Serum biomarker levels predict disability progression in patients with primary progressive multiple sclerosis.

BACKGROUND: We aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS). METHODS: A total of 141 patients with PPMS from 18 European MS centres were included. Disability progression was investigated using change in Expanded Disability Status Scale (EDSS) score over three time intervals: baseline to 2 years, 6 years and to the last follow-up. Serum levels of neurofilament light chain (sNfL), glial fibrillar acidic protein (sGFAP) and chitinase 3-like 1 (sCHI3L1) were measured using single-molecule array assays at baseline. Correlations between biomarker levels, and between biomarkers and age were quantified using Spearman's r. Univariable and multivariable linear models were performed to assess associations between biomarker levels and EDSS change over the different time periods. RESULTS: Median (IQR) age of patients was 52.9 (46.4-58.5) years, and 58 (41.1%) were men. Median follow-up time was 9.1 (7.0-12.6) years. Only 8 (5.7%) patients received treatment during follow-up. sNfL and sGFAP levels were moderately correlated (r=0.43) and both weakly correlated with sCHI3L1 levels (r=0.19 and r=0.17, respectively). In multivariable analyses, levels of the three biomarkers were associated with EDSS changes across all time periods. However, when analysis was restricted to non-inflammatory patients according to clinical and radiological parameters (n=64), only sCHI3L1 levels remained associated with future EDSS change. CONCLUSIONS: Levels of sNfL, sGFAP and sCHI3L1 are prognostic biomarkers associated with disability progression in patients with PPMS, being CHI3L1 findings less dependent on the inflammatory component associated with disease progression.

Amantadine in unvaccinated patients with early, mild to moderate COVID-19: A randomized, placebo-controlled, double-blind trial.

BACKGROUND AND PURPOSE: Adamantanes were listed as an interesting option as an early intervention against COVID-19. We aimed to evaluate the effectiveness of amantadine in preventing the progression of COVID-19 and its neurological sequelae. METHODS: Unvaccinated patients with confirmed SARS-CoV-2 infection within 5 days were enrolled. Subjects were randomized (50:50) to amantadine (AMD; 100 mg twice daily) or placebo (PLB) for 14 days. The Ordinal Scale for Clinical Improvement of the World Health Organization (OSCI-WHO) was the primary measure. Secondary endpoints included assessment for fatigue; depression, disorders of smell and taste, and sleepiness on Days 1 and 15. RESULTS: We enrolled 99 patients (49 AMD and 50 PLB). Disease progression (OSCI-WHO = 4) was observed in 6% (AMD) and 8% (PLB) patients (p > 0.05) with further deterioration (OSCI-WHO〉4) in 0% (AMD) and 8% (PLB) patients (p > 0.05). Complete recovery on Day 15 was 60% higher in the AMD compared with the PLB group (p = 0.025). There was improvement in taste (AMD: p = 0.003; PLB: p = 0.0001) and smell (AMD: p = 0.005; PLB: p = 0.0004) but not in fatigue in both groups. Improvement was observed in the AMD (p = 0.010) but not in the PLB group (p = 0.058) when assessing depression as well as sleepiness (AMD: p = 0.0002; PLB: p = 0.341). There was one death in the PLB group (2.0%) and none in the AMD group (p > 0.05) until Day 210. Overall, the drug was well tolerated. CONCLUSION: The central effects of amantadine on the nervous system with reduction of sleepiness and depression might have had a supportive effect on faster recovery in early COVID-19 patients.

Translation and cross-cultural adaptation of Polish version of Neuropathic Pain Questionnaire (NPQ-PL) and its comparisons with different questionnaires.

