Neuroimagen estructural y funcional en las enfermedades priónicas humanas

INTRODUCTION: Prion diseases are neurodegenerative disorders resulting from the accumulation of a misfolded isoform of the cellular prion protein (PrPc). They can occur as acquired, sporadic or hereditary forms. Although prion diseases show a wide range of phenotypic variations, pathological features and clinical evolution, they are all characterised by a common unfavourable course and a fatal outcome. REVIEW SUMMARY: Some variants, such as kuru, have practically disappeared, while others, for example the variant Creutzfeldt-Jakob (vCJD) or those attributable to iatrogenic causes, are still in force and pose a challenge to current medicine. There are no definitive pre-mortem diagnostic tests, except for vCJD, where a tonsil biopsy detects 100% of the cases. For this reason, diagnostic criteria dependent on statistical probability have had to be created. These require complementary examinations, such as an electroencephalogram (EEG) or the detection of 14-3-3 protein in cerebrospinal fluid (CSF). Only the "pulvinar sign" in magnetic resonance imaging (MRI) has been included as a vCJD diagnostic criterion. The present review discusses neuroimaging findings for each type of prion disease in patients with a definitive histopathological diagnosis. CONCLUSIONS: The aim is to define the usefulness of these complementary examinations as a tool for the diagnosis of this family of neurodegenerative diseases

Exogenous LRRK2G2019S induces parkinsonian-like pathology in a nonhuman primate

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease among the elderly. To understand pathogenesis and to test therapies, animal models that faithfully reproduce key pathological PD hallmarks are needed. As a prelude to developing a model of PD, we tested the tropism, efficacy, biodistribution, and transcriptional impact of canine adenovirus type 2 (CAV-2) vectors in the brain of Microcebus murinus, a nonhuman primate that naturally develops neurodegenerative lesions. We show that introducing helper-dependent (HD) CAV-2 vectors results in long-term, neuron-specific expression at the injection site and in afferent nuclei. Although HD CAV-2 vector injection induced a modest transcriptional response, no significant adaptive immune response was generated. We then generated and tested HD CAV-2 vectors expressing LRRK2 (leucine-rich repeat kinase 2) and LRRK2 carrying a G2019S mutation (LRRK2G2019S), which is linked to sporadic and familial autosomal dominant forms of PD. We show that HD-LRRK2G2019S expression induced parkinsonian-like motor symptoms and histological features in less than 4 months

Experiencia clínica del tratamiento con onabotulinumtoxin A en pacientes con migraña refractaria

To analyse our experience in the treatment of refractory chronic migraine, episodic frequent refractory migraine (>= 10 days/month), with onabotulinumtoxin A (OnabotA). PATIENTS AND METHODS. Retrospective analysis of patients with refractory migraine who underwent, at least two sessions of OnabotA pericranial injections following the PREEMPT protocol between 2008 and 2012. The efficacy of OnabotA was evaluated comparing the basal situation with 12-16 weeks after the second session. We analysed the subjective improvement of the patients, number of days with headache, preventive and abortive drugs consumption, and adverse effects. RESULTS. Forty-one patients (37 women, 4 male) were identified. 65.8% patients experienced subjective improvement after OnabotA treatment. 36.58% responded (reduction of > 50% in headache days). Differences between days with headache before the first session (24.5 +/- 7.3), and 12-16 weeks after the second session (17.4 +/- 11.6), as well as the differences between the number of abortive drugs taken before the first session (26.8 +/- 23.1) and 12-16 weeks after the second session (16.7 +/- 19.3), were statistically significant (p < 0.001). Subgroups analysis showed that all differences were significant, except for the reduction of the number of days with headache in patients with episodic frequent refractory migraine. CONCLUSION. Our work shows that treatment with OnabotA is safe and useful in patients with episodic and chronic refractory migraine, including those patients with medication overuse headache

Brain aging and Parkinson's disease: new therapeutic approaches using drugs delivery systems

ABSTRACT The etiology and pathogenesis of Parkinson’s disease (PD) is unknown, aging being the strongest risk factor for brain degeneration. Understanding PD pathogenesis and how aging increases the risk of disease would aid the development of therapies able to slow or prevent the progression of this neurodegenerative disorder. In this review we provide an overview of the most promising therapeutic targets and strategies to delay the loss of dopaminergic neurons observed both in PD and aging. Among them, handling alphasynuclein toxicity, enhancing proteasome and lysosome clearance, ameliorating mitochondrial disruptions and modifying the glial environment are so far the most promising candidates. These new and conventional drugs may present problems related to their labile nature and to the difficulties in reaching the brain. Thus, we highlight the latest types of drug delivery system (DDS)-based strategies for PD treatment, including DDS for local and systemic drug delivery. Finally, the ongoing challenges for the discovery of new targets and the opportunities for DDS-based therapies to improve and efficacious PD therapy will be discussed

