Sufficiency for PSS tracking gait disorders in multiple sclerosis: A managerial perspective.

This study primarily aimed to explore the capabilities of digitalisation in the healthcare context, focusing on a specific disease. In this case, the study examined the potential of remote monitoring of gait to address the sensitivity of multiple sclerosis progression to gait characteristics by adopting a non-invasive approach to remotely quantify gait disturbances in a patient's daily life. To better understand the managerial aspects associated with this approach, the researchers conducted a literature review along with a set of semi-structured interviews. The target population included MS patients as well as the key agents involved in their care: patients' family members, neurologists, MS nurses, physiotherapists, medical directors, and pharmacist. The study identifies the perceived barriers and drivers that could contribute to the successful deployment of PSS remote gait monitoring as a healthcare service: i) At mega-level governance. Implications on privacy and security data are notable barriers missing on the speech. ii) At macro level, funding is highlighted as main barrier. The cost and lack of health system subsidies may render initiatives unsustainable, as emphasised by the interviewees. iii) At meso level, useable data is recognised as a driver. The data collection process can align with diverse interests to create value and business opportunities for the ecosystem actors, enhance care, attract stakeholders, such as insurers and pharma, and form partnerships. iv) At micro-level processes, we find two potential barriers: wearable device and app usability (comfort, navigation, efficiency) and organisational/behavioural aspects (training, digital affinity, skills), which are crucial for value creation in innovation ecosystems among patients and healthcare professionals. Finally, we find an interesting gap in the literature and interviews. Stakeholders' limited awareness of technological demands, especially from information technologies, for a successful long-term service, can be consider two key barriers for PSS.

MicroRNAs Associated with Disability Progression and Clinical Activity in Multiple Sclerosis Patients Treated with Glatiramer Acetate.

MicroRNAs (miRNAs) are promising biomarkers in multiple sclerosis (MS). This study aims to investigate the association between a preselected list of miRNAs in serum with therapeutic response to Glatiramer Acetate (GA) and with the clinical evolution of a cohort of relapsing-remitting MS (RRMS) patients. We conducted a longitudinal study for 5 years, with cut-off points at 2 and 5 years, including 26 RRMS patients treated with GA for at least 6 months. A total of 6 miRNAs from a previous study (miR-9.5p, miR-126.3p, mir-138.5p, miR-146a.5p, miR-200c.3p, and miR-223.3p) were selected for this analysis. Clinical relapse, MRI activity, confirmed disability progression (CDP), alone or in combination (No Evidence of Disease Activity-3) (NEDA-3), and Expanded Disability Status Scale (EDSS), were studied. After multivariate regression analysis, miR-9.5p was associated with EDSS progression at 2 years (ß = 0.23; 95% CI: 0.04-0.46; p = 0.047). Besides this, mean miR-138.5p values were lower in those patients with NEDA-3 at 2 years (p = 0.033), and miR-146a.5p and miR-126.3p were higher in patients with CDP progression at 2 years (p = 0.044 and p = 0.05 respectively. These results reinforce the use of microRNAs as potential biomarkers in multiple sclerosis. We will need more studies to corroborate these data and to better understand the role of microRNAs in the pathophysiology of this disease.

Endocannabinoid levels in peripheral blood mononuclear cells of multiple sclerosis patients treated with dimethyl fumarate.

The endocannabinoid system (ECS), a signalling network with immunomodulatory properties, is a potential therapeutic target in multiple sclerosis (MS). Dimethyl fumarate (DMF) is an approved drug for MS whose mechanism of action has not been fully elucidated; the possibility exists that its therapeutic effects could imply the ECS. With the aim of studying if DMF can modulate the ECS, the endocannabinoids 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) were determined by liquid chromatography-mass spectrometry in peripheral blood mononuclear cells from 21 healthy donors (HD) and 32 MS patients at baseline and after 12 and 24 months of DMF treatment. MS patients presented lower levels of 2-AG and PEA compared to HD. 2-AG increased at 24 months, reaching HD levels. AEA and PEA remained stable at 12 and 24 months. OEA increased at 12 months and returned to initial levels at 24 months. Patients who achieved no evidence of disease activity (NEDA3) presented the same modulation over time as EDA3 patients. PEA was modulated differentially between females and males. Our results show that the ECS is dysregulated in MS patients. The increase in 2-AG and OEA during DMF treatment suggests a possible role of DMF in ECS modulation.

