A Search for New Biological Pathways in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy by Proteomic Research.

Background/Objectives: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary small vessel disease leading to significant morbidity and mortality. Despite advances in genetic diagnosis, the underlying pathophysiology remains incompletely understood. Proteomic studies offer insights into disease mechanisms by identifying altered protein expression patterns. Here, we conducted a proteomic analysis to elucidate molecular pathways associated with CADASIL. Methods: We enrolled genetically diagnosed CADASIL patients and healthy, genetically related controls. Plasma samples were subjected to proteomic analysis using the Olink platform, measuring 552 proteins across six panels. The data were analyzed from several approaches by using three different statistical methods: Exploratory Principal Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA), differential expression with moderated t-test, and gene set enrichment analysis (GSEA). In addition, bioinformatics analysis, including volcano plot, heatmap, and Variable Importance on Projection (VIP) scores from the PLS-DA model were drawn. Results: Significant differences in protein expression were observed between CADASIL patients and controls. RSPO1 and FGF-19 exhibited elevated levels (p < 0.05), while PPY showed downregulation (p < 0.05) in CADASIL patients, suggesting their involvement in disease pathogenesis. Furthermore, MIC-A/B expression varied significantly between patients with mutations in exon 4 versus exon 11 of the NOTCH3 gene (p < 0.05), highlighting potential immunological mechanisms underlying CADASIL. We identified altered pathways using GSEA, applied after ranking the study data. Conclusions: Our study provides novel insights into the proteomic profile of CADASIL, identifying dysregulated proteins associated with vascular pathology, metabolic dysregulation, and immune activation. These findings contribute to a deeper understanding of CADASIL pathophysiology and may inform the development of targeted therapeutic strategies. Further research is warranted to validate these biomarkers and elucidate their functional roles in disease progression.

Stroke-associated pneumonia according to mCDC criteria: impact on prognosis and antibiotic therapy.

Objective: The modified Centers for Disease Control and Prevention (mCDC) criteria have been proposed for diagnosing and managing stroke-associated pneumonia (SAP). The objective was to investigate the impact of SAP on stroke outcome depending on whether or not it conforms to mCDC criteria. Our secondary objective was to identify the responsible factors for antibiotic initiation in stroke patients. Methods: We conducted a prospective, multicenter, observational study of ischemic stroke patients with moderate to severe stroke (NIHSS≥4) admitted within 24 h. For 7 days, mCDC criteria were assessed daily, and infections and antibiotics were recorded. Pneumonias were divided into those fulfilling mCDC criteria (mCDC-SAP) or not (other pneumonias, OPn). The effect of each type of pneumonia on 3-month outcome was evaluated in separated logistic regression models. Factors associated with antibiotic initiation were explored using a random forest analysis. Results: Of the 342 patients studied, infections were diagnosed in 72 (21.6%), including 39 (11.7%) cases of pneumonia. Of them, 25 (7.5%) fulfilled mCDC criteria. Antibiotics were used in 92% of mCDC-SAP and 64.3% of OPn. In logistic regression analysis, mCDC-SAP, but not OPn, was an independent predictor of poor outcome [OR, 4.939 (1.022-23.868)]. The random forest analysis revealed that fever had the highest importance for antibiotic initiation. Interpretation: The mCDC criteria might be useful for detecting clinically relevant SAP, which is associated with poor outcomes. Isolated signs of infection were more important for antibiotic initiation than compliance with pre-defined criteria. Therefore, adherence to mCDC criteria might result in antibiotic saving without compromising clinical outcome.

Uncovering the neurological effects of West Nile virus during a record-breaking southern Spain outbreak in 2020-2021.

The 2020-21 West Nile Virus (WNV) outbreak in Andalusia, Spain, was the largest reported in the country, with eight cases of West Nile Neuroinvasive Disease (WNND) diagnosed in a tertiary hospital. Diagnosis of WNND is based on detecting WNV RNA, viral isolation, or demonstrating a specific immune response against the virus, with additional tests used to support the diagnosis. Treatment remains supportive, with variable outcomes. The potential efficacy of plasma exchange (PLEX) in select cases raises the possibility of an autoimmune component secondary to infectious pathology of the central nervous system. The influence of climate change on the expansion of WNV into new regions is a significant concern. It is crucial for physicians practicing in high-risk areas to be knowledgeable about the disease for early prevention and effective control measures.

Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.

We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population controls) and different aetiological subtypes. Polygenic risk scores (PRSs) for each subtype were generated and tested in the IS-COV cohort using PRSice-2 and PLINK to find genetic associations. Both analyses used the IS-COV cohort and GWAS from MEGASTROKE (67,162 stroke patients vs. 454,450 population controls), GIGASTROKE (110,182 vs. 1,503,898), and the NINDS Stroke Genetics Network (16,851 vs. 32,473). Three genomic regions were associated (p-value < 0.05) with large artery atherosclerosis (LAA) and cardioembolic stroke (CES). We found four loci targeting the genes PITX2 (rs10033464, IS-COV beta = 0.04, p-value = 2.3 × 10-2, se = 0.02), previously associated with CES, HS6ST1 (rs4662630, IS-COV beta = -0.04, p-value = 1.3 × 10-3, se = 0.01), TMEM132E (rs12941838 IS-COV beta = 0.05, p-value = 3.6 × 10-4, se = 0.01), and RFFL (rs797989 IS-COV beta = 0.03, p-value = 1.0 × 10-2, se = 0.01). A statistically significant PRS was observed for LAA. Our results suggest that IS-COV cases are genetically similar to LAA and CES subtypes. Larger cohorts are needed to assess if the genetic factors in IS-COV cases are shared with the general population or specific to viral infection.

Association of candidate genetic variants and circulating levels of ApoE/ApoJ with common neuroimaging features of cerebral amyloid angiopathy.

Introduction: Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid-ß (Aß) in brain vessels and is a main cause of lobar intracerebral hemorrhage (ICH) in the elderly. CAA is associated with magnetic resonance imaging (MRI) markers of small vessel disease (SVD). Since Aß is also accumulated in Alzheimer's disease (AD) in the brain parenchyma, we aimed to study if several single nucleotide polymorphisms (SNPs) previously associated with AD were also associated with CAA pathology. Furthermore, we also studied the influence of APOE and CLU genetic variants in apolipoprotein E (ApoE) and clusterin/apolipoprotein J (ApoJ) circulating levels and their distribution among lipoproteins. Methods: The study was carried out in a multicentric cohort of 126 patients with lobar ICH and clinical suspicion of CAA. Results: We observed several SNPs associated with CAA neuroimaging MRI markers [cortical superficial siderosis (cSS), enlarged perivascular spaces in the centrum semiovale (CSO-EPVS), lobar cerebral microbleeds (CMB), white matter hyperintensities (WMH), corticosubcortical atrophy and CAA-SVD burden score]. Concretely, ABCA7 (rs3764650), CLU (rs9331896 and rs933188), EPHA1 (rs11767557), and TREML2 (rs3747742) were significantly associated with a CAA-SVD burden score. Regarding circulating levels of apolipoproteins, protective AD SNPs of CLU [rs11136000 (T) and rs9331896 (C)] were significantly associated with higher HDL ApoJ content in the lobar ICH cohort. APOEε2 carriers presented higher plasma and LDL-associated ApoE levels whereas APOEε4 carriers presented lower plasma ApoE levels. Additionally, we observed that lower circulating ApoJ and ApoE levels were significantly associated with CAA-related MRI markers. More specifically, lower LDL-associated ApoJ and plasma and HDL-associated ApoE levels were significantly associated with CSO-EPVS, lower ApoJ content in HDL with brain atrophy and lower ApoE content in LDL with the extent of cSS. Discussion: This study reinforces the relevance of lipid metabolism in CAA and cerebrovascular functionality. We propose that ApoJ and ApoE distribution among lipoproteins may be associated with pathological features related to CAA with higher ApoE and ApoJ levels in HDL possibly enhancing atheroprotective, antioxidative, and anti-inflammatory responses in cerebral ß-amyloidosis.

The cognitive and psychiatric subacute impairment in severe Covid-19.

Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A principal component analysis extracted the main independent characteristics of the syndrome. 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases.

