Systemic erythematous lupus after treatment of multiple sclerosis with alemtuzumab.

Alemtuzumab is a humanized monoclonal antibody targeting CD52 protein that has shown great efficacy in the treatment of relapsing remitting multiple sclerosis and is associated with prolonged remission of the disease. Although it is highly effective, alemtuzumab can lead to serious adverse advents among which the most common are secondary autoimmune diseases. We present a patient who was treated with alemtuzumab for relapsing remitting multiple sclerosis. Her disease remained stable in a follow-up period of over ten years. However, during the follow-up period she developed thyroiditis one year, as well as systemic erythematous lupus seven years after the last alemtuzumab infusion, a disease not previously associated with alemtuzumab administration.

The incidence of postural orthostatic tachycardia syndrome in the population of Zagreb, Croatia.

AIM: To estimate the incidence of postural orthostatic tachycardia syndrome (POTS) in the population of Zagreb, Croatia, and to determine the patients' demographic and clinical characteristics. METHODS: From 2012-2017, we identified patients with POTS by a retrospective analysis of medical records at University Hospital Center Zagreb. Crude incidence rates were directly standardized by age according to the European and World Standard Population. RESULTS: Out of 385 patients with suspected POTS, 23 had a definitive POTS diagnosis. The annual incidence ranged from 3.3 to 14.8 per 1000000 for both sexes combined. The highest incidence rates were in the age groups 18-29 and 30-39 years, with female predominance. The mean age at diagnosis was 30.7 years (standard deviation ±9.2, range 18-52). The median duration of symptoms at diagnosis was 7.5 months (range 3-180 months). Regarding associated comorbidities, two patients had chronic gastritis and one patient had each of the following: epilepsy, prior subarachnoid hemorrhage, anxiety, mitral insufficiency, obstructive sleep apnea, hypothyreosis, and irritable bowel syndrome. In patients not fulfilling the criteria for POTS, the most common alternative diagnoses were autonomic dysfunction due to multiple sclerosis in 22, anxiety disorder in 17, epilepsy in 16, and orthostatic tachycardia due to deconditioning in 13 patients. CONCLUSION: The data obtained in this study can be used to optimize disease surveillance in population, comprehensive assessment of disease burden, and organization of health care services.

Evolution of tongue somatosensory evoked potentials in people with multiple sclerosis.

INTRODUCTION: The aim of the present study was to investigate the long-term evolution of tongue somatosensory evoked potentials (tSSEP) in people with multiple sclerosis (pwMS). METHODS: Out of initial 121 participants, after two-year follow-up, the data were available for 74 and after four-year follow-up for 58 pwMS. In all pwMS complete neurological examination, brain MRI, cervical spinal cord MRI (if available) and tSSEP were performed at baseline visit (M0). Complete neurological examination and tSSEP were performed 2 and 4 years later (M24 and M48). tSSEP results were interpreted in the form of ordinal tSSEP score and quantitative tSSEP zscore calculated from the sum of z-transformed tSSEP latencies. RESULTS: Differences in tSSEP scores and tSSEP zscores in three different timepoints showed significant worsening of both scores over time. For the tSSEP score the difference was significant for M0-M24 and M0-M48 visits, but not for M24-M48 visits. For the tSSEP zscore the difference was significant for M0-M48 and M24-M48 visits, but not for M0-M24 visits. The only significant negative predictor found for the tSSEP score improvement was presence of cervical spinal cord lesions on the MRI. A moderate to high correlation was observed between both forms of tSSEP score at all three timepoints. CONCLUSION: This study demonstrates a significant deterioration of trigeminal sensory pathway in MS over time, giving further insight into trigeminal system damage in pwMS.

Intravenous immunoglobulins for the prevention of postpartum relapses in multiple sclerosis.

