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.

Predictive Value of the Third Ventricle Width for Neurological Status in Multiple Sclerosis.

The third ventricle width (3VW) is an easily calculated measure of brain atrophy. The aim of this study was to evaluate the relation of 3VW to cognitive impairment with adjustment for demographic and clinical confounders, including depression, anxiety, and fatigue, as well as to disability in patients with multiple sclerosis (MS). Symbol Digit Modalities Test, California Verbal Learning Test, Brief Visuospatial Memory Test-Revised, Expanded Disability Status Scale (EDSS), Hospital Anxiety and Depression Scale, and Modified Fatigue Impact Scale (MFIS) were analysed in 93 patients with MS. Neuropsychological performance was compared to that of 150 healthy controls. Axial images from 3D FLAIR were used to measure 3VW. In total, 25% of MS patients were impaired in at least two neuropsychological tests. Cognitive impairment and EDSS were associated with 3VW. Age and 3VW were the strongest predictors of cognitive impairment. The multiple regression model including age, 3VW, education, EDSS, and MFIS explained 63% of the variance of neuropsychological tests results, whereas 3VW, age and duration of the disease were significant predictors of EDSS. This study confirms the predictive value of 3VW for neurological status of patients with MS, especially for cognitive impairment after adjustment for demographic and clinical confounders.

The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design.

BACKGROUND: COVID-19, a disease caused by infection with the SARS-CoV-2 virus, is asymptomatic or mildly symptomatic in most cases. Some patients, usually burdened with risk factors develop acute respiratory failure and other organ dysfunction. In such cases, the mortality rate is very high despite the use of intensive therapy. Amantadine has complex activity including antiviral, antiinflammatory and dopaminergic effects. This clinical trial will assess the efficacy and safety of amantadine in the prevention of COVID-19 progression toward acute respiratory failure and neurological complications. METHODS AND RESULTS: The trial will enroll 200 patients who are positive for SARS-CoV-2 infection and have one or more risk factors for worsening the disease. These patients will be included as hospitalized or ambulatory subjects for early treatment of illness. The recruitment will take place in 8 centers covering different regions of Poland. For 14 days they will be given either 200 mg of amantadine a day or placebo. Our hypothesis is a considerable reduction in the number of patients with progression toward respiratory insufficiency or neurological complications thanks to the treatment of amantadine. CONCLUSIONS: Demonstrating the efficacy and safety of amantadine treatment in improving the clinical condition of patients diagnosed with COVID-19 is of great importance in combating the effects of the pandemic. It has potential to influence on the severity and course of neurological complications, which are very common and persist long after the infection as long-COVID syndrome. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov identification no. NCT04854759; Eudra CT number: 2021-001144-98 (dated 27 February 2021).

The Impact of Motor Disability and the Level of Fatigue on Adherence to Therapeutic Recommendations in Patients with Multiple Sclerosis Treated with Immunomodulation.

Aim: The aim of the study was to clarify whether the motor disability and the fatigue-related syndrome affect the level of compliance with therapeutic recommendations. Methods: Prospective studies were conducted among 165 patients treated under the drug program - Treatment of Multiple Sclerosis (MS) at the Department of Neurology and Clinical Neuroimmunology of the Regional Specialist Hospital in Grudziadz (Poland). The research was carried out by the method of diagnostic survey, questionnaire technique with the use of standardized research tools. The Adherence in Chronic Diseases Scale (ACDS) was used to assess the level of compliance with therapeutic recommendations. The Expanded Disability Status Scale (EDSS) was used to assess the degree of disability, and the Modified Fatigue Impact Scale (MFIS) was used to assess the degree of disability. The Chi-square test, Shapiro-Wilk test and Kruskal-Wallis were used. Results: The statistical analysis showed that there is a relationship (p=0.0055) between the patient's motor disability assessed in the EDSS scale and the level of compliance with therapeutic recommendations assessed in the ACDS scale. The higher the patient's disability level (EDSS 4.5-6.5), the lower the treatment adherence rate. The conducted research shows that the average score in the MFIS scale for individual levels of compliance with therapeutic recommendations expressed in the ACDS scale is, respectively: for the low level - 38.3 MFIS points, for the medium level - 34.4 MFIS points and for the high level- 33.2 MFIS points. The obtained results were not statistically significant (p=0.6098). Conclusion: It was found that the level of adherence to therapeutic recommendations in patients with relapsing-remitting multiple sclerosis treated with immunomodulation in the study group remained high. There is a relationship between the patient's disability and the level of adherence to therapeutic recommendations.

