Cladribine tablets in people with relapsing multiple sclerosis: A real-world multicentric study from southeast European MS centers.

BACKGROUND: Cladribine is an oral disease-modifying drug authorized by the European Medicine Agency for the treatment of highly active relapsing multiple sclerosis (MS). OBJECTIVES: To provide real-world evidence of cladribine's effectiveness and safety in people with MS (pwMS). METHODS: A retrospective observational multi-center, multi-national study of pwMS who were started on cladribine tablets in ten centers from five European countries. RESULTS: We identified 320 pwMS treated with cladribine tablets. The most common comorbidities were arterial hypertension and depression. Three patients had resolved hepatitis B infection, while eight had positive Quantiferon test prior to cladribine commencement. There were six pwMS who had malignant diseases, but all were non-active. During year 1, 91.6% pwMS did not have EDSS worsening, 86.9% were relapse-free and 72.9% did not have MRI activity. During the second year, 90.2% did not experience EDSS worsening, 86.5% were relapse-free and 75.5% did not have MRI activity. NEDA-3 was present in 58.0% pwMS in year 1 and in 54.2% in year 2. In a multivariable logistic regression model age positively predicted NEDA-3 in year 1. The most common adverse events were infections and skin-related adverse events. Lymphopenia was noted in 54.7% of pwMS at month 2 and in 35.0% at month 6. Two pwMS had a newly discovered malignant disease, one breast cancer, and one melanoma, during the first year of treatment. CONCLUSION: Our real-world data on the effectiveness and safety of cladribine tablets are comparable to the pivotal study and other real-world data with no new safety signals.

Transverse myelitis following COVID-19: Insights from a multi-center study and systematic literature review.

INTRODUCTION: We aimed to provide insights into transverse myelitis (TM) following COVID-19 by analyzing cases treated at tertiary care neurology centers and a systemic review of the literature. METHODS: The retrospective observational multi-center study was conducted at the four university neurology departments in Croatia, Slovenia, Serbia, and Austria. We searched for acute myelitis cases that occurred during or after COVID-19. A systemic review of the literature on COVID-19 and transverse myelitis was performed. RESULTS: We identified 76 persons with TM associated with COVID-19, 13 from the multi-center study and 63 from the literature review. Most of the participants (55.6%) had an intermediate latency, 25.4% had short and 19% long latency from COVID-19 symptoms to TM. The clinical presentation consisted of the typical TM signs. More than half of the participants had inflammatory changes in the CSF, with rare patients having intrathecal OCB synthesis and positive serology for anti-MOG or anti-AQP4 antibodies. Persons with autonomic symptoms and CSF pleocytosis were significantly more common to have an intermediate latency of 8 to 21 days from COVID-19 to TM (p = 0.005 and p = 0.003; respectively). According to logistic regression analysis, only participants with lesions evident on spinal cord MRI compared to normal spinal cord MRI had reduced risks for poor recovery. >80% of participants were treated with a combination of corticosteroids and intravenous immunoglobulins or plasma exchange with 73% having incomplete recovery. CONCLUSION: Our study further characterizes clinical, laboratory, and MRI features, as well as treatment of TM associated with COVID-19.

Comparison of pain-provoked versus standard 40-min tilt table test for the conformation of vasovagal syncope.

BACKGROUND: Tilt table test represents a valuable diagnostic method in assessing patients with transient loss of consciousness and confirming the diagnosis of vasovagal syncope. However, the test lacks standardization, and various protocols exist in different centers. The aim of this study was to compare the difference in sensitivity and time-to-syncope of tilt table test with a painful stimulus provocation compared to standard test with no provocation. METHODS: This was a prospective study that included consecutive patients diagnosed with vasovagal syncope who were referred for tilt table testing. Patients were randomly assigned to two groups: group 1 with pain provocation after the first 10 min of upright position and group 2 with no provocation with further 30 min of tilt in both groups. RESULTS: In group 1, 66 (78.6%) patients developed syncope while in group 2, 35 (44.3%) patients had syncope (p < 0.001). This represents an increase of 34.3% in TTT sensitivity with the application of painful provocation. According to results of the Cox regression, the hazard for developing syncope after the 10th min of the tilt for group 2 was 0.275 of the hazard of group 1 (95% C.I. 0.170-0.444, p < 0.001). CONCLUSION: Pain provocation is a useful method for increasing sensitivity and shortening the duration of tilt table testing.

Double immune reconstitution therapy: Cladribine after alemtuzumab in the treatment of multiple sclerosis.

BACKGROUND AND PURPOSE: Alemtuzumab, a monoclonal anti-CD52 antibody, and cladribine, a purine nucleoside analogue, are used for the treatment of highly active relapsing-remitting multiple sclerosis (MS). Both are administered as two short yearly courses but possess the ability to induce long-term remission, labeling them as immune reconstitution therapies. Although disease activity after alemtuzumab administration is rare, there are a small number of people with MS who will experience disease activity despite repeated alemtuzumab treatment. METHODS: We report on six patients with MS who experienced disease activity after alemtuzumab and were subsequently treated with cladribine and followed up for up to 2 years. RESULTS: None of the patients experienced relapses during the follow-up period and in all patients Expanded Disability Status Scale values remained unchanged. All patients had lymphopenia at one time point. In patients 1 and 2, at the nadir, the lymphopenia was grade 1, in patient 3 it was grade 2 and in patients 5 and 6 it was grade 3. No infections or malignancies were recorded during the follow-up. CONCLUSION: This report provides a framework for treating people with MS with sequential immune reconstitution therapies.