OBJECTIVES: To evaluate the effect of intravenous immunoglobulins (IVIG) on prevention of postpartum relapses in women with relapsing-remitting multiple sclerosis (RRMS). METHODS: This was a retrospective study performed in Ljubljana, Slovenia where the practice for all pregnant women with RRMS is to receive IVIG after the delivery (10 g monthly, during first 6 months after delivery) and in Zagreb, Croatia where no such practice exists. The following data were collected: date of delivery, maternal age at delivery, year of the RRMS diagnosis, EDSS, disease modifying therapy prior to pregnancy, relapses in the year prior, during and in the period of one year after pregnancy. RESULTS: Data on 132 pregnancies from 112 women (mean age at delivery 31.70±4.10, average disease duration 6.34±4.33) were analyzed. There was no association between the IVIG treatment and annualized relapse rate one year after the delivery (0.27 vs 0.38, rate ratio 1.409, 95% CI 0.764-2.598, p = 0.272). No risk factors for the postpartum relapse were identified (age at delivery, duration of RRMS, EDSS prior pregnancy, disease modifying therapy prior pregnancy, relapses in the year prior pregnancy, IVIG). CONCLUSION: This study provides no evidence of benefit for postpartum administration of IVIG in women with RRMS.

Pulmonary embolism during the third cycle of alemtuzumab in a patient with relapsing multiple sclerosis.

Alemtuzumab is one of immunomodulatory drugs used for treatment of multiple sclerosis (MS). Although it is very effective it carries significant risk for various side effects. This paper reports a case of young patient who developed pulmonary embolism during the third cycle of alemtuzumab. It is suggested that awareness about possible vascular toxicity of this drug should be raised.

Recurrent atrial fibrillation after pulse corticosteroid treatment for a relapse of multiple sclerosis.

Standard therapy for a relapse of multiple sclerosis is a high dose pulse corticosteroid therapy. Cardiovascular adverse events ranging from palpitations to serious arrhythmias like atrial fibrillation and ventricular tachycardia have been associated with this treatment. The underlying mechanism behind the development of atrial fibrillation and treatment of multiple sclerosis relapse with steroids is still unclear. In this case, a 27-year-old male with multiple sclerosis is presented who developed atrial fibrillation on two occasions following two consecutive treatments with high dose methylprednisolone for the treatment of multiple sclerosis relapse. Extensive work-up revealed mild sympathetic autonomic system dysfunction. Based on this case and previous studies, we propose that a disturbed function of the autonomic system increases the risk of atrial fibrillation and/or other arrhythmias in people with multiple sclerosis.

Effect of Food Intake on Hemodynamic Parameters during the Tilt-Table Test in Patients with Postural Orthostatic Tachycardia Syndrome.

BACKGROUND AND PURPOSE: The aim of this study was to determine the effect of food intake on the heart rate (HR) in postural orthostatic tachycardia syndrome (POTS). METHODS: The following five-phase protocol was applied to 41 subjects who had a sustained HR increment of ≥30 beats/min within 10 min of standing in an initial tilt-table test: 1) 10-min supine phase, 2) 10-min 70°-tilted phase, 3) ingestion of 400 mL of Nutridrink Multi Fibre®, 4) 45-min supine phase, and 5) 10-min 70°-tilted phase. Subjects were divided into four groups: A) difference in HR for standing vs. supine (ΔHR) before the meal of ≥30 beats/min (n=13), B) ΔHR <30 beats/min before the meal but ≥30 beats/min after the meal (n=12), and C) ΔHR <30 beats/min both before and after the meal (n=16). Group D consisted of 10 healthy subjects. RESULTS: Before the meal, ΔHR was significantly higher in group A than in all of the other groups, and in group B than in group D (p<0.001). After the meal, ΔHR was significantly higher in groups A and B (p<0.001 and p<0.0001, respectively). When we pooled patients (according to their symptoms) from group A and B into a POTS group and from group C and D into a non-POTS group, an increase in HR of 25 beats/min before the meal had a sensitivity of 92.0% and a specificity of 80.8%. After the meal, an increase in HR of 30 beats/min had a sensitivity of 96.0% and a specificity of 96.2%. CONCLUSIONS: Food intake can significantly alter the results of the tilt-table test and so should be taken into account when diagnosing POTS.

Autonomic symptom burden can predict disease activity in early multiple sclerosis.