Risk and prognostic factors for SARS-CoV-2 infection in Spanish population with multiple sclerosis during the first five waves.

Background: Data on coronavirus disease 2019 (COVID-19) incidence in patients with multiple sclerosis (MS) during the first wave have been published but are scarce for the remaining waves. Factors associated with COVID-19 infection of any grade are also poorly known. The aim of this study was to analyze the incidence, clinical features, and risk factors for COVID-19 infection of any grade in patients with MS (pwMS) during waves 1-5. Methods: This study prospectively analyzes the cumulative incidence of COVID-19 from the first to the fifth waves by periodic case ascertainment in pwMS followed at the University Hospital of Getafe (UHG). Global and stratified cumulative incidence was calculated. Logistic regression models were used to estimate the weight of selected variables as risk and prognostic factors. Results: We included 431 pwMS, of whom 86 (20%) were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The overall cumulative incidence of confirmed cases was similar to that of Madrid (13,689 vs. 13,307 per 100,000 habitants) but 3 times higher during the first wave and slightly lower from the second to the fifth waves. The majority (86%) of pwMS developed mild forms of COVID-19. Smoking was the only factor associated with a decreased risk of SARS-CoV2 infection of any grade [odds ratio (OR) 0.491; 95% CI 0.275-0.878; p = 0.017]. Risk factors associated with severe forms were Expanded Disability Severity Scale (EDSS) ≥3.5 (OR 7.569; 95% CI 1.234-46.440) and pulmonary disease (OR 10.763; 95% CI 1.27-91.254). Conclusion: The incidence of COVID-19 was similar in this MS cohort to the general population. Smoking halved the risk of being infected. Higher EDSS and pulmonary comorbidity were associated with an increased risk of severe forms.

microRNA Expression and Its Association With Disability and Brain Atrophy in Multiple Sclerosis Patients Treated With Glatiramer Acetate.

Background: MicroRNAs are small non-coding RNA that regulate gene expression at a post-transcriptional level affecting several cellular processes including inflammation, neurodegeneration and remyelination. Different patterns of miRNAs expression have been demonstrated in multiple sclerosis compared to controls, as well as in different courses of the disease. For these reason they have been postulated as promising biomarkers candidates in multiple sclerosis. Objective: to correlate serum microRNAs profile expression with disability, cognitive functioning and brain volume in patients with remitting-relapsing multiple sclerosis. Methods: cross-sectional study in relapsing-remitting multiple sclerosis patients treated with glatiramer acetate. Disability was measured with Expanded Disability Status Scale (EDSS) and cognitive function was studied with Symbol Digit Modalities Test (SDMT). Brain volume was analyzed with automatic software NeuroQuant®. Results: We found an association between miR.146a.5p (rs:0.434, p=0.03) and miR.9.5p (rs:0.516, p=0.028) with EDSS; and miR-146a.5p (rs:-0.476, p=0.016) and miR-126.3p (rs:-0.528, p=0.007) with SDMT. Regarding to the brain volume, miR.9.5p correlated with thalamus (rs:-0.545, p=0.036); miR.200c.3p with pallidum (rs:-0.68, p=0.002) and cerebellum (rs:-0.472, p=0.048); miR-138.5p with amygdala (rs:0.73, p=0.016) and pallidum (rs:0.64, p=0.048); and miR-223.3p with caudate (rs:0.46, p=0.04). Conclusions: These data support the hypothesis of microRNA as potential biomarkers in this disease. More studies are needed to validate these results and to better understand the role of microRNAs in the pathogenesis, monitoring and therapeutic response of multiple sclerosis.