JC Virus Seroprevalence and JCVAb Index in Polish Multiple Sclerosis Patients Treated with Immunomodulating or Immunosuppressive Therapies.

The use of a highly-effective treatment for multiple sclerosis (MS) is associated with a severe risk of developing complications, such as progressive multifocal leukoencephalopathy (PML) caused by the John Cunningham virus (JCV). The aim of this study was to evaluate the correlation between anti-JCV Ab seroprevalence, anti-JCV AI, demographic and clinical factors as well as the type of therapy used in the Polish MS population. This is a multicentre, prospective and cross-sectional study involving 1405 MS patients. The seroprevalence of anti-JCV Ab and anti-JCV AI levels as well as AI categories were analysed with the use of a second-generation two-step ELISA test (STRATIFY JCV DxSelect). The overall prevalence of anti-JCV Ab was 65.8%. It was shown that seroprevalence increases with the patient's age. The seroprevalence was significantly associated with the treatment type, and the highest values (76%) were obtained from immunosuppressant-treated patients. Overall, 63.3% of seropositive patients had an antibody index (AI) level of >1.5. In the seropositive patient group, the mean AI level amounted to 2.09. Similarly to the seroprevalence, AI levels correlated with the patient's age; AI level for patients above 40 years old and from subsequent age quintiles plateaued, amounting to at least 1.55. Patients treated with immunosuppressants and immunomodulatory drugs obtained the highest (1.67) and lowest (1.35) AI levels, respectively. Of the immunosuppressants used, the highest mean AI levels were observed in mitoxantrone and cladribine groups, amounting to 1.75 and 1.69, respectively. In patients treated with immunomodulatory drugs, the lowest AI levels were observed in the dimethyl fumarate (DMF) group (1.11). The seroprevalence rate in the Polish MS population is one of the highest in Europe. The majority of seropositive patients had an anti-JCV Ab level qualifying them for a high-risk category. The highest mean AI levels are observed in patients receiving immunosuppressants, especially mitoxantrone and cladribine. Patients receiving immunomodulatory drugs have lower AI levels compared to treatment-naïve subjects, especially when treated with DMF. Further studies, especially longitudinal studies, are required to determine the impact of MS drugs on the seroprevalence of anti-JCV Ab and AI levels.

Memory in Polish multiple sclerosis patients - correlations with mood and fatigue. / Pamiec u polskich pacjentów ze stwardnieniem rozsianym ­ korelacje z nastrojem i zespolem zmeczenia.

OBJECTIVES: Assessment of the selected aspects of memory in Polish patients with multiple sclerosis (MS) and the associations between memory and clinical course, neurological status, mood, fatigue, and employment status. METHODS: The initial five learning trials of the California Verbal Learning Test (CVLT), the initial three learning trials of the Brief Visuospatial Memory Test-revised (BVMT-R), the Hospital Anxiety and Depression Scale and Modified Fatigue Impact Scale were administered to 100 MS patients and 150 healthy participants (HP). RESULTS: The MS group performed worse than the HP group on both the CVLT and the BVMT-R. The lowest scores were obtained by secondary progressive MS patients. There were significant differences between the MS and HP group on fatigue and depression, but not anxiety. Multivariate analysis showed worse neurological status was the only clinical predictor of memory disturbances. CVLT scores were significantly associated with employment status. CONCLUSIONS: Memory impairment occurs in patients with MS and affects employment status. Depressive symptoms, anxiety and fatigue, unlike neurological status, were not directly related to memory status.

Polish validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS battery): correlation of cognitive impairment with mood disorders and fatigue.

