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.

Efficacy and safety of mitoxantrone use in primary and secondary progressive multiple sclerosis - study site experience based on the therapy of 104 patients.

Mitoxantrone (MX) is used in patients with primary and secondary progressive as well as relapsing-remitting type of multiple sclerosis (PPMS, SPMS, RRMS). The objective of our project was to evaluate the efficacy and safety of MX use in patients with PPMS and SPMS. METHODS: The retrospective study included 104 patients (mean age 54.2 ± 9.0), with PPMS (13.46%) and SPMS (86.54%) treated with MX. During single cycle of the MX therapy a dose of 12 mg/m2 of body surface area was administered and next cycles every three months up to a total dose of 140 mg/m2 were realized. RESULTS: The course of the therapy was completed by 95 patients (91.34%) including 73 patients who received a scheduled whole dose. The average cumulative dose per patient was 75.2 mg/m2. Thirty-two patients reported nausea after MX administration, 20 revealed increase in the incidence of infection and 19 patients hair loss. Twenty-two patients discontinued therapy (seven patients because of the progress of disability). Independent risk factors for deterioration were: age and the form of PPMS (RR 1.56 [95% CI: 1.17-2.07] and RR 2.8 [95% CI: 1.08-7.21], respectively). Five patients revealed a asymptomatic decrease in EF value <50% or 10% in relation to the previous test. CONCLUSIONS: MX therapy enables us to stabilize the disease without causing any significant side effects in most patients with progressive disease as compared to patients with primary progressive disease with a comparable safety profile. Larger benefits of MX therapy are associated with the patients with secondary progressive disease.

Mechanical thrombectomy in acute stroke - Five years of experience in Poland.

OBJECTIVES: Mechanical thrombectomy (MT) is not reimbursed by the Polish public health system. We present a description of 5 years of experience with MT in acute stroke in Comprehensive Stroke Centers (CSCs) in Poland. METHODS AND RESULTS: We retrospectively analyzed the results of a structured questionnaire from 23 out of 25 identified CSCs and 22 data sets that include 61 clinical, radiological and outcome measures. RESULTS: Most of the CSCs (74%) were founded at University Hospitals and most (65.2%) work round the clock. In 78.3% of them, the working teams are composed of neurologists and neuro-radiologists. All CSCs perform CT and angio-CT before MT. In total 586 patients were subjected to MT and data from 531 of them were analyzed. Mean time laps from stroke onset to groin puncture was 250±99min. 90.3% of the studied patients had MT within 6h from stroke onset; 59.3% of them were treated with IV rt-PA prior to MT; 15.1% had IA rt-PA during MT and 4.7% - emergent stenting of a large vessel. M1 of MCA was occluded in 47.8% of cases. The Solitaire device was used in 53% of cases. Successful recanalization (TICI2b-TICI3) was achieved in 64.6% of cases and 53.4% of patients did not experience hemorrhagic transformation. Clinical improvement on discharge was noticed in 53.7% of cases, futile recanalization - in 30.7%, mRS of 0-2 - in 31.4% and mRS of 6 in 22% of cases. CONCLUSION: Our results can help harmonize standards for MT in Poland according to international guidelines.

The impact of anemia on the course and short-term prognosis in patients with first ever ischemic stroke.

BACKGROUND: Anemia is the risk factor for cerebrovascular events. The aim of this study was to evaluate the prevalence of anemia among patients with first-ever stroke and its impact on neurological state in the acute phase of the disease and the degree of disability in short-term follow-up. PATIENTS AND METHODS: The prospective study included 107 patients aged 72.81 ± 11.12 with the first-ever stroke. Each patient underwent CT of the head and blood tests, including Hb concentration on the first day of hospitalization. We have analyzed the neurological state on the first day of stroke by NIHSS and the functional status on the 14th day after the onset of stroke by mRankin scale in patients with and without anemia. Patients with anemia were additionally divided according to Hb level (less or over 11g/dl). RESULTS: Patients with Hb≤ 11g/dl significantly more often achieved a score of 4-5 points on mRankin scale on the 14th day of stroke compared to patients with anemia and Hb>11g/dl. Independent predictors of a worse functional status on the 14th day of stroke in patients with anemia include the neurological state on the 1st day and the hemispheric location of stroke; an independent predictor of death was the neurological state on the 1st day of onset. CONCLUSION: Mild anemia did not influence significantly the neurological condition in acute phase of stroke but worsened the functional status in subacute phase of stroke. The neurological state on the first day of stroke and the hemispheric location of cerebral ischemia are independent factors of poor prognosis in patients with anemia in short-term follow-up.

