Anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that destabilizes cell cycle proteins, is activated by Cdh1 in post-mitotic neurons, where it regulates axonal growth, synaptic plasticity and survival. The APC/C-Cdh1 substrate, cyclin B1, has been found to accumulate in degenerating brain areas in Alzheimer's disease and stroke. This highlights the importance of elucidating cyclin B1 regulation by APC/C-Cdh1 in neurons under stress conditions relevant to neurological disease. Here, we report that stimulation of N-methyl-Daspartate receptors (NMDARs) that occurs in neurodegenerative diseases promoted the accumulation of cyclin B1 in the nuclei of cortical neurons; this led the neurons to undergo apoptotic death. Moreover, we found that the Ser-40, Thr-121 and Ser-163 triple phosphorylation of Cdh1 by the cyclin-dependent kinase-5 (Cdk5)-p25 complex was necessary and sufficient for cyclin B1 stabilization and apoptotic death after NMDAR stimulation. These results reveal Cdh1 as a novel Cdk5 substrate that mediates cyclin B1 neuronal accumulation in excitotoxicity.

Poor prognosis after ischemic stroke or intracerebral hemorrhage is linked to a particular polymorphism in the human gene encoding p53.

Background: Vitamin K antagonist oral anticoagulants (VKA-OACs) are effective for primary and secondary prevention of embolic events. The rate of haemorrhagic neurological complications in patients admitted to neurology departments in Spain is not yet known. Aims: We aimed to determine the clinical and epidemiological characteristics of patients with intracranial haemorrhage secondary to VKA-OACs as well as the incidence of this severe complication. Methods: We conducted a retrospective, descriptive, multi-centre study using information from the medical records of all patients admitted to neurology departments, diagnosed with spontaneous intracranial haemorrhage, and treated with VKA-OACs within a 1-year period. We collected demographic and care data from centres, patients' medical records [demographic data, medical history, haemorrhage origin, vascular risk factors, concomitant treatment, and National Institutes of Health Stroke Scale (NIHSS) scores], and patients' outcome at 3 months [independence (modified Rankin Scale score <3) and mortality rate]. Results: Twenty-one hospitals serving a population of 8,155,628 inhabitants participated in the study. The total number of cases was 235, the mean age was 78.2 (SD 9.4) years, and the baseline NIHSS score was 11.6 (SD 9.5; median 9; interquartile range 14). The VKA-OACs used were acenocoumarol in 95.3% (224 patients) and warfarin in 4.7% (11 patients). The haemorrhage origin was deep in 29.8%, lobar in 25.5%, intraventricular in 11.5%, extensive in 17.4% (>100 ml), cerebellar in 12.3%, and in the brainstem in 3.4%. The international normalised ratio was within therapeutic ranges at admission (according to indication) in 29.4% (69 patients). The global incidence (cases per 100,000 inhabitants per year) is 2.88. The in-hospital mortality rate was 40%, and 24.3% of the patients were independent at 3 months, while the mortality at 3 months was 42.6%. Conclusion: VKA-OAC treatment is associated with a large percentage of all cases of spontaneous intracranial haemorrhage, an event leading to high dependence and mortality rates.

Introduction: Autologous bone marrow (BMT) or peripheral blood stem cell transplantation (PBSCT) are increasingly used to treat hematological malignancies and solid tumors. The reported incidence of neurological complications varies greatly among the different centers, ranging from 11 to 39%. Patients and Methods: In order to gain insight into the real incidence of early neurological complications (first 6 weeks) after autologous transplantation, we analyzed a series of 254 patients who underwent BMT/PBSCT for hematological malignancies (212 cases) or solid tumors (42 cases). Results: Seven patients died during the early posttransplant period (incidence: 2.4%), and one of these deaths was related to a neurological complication. Eight patients developed neurologic complications (incidence: 2.8%). None of the patients developed cerebral hemorrhage during the early posttransplant period, despite a rather restrictive platelet transfusion support. Two out of 13 patients diagnosed AML and 3 out of 36 patients diagnosed Hodgkin’s disease developed early neurological complications. Discussion and Conclusions: The neurological morbidity related to autologous transplantation was very low in our series of patients as compared to that reported in previous studies. This difference could be explained, at least in part, by a more restrictive definition of early neurologic complications.