BACKGROUND: Cognitive impairment is recognised as a significant clinical issue in Multiple Sclerosis (MS). It can occur at any stage of the disease, affecting quality of life, occupational activity, and adherence to therapy. This makes the availability of a validated assessment tool for detecting and monitoring cognitive dysfunction in multiple sclerosis essential. The Brief International Cognitive Assessment for Multiple Sclerosis is a practical and simple means of administering a battery of three neuropsychological tests, and does not require any formal neuropsychological training. OBJECTIVE: To establish the validity of BICAMS in the Polish MS population; to assess the correlations of cognitive status with demographic and clinical factors, including affective symptoms and fatigue. METHODS: BICAMS was administered to 61 MS patients and 61 HC subjects. Examination of 20 participants with MS was repeated after one to three weeks to assess test-retest reliability. The patients with MS and HC subjects also completed the Hospital Anxiety and Depression Scale (HADS) and Modified Fatigue Impact Scale (MFIS). RESULTS: The MS group performed worse than the HC group in all three BICAMS components, obtaining the following values respectively: 51.7 and 56.1 (p = 0.02) for CVLT, 25 and 28 (p = 0.03) for BVMT-R, and 48.8 and 57.2 (p < 0.001) for SDMT. All BICAMS tests had very significant correlations in test-retest reliability (r = 0.83, p < 0.001 for CVLT; r = 0.84, p < 0.001 for BVMTR; r = 0.9, p < 0.001 for SDMT). 34% of MS patients presented cognitive dysfunction based on the criterion of one or more test scores below the 5th percentile value of the HC group. Significant anxiety and depressive symptoms were reported by 31.1% and 18.0% of MS patients. 31.1% of PwMS reported significant fatigue. BICAMS test results were not associated with HADS or MFIS scores. CONCLUSIONS: The Polish version of BICAMS is a valid and reliable tool for the assessment of cognitive impairment in patients with MS.

JC Virus Seroprevalence and JCVAb Index in Polish Multiple Sclerosis Treatment-Naïve Patients.

Multiple sclerosis (MS) treatment with new agents is associated with the risk of the development of progressive multifocal leukoencephalopathy (PML). The seropositivity and a high index of anti-John Cunningham virus (JCV) antibodies are some of the risk factors for PML development. The aim of this study was to assess the seroprevalence of anti-JCVAb and JCVAb index (AI), as well as its correlations with demographic and clinical characteristics in treatment-naïve Polish MS patients. This is a multicenter, prospective, and cross-sectional study involving 665 MS patients. The overall prevalence of anti-JCVAb was 65.3%, while 63.1% of seropositive patients had an index level of >1.5. The seroprevalence was shown to increase along with the patient's age. Except for age, the prevalence of anti-JCVAb was not associated with demographic or clinical data. No correlations between the index levels and the demographic or clinical data were observed. In Poland, the seroprevalence of anti-JCVAb in treatment-naïve MS patients is one of the highest in Europe. The majority of seropositive patients had an anti-JCV antibody level denoting a high-risk category. This means that we need further studies to be conducted on the individualization of MS treatment in order to provide patients with an appropriate therapeutic safety level.

Neurochemical Changes in the Brain and Neuropsychiatric Symptoms in Clinically Isolated Syndrome.

To assess cognitive impairment and affective symptoms and their association with damage to normal-appearing white matter (NAWM) in patients with clinically isolated syndrome (CIS), we compared neuropsychological test scores between patients with CIS and healthy controls and examined correlations between these and proton magnetic resonance spectroscopy (1H-MRS) outcomes in patients with CIS. Forty patients with CIS and 40 healthy participants were tested with a set of neuropsychological tests, which included the Beck Depression Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS). Single-voxel 1H-MRS was performed on frontal and parietal NAWM of patients with CIS to assess ratios of N-acetyl-aspartate (NAA) to creatine (Cr), myo-inositol (mI), and choline (Cho), as well as mI/Cr and Cho/Cr ratios. Patients with CIS had lower cognitive performance and higher scores for the BDI and anxiety subscale of HADS than healthy controls. There were significant correlations between the following neuropsychological tests and metabolic ratios in the frontal NAWM: Stroop Color-Word Test and Cho/Cr, Symbol Digit Modalities Test and mI/Cr, as well as NAA/mI, Go/no-go reaction time, and NAA/Cho, as well as NAA/mI, Californian Verbal Learning Test, and NAA/Cr. BDI scores were related to frontal NAA/mI and parietal NAA/Cr and Cho/Cr ratios, whereas HADS-depression scores were associated with frontal NAA/Cr and NAA/mI and parietal NAA/Cr and Cho/Cr ratios. HADS-anxiety correlated with parietal NAA/Cr ratio. This study suggests that neurochemical changes in the NAWM assessed with single-voxel 1H-MRS are associated with cognitive performance and affective symptoms in patients with CIS.