High prevalence of obstructive sleep apnea syndrome in Spain's Stroke Belt.

OBJECTIVE: Spain's so-called Stroke Belt is an area with high prevalence of vascular disease. We aimed to determine the prevalence of undetected obstructive sleep apnea-hypopnea syndrome (OSAHS) among patients with acute ischemic stroke (AIS) in southern Spain. METHODS: We conducted a cross-sectional study at the Virgen Macarena University Hospital Stroke Unit during 2018 to 2019. We included patients <72 hours after AIS with a neuroimaging lesion and performed sleep tests. RESULTS: Seventy-two patients were included. The median participant age was 72 years. Mean body mass index was 27.07 kg/m2, and 40.28% were daily alcohol drinkers. Hypertension, atrial fibrillation, ischemic cardiomyopathy, and previous stroke were detected in 63.9%, 11.1%, 15.3%, and 17.6% of patients, respectively. Polygraphy was feasible in 91.38% of patients. The prevalence of OSAHS was 84.72% (apnea-hypopnea index ≥5). Patients with moderate and severe OSAHS were more likely to be obese and to have a larger neck circumference and facial palsy. The diagnostic criteria of central sleep apnea syndrome were met in only 1.38% of patients. CONCLUSIONS: The high prevalence of OSAHS found in the Spanish Stroke Belt justifies further investigation and development of a screening program as a strategy to identify patients with undetected OSAHS.

Central nervous system involvement in adult-onset relapsing hemophagocytic lymphohistiocytosis responsive to maintenance treatment with anakinra.

A 43 year-old male presented with a relapsing and progressive systemic inflammatory disorder with central nervous system (CNS) involvement. After a two years follow up, he was diagnosed with hemophagocytic lymphohistiocytosis (HLH), based on clinical, laboratory and radiological findings. Treatment was started with anakinra, a recombinant humanised interleukin-1 (IL-1) receptor antagonist. Clinical response was good. Laboratory and radiological findings showed no disease activity throughout a five years follow-up period. Several immunosuppressive agents have been used in HLH without any good outcomes. This is the first case report of HLH with CNS involvement responsive to chronic treatment with anakinra.

Lessons learned from proteome analysis of perinatal neurovascular pathologies.

INTRODUCTION: Perinatal and pediatric diseases related to neurovascular disorders cause significant problems during life, affecting a population with a long life expectancy. Early diagnosis and assessment of the severity of these diseases are crucial to establish an appropriate neuroprotective treatment. Currently, physical examination, neuroimaging and clinical judgment are the main tools for diagnosis, although these tests have certain limitations. There is growing interest in the potential value of noninvasive biomarkers that can be used to monitor child patients at risk of brain damage, allowing accurate, and reproducible measurements. AREAS COVERED: This review describes potential biomarkers for the diagnosis of perinatal neurovascular diseases and discusses the possibilities they open for the classification and treatment of neonatal neurovascular diseases. EXPERT OPINION: Although high rates of ischemic and hemorrhagic stroke exist in pediatric populations, most studies have focused on biomarkers of hypoxic-ischemic encephalopathy. Inflammatory and neuronal biomarkers such as S-100B and GFAP, in combination with others yet to be discovered, could be considered as part of multiplex panels to diagnose these diseases and potentially for monitoring response to treatments. Ideally, noninvasive biofluids would be the best source for evaluating these biomarkers in proteomic assays in perinatal patients.

[Review on the improvements in communication skills among aphasic patients through the use of portable technology.] / Revisión sobre las mejoras en la comunicación de los pacientes afásicos gracias al uso de aplicaciones digitales.

BACKGROUND: Stroke is an abrupt interruption of brain circulation that constitutes a neurological emergency. Aphasia is a language disorder caused by stroke. It can affect patients' reading, writing, comprehension and expression. The aim of the study is to find out if the use of the latest portable technologies such as tablets, computers and mobile phones can help to improve the rehabilitation of patients with aphasia. METHODS: A literature review has been carried out on the main databases; Pubmed, Scopus and Cinahl, of articles in english and spanish published between june and december 2019 following the PRISMA methodology. RESULTS: Sixty-two articles were included in which the use of technologies alongside traditional rehabilitation therapies showed that might improve the recovery of aphasic patients. Most studies have a sample size of less than fifty patients (21.7%), with only three publications having a sample size of more than 150 patients (1.86%). CONCLUSIONS: The review shows that the use of digital applications might improve aphasia rehabilitation in patients who have suffered a stroke, but more studies are needed due to the small sample size of those conducted so far and to explore whether that improvement hold up over time.