AIM OF THE STUDY: The aim of this study was to assess the validity and reliability of the Polish version of the Neuropathic Pain Questionnaire (NPQ-PL), and to compare it to other diagnostic tools. CLINICAL RATIONALE FOR THE STUDY: Neuropathic pain is a burdensome condition, of which the exact prevalence is difficult to estimate. During initial screening, pain questionnaires are helpful in alerting clinicians about the need for further evaluation. MATERIAL AND METHODS: The NPQ-PL has been developed following the guidelines for translation and cultural adaptation. A total of 140 patients with chronic pain (ChP), 90 with neuropathic pain (NP), and 50 with nociceptive pain (NoP), were enrolled into this study. RESULTS: The study group consisted of 60.71% women and 39.29% men; the mean age of patients (standard deviation, SD) was 53.22 years (15.81), and the average NPQ-PL score (SD) was 0.49 (1.27). Statistically significant relationships were found between higher age distribution and greater pain intensity in the NP group compared to the NoP group. There were also significant differences in pain levels between people of different ages, with the predominance in the elderly. Cronbach's alpha coefficient of the whole questionnaire was 0.85 and the intraclass correlation coefficient (ICC) for test-retest reliability was 0.635. Using receiver-operating characteristic (ROC) curve analysis, the area under the curve (AUC) was 0.97 and the best cut-off value was 0.002, which resulted in the highest sensitivity (93.3%) and specificity (96.0%). CONCLUSIONS AND CLINICAL IMPLICATIONS: The NPQ-PL is a valid tool for discriminating between neuropathic and nociceptive pain. It can be used by physicians of various disciplines when assessing patients with ChP of various origins.

Clinical and therapeutic challenges of smouldering multiple sclerosis.

INTRODUCTION: Assessment of the clinical course, neuroimaging and histopathological changes suggests that multiple sclerosis (MS) should not be defined merely as a focal inflammatory disease of the central nervous system (CNS) because the essence of the disease is due to a diffuse, 'smouldering', pathophysiological process. STATE OF THE ART: Progression independent of relapse activity (PIRA) is the clinical indicator of smouldering MS. Multiple pathomechanical factors determining smouldering MS have been identified, i.e. continuous activation of microglia, which is the source of smouldering inflammation and the failure of remyelination in MS. CLINICAL IMPLICATIONS: Our paper presents new neuroimaging markers, including paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs), potential methods for clinical evaluation and promising therapeutic options, i.e. Bruton's tyrosine kinase inhibitors that prevent PIRA in smouldering MS. With the duration of MS, the efficacy of the current immunomodulatory treatment is reduced, and its effect is insufficient to control smouldering MS. FUTURE DIRECTIONS: Innovative insights into the pathophysiology and clinical course warrant the need for a holistic approach to MS. The efforts of clinicians should be aimed at indicating subtle neurological deficits in physical performance and cognitive functioning to characterise the disease progression in its early stages. Undoubtedly, a new era for MS is coming in which new resonance markers will be used together with clinical methods to assess smouldering MS, and the treatment will include combination therapy with consideration of drugs that reduce relapse rates and therapy aimed at inhibiting disease progression.

External quality monitoring facilitates improvement in already well-performing stroke units: insights from RES-Q Poland.

INTRODUCTION: The Registry of Stroke Care Quality (RES-Q) is used in Poland for quality monitoring by numerous hospitals participating in the Angels Initiative. Our aim was to assess the degree of improvement in highly stroke-oriented centres that report cases to the RES-Q each year. MATERIAL AND METHODS: This retrospective analysis included Polish stroke units that from January 2017 to December 2020 contributed to the RES-Q at least 25 patients annually. RESULTS: Seventeen out of 180 Polish stroke units reported patients each year (2017, n = 1,691; 2018, n = 2,986; 2019, n = 3,750; 2020, n = 3,975). The percentage of ischaemic stroke patients treated with alteplase remained stable (26%, 29%, 30% and 28%, respectively). The door-to-needle time progressively decreased, from a median 49 minutes to 32 minutes. The percentage of patients treated ≤ 60 minutes and ≤ 45 minutes significantly increased (from 68% to 86% and from 43% to 70%, respectively), with no change observed between 2019 and 2020. Despite a general improvement in dysphagia screening (81%, 91%, 98% and 99%), screening performed within the first 24h from admission became less frequent (78%, 76%, 69% and 65%). In-hospital mortality significantly increased (11%, 11%, 13% and 15%), while the proportion of patients discharged home remained stable. CONCLUSIONS: Quality-oriented projects facilitate the improvement of stroke care, even in centres demonstrating good baseline performance. Polish stroke units that consistently reported cases to the RES-Q demonstrated improvement in terms of door-to- -needle time and dysphagia screening. However, there is still a need to shorten the time to dysphagia screening, and carefully monitor stroke unit mortality following the COVID-19 pandemic.

