Serum biomarkers at disease onset for personalized therapy in multiple sclerosis.

The potential of combining serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels to predict disability worsening in multiple sclerosis (MS) remains underexplored. We aimed to investigate whether sNfL and sGFAP values identify distinct subgroups of patients according to the risk of disability worsening and their response to disease-modifying treatments (DMTs). This multicentre study, conducted across thirteen European hospitals, spanned from July 15, 1994, to August 18, 2022, with follow-up until September 26, 2023. We enrolled MS patients who had serum samples collected within 12 months from disease onset and before initiating DMTs. Multivariable regression models were used to estimate the risk of relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and Expanded Disability Status Scale (EDSS) score of 3. Of the 725 patients included, median age was 34.2 years (IQR, 27.6-42.4), and 509 patients (70.2%) were female. Median follow-up duration was 6.43 years (IQR, 4.65-9.81). Higher sNfL values associated with an elevated risk of RAW (HR of 1.45; 95% CI 1.19-1.76; P < 0.001), PIRA (HR of 1.43; 95% CI 1.13-1.81; P = 0.003), and reaching an EDSS of 3 (HR of 1.55; 95% CI 1.29-1.85; P < 0.001). Moreover, higher sGFAP levels were linked to a higher risk of achieving an EDSS score of 3 (HR of 1.36; 95% CI 1.06-1.74; P = 0.02) and, in patients with low sNfL values, to PIRA (HR of 1.86; 95% CI 1.01-3.45; P = 0.04). We further examined the combined effect of sNfL and sGFAP levels. Patients with low sNfL and sGFAP values (NLGL) exhibited a low risk of all outcomes and served as reference. Untreated patients with high sNfL levels showed a higher risk of RAW, PIRA, and reaching an EDSS of 3. Injectable or oral DMTs reduced the risk of RAW in these patients but failed to mitigate the risk of PIRA and reaching an EDSS of 3. Conversely, high-efficacy DMTs counteracted the heightened risk of these outcomes, except for the risk of PIRA in patients with high sNfL and sGFAP levels. Patients with low sNfL and high sGFAP values (NLGH) showed an increased risk of PIRA and achieving an EDSS of 3, which remained unchanged with either high-efficacy or other DMTs. In conclusion, evaluating sNfL and sGFAP levels at disease onset in MS may identify distinct phenotypes associated with diverse immunological pathways of disability acquisition and therapeutic response.

The T1-dark-rim: A novel imaging sign for detecting smoldering inflammation in multiple sclerosis.

PURPOSE: Paramagnetic rim lesions (PRLs), usually identified in susceptibility-weighted imaging (SWI), are a promising prognostic biomarker of disability progression in multiple sclerosis (MS). However, SWI is not routinely performed in clinical practice. The objective of this study is to define a novel imaging sign, the T1-dark rim, identifiable in a standard 3DT1 gradient-echo inversion-recovery sequence, such as 3D T1 turbo field echo (3DT1FE) and explore its performance as a SWI surrogate to define PRLs. METHODS: This observational cross-sectional study analyzed MS patients who underwent 3T magnetic resonance imaging (MRI) including 3DT1TFE and SWI. Rim lesions were evaluated in 3DT1TFE, processed SWI, and SWI phase and categorized as true positive, false positive, or false negative based on the value of the T1-dark rim in predicting SWI phase PRLs. Sensitivity and positive predictive values of the T1-dark rim for detecting PRLs were calculated. RESULTS: Overall, 80 rim lesions were identified in 63 patients (60 in the SWI phase and 78 in 3DT1TFE; 58 true positives, 20 false positives, and two false negatives). The T1-dark rim demonstrated 97% sensitivity and 74% positive predictive value for detecting PRLs. More PRLs were detected in the SWI phase than in processed SWI (60 and 57, respectively). CONCLUSION: The T1-dark rim sign is a promising and accessible novel imaging marker to detect PRLs whose high sensitivity may enable earlier detection of chronic active lesions to guide MS treatment escalation. The relevance of T1-dark rim lesions that are negative on SWI opens up a new field for analysis.

Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS). METHODS: Sixty-eight patients with PPMS from 12 European MS centers were included in the study. Serum and CSF levels of a panel of complement components (CCs) were measured by multiplex enzyme-linked immunosorbent assay at a baseline time point (i.e., sampling). Mean (SD) follow-up time from baseline was 9.6 (4.8) years. Only one patient (1.5%) was treated during follow-up. Univariable and multivariable logistic regressions adjusted for age, sex, and albumin quotient were performed to assess the association between baseline CC levels and disability progression in short term (2 years), medium term (6 years), and long term (at the time of the last follow-up). RESULTS: In short term, CC played little or no role in disability progression. In medium term, an elevated serum C3a/C3 ratio was associated with a higher risk of disability progression (adjusted OR 2.30; 95% CI 1.17-6.03; p = 0.040). By contrast, increased CSF C1q levels were associated with a trend toward reduced risk of disability progression (adjusted OR 0.43; 95% CI 0.17-0.98; p = 0.054). Similarly, in long term, an elevated serum C3a/C3 ratio was associated with higher risk of disability progression (adjusted OR 1.81; 95% CI 1.09-3.40; p = 0.037), and increased CSF C1q levels predicted lower disability progression (adjusted OR 0.41; 95% CI 0.17-0.86; p = 0.025). DISCUSSION: Proteins involved in the activation of early complement cascades play a role in disability progression as risk (elevated serum C3a/C3 ratio) or protective (elevated CSF C1q) factors after 6 or more years of follow-up in patients with PPMS. The protective effects associated with C1q levels in CSF may be related to its neuroprotective and anti-inflammatory properties.

Clinical characteristics and impact on patient-reported outcomes and quality of life of people with ambulatory secondary progressive multiple sclerosis: Discover study.

BACKGROUND: People with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population. METHODS: DISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected. RESULTS: A total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6-6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score. Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs. CONCLUSIONS: PwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs.

Biomarcadores en esclerosis múltiple / Biomarkers in multiple sclerosis

La esclerosis múltiple es la enfermedad neurológica discapacitante más frecuente en adultos jóvenes. En su desarrollo intervienen procesos independientes de inflamación, desmielinización, neurodegeneración, gliosis y reparación, responsables de la heterogeneidad y variabilidad individual en la expresión de la enfermedad, del pronóstico y de la respuesta al tratamiento. Como parte de la medicina personalizada, los avances en la búsqueda de nuevos biomarcadores han identificado candidatos prometedores que pueden resultar de utilidad para el diagnóstico precoz de la enfermedad, para detectar perfiles pronósticos y evolutivos de la enfermedad, y para monitorizar la respuesta al tratamiento. Lamentablemente, pocos de ellos se han validado adecuadamente, lo cual impide su aplicación en la práctica clínica. Dados los últimos resultados, los expertos recomiendan un giro en la investigación, no tanto hacia el descubrimiento de nuevas moléculas o técnicas de imagen, sino hacia una validación clínica de estos marcadores, con el objetivo de promover la investigación translacional. Esta revisión ofrece una actualización de la información disponible acerca de los biomarcadores en esclerosis múltiple actualmente validados y potencialmente candidatos, y su utilidad en el diagnóstico, pronóstico, evaluación de la progresión de la discapacidad ocasionada por la enfermedad y de la respuesta terapéutica (AU)

Multiple sclerosis is the most frequent disabling neurological disease in young adults. Its development includes independent processes of inflammation, demyelination, neurodegeneration, gliosis and repair, which are responsible for the heterogeneity and individual variability in the expression of the disease, its prognosis and response to treatment. As part of personalised medicine, the progress made in the search for new biomarkers has identified promising candidates that may be useful for the early diagnosis of the disease, for detecting prognostic and developmental profiles of the disease, and for monitoring the response to treatment. Unfortunately, few of them have been validated adequately, which prevents them from being applied in clinical practice. In view of the latest findings, the experts recommend orienting research in another direction, not so much towards the discovery of new molecules or imaging techniques, but instead towards a clinical validation of these markers, with the aim of fostering translational research. This review offers an update on the information about the biomarkers in multiple sclerosis that have currently been validated and are thus potential candidates, as well as looking at their value in the diagnosis, prognosis, evaluation of the development of the disability caused by the disease and the response to therapy (AU)

Pupila del jardinero / Gardener pupil

No disponible

Encefalitis herpética. Falsos negativos de la reacción en cadena de la polimerasa en líquido cefalorraquídeo / False-negative polymerase chain reaction test in cerebrospinal fluid in herpes simplex encephalitis

No disponible

Neuropatía trigeminal bilateral por neurosarcoidosis: hallazgos clínicos, radiológicos y neurofisiológicos distintivos / Bilateral trigeminal neuropathy in neurosarcoidosis: clinical, radiological and neurophysiological distinctive findings