Cancer diagnosis in a Spanish cohort of multiple sclerosis patients under dimethylfumarate treatment.

BACKGROUND: Potential increase of cancer incidence is one of the main safety concerns of the disease-modifying therapies employed in Multiple Sclerosis (MS). OBJECTIVE: Detailed description of patients who developed cancer among a prospective cohort of Spanish MS patients on dimethyl fumarate (DMF) treatment. METHODS: We describe patients who developed cancer among a cohort of 886 MS patients on DMF treatment (2681 patient-years), with a median time of exposure of 39.5 months (IQR 23-51.5), who participated in a multicentre and prospective real-world study conducted in 16 Spanish National Health System hospitals from February 2014 to May 2019. Local researchers were periodically contacted by the investigation team to monitor safety issues. Cancer histories were collected from the medical records and the information was updated at July 30th 2020. RESULTS: Eight Caucasian women developed cancer, which accounts for 0.9% and an accumulated malignancy rate of 298.39 cases per 100,000 patient-years of DMF exposure. At the time of cancer diagnosis, age was between 33 to 67 years and median time on DMF treatment 16.5 months (range 1-53). Two patients had familiar history of cancer. No specific cancer lines were found (breast cancer in 2 cases, thyroid in 3, urothelial carcinoma, cervix and a progression to leiomyosarcoma from a mitotically active leiomyoma). DMF was withdrawn during cancer treatment in 6 patients and reintroduced later. All cancers except one are in complete remission. The patient with leiomyosarcoma died by cancer progression. CONCLUSION: A relationship between cancers and DMF is unlikely because the malignancy rate was similar to that of the age-and sex-matched general population, and because of the absence of specific tumour cell lines. Nevertheless, as with other immunosuppressive DMTs, clinicians treating MS should be aware of any potential cancer symptom and demand proper testing.

Predicting conversion to multiple sclerosis by assessing cognitive impairment in radiologically isolated syndrome.

Up to a third of patients with radiologically isolated syndrome (RIS) exhibit lower-than-expected cognitive performances in neuropsychological evaluations, but the relationship between cognitive impairment (CI) and quantitative magnetic resonance (MRI) measures has not been stablished. Furthermore, the prognostic role of CI in RIS for conversion to MS is currently unknown. We assessed 17 patients with RIS and 17 matched healthy controls (HC) with a neurophychological battery and a 3T MRI. Six patients (35,3%) fulfilled our criterion for CI (scores 2 SDs below the mean of HC in at least two cognitive tests) (ci-RIS). The ci-RIS subgroup showed lower values of normalized brain and gray matter volumes when compared to HC. After a median follow-up time of 4.5 years, the ci-RIS subgroup presented a higher conversion rate to MS, suggesting that CI might be an independent risk factor for conversion to MS.

Assessing fatigue in multiple sclerosis: Psychometric properties of the five-item Modified Fatigue Impact Scale (MFIS-5).

Fatigue in multiple sclerosis is a key symptom associated with work-related problems and poor quality of life outcomes. The five-item Modified Fatigue Impact Scale is a brief self-assessment tool for measuring the impact of fatigue on cognitive, physical and psychosocial function. A non-interventional, cross-sectional study was conducted to assess dimensionality and item characteristics of the five-item Modified Fatigue Impact Scale in multiple sclerosis. A total of 302 subjects were studied. Mokken analysis found the five-item Modified Fatigue Impact Scale is a strong one-dimensional scale (overall scalability index H = 0.67) with high reliability (Cronbach's alpha = 0.90). The confirmatory factor analysis model confirmed the one-dimensional structure (comparative fit index = 1.0, root-mean-square error of approximation = 0.035). Samejima's model fitted well as an unconstrained model with different item difficulties. The five-item Modified Fatigue Impact Scale shows appropriate psychometric characteristics and may constitute a valuable and easy-to-implement addition to measure the impact of fatigue in clinical practice.