Analysis of seroconversion following COVID-19 vaccination among multiple sclerosis patients treated with disease-modifying therapies in Poland.

CLINICAL RATIONALE FOR THE STUDY: The rapid spread of SARS-CoV-2 throughout the world has highlighted the importance of vaccinations to control the pandemic and to protect people at risk for severe disease courses. Disease-modifying therapies (DMT) in multiple sclerosis (MS), whether immunomodulatory or immunosuppressive, may affect the immune response. Therefore, the question arose as to whether these vaccinations would be effective. AIM OF THE STUDY: We planned a study to assess the immune response to SARS-CoV-2 vaccines by type of therapy. MATERIAL AND METHODS: Participants were recruited from 14 Polish MS centres. The data was obtained by neurologists using a questionnaire. We collected data on 353 MS patients (269 females, 84 males) who received complete primary SARS-CoV-2 vaccination. All persons with MS (PwMS) were treated with disease-modifying therapies. RESULTS: 305 out of 353 PwMS (86.4%) were positive for IgG Abs against SARS-CoV-2 S domain S1 Ag after vaccination. A strong immune response was noted in 129 PwMS (36.5%). The rate of seroconversion after SARS-CoV-2 vaccination in PwMS who received immunomodulatory DMTs (interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab) was 91.5%, in PwMS receiving immune reconstruction therapy (alemtuzumab, cladribine) was 92%, and in immunosuppressive DMTs (fingolimod, ocrelizumab), the seroconversion rate was 59%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study shows that, in PwMS receiving immunomodulatory therapy, the immune response to vaccination is generally excellent. Even in immunosuppressive patients, seroconversion is satisfactory.

Modulation of neurotrophic factors in the treatment of dementia, stroke and TBI: Effects of Cerebrolysin.

Neurotrophic factors (NTFs) are involved in the pathophysiology of neurological disorders such as dementia, stroke and traumatic brain injury (TBI), and constitute molecular targets of high interest for the therapy of these pathologies. In this review we provide an overview of current knowledge of the definition, discovery and mode of action of five NTFs, nerve growth factor, insulin-like growth factor 1, brain derived NTF, vascular endothelial growth factor and tumor necrosis factor alpha; as well as on their contribution to brain pathology and potential therapeutic use in dementia, stroke and TBI. Within the concept of NTFs in the treatment of these pathologies, we also review the neuropeptide preparation Cerebrolysin, which has been shown to resemble the activities of NTFs and to modulate the expression level of endogenous NTFs. Cerebrolysin has demonstrated beneficial treatment capabilities in vitro and in clinical studies, which are discussed within the context of the biochemistry of NTFs. The review focuses on the interactions of different NTFs, rather than addressing a single NTF, by outlining their signaling network and by reviewing their effect on clinical outcome in prevalent brain pathologies. The effects of the interactions of these NTFs and Cerebrolysin on neuroplasticity, neurogenesis, angiogenesis and inflammation, and their relevance for the treatment of dementia, stroke and TBI are summarized.

Hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: The ADVANCE-CIDP 1 randomized controlled trial.

