Dystonia: sparse synapses for D2 receptors in striatum of a DYT1 knock-out mouse model

Dystonia pathophysiology has been partly linked to downregulation and dysfunction of dopamine D2 receptors in striatum. We aimed to investigate the possible morpho-structural correlates of D2 receptor downregulation in the striatum of a DYT1 Tor1a mouse model. Adult control Tor1a+/+ and mutant Tor1a+/− mice were used. The brains were perfused and free-floating sections of basal ganglia were incubated with polyclonal anti-D2 antibody, followed by secondary immune-fluorescent antibody. Confocal microscopy was used to detect immune-fluorescent signals. The same primary antibody was used to evaluate D2 receptor expression by western blot. The D2 receptor immune-fluorescence appeared circumscribed in small disks (~0.3–0.5 μm diameter), likely representing D2 synapse aggregates, densely distributed in the striatum of Tor1a+/+ mice. In the Tor1a+/− mice the D2 aggregates were significantly smaller (μm2 2.4 ± SE 0.16, compared to μm2 6.73 ± SE 3.41 in Tor1a+/+) and sparse, with ~30% less number per microscopic field, value correspondent to the amount of reduced D2 expression in western blotting analysis. In DYT1 mutant mice the sparse and small D2 synapses in the striatum may be insufficient to “gate” the amount of presynaptic dopamine release diffusing in peri-synaptic space, and this consequently may result in a timing and spatially larger nonselective sphere of influence of dopamine action

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 \ub1 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

Stimulation of astrocytes affects cytotoxic brain edema

Cytotoxic brain edema has been produced in rats by subacute intoxication with triethyltin (TET). Some animals were allowed to recover spontaneously, others were post-treated with an extract of Ginkgo biloba (EGB) for 1 to 4 weeks, beginning 3 days after intoxication was stopped. The time course of the resolution of the edema was studied biochemically and morphologically by light microscopy, histochemistry and electron microscopy (EM). Morphometric evaluation showed that the spontaneous reabsorption of TET-induced edema was very slow: it was evident only 2 weeks after ending TET administration and it required more than 4 weeks to be completed. EGB therapy markedly decreased the vacuolation, as well as the abnormal levels of water and sodium contents, 1 week after beginning the treatment. Less influence of EGB was observed at the later stages. During spontaneous recovery, astroglial cells in the edematous white matter of TET-intoxicated animals showed short and swollen processes containing few organelles, low levels of NADH- and NADPH-tetrazolium reductase activities and glial fibrillary acidic protein (GFAP)-immunofluorescence for about 2 weeks. During EGB therapy the astrocytes regained their cellular processes, containing intense oxidative enzyme activities and GFAP-immunofluorescence as early as after 1 week of treatment. In the EM, astrocytes often appeared hypertrophic, surrounding myelin vacuoles and displaying phagocytosis of myelin debris. We conclude that EGB can accelerate the reabsorption of TET-induced cerebral edema and improve the astroglial reaction

Prognostic evaluation of brainstem hematomas: the role of CT scan and brainstem auditory evoked potentials

6 cases of brainstem hematoma were studied utilizing CT scan and brainstem auditory evoked potential (BAEP) recordings. CT scan did not contribute to an early discrimination between primary and secondary hematomas. Size of the hematoma and the presence of blood in the CSF did not represent evident signs in differentiating benign from unfavourable brainstem hematomas or hemorrhages. BAEP recordings showed the presence of electrophysiological anomalies at the level of the lesion, demonstrating that bleeding as well as tumor in the brainstem can provoke a focal damage