[Anti-NMDA receptor encephalitis - case report]. / Zapalenie mózgu z przeciwcialami przeciwko receptorowi NMDA - opis przypadku.

We present a patient with multiple sclerosis, diagnosed at the age of 16.5, in whom mental and orientation disturbances, strange behaviour as well as bizarre dyskinesias of the face and extremities occurred at age 20. After several days, tonic-clonic status epilepticus developed. Head computed tomography showed no abnormalities. Lumbar puncture revealed a pleocytosis of 20/3, which became normal after treatment. Seizures were brought under control, but the psychiatric symptoms persisted; they subsided after a dozen or so weeks. Magnetic resonance of the head and cervical spinal cord did not show any new abnormalities. After another several months, all symptoms recurred. A wide range of laboratory tests, as well as positron emission tomography, did not reveal any abnormalities. Suspicion of autoimmune encephalitis led to a test for serum anti-NMDA-receptor antibodies that confirmed the diagnosis. After immunotherapy, our patient improved and was transferred for rehabilitation.

Frequency of the C677T variant of the methylenetetrahydrofolate reductase (MTHFR) gene in patients with migraine with or without aura - a preliminary report.

BACKGROUND AND PURPOSE: The aim of our study was to evaluate the frequency of the C677T variant in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with migraine with or without aura and to find an association between this variant and vascular lesions in magnetic resonance imaging of the head, presence of patent foramen ovale (PFO) and increased level of homocysteine. MATERIAL AND METHODS: Ninety-one patients with migraine, aged 19-57, were investigated in this study. The MTHFR C677T variant was genotyped in this group and levels of homocysteine, folic acid and vitamin B12 were measured. Transcranial Doppler sonography with test for PFO detection by injection of air contrast during the Valsalva manoeuvre was performed in each patient. RESULTS: Frequency of the C677T variant in the MTHFR gene was similar in patients and controls. Hyperhomocysteinaemia was significantly more frequent in migraine patients with the C677T variant. The prevalence of PFO was significantly higher in migraine patients with aura and the homozygous variant of the MTHFR gene. CONCLUSIONS: Frequency of the C677T variant in the MTHFR gene was similar in patients and controls. Significantly more frequent prevalence of PFO in migraine patients with aura (with homozygous recessive genotype of MTHFR probably suggests their common genetic basis. Hyperhomocysteinaemia was significantly more frequent in migraine patients with the C677T variant, which could be an additional risk factor of this disease.

Factors associated with the symptomatic status of carotid artery stenosis: identification in a cross-sectional study and development of a scoring system.

INTRODUCTION: The identification of asymptomatic patients at high risk of internal carotid artery (ICA) stenosis destabilization and symptom occurrence is crucial for prognosis estimation. OBJECTIVES: This study aimed to determine differences between patients with symptomatic and asymptomatic ICA stenosis and to develop a predictive model for the risk of symptomatic stenosis based on data collected in routine clinical practice. PATIENTS AND METHODS: The study included 163 patients with asymptomatic and 182 patients with symptomatic ICA stenosis greater than 70%. The study groups were compared in terms of stroke risk factors and comorbidities, coexisting ICA stenosis on the contralateral side, atherosclerosis in other arterial territories, and the morphology of atherosclerotic plaque assessed by transcervical ultrasound. RESULTS: Independent risk factors for symptomatic ICA stenosis included: male sex (odds ratio [OR], 2.94; 95% CI, 1.87-4.32; P <0.001), diabetes (OR, 2.86; 95% CI, 1.62-5.12; P <0.001), body mass index >25 kg/m2 (OR, 1.81; 95% CI, 1.72-1.86; P <0.001), chronic kidney disease (OR, 3.34; 95% CI, 1.34-8.87; P = 0.007), increased­risk features of ultrasound plaque morphology (OR, 2.52; 95% CI, 1.29-3.72; P = 0.009), and coexisting atherosclerosis in 3 or 4 vascular areas (OR, 3.72; 95% CI, 1.77-7.23; P <0.001).The sensitivity and specificity of the scoring model designed to estimate the risk of symptomatic ICA stenosis reached 77.6% and 76.9%, respectively. CONCLUSIONS: This cross­sectional study indicated that the analysis of selected imaging and clinical parameters may enable clinicians to estimate the risk of symptomatic ICA stenosis. The proposed scoring system requires further prospective validation.