BACKGROUND AND AIMS: ADVANCE-CIDP 1 evaluated facilitated subcutaneous immunoglobulin (fSCIG; human immunoglobulin G 10% with recombinant human hyaluronidase) efficacy and safety in preventing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) relapse. METHODS: ADVANCE-CIDP 1 was a phase 3, double-blind, placebo-controlled trial conducted at 54 sites in 21 countries. Eligible adults had definite or probable CIDP and adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores of 0-7 (inclusive), and received stable intravenous immunoglobulin (IVIG) for ≥12 weeks before screening. After stopping IVIG, patients were randomized 1:1 to fSCIG 10% or placebo for 6 months or until relapse/discontinuation. fSCIG 10% was administered at the same dose (or matching placebo volume) and interval as pre-randomization IVIG. The primary outcome was patient proportion experiencing CIDP relapse (≥1-point increase in adjusted INCAT score from pre-subcutaneous treatment baseline) in the modified intention-to-treat population. Secondary outcomes included time to relapse and safety endpoints. RESULTS: Overall, 132 patients (mean age 54.4 years, 56.1% male) received fSCIG 10% (n = 62) or placebo (n = 70). CIDP relapse was reduced with fSCIG 10% versus placebo (n = 6 [9.7%; 95% confidence interval 4.5%, 19.6%] vs n = 22 [31.4%; 21.8%, 43.0%], respectively; absolute difference: -21.8% [-34.5%, -7.9%], p = .0045). Relapse probability was higher with placebo versus fSCIG 10% over time (p = .002). Adverse events (AEs) were more frequent with fSCIG 10% (79.0% of patients) than placebo (57.1%), but severe (1.6% vs 8.6%) and serious AEs (3.2% vs 7.1%) were less common. INTERPRETATION: fSCIG 10% more effectively prevented CIDP relapse than placebo, supporting its potential use as maintenance CIDP treatment.

Cladribine tablets for highly active relapsing-remitting multiple sclerosis in Poland: a real-world, multi-centre, retrospective, cohort study during the COVID-19 pandemic.

INTRODUCTION: Treatment with cladribine tablets is indicated in highly active relapsing-remitting multiple sclerosis (RRMS). Cladribine tablets proved safe and effective in the pivotal CLARITY trial, but that trial included primarily treatment-naïve patients. In clinical practice however, cladribine tablets are often given to patients who have failed other treatments. Therefore, this study investigated the real-world safety and efficacy of cladribine tablets. MATERIAL AND METHODS: We gathered data from nine MS clinical centres across Poland for patients with RRMS who started treatment with cladribine tablets from December 2019 to June 2022. RESULTS: We enrolled 140 patients, with follow-up data available for 136 in year 1 and for 66 in year 2. At baseline, the mean age was 35.6 years, mean disease duration was 7.3 years, median EDSS score was 2.5, and 94% of patients were treatment- -experienced. Thirty-nine patients (27.9%) had undergone COVID-19, and 94 (67.1%) were vaccinated against COVID-19. The annualised relapse rate (ARR) decreased from 1.49 at baseline to 0.33 in year 1 (p < 0.001) and to 0.25 in year 2 (p < 0.001). The percentage of relapse-free patients increased from 11.5% at baseline to 70.2% in year 1 and 82.1% in year 2. The percentage of patients with active lesions decreased from 91.4% at baseline to 36.2% in year 1 and 18.2% in year 2. EDSS score remained stable or improved in 83.7% of patients in year 1 and 89.6% in year 2. No evidence of disease activity (NEDA-3) was achieved in 42.7% of patients in year 1 and 66.7% in year 2. Only one patient (0.72%) had grade 4 lymphopenia and 21 (15.1%) had grade 3 lymphopenia. Varicella zoster virus infections occurred in three patients. Eight patients discontinued treatment with cladribine: five due to inefficacy, one due to lymphopenia, and two due to a personal decision. CONCLUSIONS: Cladribine tablets proved safe and effective in a real-world cohort of treatment-experienced patients. However, the efficacy measures improved to a lesser extent in our cohort than in the pivotal clinical trial, which is probably due to a higher proportion of treatment-experienced patients in our cohort.

Fluid phase biomarkers in multiple sclerosis.

