Theory of Mind in Parkinson's disease

Amyloid-beta peptide (Aβ) is believed to be central in the pathogenesis of Alzheimer's disease (AD) characterized by cognitive deficits. However, it remains uncertain which form(s) of Aβ pathology is responsible for the cognitive deficits in AD. In the present study, the cognitive deficits and the profiles of Aβ pathology were characterized in the 12-month-old APPswe/PS1dE9 double transgenic mice, and their correlations were examined. Compared with non-transgenic littermates, the middle-aged APPswe/PS1dE9 mice exhibited spatial learning and memory deficits in the water maze test and long-term contextual memory deficits in the step-down passive avoidance test. Among the middle-aged APPswe/PS1dE9 mice, hippocampal soluble Aβ1-40 and Aβ1-42 levels were highly correlated with spatial learning deficits and long-term contextual memory deficits, as well as cortical and hippocampal soluble Aβ1-40 and Aβ1-42 levels were strongly correlated with spatial memory deficits. By contrast, no significant correlations were observed between three measures of cognitive functions and amyloid plaque burden (total Aβ plaque load and fibrillar Aβ plaque load), total Aβ levels (Aβ1-40 and Aβ1-42), as well as insoluble Aβ levels (Aβ1-40 and Aβ1-42). Stepwise multiple regression analysis identified hippocampal soluble Aβ1-40 and Aβ1-42 levels as independent factors for predicting the spatial learning deficits and the long-term contextual memory deficits, as well as hippocampal and cortical soluble Aβ1-40 and Aβ1-42 levels as independent factors for predicting the spatial memory deficits in transgenic mice. These results demonstrate that cognitive deficits are highly related to the levels of soluble Aβ in middle-aged APPswe/PS1dE9 mice, in which soluble Aβ levels are only a tiny fraction of the amount of total Aβ levels. Consequently, our findings provide further evidence that soluble Aβ might primarily contribute to cognitive deficits in AD, suggesting that reducing the levels of soluble Aβ species would be a therapeutic intervention for AD patients even with large deposits of aggregated, insoluble Aβ.     

Prevalence of nonmotor symptoms in Parkinson's disease in an international setting; study using nonmotor symptoms questionnaire in 545 patients.

2006, there was, no single instrument (questionnaire or scale) for attempting a comprehensive assessment of the wide range of nonmotor symptoms (NMS) of Parkinson's disease (PD). The PD nonmotor group, a multidisciplinary group of experts including patient group representatives developed and validated the NMS screening questionnaire (NMSQuest) comprising 30 items. The NMSQuest is a self completed screening tool designed to draw attention to the presence of NMS. In this paper, we present the results gathered from 545 patients using the definitive version of the NMSQuest highlighting the prevalence of the wide range of NMS flagged in the NMSQuest from consecutive PD patients in an international setting.     

Preventive Effects of Hyperbaric Oxygen in Cluster Headache

The effect of a 2-week course of hyperbaric oxygen on both the duration and frequency of cluster headache attacks was tested in four patients suffering from chronic cluster headache with no clear response to pharmacological treatments. Two patients (two courses in one case) dramatically improved while on hyperbaric oxygen treatment, this positive response remaining for 2 and 31 days posttreatment. Case 3 only improved in frequency, while the remaining patient showed no benefit. These findings suggest that daily hyperbaric oxygen treatment can be used as a transient preventive treatment for desperate cluster headache sufferers.     

Correction of metachromatic leukodystrophy in the mouse model by transplantation of genetically modified hematopoietic stem cells

Gene-based delivery can establish a sustained supply of therapeutic proteins within the nervous system. For diseases characterized by extensive CNS and peripheral nervous system (PNS) involvement, widespread distribution of the exogenous gene may be required, a challenge to in vivo gene transfer strategies. Here, using lentiviral vectors (LVs), we efficiently transduced hematopoietic stem cells (HSCs) ex vivo and evaluated the potential of their progeny to target therapeutic genes to the CNS and PNS of transplanted mice and correct a neurodegenerative disorder, metachromatic leukodystrophy (MLD). We proved extensive repopulation of CNS microglia and PNS endoneurial macrophages by transgene-expressing cells. Intriguingly, recruitment of these HSC-derived cells was faster and more robust in MLD mice. By transplanting HSCs transduced with the arylsulfatase A gene, we fully reconstituted enzyme activity in the hematopoietic system of MLD mice and prevented the development of motor conduction impairment, learning and coordination deficits, and neuropathological abnormalities typical of the disease. Remarkably, ex vivo gene therapy had a significantly higher therapeutic impact than WT HSC transplantation, indicating a critical role for enzyme overexpression in the HSC progeny. These results indicate that transplantation of LV-transduced autologous HSCs represents a potentially efficacious therapeutic strategy for MLD and possibly other neurodegenerative disorders.     

Invasive strategy following fibrinolysis in ST-elevation acute myocardial infarction.

BACKGROUND: A recognized drawback of ST-elevation acute myocardial infarction (STEMI) after fibrinolysis is persistent coronary occlusion or a less than TIMI 3 flow. The present study describes the results of systematic pre-discharge coronary angiography and revascularization, whenever indicated, following fibrinolytic therapy for STEMI. METHODS: Consecutive patients admitted with the diagnosis of STEMI between April 1, 2000 and April 30, 2002 were included in the study. Patients with contraindications to thrombolytic therapy and/or patients not eligible for angiography were excluded. All patients received "accelerated" treatment with alteplase and had a coronary angiography at least 24 hours later, in order to perform, if anatomically feasible, angioplasty with stenting. Angioplasty of non-infarct-related coronary arteries was allowed. The mortality, reinfarction and new revascularization rates were evaluated during index hospitalization and up to 30 days and 6 months. RESULTS: Eighty patients underwent cardiac catheterization at a median of 6.5 days following admission; in 86.3% of cases a patent infarct-related artery was found; in 71% of patients a coronary angioplasty was performed, with stenting in 88% of cases. Procedure-related complications were infrequent. No deaths occurred during hospitalization and at 30 days; at 6 months the mortality rate was 1.3%. In-hospital reinfarction occurred in 3.8% of patients, in 4% at 30 days and in 5.3% at 6 months. The rate of any new revascularization was 2.6% at 30 days and 11% at 6 months. CONCLUSIONS: Although obtained in a small observational study, our data, unlike those from previous studies, suggest that an invasive strategy after fibrinolysis in STEMI is safe and associated with low mortality and morbidity rates in the short and medium-terms.