Modified Rio Score with Platform Therapy Predicts Treatment Success with Fingolimod and Natalizumab in Relapsing-Remitting Multiple Sclerosis Patients.

BACKGROUND: Reliable markers of disease outcomes in multiple sclerosis (MS) would help to predict the response to treatment in patients treated with high efficacy drugs. No evidence of disease activity (NEDA) has become a treatment goal whereas the modified Rio score (MRS) predicts future suboptimal responders to treatment. The aim of our study was to identify factors that would predict poor response to treatment with natalizumab and fingolimod. METHODS: In the multicenter prospective trial, 336 subjects were enrolled, initiating therapy with natalizumab (n = 135) or fingolimod (n = 201). Data on relapse rate, the expanded disability status scale, and MRI results were collected, and MRS was estimated. RESULTS: NEDA-3 after the first year of therapy was 73.9% for natalizumab and 54.8% for fingolimod (p < 0.0001). Patients with MRS = 0 in the last year on platform therapy had the best NEDA-3 (71%) and patients with MRS = 3 had the worst NEDA-3 (41%) in the first year of treatment with the second-line therapy. CONCLUSION: We conclude that switching to the second-line therapy should occur earlier to enable better results for patients treated with natalizumab or fingolimod. The outcome on both drugs is better with better neurological conditions and lower MRS of the patient on the platform therapy.

Effect of comorbidities on the course of multiple sclerosis.

OBJECTIVE: The clinical condition of multiple sclerosis (MS) patients depends not only on the course of MS but also on their lifestyle and comorbidities. This study aimed to assess the effect of selected comorbidities, lifestyle-related factors and clinical data available at the time of MS diagnosis, on the disease activity and the disability progression in patients with relapsing-remitting multiple sclerosis (RRMS). PATIENTS AND METHODS: Based on clinical relapses over a period of 12 months of observation and the results of MRI scans, 138 patients with RRMS were qualified into two groups: 'active' or 'stable' course of the disease. Patients from both groups were compared regarding the clinical data determined at diagnosis, comorbidities and lifestyle-related factors. Similar comparisons were carried out between patients with EDSS < 3 vs, patients with EDSS ≥ 3. RESULTS: No significant differences in comorbidities and lifestyle-related data between the stable and active group were detected. Arterial hypertension, hyperlipidemia, higher BMI values, older age and a lower education level, were found more frequently in patients with EDSS ≥ 3. Oligoclonal bands, multifocal clinical manifestation as the first relapse, higher EDSS score and many T2 MRI lesions at the diagnosis were detected significantly more often in the active group. Motor or brainstem/cerebellum damage symptoms as the first relapse were observed more frequently in patients with EDSS ≥ 3. CONCLUSIONS: Cardiovascular diseases may exacerbate disability progression in MS patients. Relapses and radiological activity do not depend on chronic comorbidities. Clinical data available at the diagnosis may be useful in forecasting a distant course of MS.

Diagnostic methods used in searching for markers of atrophy in patients with multiple sclerosis.