OBJETIVO: El ictus es una interrupción brusca de la circulación cerebral que constituye una urgencia neurológica. La afasia es un trastorno del lenguaje provocado por el ictus, el cual puede afectar a la lectura, la escritura, la comprensión y la expresión de los pacientes. El objetivo del estudio es saber si el uso de las aplicaciones digitales desarrolladas en las tecnologías más recientes como son tabletas, ordenadores y teléfonos móviles pueden ayudar a mejorar la rehabilitación de los pacientes con afasia. METODOS: Se realizó una revisión bibliográfica en las principales bases de datos (Pubmed, Scopus y Cinahl) de artículos en inglés y español publicados entre junio y diciembre de 2019 siguiendo la metodología PRISMA. RESULTADOS: Se incluyeron 62 artículos, en los que se mostró que el uso de las aplicaciones digitales, junto a las terapias tradicionales de rehabilitación, podría mejorar la recuperación de los pacientes afásicos. La mayoría de los estudios tenían un tamaño muestral inferior a cincuenta pacientes, (21,7%) habiendo sólo tres publicaciones que tuvieran un tamaño muestral superior a 150 pacientes (1,86%). CONCLUSIONES: La revisión muestra que el uso de aplicaciones digitales es una ayuda para la rehabilitación de la afasia en pacientes que han sufrido un ictus, pero son necesarios más estudios debido al bajo tamaño muestral de los que se han realizado, y para comprobar si esas mejorías se mantienen en el tiempo.

Revisión sobre las mejoras en la comunicación de los pacientes afásicos gracias al uso de aplicaciones digitales / Review on the improvements in communication skills among aphasic patients through the use of portable technology

OBJETIVO: El ictus es una interrupción brusca de la circulación cerebral que constituye una urgencia neurológica. La afasia es un trastorno del lenguaje provocado por el ictus, el cual puede afectar a la lectura, la escritura, la comprensión y la expresión de los pacientes. El objetivo del estudio es saber si el uso de las aplicaciones digitales desarrolladas en las tecnologías más recientes como son tabletas, ordenadores y teléfonos móviles pueden ayudar a mejorar la rehabilitación de los pacientes con afasia. MÉTODOS: Se realizó una revisión bibliográfica en las principales bases de datos (Pubmed, Scopus y Cinahl) de artículos en inglés y español publicados entre junio y diciembre de 2019 siguiendo la metodología PRISMA. RESULTADOS: Se incluyeron 62 artículos, en los que se mostró que el uso de las aplicaciones digitales, junto a las terapias tradicionales de rehabilitación, podría mejorar la recuperación de los pacientes afásicos. La mayoría de los estudios tenían un tamaño muestral inferior a cincuenta pacientes, (21,7%) habiendo sólo tres publicaciones que tuvieran un tamaño muestral superior a 150 pacientes (1,86%). CONCLUSIONES: La revisión muestra que el uso de aplicaciones digitales es una ayuda para la rehabilitación de la afasia en pacientes que han sufrido un ictus, pero son necesarios más estudios debido al bajo tamaño muestral de los que se han realizado, y para comprobar si esas mejorías se mantienen en el tiempo

BACKGROUND: Stroke is an abrupt interruption of brain circulation that constitutes a neurological emergency. Aphasia is a language disorder caused by stroke. It can affect patients' reading, writing, comprehension and expression. The aim of the study is to find out if the use of the latest portable technologies such as tablets, computers and mobile phones can help to improve the rehabilitation of patients with aphasia. METHODS: A literature review has been carried out on the main databases; Pubmed, Scopus and Cinahl, of articles in english and spanish published between june and december 2019 following the PRISMA methodology. RESULTS: Sixty-two articles were included in which the use of technologies alongside traditional rehabilitation therapies showed that might improve the recovery of aphasic patients. Most studies have a sample size of less than fifty patients (21.7%), with only three publications having a sample size of more than 150 patients (1.86%). CONCLUSIONS: The review shows that the use of digital applications might improve aphasia rehabilitation in patients who have suffered a stroke, but more studies are needed due to the small sample size of those conducted so far and to explore whether that improvement hold up over time