BACKGROUND: We aimed to evaluate the role of autonomic nervous system (ANS) abnormalities on disease activity (relapses and new MRI lesions) and disease progression in people with clinically isolated syndrome (pwCIS). METHODS: Out of 121 consecutive pwCIS, data on disease activity and progression after 2.9 (1.4-4.1) years of follow-up, was available for 94 pwCIS. Baseline characteristics included MRI parameters, Composite Autonomic System Score-31 (COMPASS-31), Composite Autonomic Scoring Scale, and supine and standing levels of epinephrine and norepinephrine. RESULTS: Univariable logistic regression analysis revealed three predictors for occurrence of new relapse, COMPASS-31 > 7.32, total number of T2 lesions > 3 and decreasing supine level of epinephrine. The Kaplan-Meier survival analysis showed that patients with COMPASS-31 > 7.32 have statistically significant lower probability that they will be relapse free (p = 0.013). It has also showed that the relative risk reduction for occurrence of new relapse in participants with COMPASS < 7.32 was 46%. The multivariable regression model confirmed that COMPASS-31 > 7.32 and total number of T2 lesions > 3 increase the likelihood and the increasing supine level of epinephrine reduces the likelihood for a relapse. Finally, results of the Cox regression analysis showed, that after controlling for age, sex, total number of T2 lesions > 3 and supine level of epinephrine, the hazard for occurrence of new relapse for participants with COMPASS-31 > 7.32 is 2.7 times that of participants with COMPASS-31 < 7.32. CONCLUSION: This study provides evidence that ANS is an important contributor to development of disease activity in pwCIS.

Performance of the COMPASS-31 questionnaire with regard to autonomic nervous system testing results and medication use: a prospective study in a real-life setting.

The aim of this study was to investigate the performance of the Composite Autonomic System Score-31 (COMPASS-31) questionnaire in a real-life setting in consecutive patients referred to the laboratory for objective testing of the autonomic nervous system (ANS), with the hypothesis that COMPASS-31 results differ depending on medications and findings of the tilt table test results. One hundred seventy-one consecutive patients (125 females, mean age 41.5 ± 19.3) referred for testing of the ANS were enrolled. Before testing, all patients completed the recently validated Croatian version of COMPASS-31. The following data were systematically collected for all patients: age, sex, diagnoses, and medications. Results of COMPASS-31 were significantly higher in patients taking medications with a known influence on the ANS (p < 0.001). Patients with postural orthostatic tachycardia had significantly higher orthostatic intolerance and vasomotor domains of COMPASS-31 (p = 0.048 and p = 0.022, respectively). Patients with a cardiovagal score ≥ 1 had a significantly higher vasomotor domain of COMPASS-31 compared to patients with normal results of ANS tests (p = 0.030). These findings suggest the COMPASS-31 might be a valuable screening tool for autonomic dysfunctions, as it is associated with impaired ANS tests, but usage of medications that modify the ANS should always be taken into account.

Toxic liver injury after high-dose methylprednisolone in people with multiple sclerosis.

The standard therapy of multiple sclerosis (MS) relapse is high-dose pulse corticosteroid therapy. Although commonly applied and usually well tolerated it may as well carry certain risks for people with MS, the more severe of them being hepatotoxicity. This report describes three cases of acute liver injury following pulse corticosteroid therapy with reference to other possible causative factors. Caution should be exercised when applying high-dose methylprednisolone given the potential liver related adverse events it may cause.

Establishing the diagnosis of multiple sclerosis in Croatian patients with clinically isolated syndrome: 2010 versus 2017 McDonald criteria.