PURPOSE OF REVIEW: Multiple sclerosis (MS) is highly heterogenic disorder with respect to clinical course, diagnosis, and treatment response. There is an urgent need to search for simply and reliable fluid body biomarker which would assist the diagnosis and prediction of clinical and treatment prognosis. RECENT FINDINGS: 'Traditional' MS biomarkers, with exception of cerebrospinal fluid oligoclonal bands, still are having limited clinical value. Therefore, there is growing interest in novel molecules and ingredients. The most robust results have been generated with regard to cerebrospinal fluid and serum levels of neurofilament light chains (NfL). However, there are still some limitations related to specificity of NfL which delays its use in everyday practice. We present a new approach to search for biomarkers involving extracellular RNA, particularly microRNA (miRNA), and small extracellular vesicles. MiRNA represents an important molecular mechanism influencing gene expression, including those involved in MS pathogenesis and extracellular vesicles transfer multiple cargo, including myelin molecules from parental cells of central nervous system to the long-distance targets. SUMMARY: MiRNAs which control gene expression in cells involved in autoimmune processes in MS as well as extracellular vesicles transferring myelin content might generate a new promising categories of biomarkers of MS.

Targeting pain in the long-term treatment of cervical dystonia with botulinum toxin A.

AIMS: Cervical pain is one of the most common non-motor symptoms of cervical dystonia (CD) and affects from 54.6% to 88.9% of patients. To date, minority of studies investigated the relevance of pain in a long-term botulinum toxin (BoNT) therapy of CD. The aim of the study was to define an impact of cervical pain on the disease severity and disability, as well as to assess antinociceptive BoNT efficacy in a long-term treatment of CD. MATERIALS AND METHODS: In this case-control study, CD patients who received stable doses of BoNT for at least 3 years were assessed with the use of validated scales. Participants were divided into two groups depending on the occurrence of CD-related pain. RESULTS: We examined 50 participants who received a mean of 24 injection cycles (6-51) of BoNT during a mean treatment period of 10.3 years (3.0-23.5). Participants with cervical pain (68.0%) were characterized by higher scores in all scales used in this study: TWSTRS severity (p = 0.030), disability (p < 0.001), total (p < 0.001) and TSUI score (p = 0.046). Pain reduction following BoNT injection lasted longer than muscle relaxation in 85.3% of patients. Pain improvement between first and last BoNT injection cycle was reported by 76.5% of patients with CD-related pain. CONCLUSIONS: The presence of cervical pain in CD may increase the severity of muscular symptoms and disease-related disability. BoNT has a noticeable antinociceptive effect in the long-term treatment of CD.

Onabotulinumtoxin A (ONA-BoNT/A) in the treatment of chronic migraine.

Migraine is a common primary headache disease, which reduces quality of life. About 8% of migraineurs suffer from chronic migraine (CM), which is the most severe and troublesome type. It has been proven that onabotulinumtoxinA (ONA-BoNT/A) significantly improves CM, presumably inhibiting the release of calcitonin gene-related peptide (CGRP) and other neurotransmitters from c-fibres endings, and thus decreasing activation of nociceptive pathways and transmission of pain. The aim of this position paper was to assess the place of ONA-BoNT/A for the prophylaxis of CM in adults. The authors have compared the efficacy, safety and tolerance of the toxin to those of classical oral preventive therapies as well as to recently introduced anti-CGRP-pathway monoclonal antibodies. The results of randomised controlled studies of ONA-BoNT/A have been compared to open label (real world practice) trials.

Systematic review and network meta-analysis (NMA) for cladribine tablets in achieving sustained disability improvement (SDI) in multiple sclerosis.