Alteration profile of executive functions in multiple sclerosis.

OBJECTIVE: Executive functions (EF) in multiple sclerosis (MS) have been only partially studied, mainly trough the evaluation of subfunctions. The main objective was to analyse the EF alteration profile in a patients with MS sample. PARTICIPANTS AND METHODS: Case-control study, 100 patients with MS and 30 controls were evaluated by the following tests: Comprehensive Trail Making Test, Stroop Test, Wisconsin Card Sorting Test, picture completion, letter-number sequencing, comprehension and similarities of the WAIS-III scale, phonological and semantic fluency, zoo map test, temporal judgment and behavioural Dysexecutive Questionnaire (DEX-Q) of the Behavioural Assessment of the Dysexecutive Syndrome. Scores below normative values were considered pathological. Factorial analysis was used to simplify the deficits, and multiple regression and ANOVA statistics were used to analyse the relationship between clinical and cognitive variables. RESULTS: Seventy-four patients had a recurrent-relapsing course, the mean degree of disability by Expanded disability Status Scale (EDSS) was 2.7 and the mean time of evolution was 9.94 years. Eighty-five per cent presented alterations in 3 or more EF tests and 71% in 5 or more. In the factorial analysis, three groups of functions were involved: (i) cognitive flexibility (ii) inhibition and (iii) abstraction ability. Patients with a progressive course and a high EDSS had a significantly worse performance (P < 0.05). The patients showed a low awareness of their deficit in the DEX-Q. CONCLUSIONS: Cognitive flexibility, inhibition and abstraction ability were the three components of EF most deficient. The patients with the worst performance were those with progressive forms and a high EDSS.

Neuropsychological syndromes in multiple sclerosis / Síndromes neuropsicológicos en la esclerosis múltiple

Background: Cognitive impairment in multiple sclerosis (MS) is common (45-65%).Deficits occur in speed of information processing (SIP), memory, attention, executive functions (EF) and visuoconstruction. Involvement of cognitive functions like language and gnosis is rare and lesser known. Our aim is to describe the cognitive function and the clinical and radiological features of five patients with MS and with neuropsychological syndromes (NPS). Method: Retrospective review of MS patients with NPS studied, using specific tests of SIP, memory, attention, EF, visuo-spatial abilities, praxis and language. Results: The sample included four women (3 relapsing-remitting MS/1 secondary progressive MS) and one man with primary progressive MS (aged between 30-55 years). Cognitive symptoms were the initial complaint in three cases. Three cases presented apperceptive agnosia and constructive apraxia, one case presented alexia with agraphia and the fifth patient presented motor aphasia. Four patients suffered cognitive dysfunction considered typical of MS. Magnetic resonance imaging (MR) in all cases showed high lesion volumes in T1 and T2- weighted sequences. A good correlation was observed between cognitive deficits and the location of the lesions in four patients. Conclusions: NPS may be the initial complaint in MS patients, often associated with other cognitive deficits, and it shows a close relationship with lesion location (AU)

Antecedentes: entre el 45-65% de los pacientes con esclerosis múltiple (EM) manifiestan déficits cognitivos en velocidad de procesamiento de la información (VPI), atención, memoria, funciones ejecutivas (FE) y visuoconstrucción. La alteración del lenguaje y la gnosis visual es infrecuente y poco reconocida. El objetivo es la descripción cognitiva, clínica y radiológica de cinco pacientes con EM con síndromes neuropsicológicos (SNPS). Método: revisión retrospectiva de pacientes de EM con SNPS estudiados mediante test específicos de atención, memoria, VPI, FE, visuoconstrucción, gnosis visual y lenguaje. Resultados: la muestra incluyó cuatro mujeres (3 EM remitente recurrente, 1 EM secundaria progresiva) y un varón con EM primaria progresiva (edades entre 30-55 años). Los déficits cognitivos fueron el síntoma inicial en 3 casos. Tres presentan agnosia aperceptiva y apraxia constructiva, uno alexia con agrafia y el quinto afasia motora. Cuatro asocian disfunción cognitiva ‘típica’ de EM. En resonancia magnética observamos alto volumen lesional en secuencias potenciadas en T1 y T2 y correlación entre los déficits cognitivos y la localización de las lesiones en 4 de ellos. Conclusiones: los SNPS pueden ser la queja inicial en la EM, con frecuencia se asocian a otros déficits cognitivos y manifiestan una estrecha relación con la localización de la lesión (AU)

Neuropsychological syndromes in multiple sclerosis.