Espectro clínico del SUNCT y de la neuralgia trigeminal secundarios: un abordaje multidisciplinar desde urgencias / Clinical spectrum of associated SUNCT (shortlasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) and trigeminal neuralgia: a multidisciplinary approach in the emergency department

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Agrupación de casos de síndrome de Guillain-Barré atípico: ¿es necesario redefinir los criterios diagnósticos y los protocolos microbiológicos? / Atypical Guillain-Barré syndrome clustering: is it necessary to reconsider the diagnostic criteria and microbiological protocol?

Introducción. El síndrome de Guillain-Barré se define clásicamente como una polirradiculopatía aguda simétrica ascendente, si bien existen variantes atípicas que dificultan el diagnóstico. Casos clínicos. Se recogen las historias clínicas de seis pacientes de nuestra área hospitalaria durante el primer trimestre de 2013. Se han realizado punciones lumbares, electroneurograma-electromiograma y analíticas con autoinmunidad en todos los casos. El conjunto de la muestra destaca por la presencia de características atípicas, como hiporreflexia tardía, mayor frecuencia de asimetría y afectación distal, así como fiebre inicial. Desde el punto de vista neurofisiológico, todos los pacientes presentan formas axonales de tipo sensitivomotoras y las alteraciones de la onda F son el dato más precoz. Se identifica una variante de síndrome de Miller Fisher asociada a paresia faciocervicobraquial y síndrome de vasoconstricción cerebral reversible. Otro caso aúna las variantes de paresia braquial bilateral y polirradiculopatía lumbar en el contexto de infección aguda por influenza A. La variante saltatoria ha sido demostrada en otro paciente. Todos los pacientes han recibido tratamiento con inmunoglobulinas, y en dos de ellos se sumó la plasmaféresis como terapia adicional. Conclusiones. La agrupación de seis casos axonales con características clínicas atípicas justifica la necesidad del conocimiento de estas variantes para lograr un diagnóstico y un tratamiento precoz. La hiporreflexia tardía y las formas faciocervicobraquiales, saltatorias y lumbares deben considerarse dentro del espectro del síndrome de Guillain-Barré. El estudio etiológico debe incluir el cribado de numerosos patógenos, entre los que debe incluirse el virus influenza (AU)

Introduction. Guillain-Barré syndrome is classically defined as a symmetrical ascending acute polyradiculoneuropathy, although there are atypical variants that make diagnosis difficult. CASE REPORTS. The medical data of six patients in our hospital area are collected during the first quarter of 2013. Lumbar punctures, imaging, neurophysiological studies, ganglioside antibodies and serologies have been proposed in all cases. We focus on the atypical features as late hyporeflexia, increased frequency of asymmetry and distal paresis and initial fever. From a neurophysiological point of view, all patients presented sensorimotor axonal forms. The most consistent datas in early studies is the F wave’s alteration. A Miller Fisher variant associated with faciocervicobraquial paresis and cerebral reversible vasoconstriction syndrome has been detected. A bilateral brachial paresis and lumbar polyradiculopathy in the context of influenza A infection is other interesting case. The saltatory variant with cranial nerve involvement and lower limbs paresis has been demonstrated in one patient. Bands in cerebrospinal fluid are positive in three cases and anti-ganglioside antibodies in one patient. The syndrome of inappropriate secretion of antidiuretic hormone may explain some of the hyponatremias registered. The first line of treatment are inmunoglobulins in all patients. Plasmapheresis exchanges has been used as an additional therapy in four cases. Conclusions. These clusters of six axonal cases with atypical clinical features justifies the need for knowledge of these variants in order to achieve an early treatment. Late hyporeflexia and brachialfaciocervico, saltatory and lumbar forms should be considered in the spectrum of Guillain-Barré syndrome. The etiological study should rule out a lots of pathogens as influenza (AU)