Sporadic Creutzfeldt-Jakob disease VM1: phenotypic and molecular characterization of a novel subtype of human prion disease

Creutzfeldt-Jakob disease; Prion disease; Prion strainsMalaltia de Creutzfeldt-Jakob; Malalties priòniques; Soques de prionsEnfermedad de Creutzfeldt-Jakob; Enfermedad priónica; Cepas de prionesThe methionine (M)-valine (V) polymorphic codon 129 of the prion protein gene (PRNP) plays a central role in both susceptibility and phenotypic expression of sporadic Creutzfeldt-Jakob diseases (sCJD). Experimental transmissions of sCJD in humanized transgenic mice led to the isolation of five prion strains, named M1, M2C, M2T, V2, and V1, based on two major conformations of the pathological prion protein (PrPSc, type 1 and type 2), and the codon 129 genotype determining susceptibility and propagation efficiency. While the most frequent sCJD strains have been described in codon 129 homozygosis (MM1, MM2C, VV2) and heterozygosis (MV1, MV2K, and MV2C), the V1 strain has only been found in patients carrying VV. We identified six sCJD cases, 4 in Catalonia and 2 in Italy, carrying MV at PRNP codon 129 in combination with PrPSc type 1 and a new clinical and neuropathological profile reminiscent of the VV1 sCJD subtype rather than typical MM1/MV1. All patients had a relatively long duration (mean of 20.5 vs. 3.5 months of MM1/MV1 patients) and lacked electroencephalographic periodic sharp-wave complexes at diagnosis. Distinctive histopathological features included the spongiform change with vacuoles of larger size than those seen in sCJD MM1/MV1, the lesion profile with prominent cortical and striatal involvement, and the pattern of PrPSc deposition characterized by a dissociation between florid spongiform change and mild synaptic deposits associated with coarse, patch-like deposits in the cerebellar molecular layer. Western blot analysis of brain homogenates revealed a PrPSc type 1 profile with physicochemical properties reminiscent of the type 1 protein linked to the VV1 sCJD subtype. In summary, we have identified a new subtype of sCJD with distinctive clinicopathological features significantly overlapping with those of the VV1 subtype, possibly representing the missing evidence of V1 sCJD strain propagation in the 129MV host genotype

Prevenció i control de les encefalopaties espongiformes transmissibles als centres sanitaris

Transmissible spongiform encephalopathy; Prevention; Decontamination of infectious wasteEncefalopaties espongiformes transmissibles; Prevenció; Descontaminació de residus infecciososEncefalopatias espongiformes transmisibles; Prevención; Descontaminación de residuos infecciososDocumento que trata sobre la prevención y el control de las encefalopatías espongiformes transmisibles en los centros sanitarios. Ofrece información tanto del agente causal como de la cadena epidemiológica y va dirigida a los profesionales sanitarios que tienen o pueden tener relación con enfermos afectados por estos procesos.Document que tracta sobre la prevenció i el control de les encefalopaties espongiformes transmissibles als centres sanitaris. Ofereix informació tant de l’agent causal com de la cadena epidemiològica i va adreçada als professionals sanitaris que tenen o que poden tenir relació amb malalts afectats per aquests processos

Variably protease-sensitive prionopathy presenting within ALS/FTD spectrum

We report clinico‐pathological features of a 65‐year‐old woman and a 56‐year‐old man with a 5‐year clinical history who had clinical and neuropathological characteristics of upper and lower motor neuron disease consistent with amyotrophic lateral sclerosis, and a frontotemporal atrophy pattern in case 2 without TDP‐43 pathology. Instead, spongiform change and pathological prion protein deposits were observed in several brain regions. No prion protein gene mutations were found. Western blot analysis showed a five‐band profile compatible with variably protease‐sensitive prionopathy. We conclude that this disease can display prolonged disease duration and clinico‐pathological features within the ALS/FTLD spectrum.This work was funded by Department of Public Health Generalitat de Catalunya grant ; Spanish “Ministerio de Economía y Competitividad, Subprograma Técnicos de Apoyo 2014” grant ; Spanish Fondo de Investigaciones Sanitarias grant FIS PI16‐01673‐FEDER; Spanish Ministry of Health ‐ Instituto Carlos III grant Miguel Servet ‐ CP16/00041; Fundació La Marató de TV3 grant 20141610