INTRODUCTION: This study was performed to compare probabilities of SDI on the Expanded Disability Status Scale (EDSS) in patients with relapsing-remitting multiple sclerosis (RRMS), treated with cladribine tablets (CT) or fingolimod (FTY), natalizumab (NAT), alemtuzumab (ALE) and ocrelizumab (OCR). CLINICAL RATIONALE FOR THE STUDY: Progression of neurological disability as measured by the EDSS has been a common endpoint in multiple sclerosis (MS) trials. Novel therapies can not only slow this process, but in some patients even reverse it. This effect can be measured by the sustained disability improvement (SDI) - an endpoint that seems to continuously gain importance in clinical practice. Despite that, SDI has rarely been explored as an outcome in MS clinical studies, mostly as post-hoc analyses from randomised trials or as retrospective analyses based on patient registry records. MATERIAL AND METHODS: A systematic review was conducted in Medline, Embase and Cochrane to identify clinical trials (RCT or non-RCT) evaluating 6-month SDI. An indirect comparison via network meta-analysis (NMA) was performed. Bayesian inference with Markov chains Monte Carlo methods were applied. RESULTS: Eight trials presenting SDI results and applicable for NMA were included: six non-RCTs, with control groups selected by propensity score matching, and two RCTs. NMA results revealed that probability of achieving 6-month SDI with CT was significantly higher compared to all other high efficacy disease-modifying drugs with available data - HR (95% Crl - Bayesian Credibility Interval) vs. FTY: 4.98 (2.11-11.79); vs. NAT: 3.12 (1.31-7.27); vs. ALE: 9.29 (3.40-25.21). The main results were confirmed in the sensitivity analyses. CONCLUSIONS: Of all considered therapies, treatment with cladribine tablets was associated with a higher probability of sustained disability improvement in RRMS patients. As this conclusion is based on available clinical data of limited quality, future studies, as well as real-world data, would be valuable to provide further evidence regarding the comparative effectiveness of RRMS therapies.

Cladribine suppresses disease activity in neuromyelitis optica spectrum disorder: a 2-year follow-up study.

BACKGROUND AND PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) is a difficult condition to treat. Cladribine selectively and transiently depletes B and T lymphocytes, leading to long-lasting immune reconstitution. This report describes observations from 24 months of follow-up after cladribine in NMOSD patients. METHODS: This is a retrospective analysis of a case series including 12 seropositive patients with NMOSD. Patients were given cladribine by subcutaneous injections in a series of several 2-day cycles of 20 mg administered at intervals of 4-6 weeks. Thus, the full treatment course delivered a cumulative bioavailable dose similar to that approved for treatment of multiple sclerosis. Annualized relapse rate (ARR), disability (Expanded Disability Status Scale [EDSS] score) and safety in the 24 months preceding and the 24 months following the initiation of cladribine treatment were assessed. RESULTS: The mean ARR in the 24 months preceding cladribine treatment was 1.04 (95% confidence interval [CI] 0.67-1.62). The mean ARR in the 24 months following initiation of cladribine treatment was 0.21 (95% CI 0.08-0.56). The ratio in the rate of events post versus prior cladribine initiation was 0.20 (95% CI 0.07-0.59) and highly significant (p = 0.0073). The EDSS score did not change over the follow-up period (2.5 ± 1.7; mean ± SD) compared to baseline (2.5 ± 1.5; mean ± SD). No serious adverse events considered to be linked to cladribine were observed during follow-up. CONCLUSIONS: Cladribine was safe in NMOSD patients over a 2-year observation period. Cladribine treatment was associated with clinical stabilization, as evidenced by significantly decreased ARR and no progression of EDSS score.

A Retrospective Analysis of Pain Etiology in Middle-Aged Patients with Peripheral Neuropathy.

Background and Objectives: Correct assessment and a multidisciplinary approach appear to be extremely important in preventing peripheral neuropathy and its complications. The purpose of this study was to find the correlations and dissimilarities between different types of peripheral neuropathy, the occurrence of pain, and laboratory results. Materials and Methods: This retrospective study assessed 124 patients who were hospitalized in our neurology department due to various types of sensory or motor disturbances. The patients were eventually diagnosed with peripheral neuropathy, based on the electrophysiological study, anamnesis, physical examination, and laboratory results. The whole group was subjected to statistical analysis. Results: The mean age of patients was over 56 years, with a slight woman predominance. A statistically significant (p < 0.05) relationship between the place of residence and gender was seen, where more men than women live in the rural area, while more women than men live in the urban area. Most often we observed symmetric, sensorimotor, demyelinating, inflammatory, and chronic neuropathy. More than 40% of patients reported pain. A statistically significant correlation between the evolution/severity and the occurrence of pain was seen in subacute type (p < 0.05) and small fibre neuropathy (p < 0.01). Conclusions: A higher incidence of peripheral neuropathy in middle-aged people will become essential in the aging society with lifestyle and chronic disorders. Peripheral neuropathy is slightly more common in women than men and its occurrence may be influenced by work performed or internal and external factors. In the study group, more than 40% of patients reported pain, therefore the pain measurement for each patient should be implemented and repeated at every visit. An assessment of sodium level and, in women, markers of neuroinflammation level in the various types of peripheral neuropathy may be an interesting direction for the future.