No disponible

Absceso cerebral del adulto por Listeria monocytogenes: presentación de 6 casos y revisión de la literatura médica / Brain abscess due to Listeria monocytogenes in adults: Six cases and review of the literature

Introducción Listeria monocytogenes es un bacilo grampositivo, con especial tropismo por el sistema nervioso central (SNC). El absceso cerebral por Listeria es una entidad insuficientemente conocida, a pesar de que representa el 10% de las infecciones del SNC por este microorganismo. Métodos A continuación se presentan 6 pacientes con absceso cerebral por L. monocytogenes que ingresaron de forma consecutiva en el Hospital Universitario de Bellvitge durante los últimos 7 años. Se revisa también la literatura médica de los últimos 40 años hallando 70 pacientes con absceso cerebral por Listeria. Se describen las características epidemiológicas, clínicas, microbiológicas, radiológicas y evolutivas. Resultados El absceso cerebral por Listeria es una entidad de mal pronóstico y con elevada mortalidad. Conclusión Se requiere un elevado índice de sospecha para su detección precoz y tratamiento antibiótico correcto que redunde en una mejor evolución. La sospecha debe fundamentarse en la presencia de fiebre o febrícula junto con focalidad neurológica, sobre todo en pacientes inmunodeprimidos o diabéticos (AU)

Introduction Listeria monocytogenes is a gram-positive bacillus, with special tropism for the central nervous system (CNS). Brain abscess caused by Listeria has not been extensively studied, although it accounts for 10% of CNS infections due to this microorganism. Methods We present 6 patients with Listeria brain abscess consecutively admitted to Bellvitge University Hospital over the last 7 years. A literature review covering 40 years retrieved 70 patients with Listeria brain abscess. The epidemiologic, clinical, microbiological, and radiological findings related to this entity, and the outcome features are described. Results Brain abscess due to Listeria has a poor prognosis and is associated with elevated mortality. Conclusion A high index of suspicion is needed to reach an early diagnosis and establish appropriate antibiotic treatment, which will improve the outcome of this condition. Suspicion is based on the presence of fever and neurological symptoms, particularly in immunodepressed or diabetic patients (AU)

Peripheral facial palsy after varicella. Report of two cases and review of the literature

Background There is little information regarding peripheral facial palsy (PFP) as a complication of varicella. We describe 2 adults who developed varicella-related PFP, in 1 case as a part of Guillain-Barré syndrome (GBS), and review all reported cases of this condition. Methods MEDLINE search. ResultsA total of 10 cases of isolated varicella-associated PFP have been reported. PFP was diagnosed 3 to 16 days after the onset of skin manifestations. Four (40%) patients developed bilateral PFP. Two patients had varicella meningitis; both were PCR-positive for varicella-zoster virus (VZV) in CSF. CSF IgG antibodies against VZV were demonstrated in 2 other patients. One patient had slight CSF albumino-cytological dissociation. Five patients were treated with acyclovir, and 3 of them also received corticosteroids. Most patients showed a favorable course, with partial or complete recovery of PFP. Results In addition, 17 patients with GBS after the onset of varicella were reviewed. Mean time to the development of GBS after varicella onset was 9.3 days, and 9 patients had PFP as a part of the neurologic picture. Seven patients (41%) developed respiratory failure requiring mechanical ventilation. Six patients received treatment with intravenous immunoglobulin, and all of them showed optimal evolution. One patient died. Conclusions Isolated PFP and GBS are rare peripheral nerve complications after varicella. Treatment should be individualized for each case, depending on the severity of the condition and the clinical evolution (AU)

Antecedentes Existe escasa información referente a la parálisis facial periférica (PFP) como complicación posvaricela. En este artículo se describen 2 casos, uno de ellos en relación al Sd. de Guillain-Barré (SGB) y se revisa lo descrito anteriormente en la literatura. Métodos Revisión en MEDLINE. Resultados Se han descrito 10 casos de PFP relacionada con varicela. La PFP se ha diagnosticado de 3 a 16 días después de la aparición de las lesiones cutáneas. Cuatro (40%) pacientes desarrollaron PFP bilateral. Dos pacientes tuvieron meningitis por varicela, ambos tenían PCR de virus varicella-zoster positivo en LCR. Se documentó la presencia de anticuerpos Ig G en LCR frente VZV en otros 2 pacientes. Un paciente tenía disociación albúmino-citológica en LCR. Cinco pacientes fueron tratados con aciclovir y 3, concomitantemente, con corticoides. La mayoría de pacientes mostró una buena evolución, con una resolución total o parcial de la PFP. A su vez, analizamos 17 pacientes con pacientes SGB después de varicela. El tiempo medio de desarrollo el SGB fue de 9,3 días. Nueve pacientes presentaron PFP en relación con el episodio de SGB. Siete (41%) pacientes presentaron insuficiencia respiratoria grave que precisó de ventilación mecánica. Seis pacientes recibieron tratamiento con inmunoglobulinas, todos ellos con una buena evolución. Un paciente falleció. Conclusiones La PFP y el SGB son complicaciones poco frecuentes de después de la varicela. El tratamiento se debe individualizar en cada caso, dependiendo de la gravedad y la evolución clínica (AU)