Background: Horizontal Canal Cupulolithiasis (hc-BPPV-cu) can mimic a pathology of central origin, so a careful examination is essential to prevent misdiagnosis. Methods: Retrospective cross-sectional cohort study of 45 patients suffering from suspected hc-BPPV-cu. We recorded whether patients first presented through an ENT Emergency Department (ED) or through an Outpatient Otolaryngology Clinic (OC). Results: We found statistically significant differences (p < 0.05) between the OC versus the ED in relation to the time between symptom onset and first assessment (79.7 vs. 3.6 days, respectively), the number of therapeutic maneuvers (one maneuver in 62.5% vs. 75.9%, and more than one in 25.1% vs. 13.7%), and multi-canal BPPV rate (43.8% vs. 3.4%). hc-BPPV-cu did not resolve in 2 patients (12.5%) from the OC and in 3 (10.3%) from de ED, all of which showed central pathology. Discussion: There are no prior studies that analyze the approach to hc-BPPV-cu in the ED. The benefits of early specialist input are early identification of central positional nystagmus, a decrease in symptom duration, reduced number of therapeutic maneuvers required for symptom resolution, and lower rates of iatrogenic multi-canal BPPV. Conclusion: A comprehensive approach to hc-BPPV-cu in the ED allows both more effective treatment and early identification of central disorder mimics.

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ICH in patients treated with VKA is associated with high mortality rates; mortality in these patients is mainly and independently associated with the clinical situation at stroke onset.

Introducción y objetivo: El acúfeno conforma junto con los episodios de vértigo, hipoacusia neurosensorial y la sensación de plenitud ótica los síntomas cardinales de la Enfermedad de Ménière. No alcanzando la importancia que le corresponde en el manejo de esta enfermedad, el acúfeno repercute profundamente en la vida de los pacientes, sobre todo en la esfera psicológica. Método: Se seleccionaron 15 pacientes con Enfermedad de Ménière diagnosticados según los criterios de la Sociedad de Bárány en Hospital Universitario de Salamanca. Se registraron variables específicas para el análisis de los síntomas cardinales de la enfermedad de Ménière. Se recogieron datos sobre la edad de aparición y años de evolución de la enfermedad y de la misma manera para el acúfeno, la afectación bilateral o unilateral de la misma y en este último supuesto, el oído afecto. Se sometió a los pacientes a estudio audiométrico junto con acufenometría. Se valoraron los principales parámetros definitorios del acúfeno: frecuencia (Hz), intensidad (dB), umbral de enmascaramiento (dB) e inhibición residual (segundos).  Los pacientes realizaron el test Tinnitus Handicap Inventory (THI) y Escala visual analógica (VAS). La valoración de alteraciones en el estado de ánimo se obtuvo a través de la Escala Hospitalaria de Ansiedad y Depresión (HADS). Resultados: La edad media de diagnóstico de la Enfermedad de Ménière es 47,47 años. Las medias de pérdida auditiva en cada frecuencia por la enfermedad de Ménière se sitúan en torno a los 50 dB. El acúfeno no predomina en ninguno de los oídos (p>0,05). Se determinó una relación fuertemente significativa entre THI y VAS (r=0,72; p<0,01). Tanto THI como VAS no se relacionaron con los valores de la media de las pérdidas auditivas de ambos oídos. Los pacientes con más de dos años de evolución de la enfermedad se corresponden estadísticamente con puntuaciones mayores en THI y en la subescala de depresión del HADS (r= 0,821; p=0,001). Discusión: La intensidad del acúfeno, cuantificada de manera subjetiva con THI, no se relaciona con el grado de pérdida auditiva en los pacientes con Enfermedad de Ménière. El estudio de la esfera psicológica a través de la escala HADS demuestra la existencia de trastornos del ánimo en estos pacientes, prevaleciendo la patología depresiva en aquellos que presentan acúfenos de larga evolución.