Risk Acceptance in Multiple Sclerosis Patients on Natalizumab Treatment

Objective: We aimed to investigate the ability of natalizumab (NTZ)-treated patients to assume treatment-associated risks and the factors involved in such risk acceptance.Methods: From a total of 185 patients, 114 patients on NTZ as of July 2011 carried out a comprehensive survey. We obtained disease severity perception scores, personality traits' scores, and risk-acceptance scores (RAS) so that higher RAS indicated higher risk acceptance. We recorded JC virus status (JCV+/-), prior immunosuppression, NTZ treatment duration, and clinical characteristics. NTZ patients were split into subgroups (A-E), depending on their individual PML risk. Some 22 MS patients on first-line drugs (DMD) acted as controls.Results: No differences between treatment groups were observed in disease severity perception and personality traits. RAS were higher in NTZ than in DMD patients (p<0.01). Perception of the own disease as a more severe condition tended to predict higher RAS (p=0.07). Higher neuroticism scores predicted higher RAS in the NTZ group as a whole (p=0.04), and in high PML-risk subgroups (A-B) (p=0.02). in low PML-risk subgroups (C-E), higher RAS were associated with a JCV+ status (p=0.01). Neither disability scores nor pre-treatment relapse rate predicted RAS in either group.Conclusions: Risk acceptance is a multifactorial phenomenon, which might be partly explained by an adaptive process, in light of the higher risk acceptance amongst NTZ-treated patients and, especially, amongst those who are JCV seropositive but still have low PML risk, but which seems also intimately related to personality traits.Bayer Health CareMerck SeronoTEVAVall dHebron Univ Hosp, Dept Neurol Neuroimmunol, Multiple Sclerosis Ctr Catalonia Cemcat, Barcelona, SpainUniversidade Federal de São Paulo, Dept Neurol & Neurosurg, São Paulo, BrazilUniv Hosp Principe de Asturias, Dept Neurol, Madrid, SpainUniversidade Federal de São Paulo, Dept Neurol & Neurosurg, São Paulo, BrazilWeb of Scienc

Lesion topographies in multiple sclerosis diagnosis

To assess the contributions of cortico-juxtacortical and corpus callosum lesions to multiple sclerosis diagnosis and to compare the value of ≥1 vs ≥3 periventricular lesions in clinically isolated syndromes (CIS). Step 1: We evaluated lesion topography classifications in 657 patients with CIS with stepwise Cox proportional hazards regression models considering second attack as the outcome. Step 2: We established 2 dissemination in space (DIS) versions according to the periventricular lesion cutoffs of ≥1 and ≥3 and assessed their performance at 10 years with second attack as the outcome, first individually and then combined with dissemination in time (DIT) in all cases (n = 326), by age, and by CIS topography. Step 1: The models (hazard ratios [95% confidence interval]) favored ≥1 over ≥3 periventricular lesions (2.5 [1.7-3.6]) and cortico-juxtacortical over juxtacortical lesions (1.4 [1.0-1.8]). Callosal lesions were not selected. Step 2: DIS specificity with ≥1 periventricular lesions was slightly lower than with ≥3 (59.1 vs 61.4) and the same after adding DIT (88.6). Regarding age, ≥3 periventricular lesions improved DIS specificity over ≥1 lesions in the 40-49 years of age bracket (66.7 vs 58.3). This difference disappeared when adding DIT (83.3). Optic neuritis had a similar pattern when evaluating CIS topographies. Our results comply with the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) consensus recommendation of combining cortical and juxtacortical lesions into a single term when possible. Concerning periventricular lesions, maintaining the current ≥1 cutoff in the McDonald criteria does not compromise specificity in typical CIS cases, but attention should be paid to older patients or optic neuritis cases