Perfil neuropsicológico de la degeneración lobar frontotemporal

La degeneración lobar frontotemporal engloba tres síndromes diferentes, que comparten características clínicas y patológicas comunes, dificultando así su diagnóstico en estadios iniciales. Se incluyen en este grupo las tres variantes de la demencia frontotemporal, el síndrome corticobasal y el síndrome de parálisis supranuclear progresiva. Se ha llevado a cabo una revisión del perfil neuropsicológico de cada uno de los síndromes, que permita clarificar las características fundamentales que los definen y ayudar a diferenciarlos de otras demencias. Se ha hecho una revisión de los diferentes trabajos publicados en la literatura al respecto, describiendo las características clínicas, patológicas y los hallazgos de imagen fundamentales de cada entidad para describir de manera exhaustiva los hallazgos en los diferentes dominios neuropsicológicos y su progresión. Aunque existe un solapamiento entre los síndromes que conforman la degeneración lobar frontotemporal, la comparación del perfil neuropsicológico de las mismas entre sí y frente a otras demencias permite establecer características propias de su perfil neuropsicológico para llevar a cabo un diagnóstico diferencial.Frontotemporal lobar degeneration encompasses three different syndromes, with clinical and pathologic commonalities, making diagnosis difficult in early stages. Three subtypes are recognized: frontotemporal dementia and its three variants, corticobasal syndrome and supranuclear palsy syndrome. The objective of this study is to review the neuropsychological features of each syndrome in order to differentiate amongst subtypes as well as from other forms of dementia. We review multiple studies from the literature, highlighting the main clinical features, neuropathology and changes in brain imaging of each syndrome. Subsequently, we describe the neuropsychological profile compared to other dementias, and how it progresses over time. Although there is an overlap amongst the different subtypes of frontotemporal lobar degeneration, neuropsychological profiles can help identify subtypes and discriminate frontotemporal lobar degeneration from other forms of dementia

Interferometry of Direct Photons in Central 280Pb+208Pb Collisions at 158A GeV

Two-particle correlations of direct photons were measured in central 208Pb+208Pb collisions at 158 AGeV. The invariant interferometric radii were extracted for 100<K_T<300 MeV/c and compared to radii extracted from charged pion correlations. The yield of soft direct photons, K_T<300 MeV/c, was extracted from the correlation strength and compared to theoretical calculations.Comment: 5 pages, 4 figure

Event-by-Event Fluctuations in Particle Multiplicities and Transverse Energy Produced in 158.A GeV Pb+Pb collisions

Event-by-event fluctuations in the multiplicities of charged particles and photons, and the total transverse energy in 158$\cdot A$ GeV Pb+Pb collisions are studied for a wide range of centralities. For narrow centrality bins the multiplicity and transverse energy distributions are found to be near perfect Gaussians. The effect of detector acceptance on the multiplicity fluctuations has been studied and demonstrated to follow statistical considerations. The centrality dependence of the charged particle multiplicity fluctuations in the measured data has been found to agree reasonably well with those obtained from a participant model. However for photons the multiplicity fluctuations has been found to be lower compared to those obtained from a participant model. The multiplicity and transverse energy fluctuations have also been compared to those obtained from the VENUS event generator.Comment: To appear in Physical Review C; changes : more detailed discussion on errors and few figures modifie

Scaling of Particle and Transverse Energy Production in 208Pb+208Pb collisions at 158 A GeV

Transverse energy, charged particle pseudorapidity distributions and photon transverse momentum spectra have been studied as a function of the number of participants (N_{part}) and the number of binary nucleon-nucleon collisions (N_{coll}) in 158 A GeV Pb+Pb collisions over a wide impact parameter range. A scaling of the transverse energy pseudorapidity density at midrapidity as N_{part}^{1.08 \pm 0.06} and N_{coll}^{0.83 \pm 0.05} is observed. For the charged particle pseudorapidity density at midrapidity we find a scaling as N_{part}^{1.07 \pm 0.04} and N_{coll}^{0.82 \pm 0.03}. This faster than linear scaling with N_{part} indicates a violation of the naive Wounded Nucleon Model.Comment: 13 pages, 16 figures, submitted to European Physical Journal C (revised results for scaling exponents