Internal carotid and vertebral artery dissections - a comparison of clinical, radiological and prognostic characteristics.

AIM OF STUDY: To examine whether baseline characteristics, potential risk factors, clinical symptoms, radiological presentation, and long-term outcomes differ between internal carotid artery dissection (ICAD) and vertebral artery dissection (VAD). CLINICAL RATIONALE FOR STUDY: Cervical artery dissection (CeAD) is a major cause of cerebral ischaemia in young adults. Its clinical course is highly variable, resulting in challenges in making a proper diagnosis. METHODS: We performed a retrospective analysis of 31 patients (mean age 42.2 years) with CeAD (18 with ICAD, 13 with VAD) treated in our neurology department from 2008 to 2018. Appropriate imaging confirmed the diagnosis of CeAD. RESULTS: Patients with ICAD presented Horner syndrome significantly more often (44.4% vs 7.6%; p = 0.04). Patients with VAD more often had ischaemic events (ischaemic stroke, TIA or transient blindness) (84.6% vs 44.6%; p = 0.0032). Ischaemic stroke was more severe in patients with ICAD [(median NIHSS 6, interquartile range 4-12) vs VAD (median NIHSS 4, interquartile range 1.5-5.5), p = 0,03]. Occlusion occurred more often in patients with VAD (69.2% vs 22.2%; p = 0.013). Most patients had a favourable outcome (mRS 0-2). CONCLUSIONS AND CLINICAL IMPLICATIONS: In a series of patients with CeAD, we observed significant differences between VAD and ICAD in terms of clinical symptoms and radiological features.

Direct admission vs. secondary transfer for mechanical thrombectomy: long-term clinical outcomes from a single Polish Comprehensive Stroke Centre.

INTRODUCTION: We aimed to compare 3-month clinical outcomes after mechanical thrombectomy (MT) in patients transferred directly to a comprehensive stroke centre ('mothership', MS) to the outcomes of patients transferred secondarily from primary stroke centres ('drip-and-ship', DAS) in Lubelskie province, the third largest province in Poland. MATERIAL AND METHODS: In a prospective stroke registry, all patients with large vessel occlusion in anterior circulation admitted within six hours of onset and treated with MT between 2017 and 2020 were retrospectively analysed. RESULTS: A total of 400 patients was evaluated: 267 treated with the MS approach and 133 with the DAS approach. Time from stroke onset to groin puncture was shorter in the MS group. There was a significant difference in 3-month excellent clinical outcomes (mRS 0-1) between these two groups (32.9% of MS patients vs. 22.5% of DAS patients, p < 0.05), but there was no difference if the 3-month endpoint was expressed as mRS ≤ 2 (42.3% of MS vs. 34.5% of DAS patients, p = 0.13). The rate of symptomatic intracranial haemorrhage and mortality was comparable in both groups. CONCLUSIONS: Our study shows that direct admission to a comprehensive stroke centre resulted in more patients achieving excellent treatment outcomes (mRS 0-1). At the same time, the superiority of the MT model over the DAS model in obtaining mRS 0-2 was not unequivocally demonstrated. Further studies are needed to determine the best stroke model for patients potentially eligible for MT.

Secondary progressive multiple sclerosis - from neuropathology to definition and effective treatment.