BACKGROUND: Cognitive impairment in multiple sclerosis (MS) is common (45-65%).Deficits occur in speed of information processing (SIP), memory, attention, executive functions (EF) and visuoconstruction.Involvement of cognitive functions like language and gnosis is rare and lesser known. Our aim is to describe the cognitive function and the clinical and radiological features of five patients with MS and with neuropsychological syndromes (NPS). METHOD: Retrospective review of MS patients with NPS studied, using specific tests of SIP, memory, attention, EF, visuo-spatial abilities, praxis and language. RESULTS: The sample included four women (3 relapsing-remitting MS/1 secondary progressive MS) and one man with primary progressive MS (aged between 30-55 years). Cognitive symptoms were the initial complaint in three cases. Three cases presented apperceptive agnosia and constructive apraxia, one case presented alexia with agraphia and the fifth patient presented motor aphasia. Four patients suffered cognitive dysfunction considered typical of MS. Magnetic resonance imaging (MR) in all cases showed high lesion volumes in T1 and T2-weighted sequences. A good correlation was observed between cognitive deficits and the location of the lesions in four patients. CONCLUSIONS: NPS may be the initial complaint in MS patients, often associated with other cognitive deficits, and it shows a close relationship with lesion location.

Executive function and memory in patients with relapsing-remitting multiple sclerosis / Función ejecutiva y memoria en pacientes con esclerosis múltiple recurrente-remitente

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system very heterogeneous in its characteristics. In contrast to the well known sensitive/motor deficits, the cognitive dysfunction has only been analyzed in the last few decades. Attention, executive function, and memory were assessed in 28 patients with recurrent-remittent MS (RRMS) (duration, median 7 years; EDSS median 2) by means of a specific neuropsychological battery. Depression (BDI), anxiety (STAI) and fatigue (FSS) were also assessed. Twenty-five of these patients were selected for statistical study because they presented deficits in some cognitive areas. Twenty-four percent of the patients displayed memory deficits and 80% showed attention and executive function deficits related to prefrontal lobe function. No global memory difficulties were found, except for immediate visual memory of complex elements (immediate recall of the Rey figure), although the visual reproduction I subtest of the WMSR was unaffected. In RRMS patients with a relatively short duration and low level of incapacity, cognitive impairments mainly affected prefrontal functions. The difficulties in immediate visual memory of complex elements could also be explained by a failure in these areas, due to the alteration of the organization and strategic use of the material to be encoded (AU)

La esclerosis múltiple (EM) es una enfermedad inflamatoria crónica del sistema nervioso central muy heterogénea en sus manifestaciones. A diferencia de los déficits sensitivos-motores, muy bien estudiados, los aspectos cognitivos están siendo analizados sólo en las últimas décadas. A 28 pacientes con EM recurrente-remitente (EMRR) (tiempo de evolución, mediana 7 años; EDSS, mediana 2) se les realizó una evaluación de atención, función ejecutiva y memoria mediante una batería neuropsicológica específica.Se evaluaron también el grado de depresión (BDI), ansiedad (STAI) y fatiga (EGF). Veinticinco fueron seleccionados para el estudio por presentar alteración en algún aspecto cognitivo. El 24% mostraba disminución en memoria y el 80% en atención y funciones ejecutivas relacionadas con regiones prefrontales. No se observaron dificultades globales de memoria, salvo en memoria inmediata visual de elementos complejos (Figura de Rey reproducción inmediata), sin afectarse la prueba de reproducción visual I de la WMS-R. En pacientes con EMRR con un tiempo medio de evolución y bajo nivel de incapacidad, las alteraciones cognitivas afectan fundamentalmente a funciones atribuidas a regiones prefrontales. Las dificultades en memoria inmediata visual de elementos complejos se explicarían también por un fallo de estas áreas al alterarse la organización y uso estratégico del material a codificar (AU)