Recommendations of the Polish Medical Society of Radiology and the Polish Society of Neurology for a protocol concerning routinely used magnetic resonance imaging in patients with multiple sclerosis.

Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis that is essential for the detection and follow-up of the disease. OBJECTIVE: The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of their recommendations for investigations routinely conducted in magnetic resonance imaging departments in patients with multiple sclerosis. This version includes new data and practical comments for electroradiology technologists and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics necessary for establishing a diagnosis, as well as for MS patient monitoring, which directly translates into significant clinical decisions. INTRODUCTION: Multiple sclerosis (MS) is a chronic immune mediated inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in a CNS destruction process disseminated in time (DIT) and space (DIS). MRI detects focal lesions in the white and grey matter with high sensitivity (although with significantly lower specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume (GMV) and white matter volume (WMV) as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, and hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in MR techniques, as well as advances in postprocessing the obtained data, has driven the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MR imaging is unquestionably the best diagnostic tool available to follow up the course of the disease and support clinicians in choosing the most appropriate treatment strategy for their MS patient. However, to diagnose and follow up MS patients on the basis of MRI in accordance with the latest standards, the MRI study must adhere to certain quality criteria. Such criteria are the subject of this paper.

An international multicenter efficacy and safety study of IqYmune in initial and maintenance treatment of patients with chronic inflammatory demyelinating polyradiculoneuropathy: PRISM study.

This prospective, multicenter, single-arm, open-label phase 3 study aimed to evaluate the efficacy and safety of IqYmune in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients received one induction dose of 2 g/kg and then seven maintenance doses of 1 g/kg at 3-week intervals. The primary endpoint was the responder rate at the end of study (EOS), defined as an improvement of ≥1 point on the adjusted inflammatory neuropathy cause and treatment (INCAT) disability scale. The responder rate was compared with the responder rate of a historical placebo group (33.3%). Secondary endpoints included changes from baseline to EOS of adjusted INCAT disability score, grip strength, Medical Research Council (MRC) sum score, Rasch-modified MRC sum score, Rasch-built overall disability scale score and the clinical global impression. Forty-two patients, including 23 Ig-naïve and 19 Ig-pre-treated, were included in the efficacy set. The overall response rate at EOS was 76.2% (95% confidence interval [60.5%-87.9%]). The superiority of IqYmune compared to the historical placebo control was demonstrated (P < .0001). The responder rate was numerically higher in Ig-pre-treated than in Ig-naïve patients but confidence intervals were overlapping (84.2% [60.4%-96.6%] vs 69.6% [47.1%-86.8%]). All secondary endpoints confirmed this conclusion. The median time to response was 15 weeks [8.9-19.1 weeks]. A total of 156 adverse events including five serious were considered related to IqYmune, 87.2% were mild. Neither hemolysis nor signs of renal or hepatic impairment were observed. These results demonstrate that IqYmune is an effective and well-tolerated treatment in patients with CIDP.

Recommendations of the Polish Medical Society of Radiology and the Polish Society of Neurology for the routinely used magnetic resonance imaging protocol in patients with multiple sclerosis.

Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis (MS) that is essential for the detection and follow-up of the disease. The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of the recommendations for examinations routinely conducted in magnetic resonance imaging departments in patients with MS, which include new data and practical comments for electroradiology technicians and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics that are necessary to establish a diagnosis as well as monitor patients with MS, which directly translates into significant clinical decisions. MS is a chronic idiopathic inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in the CNS destruction process disseminated in time and space. MRI detects focal lesions in the white and grey matter with high sensitivity (with significantly less specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume and white matter volume as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in magnetic resonance techniques, as well as the abilities of postprocessing the obtained data, has become the basis for the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MRI is unquestionably the best diagnostic tool used to follow up the course of the disease and to treat patients with MS. However, to diagnose and follow up the patients with MS on the basis of MRI in accordance with the latest standards, an MRI study must meet certain quality criteria, which are the subject of this paper.

Behavioral variant frontotemporal dementia with dominant gait disturbances - case report. / Wariant behawioralny otepienia czolowo-skroniowego z dominujacymi zaburzeniami chodu w obrazie klinicznym - opis przypadku.

