Cerebral cortex demyelination and oligodendrocyte precursor response to experimental autoimmune encephalomyelitis.

Abstract Experimentally induced autoimmune encephalomyelitis (EAE) in mice provides an animal model that shares many features with human demyelinating diseases such as multiple sclerosis (MS). To what extent the cerebral cortex is affected by the process of demyelination and how the corollary response of the oligodendrocyte lineage is explicated are still not completely known aspects of EAE. By performing a detailed in situ analysis of expression of myelin and oligodendrocyte markers we have identified areas of subpial demyelination in the cerebral cortex of animals with conventionally induced EAE conditions. On EAE-affected cerebral cortices, the distribution and relative abundance of cells of the oligodendrocyte lineage were assessed and compared with control mouse brains. The analysis demonstrated that A2B5+ glial restricted progenitors (GRPs) and NG2+/PDGFR-α+ oligodendrocyte precursor cells (OPCs) were increased in number during "early" disease, 20 days post MOG immunization, whereas in the "late" disease, 39 days post-immunization, they were strongly diminished, and there was an accompanying reduction in NG2+/O4+ pre-oligodendrocytes and GST-π mature oligodendrocytes. These results, together with the observed steady-state amount of NG2−/O4+ pre-myelinating oligodendrocytes, suggested that oligodendroglial precursors attempted to compensate for the progressive loss of myelin, although these cells appeared to fail to complete the last step of their differentiation program. Our findings confirm that this chronic model of EAE reproduces the features of neocortex pathology in progressive MS and suggest that, despite the proliferative response of the oligodendroglial precursors, the failure to accomplish final differentiation may be a key contributing factor to the impaired remyelination that characterizes these demyelinating conditions

'Pure' Constructional Apraxia—A Cognitive Analysis of a Single Case

We report on a patient affected by selective drawing disabilities. The patient could correctly reproduce and draw simple geometric figures on request, but when he tried to reproduce more complex drawings or to draw common objects he performed very poorly. To identify the cognitive impairment in this patient, we adopted two test batteries based on recent information-processing models of drawing. Results showed that the patient's drawing disabilities were independent of visuo-perceptual and executive impairments. These findings support recent cognitive models of drawing abilities: some intermediate stages of drawing exist at which information is processed to prepare and guide motor output, and which may be selectively disrupted after discrete cerebral lesions

Explicit recognition of emotional facial expressions is shaped by expertise: evidence from professional actors

Can reading others' emotional states be shaped by expertise? We assessed processing of emotional facial expressions in professional actors trained either to voluntary activate mimicry to reproduce character's emotions (as foreseen by the “Mimic Method”), or to infer others' inner states from reading the emotional context (as foreseen by “Stanislavski Method”). In explicit recognition of facial expressions (Experiment 1), the two experimental groups differed from each other and from a control group with no acting experience: the Mimic group was more accurate, whereas the Stanislavski group was slower. Neither acting experience, instead, influenced implicit processing of emotional faces (Experiment 2). We argue that expertise can selectively influence explicit recognition of others' facial expressions, depending on the kind of “emotional expertise”

Differential neuropsychological profiles in Parkinsonian patients with or without vascular lesions.

The purpose of this study is to compare the neuropsychological profile of patients affected by parkinsonism and vascular lesions to that in patients with PD alone (PD) and to evaluate whether the brain vascular lesion load is associated with neuropsychological variables. Thirty-six nondemented patients with parkinsonism were divided into 3 groups of 12 patients each, according to both clinical history and the presence of brain vascular lesions and/or dopaminergic denervation as revealed by magnetic resonance and dopamine transporter imaging, respectively. The first group had vascular lesions without dopaminergic denervation (VP group); the second group had vascular lesions and dopaminergic denervation (DD) (VP+DD group); and the third group consisted of patients with dopaminergic denervation (PD group) without vascular lesions. All patients underwent neurological and neuropsychological assessments. The groups differed in disease duration, age at onset, and cerebrovascular risk factors. The VP and VP+DD groups performed worse than the PD group on frontal/executive tasks. Regardless of the presence of dopaminergic denervation, cerebrovascular lesions in hemispheric white matter, basal ganglia, and cerebellum have an important effect in determining early onset and severity of cognitive impairment in patients with parkinsonism

Impaired Conscious Recognition of Negative Facial Expressions in Patients with Locked-in Syndrome

The involvement of facial mimicry in different aspects of human emotional processing is widely debated. However, little is known about relationships between voluntary activation of facial musculature and conscious recognition of facial expressions. To address this issue, we assessed severely motor-disabled patients with complete paralysis of voluntary facial movements due to lesions of the ventral pons [locked-in syndrome (LIS)]. Patients were required to recognize others’ facial expressions and to rate their own emotional responses to presentation of affective scenes.LISpatientswere selectivelyimpairedin recognition of negativefacial expressions,thusdemonstratingthatthe voluntary activation of mimicry represents a high-level simulation mechanism crucially involved in explicit attribution of emotions

Pathological gambling in Parkinson's disease. A comprehensive review

Pathological gambling (PG) and other Impulse Control Disorders (ICDs), such as hypersexuality, compulsive eating and buying, are often reported in Parkinson's disease (PD). The prevalence of PG is 2.2%-7% in treated PD patients, which is higher than the background population rate. As other non motor symptoms in PD, PG is frequently under-reported by patients and caregivers and may be under-recognized by the treating physicians. Factors associated with PG include male sex, younger age or younger age at PD onset, personal or family history of substance abuse or ICD, a personality profile characterized by impulsiveness, and treatment with dopamine agonists (DA) more than with levodopa (l-dopa). The DA effect seems to be a class effect and not specific for any DA. Neurofunctional studies suggest that medication-induced downregulation of frontostriatal connections and upregulation of striatum might combine to induce impulsive behavior. A dysfunction of fronto-subcortical circuits in PD patients with PG is also supported by neuropsychological findings of impaired executive control and monitoring abilities. Management of ICDs in PD is complex, and until now only discontinuation and/or tapering of DA treatment seem to be an effective management strategy for ICDs in PD. There is no empirical evidence supporting the use of psychiatric drugs for PG such as antipsychotics and antidepressants. Data regarding the effect of deep brain stimulation (DBS), particularly of subthalamic nucleus, on PG and ICDs in PD are still limited and sometimes conflicting since improvement of PG or new onset of PG after surgery have been reported

Durvalumab and multiple sclerosis: a causal link or simple unmasking?

Non applicabile - Letter to the edito

Vitamin D: Mechanism of action and biological effects in uterine fibroids

Uterine fibroids (UFs) are the most common benign gynecological tumors. It was esti-mated that fifty percent of women presenting with UFs has symptomatology that negatively in-fluences their quality of life. Pharmacological and/or surgical treatments are frequently required, depending on the woman’s desire to preserve fertility, with a high impact on healthcare costs. Generally, the use of currently available pharmacological treatments may lead to side effects. Therefore, there is a growing interest in a natural and safe approach for UFs. In recent years, epi-demiological studies reported a vitamin D deficiency in patients with UFs raised interest in the potential biological effects of vitamin D supplementation. In vitro studies proved vitamin D efficacy in inhibiting UFs growth by targeting pathways involved in the regulation of various biological processes, including proliferation, extracellular matrix (ECM) remodeling, DNA repair, signaling and apoptosis. However, clinical studies supported only in part the beneficial effects of vitamin D supplementation in reducing UFs growth and tumor volume. Randomized controlled trials and large population studies are mandatory as the potential clinical benefits are likely to be substantial