Antisèptics i desinfectants

Centres sanitaris; Desinfecció; HigieneHealth centers; Disinfection; HygieneCentros sanitarios; Desinfección; HigieneL’actualització que han fet els autors d’aquesta segona edició d’Antisèptics i desinfectants ha comportat un treball rigorós i complex en el qual s’ha combinat la informació científica disponible sobre els diversos productes i tècniques amb l’experiència dels professionals que desenvolupen la seva activitat als nostres hospitals, per la qual cosa s'espera que el producte final sigui realment d’utilitat i respongui als interrogants que el dia a dia ens posa sobre la taula.This update of the second edition of Antiseptics and Desinfectants has resulted a complex and rigorous work which combine the available scientific information on various products and techniques with the experience of professionals who develop their activity in hospitals, so it is expected that the final product will be really helpful and it will answer daily questions.La actualización que han hecho los autores de esta segunda edición de Antisépticos y desinfectantes ha supuesto un trabajo riguroso y complejo en el que se ha combinado la información científica disponible sobre los diversos productos y técnicas con la experiencia de los profesionales que desarrollan su actividad en nuestros hospitales, por lo que se espera que el producto final sea realmente de utilidad y responda a los interrogantes que el día a día nos pone sobre la mesa

Optic Nerve Topography in Multiple Sclerosis Diagnosis

To assess the added value of the optic nerve region (by using visual evoked potentials [VEPs]) to the current diagnostic criteria. From the Barcelona clinically isolated syndrome (CIS) cohort, patients with complete information to assess dissemination in space (DIS), the optic nerve region, and dissemination in time at baseline (n = 388) were selected. Modified DIS (modDIS) criteria were constructed by adding the optic nerve to the current DIS regions. The DIS and modDIS criteria were evaluated with univariable Cox proportional hazard regression analyses with the time to the second attack as the outcome. A subset of these patients who had at least 10 years of follow-up or a second attack occurring within 10 years (n = 151) were selected to assess the diagnostic performance. The analyses were also performed according to CIS topography (optic neuritis vs non-optic neuritis). The addition of the optic nerve as a fifth region improved the diagnostic performance by slightly increasing the accuracy (2017 DIS 75.5%, modDIS 78.1%) and the sensitivity (2017 DIS 79.2%, modDIS 82.3%) without lowering the specificity (2017 DIS 52.4%, modDIS 52.4%). When the analysis was conducted according to CIS topography, the modDIS criteria performed similarly in both optic neuritis and non-optic neuritis CIS. The addition of the optic nerve, assessed by VEP, as a fifth region in the current DIS criteria slightly improves the diagnostic performance because it increases sensitivity without losing specificity

Guia per a la prevenció i el control de les encefalopaties espongiformes transmissibles

Control sanitari; Malaltia de les vaques boges; Seguretat dels alimentsHealth control; Mad cow disease; Food safetyControl sanitario; Enfermedad de las vacas locas; Seguridad de los alimentosAquesta guia pretén ser, en el context actual, una eina de treball útil per a totes les persones relacionades professionalment amb aquestes malalties en diversos àmbits com la medicina, la veterinària, els laboratoris de diagnòstic i diverses disciplines de la salut pública (epidemiologia, seguretat alimentària, etc.). Per això s’ha comptat amb la col·laboració professional d’investigadors de reconegut prestigi en el món acadèmic i sanitari i de professionals vinculats a les accions operatives de control i prevenció

Association of Early Progression Independent of Relapse Activity With Long-term Disability After a First Demyelinating Event in Multiple Sclerosis