INTRODUCTION: There is no single, commonly accepted, standard definition of secondary progressive multiple sclerosis (SPMS), an absence that poses a challenge for clinicians. STATE OF THE ART: SPMS is characterised by inflammation, neurodegeneration and disease progression with the presence or absence of relapses. No biochemical or radiological biomarkers are currently available to indicate the precise secondary progressive course in individual patients. The retrospective approach to identifying SPMS patients raises many difficulties, especially in terms of determining the time point of progression. Currently, the most precise diagnosis of SPMS is based on the definition proposed by Lorscheider et al., where SPMS is defined as a disability progression by 1 step on the Expanded Disability Status Scale (EDSS) in patients with EDSS ≤ 5.5 or of 0.5 EDSS steps in patients with EDSS ≥ 6 in the absence of a relapse, a minimum EDSS score of 4 and pyramidal functional system (FS) score of 2, and confirmed progression over ≥ 3 months, including confirmation within the leading FS. CLINICAL IMPLICATIONS: The need to establish criteria for the diagnosis of SPMS is currently of crucial importance due to emerging treatment opportunities including siponimod, a sphingosine 1-phosphate (S1P) receptor modulator selective for S1P1 and S1P5 receptors. It is reasonable to introduce drugs at the earliest possible stage of lesion progression to reduce inflammation a nd t o p rotect t he c entral n ervous s ystem ( CNS) a gainst i rreversible n eurodegeneration. FUTURE DIRECTIONS: Further studies with prospective, multicentre and long term follow-up design are needed to provide better insights into SP course in MS patients. This should be supported by radiological, biochemical and pathological evaluations to help establish reliable and sensitive biomarkers to guide clinical practice.

Smoking as a risk factor of onset and relapse of Multiple Sclerosis - a review.

INTRODUCTION AND OBJECTIVE: Multiple Sclerosis (MS) is a chronic demyelinating disease caused by damage to myelin in the brain and spinal cord. The cause of the disease is unclear, but it is probably correlated with dysregulation of the immunological system, as well as non-modifiable and modifiable risk factors. Unfortunately, there is no cure for MS. However, the course of the condition has been shown to be modifiable by treatment and various environmental factors. Cigarette smoking is one of the most common addictions around the world, and may be a key modifiable risk factor in MS. Here, we review data available on Pubmed and Scopus from the last 10 years. The following consecutive key words were used in our search: "multiple sclerosis", "smoking", "cigarette", "impact", "progression", and "tobacco". This search yielded 248 initial articles, 43 of which were included in our review. CURRENT STATE OF KNOWLEDGE: In our review, we have examined the impact of smoking on the immunology, course, treatment, relapse, recurrence, quality of life, and changes visualised on MRI among patients with MS in general. We have also explored these patterns in MS subtypes. In general, smoking is reported to have negative effects on MS, including a decrease in quality of life, as well as cognitive and mental state, and an increase in disability, as well as in the frequency of relapses and recurrences. CLINICAL IMPLICATIONS: Smoking has a widespread negative impact on patients with MS. Thus, it is important to educate patients and to help them to give up smoking to improve their health and quality of life. FUTURE DIRECTIONS: Further research about the impact of smoking and nicotine on MS and other neurodegenerative diseases is needed; in particular, research on e-cigarettes.

Biomarkers in Multiple Sclerosis: a review of diagnostic and prognostic factors.

INTRODUCTION: Multiple Sclerosis (MS) is a chronic, demyelinating disease of the central nervous system which affects mostly young people. Because it leads to disability and cognitive impairment, it is crucial to recognise MS at an early stage. STATE OF THE ART: Magnetic resonance imaging is the golden standard in MS diagnosis. However, it is not an infallible diagnostic tool, especially at the stage of clinically isolated syndrome. The incorporation of oligoclonal bands in the diagnostic process of MS is a step towards the extension of diagnostic methods. Recently, a lot of research has been carried out on potential biomarkers in blood serum and cerebrospinal fluid that may be useful in the diagnosis of MS. CLINICAL IMPLICATIONS: This article summarises current knowledge on the use of new prognostic factors such as neurofilament light chain, chitinase 3-like 1 and 2, heat shock proteins, and tubulins in MS. FUTURE DIRECTIONS: Despite numerous studies on the use of biomarkers in the diagnosis of MS, more extensive research is needed to determine the clinical usefulness of these molecules and to develop diagnostic tests applicable in everyday practice. This in turn may result in earlier MS detection, faster implementation of treatment, and better therapeutic effects.