Executive function and memory in patients with relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system very heterogeneous in its characteristics. In contrast to the well known sensitive/motor deficits, the cognitive dysfunction has only been analyzed in the last few decades. Attention, executive function, and memory were assessed in 28 patients with recurrent-remittent MS (RRMS) (duration, median 7 years; EDSS median 2) by means of a specific neuropsychological battery. Depression (BDI), anxiety (STAI) and fatigue (FSS) were also assessed. Twenty-five of these patients were selected for statistical study because they presented deficits in some cognitive areas. Twenty-four percent of the patients displayed memory deficits and 80% showed attention and executive function deficits related to prefrontal lobe function. No global memory difficulties were found, except for immediate visual memory of complex elements (immediate recall of the Rey figure), although the visual reproduction I subtest of the WMS-R was unaffected. In RRMS patients with a relatively short duration and low level of incapacity, cognitive impairments mainly affected prefrontal functions. The difficulties in immediate visual memory of complex elements could also be explained by a failure in these areas, due to the alteration of the organization and strategic use of the material to be encoded.

Butyrylcholinesterase, ApoE and Alzheimer's disease in a population from the Canary Islands (Spain).

AIM: Cholinergic dysfunction is a major neurochemical feature in Alzheimer's disease (AD), accountable for many cognitive dysfunctions and some psychiatric symptoms. Butyrylcholinesterase (BChE) is one of the cholinesterases with increased activity in the brain of Alzheimer's patients. Several mutations code for different BChE, such as the K variant, which is the most common and is capable of reducing BChE activity by 30%. We studied the relationship between this K variant and Alzheimer's disease in our population from the Canary Islands (Spain). PATIENTS AND METHODS: We used DNA PCR-RFLP techniques to compare 282 patients who had been diagnosed with probable Alzheimer's disease--according to NINCS-ADRDA criteria--with 312 control subjects confirmed to be free of cognitive impairment as assessed by using the CAMDEX cognitive subscale CAMCOG. RESULTS: In our population the K variant of BChE is linked to the age of diagnosis of Alzheimer's disease, since AD individuals with this allele presented the disease at a later stage. No other susceptibility relations are exposed in this study. In addition, the BChE allelic frequencies in our population are higher than those previously reported.

Current clinical spectrum of neurosyphilis in immunocompetent patients.

BACKGROUND: Neurosyphilis (NS) is nowadays a less frequent disease. Its incidence and clinical spectrum have changed over time. OBJECTIVE: To estimate the incidence of NS and describe the clinical spectrum of NS in immunocompetent patients in the last decade. METHODS: Demographic and clinical features, cerebrospinal fluid (CSF) changes, neuroimaging findings and outcome were retrospectively analyzed. RESULTS: Forty-three patients met NS criteria. The yearly incidence was 0.2- 2.1 cases per 100,000 inhabitants. The mean age was 48.1 years, males being more frequently involved. The most frequent clinical patterns were meningovascular (30.2%), meningeal (25.6%) and general paresis (25.6%). Compared to prepenicillin series, we observed a decrease in late forms, mainly tabes dorsalis. CSF titers studied by the Venereal Disease Research Laboratory were higher in early NS. Neuroimaging findings were nonspecific. Outcome was better for early forms. CONCLUSIONS: Compared to the preantibiotic era, a lower frequency of late NS was observed, similar to that reported in other modern series which include patients with HIV infection. Therefore, this trend seems to be due to the impact of antibiotics rather than to HIV infection.