This cohort study investigates the long-term outcomes of patients who develop progression independent of relapse activity after a first demyelinating event in multiple sclerosis. What are the long-term outcomes of patients developing progression independent of relapse activity (PIRA) after a first demyelinating event in multiple sclerosis? In this longitudinal cohort study including 1128 patients with a first demyelinating event in multiple sclerosis, presenting with PIRA was associated with significantly shorter times to developing severe disability compared with not presenting with PIRA. Patients presenting with PIRA within the first 5 years of multiple sclerosis had a significantly 26-fold greater risk of developing severe disability than patients whose first PIRA appeared late in the disease. Results suggest that presenting with PIRA after a first demyelinating event in multiple sclerosis is an ominous prognosis, especially if it occurs early in the disease course. Progression independent of relapse activity (PIRA) is the main event responsible for irreversible disability accumulation in relapsing multiple sclerosis (MS). To investigate clinical and neuroimaging predictors of PIRA at the time of the first demyelinating attack and factors associated with long-term clinical outcomes of people who present with PIRA. This cohort study, conducted from January 1, 1994, to July 31, 2021, included patients with a first demyelinating attack from multiple sclerosis; patients were recruited from 1 study center in Spain. Patients were excluded if they refused to participate, had alternative diagnoses, did not meet protocol requirements, had inconsistent demographic information, or had less than 3 clinical assessments. Exposures included (1) clinical and neuroimaging features at the first demyelinating attack and (2) presenting PIRA, ie, confirmed disability accumulation (CDA) in a free-relapse period at any time after symptom onset, within (vs after) the first 5 years of the disease (ie, early/late PIRA), and in the presence (vs absence) of new T2 lesions in the previous 2 years (ie, active/nonactive PIRA). Expanded Disability Status Scale (EDSS) yearly increase rates since the first attack and adjusted hazard ratios (HRs) for predictors of time to PIRA and time to EDSS 6.0. Of the 1128 patients (mean [SD] age, 32.1 [8.3] years; 781 female individuals [69.2%]) included in the study, 277 (25%) developed 1 or more PIRA events at a median (IQR) follow-up time of 7.2 (4.6-12.4) years (for first PIRA). Of all patients with PIRA, 86 of 277 (31%) developed early PIRA, and 73 of 144 (51%) developed active PIRA. Patients with PIRA were slightly older, had more brain lesions, and were more likely to have oligoclonal bands than those without PIRA. Older age at the first attack was the only predictor of PIRA (HR, 1.43; 95% CI, 1.23-1.65; P <.001 for each older decade). Patients with PIRA had steeper EDSS yearly increase rates (0.18; 95% CI, 0.16-0.20 vs 0.04; 95% CI, 0.02-0.05; P < .001) and an 8-fold greater risk of reaching EDSS 6.0 (HR, 7.93; 95% CI, 2.25-27.96; P = .001) than those without PIRA. Early PIRA had steeper EDSS yearly increase rates than late PIRA (0.31; 95% CI, 0.26-0.35 vs 0.13; 95% CI, 0.10-0.16; P < .001) and a 26-fold greater risk of reaching EDSS 6.0 from the first attack (HR, 26.21; 95% CI, 2.26-303.95; P = .009). Results of this cohort study suggest that for patients with multiple sclerosis, presenting with PIRA after a first demyelinating event was not uncommon and suggests an unfavorable long-term prognosis, especially if it occurs early in the disease course

Automatic assessment of the 2-minute walk distance for remote monitoring of people with multiple sclerosis

The aim of this study was to investigate the feasibility of automatically assessing the 2-Minute Walk Distance (2MWD) for monitoring people with multiple sclerosis (pwMS). For 154 pwMS, MS-related clinical outcomes as well as the 2MWDs as evaluated by clinicians and derived from accelerometer data were collected from a total of 323 periodic clinical visits. Accelerometer data from a wearable device during 100 home-based 2MWD assessments were also acquired. The error in estimating the 2MWD was validated for walk tests performed at hospital, and then the correlation (r) between clinical outcomes and home-based 2MWD assessments was evaluated. Robust performance in estimating the 2MWD from the wearable device was obtained, yielding an error of less than 10% in about two-thirds of clinical visits. Correlation analysis showed that there is a strong association between the actual and the estimated 2MWD obtained either at hospital (r = 0.71) or at home (r = 0.58). Furthermore, the estimated 2MWD exhibits moderate-to-strong correlation with various MS-related clinical outcomes, including disability and fatigue severity scores. Automatic assessment of the 2MWD in pwMS is feasible with the usage of a consumer-friendly wearable device in clinical and non-clinical settings. Wearable devices can also enhance the assessment of MS-related clinical outcomes