Brain MRI post-processing with MAP07 in the preoperative evaluation of patients with pharmacoresistant epilepsy - Croatian single centre experience.

OBJECTIVE: This study aimed to determine the role of brain MRI post-processing method MAP07 (Morphometric Analysis Program) in detecting epileptogenic brain lesions in patients with pharmacoresistant epilepsy (PE). MAP07 is a sophisticated diagnostic program that offers several morphometric maps and facilitates the detection and localization of hippocampal sclerosis (HS), focal cortical dysplasias (FCD), and other types of cortical malformations, which could be undetected by conventional visual MRI analysis (CVA). METHODS: 120 patients aged > 16 years with PE have been recruited. 3 T MRI was performed according to epilepsy imaging protocol followed by image postprocessing with a fully automated MATLAB script, MAP07, by applying SPM5 algorithms. Statistical analysis was performed in IBM SPSS Statistics, version 25.0. RESULTS: Analysis in our patients showed a high sensitivity of MAP07 with low specificity and with a high proportion of false-positive patients. After MRI analysis, out of 120 patients, 32 were found to have no structural abnormalities by conventional visual analysis in whom after MAP07 in 5 patients structural lesions were found (in one HS, in one FCD, in two perinatal vascular lesions, and in one hippocampal hyperintensity). There was a quite high overall coincidence of the findings of MAP07 and MRI for the detection of FCD, HS, perinatal ischemia/chronic vascular lesions, heterotopias, and polymicrogyria (kappa coefficient above 0.700). CONCLUSIONS: MAP07 analysis is a useful, additional, and automated method that may guide re-evaluation of MRI by highlighting suspicious cortical regions, as a complementary method to CVA, by enhancing the visualization of cortical malformations and lesions.

Factors Contributing to the Reduction of Pain during Electromyography and Nerve Conduction Studies.

BACKGROUND: Electromyography (EMG) and nerve conduction studies (NCS) are an unpleasant and sometimes painful examinations. Pain can reduce patient's compliance and have a negative effect on the examination results. Different studies report that music affects pain perception by acting as a distractor, by inducing positive emotional valence or through the concept of convergence of different sensory modalities. The aim of this study was to explore the effect of music and different environmental and sociodemographic factors on pain perception during EMG and NCS. SUBJECTS AND METHODS: Sixty patients with suspected neuromuscular disease were randomized into music and control group. Specific questionnaire assessed sociodemographic characteristics, medical history, examination waiting time, examination extent and biometeorological forecast. The numerical rating scale was used for the evaluation of pain. The examiner evaluated patient's compliance after the examination. RESULTS: NCS was less painful for patients in the music group (p=0.03), as well as for more cooperative patients (p=0.011). For patients who previously underwent EMG/NCS, present NCS was more painful (p=0.001), regardless of the music intervention (p=0.019). EMG was more painful for older patients (p=0.041). Patients with lower level of education reported lower pain during NCS (p=0.026). Gender, financial satisfaction, biometeorological forecast, diabetes, depression or malignant disease, use and dosing of analgesics or antidepressants, symptoms, examination waiting time and the examination extent had no effect on pain perception. CONCLUSIONS: Music significantly decreased the perception of pain associated with NCS, but not the EMG portion of the examination. During EMG pain level was not significantly reduced, but the median of pain was still lower. Generally, the pain level during NCS, unlike the one during EMG, was affected by patients' compliance, level of education and painful predetermination. We propose using music during EMG/NCS because it can make the examination more comfortable for the patient and thus contribute to better quality of this examination.

Tongue somatosensory-evoked potentials in microvascular decompression treated trigeminal neuralgia.

Somatosensory-evoked potentials of the tongue (tSSEP) provide useful information about trigeminal-afferent pathway. The aim of this study was to evaluate tSSEP in trigeminal neuralgia (TN) treatment with microvascular decompression. Two patients with trigeminal neuralgia refractory to conservative treatment underwent microvascular decompression of the trigeminal nerve. tSSEP was performed a month prior to surgery and in the month after the surgery in both patients. Pain frequency and tSSEP were analyzed before and after surgery. In both patients, a complete resolution of pain occurred. In patient 1, tSSEP latencies became shorter than before surgery and wave N1 appeared. The intensity of stimulation necessary to reach the threshold was 4 mA before the surgery and 1 mA after the surgery. A complete recovery of tSSEP after the operation was achieved in patient 2. The results of present study demonstrate potential value of tSSEP in pre-surgery evaluation and post-surgery follow-up of TN patients.