MR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and ...brain tumors. MRgFUS could become a therapeutic tool for drug delivery of putative neurorestorative therapies. Treatment for Parkinson's disease with dementia (PDD) is an important unmet need. We initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility phase I clinical trial (NCT03608553), which is still in progress. The primary outcomes of the study were to demonstrate the safety, feasibility and reversibility of BBB disruption in PDD, targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. Changes in β-amyloid burden, brain metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements. Five patients were recruited from October 2018 until May 2019, and received two treatment sessions separated by 2-3 weeks. The results are set out in a descriptive manner. Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. We report BBB opening in the parieto-occipito-temporal junction in 8/10 treatments in 5 patients as demonstrated by gadolinium enhancement. In all cases the procedures were uneventful and no side effects were encountered associated with BBB opening. From pre- to post-treatment, mild cognitive improvement was observed, and no major changes were detected in amyloid or fluorodeoxyglucose PET. MRgFUS-BBB opening in PDD is thus safe, reversible, and can be performed repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders.
Since COVID-19 was first reported, different neurological complications have been acknowledged, but their description is constantly evolving. We report a case of concurrent tonic pupil and trochlear ...nerve palsy in this context. A 62-year-old man reported a 5-day history of binocular vertical diplopia and blurred vision in his left eye, noticing that his left pupil was dilated. He had suffered a flu-like syndrome 2 weeks before. Clinical exam showed a right trochlear nerve palsy and a left mydriatic pupil. MRI, X chest ray, and analytical results were normal. Antibodies for SARS-CoV-2 were positive (low IgM and high IgG titers). Antiganglioside antibodies were negative. A 0.125% pilocarpine test confirmed Adie’s pupil diagnosis. The patient was treated with a tapered prednisone dose with resolution of his diplopia but no change in Adie’s pupil. This is the first case reporting Adie’s pupil as a postinfectious manifestation of COVID-19. An immune-mediated mechanism is presumed.
La resistencia al servicio militar obligatorio en España durante el último tercio del siglo XX, sirvió para articular un importante movimiento antimilitarista y juvenil. Este movimiento comenzó ...durante la década de los setenta muy ligado a la doctrina de la noviolencia y su vinculación con la objeción de conciencia. Durante la década siguiente la resistencia al servicio militar se hizo cada vez más extensa entre la juventud española. La extendida desobediencia a las leyes de conscripción acabó forzando el fin del servicio militar obligatorio. Para conseguir este objetivo, los jóvenes desobedientes tuvieron que hacer frente a diversos contextos políticos, redefiniendo sus estrategias, logrando conseguir un paulatino aumento de apoyos sociales, consiguiendo un constante trasvase generacional y sobre todo asumiendo y convirtiendo la represión derivada de la desobediencia a las leyes en algo dañino para el propio Gobierno.
Objective. The aim of the present work is to analyze certain psychological features in a group of patients diagnosed with Epicrania fugax (EF; that has been recently included in the appendix of the ...International Classification of Headache Disorders, third edition, beta version), as well as their association with diverse demographic and clinical characteristics of the sample.
Design. Case-control.
Method. Perceived Stress Scale (PSS), Stress Coping (COPE), Big Five Personality Traits (NEO-FFI), Depression (BDI-II), and Trait Anxiety (STAI) were evaluated in 23 patients with EF and 23 matched healthy controls. Differences between EF patients and controls were analyzed using the Mann-Whitney U test. Differences in psychological features as a function of the demographic and clinical characteristics were examined using one-way Analysis of Variance (ANOVA), Mann-Whitney U test, or Pearson’s correlations.
Results. The two groups differed significantly from each other in Denial, Trait anxiety, and Depression. Low-frequency epicrania patients scored significantly higher than controls in Perceived stress, Neuroticism, Denial, Self-blame, Trait anxiety, and Depression and higher than high-frequency EF in Venting.
Conclusions. The results initially suggest the absence of substantial differences between patients suffering of EF and healthy controls. On the contrary, low-frequency EF patients show a distinctive “negative (unhealthy) psychological profile,” in opposition to high-frequency EF patients. This circumstance highlights the potential need to consider low- frequency EF patients as a target for psychological intervention in combination with the most common medical procedures. Longitudinal studies are necessary to correctly elucidate the influence of these psychological variables on the course of EF.
SORL1 Variants in Familial Alzheimer's Disease Gómez-Tortosa, Estrella; Ruggiero, María; Sainz, Ma José ...
Journal of Alzheimer's disease,
01/2018, Letnik:
61, Številka:
4
Journal Article
Recenzirano
The SORL1 gene encodes a protein involved in the amyloidogenic process, and its variants have been associated with Alzheimer's disease (AD) physiopathology. We screened for SORL1 variants in 124 ...familial (44 early- and 80 late-onset) dementia of Alzheimer type (DAT) cases. Nine potentially pathogenic changes (three not previously reported and six rare variants) were found in nine probands (7%). After screening the control population and siblings (presence in at least 1/200 controls and/or absence of segregation pattern), a causal relationship with the disease was considered unlikely in six variants and uncertain in one. The change Trp848Ter and a splice-site variant remained likely correlated with the disease. SORL1 mutations are present in 7% of our familial DAT cohort, though in most cases cannot be considered the direct cause of the disease.
Introduction
Intermittent fever has been occasionally related to migraine, either as a migraine equivalent or as a migraine accompaniment. We present a case of recurrent increase in body temperature ...consistently associated with migraine headaches.
Methods
A 15‐year‐old girl reported a 3‐year lasting history of migraine without aura, with a feeling of warmth occurring in each episode. Ancillary tests did not show any evidence of secondary headaches or any systemic disease. A 2‐month headache diary was obtained, with daily records of headache intensity (0, no headache; 1, mild pain; 2, moderate pain; 3, severe pain) and simultaneous measurements of axillary temperature. Both parameters were registered in the evening, at 6:00 pm every day. The distribution of headache intensity and body temperature as well as the relationship between both variables over time were analyzed with nonparametric tests.
Results
The number of days without pain was 28 (45.2%); a mild headache was present on 13 days (21%), a moderate headache on 15 days (24.2%), and a severe headache on 6 days (9.7%). Headache days were associated with higher body temperature than headache‐free days (median values: 37.3°C vs 36.6°C; Mann–Whitney U‐test, P < 0.001). Moreover, a positive correlation was found between headache intensity and body temperature (Spearman's rho coefficient: 0.83, P < 0.001).
Conclusions
Recurrent increase in body temperature may be another manifestation of the complex clinical spectrum of migraine. This symptom is probably related to hypothalamic involvement.
This paper analyzes rivalry between transport facilities in a model that includes two sources of horizontal differentiation: geographical location and departure time. We explore how both sources ...influence facility fees and the price of the service offered by downstream carriers. Travelers’ costs include a fare, a transportation cost to the facility and a schedule delay cost. The interactions in the facility-carrier model are represented as a sequential three-stage game in fees, times and fares. Duopolistic competition leads to an identical departure time across carriers when their operating costs do not vary with the time of day, but generally leads to distinct service times when this cost is time-dependent. We also find that higher per-passenger commercial revenue at one facility induces a lower fee charged by both facilities to their carrier and a lower fare charged by both carriers at their departure facility, while a lower marginal operating cost for one carrier implies a higher fee at its departure facility, a lower fee at the rival carrier’s facility and a lower fare at both facilities. Finally, we show that the socially optimal schedule differentiation decreases in the distance between facilities and in the unit transportation cost incurred by travelers, and increases in the unit schedule delay cost incurred by travelers as well as in the marginal time cost faced by carriers.
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