Encefalitis herpética del adulto: experiencia de 15 años / Adult herpes simplex encephalitis: Fifteen years’ experience

Introduction: Herpes simplex encephalitis (HSE) is the most frequent cause of sporadic necrotizing encephalitis in adults. The aim of this study is to describe the characteristics of HSE and the factors influencing its outcome. Material and methods: Retrospective study of patients diagnosed with HSE in a tertiary care teaching hospital over a 15-year period. Diagnosis was based on a consistent clinical profile for HSE, plus either a PCR-positive CSF HSV study or consistent brain neuroimaging findings. Patients were divided into 2 groups according to the modified Rankin Scale: good outcome (Grades ≤2) and poor outcome (Grades ≥3).Results: Thirty-five patients were included. Mean age was 53.9 years. More than half presented febricula or fever, headache, disorientation, behavioral changes, decreased level of consciousness, or neurological deficit. CSF glucose concentration was normal in all patients and WBC count was normal in 8 (23%). PCR for HSV was positive in 92% and cranial MRI was suggestive of HSE in 100% of patients. Mortality was 8.6%. In relation to outcome, age (OR=1.079; 95% CI, 1.023–1.138) and serum albumin level at admission (OR=0.87; 95% CI, 0.794–0.954) were independent prognostic factors at discharge. At 6 months, days of fever after initiation of acyclovir therapy (OR=1.219; 95% CI, 1.046–1.422) and serum albumin level at admission (OR=0.917; 95% CI, 0.87–0.967) were independent prognostic factors.Conclusions: Normal brain MRI or detection of low CSF glucose concentration requires consideration of diagnoses other than HSE. Age, serum albumin level at admission, and days of fever after initiation of acyclovir therapy were independent prognostic factors of the disease (AU)

Introducción: la encefalitis herpética (EH) es la causa más frecuente de encefalitis necrosante esporádica del adulto. El objetivo es describir las características de la EH y sus factores pronósticos. Material y métodos: estudio retrospectivo de los pacientes ingresados en un hospital universitario de tercernivel y diagnosticados de EH durante un periodo de 15 años. El diagnóstico se estableció según el cuadro clínico compatible, junto con una prueba de reacción en cadena de la polimerasa(PCR) positiva para el virus del herpes simple (VHS) y/o una prueba de neuro imagen compatible. Se dividió a los pacientes en dos grupos de acuerdo con la Escala de Rankin modificada: buen pronóstico (grados p2) y mal pronóstico(grados X3).Resultados: se estudió a un total de 35 pacientes con una media de edad de 53,9 años. La mayoría presentaba febrícula o fiebre, cefalea, desorientación, alteración conductual, disminución del nivel deconciencia o focalidad neurológica. Todos los pacientes presentaron normoglucorraquia y el recuento leucocitario en el líquido cefalorraquídeo fue normal en 8 (23%)pacientes. La PCR para VHS resultó positiva en el 92% y la resonancia magnética (RM) craneal fue compatible con EH en el 100% de los pacientes. La mortalidad fue del 8,6%. La edad (odds ratio [OR] ¼ 1,079; intervalo de confianza [IC]del 95%, 1,023–1,138) y las concentraciones de seroalbúmina al ingreso (OR ¼ 0,87; IC del 95%, ,0,794–0,954) resultaron factores pronósticos independientes al alta. A los 6 meses, los días de fiebre después de la instauración del tratamiento con aciclovir (OR ¼ 1,219; ICdel95%, 1,046–1,422) y las concentraciones de seroalbúmina al ingreso (OR ¼ 0,917; IC del 95%, 0,87–0,967) resultaron factores pronósticos independientes (AU)

Absceso cerebral por Eikenella corrodens y Streptococcus intermedius asociado a tumor carcinoide del tubo digestivo / Brain abscess caused by Eikenella corrodens and Streptococcus intermedius associated wit bowel carcinoid tumour

No disponible