The results of available studies on assessment of neurodegenerative lesions in multiple sclerosis (MS) patients using different approaches have not been conclusive. Currently, clinical assessment is the most commonly used (involving primarily mobility assessment), along with magnetic resonance imaging and electrophysiological testing. In this review we describe available clinical, neuroimaging, electrophysiological and laboratory tests used to assess the neurodegeneration in MS. Laboratory markers to determine the risk of disease, its conversion and prognosis in MS patients are being constantly sought. Cerebrospinal fluid (CSF) sample collection is invasive and constitutes a burden to a patient, so serum biomarkers are being investigated. Optimistic preliminary results of studies assessing neurofilament light chains (NFL) in serum of MS patients, encourage further research. The possibility to use such marker (or a group of markers) would significantly facilitate clinical decisions at the stage of diagnosis and treatment. Currently used treatments have limited efficacy and are associated with numerous adverse effects. Additional information from available clinical, imaging, electrophysiological or laboratory biomarker or a group of biomarkers, which predict the course and prognosis, will facilitate choosing optimal treatment and its escalation at the relevant stage. CONCLUSION: Using the diagnostic panel consisting of imaging, neurophysiology and serology testing along with clinical and neuropsychological assessment may improve the reliability of diagnostic instruments evaluating cerebral atrophy in MS patients.

Multifactorial effects of vildagliptin added to ongoing metformin therapy in patients with type 2 diabetes mellitus.

BACKGROUND: To assess the efficacy of a vildagliptin and metformin combination therapy to a metformin monotherapy in type 2 diabetes mellitus patients. METHODS: Sixty-one patients with diabetes inadequately controlled by a metformin monotherapy were randomized to treatment with a combination therapy of vildagliptin 100mg and a metformin versus metformin monotherapy. This was a 12-week randomized parallel group study. During the study we assessed parameters of glycemic and lipid metabolism as well as the treatment effects on the release of proinflammatory and antiinflammatory cytokines. RESULTS: Compared with baseline values we observed a significant improvement of glycaemic parameters such as HbA1c, FPG, PPG, FPI, HOMA-IR and HOMA-ß index as well as decrease of TCh, TG and LDL and an increase of HDL with the greatest extent of vildagliptin plus a low-dose metformin therapy group. A metformin combination therapy significantly decreased such inflamation parameters as hs-CRP, ox-LDL, TNF-α and IL-1ß levels relative to monotherapies. All treatments were well tolerated and there was no incidence of hypoglycaemia. CONCLUSIONS: Vildagliptin added to an ongoing metformin therapy allows to achieve better metabolic control parameters in comparison with a metformin monotherapy and the combination treatment is well tolerated and has a low risk of serious adverse effects.

Progesterone therapy in women with epilepsy.

BACKGROUND: Progesterone with its anti-seizure effect plays a role in the pathophysiology of catamenial epilepsy which affects 31-60% of epileptic women. In this study, an attempt to treat women suffering from catamenial epilepsy with progesterone, as an adjuvant drug, was made. METHODS: The treatment was given to 36 women aged 20-40 years (mean age: 30.75±6.05) with seizures in the entire second half of the menstrual cycle, who were found to have low serum levels of progesterone on days 22, 27, 28 of the cycle in comparison with a control group of healthy women. The patients were administered progesterone in a daily dose of 50 mg on days 16-25 of each cycle. The serum levels of antiepileptic drugs were assayed. The period of progesterone therapy ranged from 3 to 45 months (17.7 on average). RESULTS: Three patients were free of secondary generalized seizures, and one--of simple partial seizures. A decline in the frequency of primary and secondary generalized seizures by 20-96% (55.9% on average) was accomplished in 18 patients (primary generalized by 20-96%--54.7% on average, and secondarily generalized by 38-85%--59% on average). A decline in the frequency of complex partial seizures by 38-87% (63.1% on average) was achieved in 15 women. In 1 patient, the frequency of myoclonic seizures decreased by 46%. There was no improvement in 5 women (3 patients with generalized, 1 with complex partial and 1 with simple partial seizures). An exacerbation of seizure frequency occurred in 5 patients. Adverse effects were not found in any of the subjects. The average concentrations of antiepileptic drugs during hormonal therapy were in the therapeutic range. CONCLUSION: Progesterone combined with antiepileptic therapy was well tolerated and resulted in a significant reduction of seizure frequency in majority of patients with catamenial epilepsy.