AIM: To compare the sensitivity, specificity and accuracy of the 2010 and 2017 revisions of the McDonald criteria in a Croatian cohort of patients with a clinically isolated syndrome (CIS). METHODS: Prospectively collected data from 113 patients were retrospectively analyzed. Sensitivity, specificity and accuracy for both criteria were calculated regarding conversion to clinically definite multiple sclerosis (Poser CDMS) or multiple sclerosis (MS) (defined as fulfilment of clinical or MRI evidence for dissemination in space and the development of a second relapse and/or ≥1 new T2 lesions on the follow-up MRIs) during a two-year follow-up. Survival analysis was performed to estimate the cumulative risk of patients developing Poser CDMS. Binary logistic regression model was used to determine which variables are statistically significant predictors for the conversion to MS. RESULTS: The 2017 revision had higher sensitivity (85 vs. 30% and 85 vs. 41%) and lower specificity (33 vs. 63% and 63 vs. 85%) compared to the 2010 revisions, for conversion to Poser CDMS and MS, respectively. Patients who did not meet the 2017 McDonald criteria had a higher chance of conversion-free survival for Poser CDMS than those who met the 2017 McDonald criteria (p = 0.037). Results of the multivariate regression analysis revealed that patients who at baseline fulfilled 2017 revisions of the McDonald criteria have the increased likelihood of conversion to MS (Exp(B) 9.68, 95%CI 3.62-25.90, p < 0.00001). CONCLUSION: This study provides new information about the application of the 2017 revisions of the McDonald criteria in a Croatian cohort of patients with typical CIS.

Video head impulse test can detect brainstem dysfunction in multiple sclerosis.

BACKGROUND: The aim of this study was to investigate the potential role of video head impulse test (vHIT) in the detection of brainstem lesions in patients with multiple sclerosis (MS). METHODS: Sixty-eight participants were enrolled and divided into two groups: 39 healthy subjects (HC) (78 ears, 20 females, mean age 25,3±6,3) and 29 MS patients (58 ears, 14 females, mean age 33,7±7,7). Both groups underwent vHIT, and in MS group MRI was analyzed for the presence of brainstem lesions. vHIT pathology was defined as presence of overt saccades (<200ms) or lateral gain lower than 0.8 for lateral canal, and presence of overt saccades (<200ms) or posterior/anterior slope lower than 0.7. RESULTS: In HC, decreased gain on horizontal canals was found in 8 out of 78 ears (11%), while 16 out of 58 ears (38%) had pathological results in the MS group. Mean gain of the lateral canals (60ms) was significantly reduced in MS group compared to HC (0.874±0143 vs. 0.954±0,170, p=0.004, respectively). Compared to HC overt saccades <200ms in the lateral canals (p=0.018) and in the posterior canals (p=0.011), overt saccades >200ms in lateral (p<0.001), anterior (p=0.019) and posterior canals (p=0.009), and covert saccades in the anterior (p=0.042) and posterior canals (p=0.046) were more frequent in the MS group. There was statistically significant association between the presence of BS MR lesions and bilateral pathology on vHIT for lateral semicircular canal (χ(1)=3.982, p=0.046). CONCLUSION: These results indicate that vHIT can detect brainstem dysfunction in patients with MS.

Vestibular evoked myogenic potentials and video head impulse test in patients with vertigo, dizziness and imbalance.

The aim of this study was to compare vestibular evoked myogenic potentials (VEMP) and video head impulse test (vHIT) results in patients presenting with vertigo and dizziness. We retrospectively analyzed data of all patients with the chief complaint of vertigo, dizziness, or imbalance that underwent VEMP and vHIT from January 2015 to January 2016. A total of 117 patients (73 females, mean age 53.92±16.76) fulfilled inclusion criteria: group 1 included patients with the final diagnosis of vestibular neuritis (VN) (N=31 (16 right and 15 left VN)), group 2 included patients with the final diagnosis of vertigo of central origin (N=23) and group 3 included patients with the final diagnosis of unspecified dizziness (N=63). There was significant correlation between oVEMP asymmetry and asymmetry of the lateral canals 60ms gains on vHIT (r=0.225, p=0.026). Significant correlation between oVEMP and vHIT asymmetry was present in VN patients (r=0.749, p<0.001), while no correlation was found in the groups 2 and 3. oVEMP and vHIT lateral canals asymmetries were significantly greater in patients with vestibular neuritis. Furthermore, positive correlations of oVEMP amplitudes with 60ms gain of the lateral semicircular canal and slope of the anterior semicircular canal on vHIT, and cVEMP with slope of the posterior semicircular canal on the vHIT were found. These changes were significantly more pronounced in patients with vestibular neuritis. In conclusion, VEMPs and vHIT data should be used complementarily; asymmetry on both tests strongly supports peripheral vestibular system involvement.