MS patients and healthy controls, although it could have been expected according to the experience and customary expectations in such cases. CONCLUSION: MS patients are mainly satisfied with what they have achieved previously as young people; they become dissatisfied in relation to the possible economic and social prospects, and they are aware of their disabilities and weaknesses, inability for professional development, working and workplace relationships, more difficult money acquisition, etc.

Progression of optic neuritis to multiple sclerosis in the County of Split-Dalmatia, Croatia.

The aim of this study was to determine the incidence of monosymptomatic optic neuritis (MON) and progression of MON to multiple sclerosis (MS) from the Mediterranean region of southern Europe in the County of Split-Dalmatia, Croatia during the 11 years period from 1991 to 2001. This study was made retrospectively on the 87 cases (59 female, aged 25.9 +/- 11.3 and 28 male aged 29.9 +/- 9.2) of MON, which were treated at the Department of Ophthalmology and Department of Neurology, Split, University Hospital, from January 1991 to December 2001. In each case the diagnosis was confirmed by a chart review and cases were ascribed to the data of admittance at hospital. The annual incidence of MON was 1.9 per 100,000 (95% CI, 0.4-3.5). The incidence among males was 1.2 (95% CI, 0-2.9) cases / 100,000 per year and 2.5 (95% CI, 0.1-4.9) among females. A significant seasonal variations in the incidence of MON was not found (chi2 = 6.81, p = 0.08). MS developed in 20 of 87 patients (22.9%) and median time was 25 (SE 8) months, (95% CI, 9-41) after the MON onset. After two years 12.6% of patients with MON developed MS, 20.6% after 5 years and 22.9% after 10 years. MS was slightly but not significantly more frequent in women than in men (chi2 = 0.72, p = 0.3). In conclusion, the progression of MON to MS in the County of Split-Dalmatia, Croatia was at a relatively moderate frequency.

Neurotoxicity that may mimic progressive multifocal leukoencephalopathy in patient with transplanted kidney.

We present the 55-year-old woman who has had kidney transplantation three times. She has been treated with immunosuppressive therapy and lamivudine for hepatitis B and C. Nine years after the last transplantation she showed neurological symptoms that presented in the form of confusion and epileptic seizures of the grand mal type. A brain MRI showed large oval zones of hyperintense MR signal in T2-weighted image and hypointense in T1-weighted image around the frontal horns of the lateral ventricles, bilaterally and in both cerebellar hemispheres. After reduction in immunosuppression and the exclusion of lamivudine from therapy, the patient was stable with normal neurological status during the course of next five years. We start from the assumption that the concomitant use of cyclosporin with mycophenolate mofetil and lamivudine, despite normal concentrations of cyclosporin, might cause the accumulation of toxic metabolites and lead to neurotoxicity that mimics PML in a chronic viral environment.

[Risk factors and carotid atherosclerosis in patients with transient ischaemic attack]. / Cimbenici rizika i karotidna ateroskleroza u bolesnika s tranzitornom ishemijskom atakom.

In order to identify association between serum lipid levels, hypertension, smoking, diabetes and the severity of carotid atherosclerosis, ultrasonography of extracranial arteries was performed in 56 male patients (age: x = 62.9 years, S.D.= 9.4) with transient ischaemic attack. According to color Doppler criteria, patients were divided into two groups--Group I: < 50%, Group II: > or = 50% stenosis of the carotid artery. In Group I, there were 36 (64.3%), and in Group II 20 (35.7%) patients. No significant differences between those two groups were found regarding mean levels of total cholesterol, LDL- and HDL-cholesterol, and triglycerides (normolipemic levels were found in both groups). Two groups were compared also concerning the incidence of hypertension, diabetes and smoking, and no significant difference was found, as well. Stepwise multiple logistic regression analysis revealed that only age significantly increased the risk of severe carotid atherosclerosis (odds ratio 2.0, 95% CI: 1-4.3). These results show the influence of age in pathogenesis of carotid atherosclerosis.