INTRODUCTION.: Behavioural variant frontotemporal dementia is a clinically and pathologically heterogeneous neurodegenerative disorder, characterised by progressive behavioural changes and executive function impairment. It is the second most common neurodegenerative cause of dementia after Alzheimer's type dementia. Atypical course of the disease, including cases with other symptoms relevantly interfering with the clinical picture, provides a challenge in the diagnostic process. AIM AND MATERIAL.: The aim of this paper is to present a case of patient with BvFTD and gait disturbance as a main reported symptom masking behavioural changes and cognitive function impairment. Gait disturbance commonly occurs at the late stage of dementia disorders. It results from gait apraxia, extrapyramidal syndrome or motor neuron dysfunction. However, it is not a predominant symptom of behavioural variant frontotemporal dementia excluding terminal stage of the disease. RESULTS: Presented case emphasises the significance of accurately gathered anamnesis with patient and his family. Behavioural variant frontotemporal dementia should be considered in cases of unexplained gait abnormalities.

Demyelinating lesions in the cervical cord in multiple sclerosis 10 years after onset of the disease. Correlation between MRI parameters and clinical course.

BACKGROUND AND PURPOSE: Demyelinating lesions in spinal cord in multiple sclerosis (MS) are found in magnetic resonance imaging (MRI) in 47-90% of patients; spinal cord atrophy, however, which is a measure of axonal loss and correlates with disability, is found in 13-41% of patients. Presence and character of lesions depend on the duration and progression of the disease. The aim of this study was to estimate the presence, character and location of lesions and cervical cord atrophy in MRI performed 10 years after the onset of MS in relation to the clinical course. MATERIAL AND METHODS: 60 patients (41 females and 19 males) with definite MS according to McDonald's criteria were studied. The age of patients ranged from 29 to 62 years and disease duration ranged from 11 to 40 years. The MS group comprised 20 patients with secondary progressive MS (SPMS), 20 patients with primary progressive MS (PPMS) and 20 patients with benign form of MS (BMS). Spinal cord MRI was performed in conventional T1 and T2-weighted sequences. RESULTS: Demyelinating lesions were found in 62% of patients (50% of patients with BMS, 60% with PPMS and 75% with SPMS). 42 intrinsic focal lesions were identified in 18 patients and diffuse lesions of spinal cord were noted in 19 patients. Focal lesions were seen in patients with BMS, whereas SPMS patients had diffuse cervical cord abnormalities, and PPMS patients exhibited both forms of changes. 60% of intrinsic focal lesions were located at C3-C5 levels. Medium-sized lesions prevailed in BMS form; in PPMS form small and medium-size lesions, and in SPMS form large lesions (>10 mm) were more frequent. The spinal cord was atrophic in 8% of patients (10% of patients with PPMS and 15% with SPMS). In BMS no atrophy of the cervical cord was observed. We did not find focal demyelinating lesions in the cervical segment of patients with spinal cord atrophy. CONCLUSIONS: Presence and character of demyelinating lesions in cervical cord ten years after onset of MS is significantly related to the clinical form of the disease. The mid-cervical region of the spinal cord appeared to be the commonest location of the focal lesions. Cervical cord atrophy was more frequent in patients with PPMS and SPMS, but it was not accompanied with intrinsic focal cord lesions.

[Demyelinating lesions in cervical spinal cord and disability in multiple sclerosis patients]. / Zmiany demielinizacyjne w rdzeniu szyjnym a niewydolnosc ruchowa w stwardnieniu rozsianym.

BACKGROUND AND PURPOSE: In multiple sclerosis (MS) lesions appear both in brain and cervical cord. The aim of this study was to estimate the presence of MRI changes in cervical cord depending on the course, duration of the disease and a disability. MATERIAL AND METHODS: Clinical measures included 66 patients suffering from MS, the diagnosis was made according to McDonald's criteria. Patients were aged from 18 to 62 (41 women and 25 men). RESULTS: In patients with relapsing-remitting form (EDSS 1-4) single lesions were seen whereas secondary progressive patients (EDSS 3-7) had diffuse demyelinating lesions and primary progressive patients (EDSS 4-8)--both kinds of changes. It has been shown that the lesions occurred as the disease proceeds. Patients without demyelinating lesions in cervical cord had EDSS from 1 to 3 and the duration of their disease was longer than 10 years (benign MS). CONCLUSIONS: The duration of the disease depends on the presence and character of demyelinating lesions in cervical cord to a large extent. That dependence was not noticed in a primary progressive form. In benign MS there were no lesions in cervical cord.