A cross-sectional multicenter study of cognitive and behavioural features in multiple system atrophy patients of the parkinsonian and cerebellar type

Imaging and neuropathology studies have demonstrated significant abnormalities not only in subcortical, but also in cortical regions of patients with multiple system atrophy (MSA). This raises the possibility that cognitive dysfunction may contribute to the clinical spectrum of this disorder to a greater extent than it is currently not widely appreciated. In this cross-sectional multicenter study from the European multiple system atrophy study group (http://www.emsa-sg.org), we applied an extensive neuropsychological test battery in a series of 61 clinically diagnosed probable MSA patients. The results demonstrated that general cognitive decline as assessed by MMSE was uncommon (2 out of 61 patients <24). In contrast, frontal lobe-related functions (as measured by FAB) were impaired in 41 % of patients, with abstract reasoning and sustained attention less compromised. This pattern was similar to our control group of 20 patients with Parkinson’s disease (matched for disease duration and age at onset). There was no difference in cognitive performance between MSA patients with the parkinsonian versus the cerebellar variant. Behaviourally, MSA patients had greater depression than PD and in the case of MSA of the cerebellar variant significantly lower anxiety. Our data show that cognitive abnormalities are relatively frequent in multiple system atrophy and this involves primarily frontal-executive functions. Their contribution to clinical disability and disease progression needs to be addressed in larger prospective studies.     

Vitamin D deficiency in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder affecting, among others, the endocrine system, with derangement of steroid hormones functions. Vitamin D is a steroid recognized for its role in calcium homeostasis. In addition, vitamin D influences muscle metabolism by genomic and non-genomic actions, including stimulation of the insulin-like-growth-factor 1 (IGF1), a major regulator of muscle trophism. To verify the presence of vitamin D deficit in DM1 and its possible consequences, serum 25-hydroxyvitamin D (25(OH)D), calcium, parathormone (PTH), and IGF1 levels were measured in 32 DM1 patients and in 32 age-matched controls. Bone mineral density (BMD) and proximal muscle strength were also measured by DXA and a handheld dynamometer, respectively. In DM1 patients, 25(OH)D levels were reduced compared to controls, and a significant decrease of IGF1 was also found. 25(OH)D levels inversely correlated with CTG expansion size, while IGF1 levels and muscle strength directly correlated with levels of 25(OH)D lower than 20 and 10 ng/ml, respectively. A significantly higher percentage of DM1 patients presented hyperparathyroidism as compared to controls. Calcium levels and BMD were comparable between the two groups. Oral administration of cholecalciferol in 11 DM1 patients with severe vitamin D deficiency induced a normal increase of circulating 25(OH)D, ruling out defects in intestinal absorption or hepatic hydroxylation. DM1 patients show a reduction of circulating 25(OH)D, which correlates with genotype and may influence IGF1 levels and proximal muscle strength. Oral supplementation with vitamin D should be considered in DM1 and might mitigate muscle weakness.     

Patients with rest-tremor and scans with ipsilateral dopaminergic deficit

Dopamine transporter imaging is typically abnormal in Parkinson’s disease and shows reduced striatal uptake, which is typically greater contralateral to the clinically more affected side. However, tremor-dominant Parkinson’s disease patients may have significantly lower uptake in the striatum ipsilateral to the rest-tremor compared to akinetic-rigid PD patients, implying a possible role of an ipsilateral deficit in the generation of rest-tremor.We report here three patients with rest-tremor and the unexpected finding of an ipsilateral presynaptic dopaminergic deficit with normal uptake contralateral to the rest-tremor in dopamine transporter imaging. We divided them in two groups, with and without a corresponding structural lesion in brain imaging. These data may suggest a role of ipsilateral dopaminergic deficit in the generation of rest-tremor. An explanation of these findings could be damage of crossed dopaminergic fibres from the substantia nigra to thalamus, which can cause motor impairment ipsilateral to dopamine depletion experimentally. This is speculative but there is no doubt that these cases exist and we encourage others to report similar cases, as this may assist in the better understanding of the yet unknown pathophysiology of rest-tremor.     

Cognitive and MRI correlates of orthostatic hypotension in Parkinson’s disease

Orthostatic hypotension (OH) is a frequent nonmotor feature of Parkinson’s disease (PD), and its occurrence has been associated with cognitive impairment. The underlying mechanism could be mediated by development of cerebrovascular disease induced by chronic or episodic hypoperfusion, but the extent of brain vascular load in PD patients with OH has never been investigated. This study aimed to assess the relationship between OH and cognitive function in PD patients and to investigate the contribution of brain vascular lesions. Forty-eight PD patients underwent a tilt table test (TT) to assess supine and orthostatic blood pressure as well as an extensive neuropsychological evaluation to evaluate cognitive function. Brain magnetic resonance imaging was acquired in 44/48 patients and analyzed by a visual semiquantitative scale. Twenty-three patients presented OH at TT (13/23 were symptomatic), and 25 did not. There were no differences in motor severity or disease duration between patients with and without OH. In patients with OH we found significantly worse cognitive performance in specific tasks, such as sustained attention, visuospatial and verbal memory, compared with patients without OH. However, there were no differences in vascular burden between the two groups. Our study confirms that there is an association between OH and selective cognitive deficits in PD, but rebuts the hypothesis that this is underlined by the development of cerebrovascular disease.     

Prolonged distal motor latency of median nerve does not improve diagnostic accuracy for CIDP

Journal of Neurology - Compression of the median nerve at the carpal tunnel can give demyelinating features and result in distal motor latency (DML) prolongation fulfilling the EFNS/PNS...     

Effect of myo-inositol and melatonin versus myo-inositol,in a randomized controlled trial,for improving in vitro fertilization of patients with polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) induces anovulation in women of reproductive age, and is one of the pathological factors involved in the failure of in vitro fertilization (IVF). Indeed, PCOS women are characterized by poor quality oocytes. Therefore, a treatment for enhancing oocyte quality becomes crucial for these patients. Myo-Inositol and melatonin proved to be efficient predictors for positive IVF outcomes, correlating with high oocyte quality. We tested the synergistic effect of myo-inositol and melatonin in IVF protocols with PCOS patients in a randomized, controlled, double-blind trial. Five-hundred twenty-six PCOS women were divided into three groups: Controls (only folic acid: 400?mcg), Group A (Inofolic® plus, a daily dose of myo-inositol: 4000?mg, folic acid: 400?mcg, and melatonin: 3?mg), and Group B (Inofolic®, a daily dose of myo-inositol: 4000?mg, and folic acid: 400?mcg). The main outcome measures were oocyte and embryo quality, clinical pregnancy and implantation rates. The treatment lasted from the first day of the cycle until 14 days after embryo transfer. Myo-inositol and melatonin have shown to enhance, synergistically, oocyte and embryo quality. In consideration of the beneficial effect observed in our trial and on the bases of previous studies, we decided to integrate routinely MI and M supplementation in the IVF protocols. The same treatment should be taken carefully in consideration in all procedures of this kind.     

Comparison of methylprednisolone and ketoprofen after multiple third molar extraction: a randomized controlled study

In a prospective, double blind, and randomized study, we compared methylprednisolone and ketoprofen after anesthesia for multiple third molar extraction. In addition to paracetamol, 90 patients were allocated to receive intravenously either ketoprofen 100 mg or methylprednisolone 1 mg/kg. Severity of pain was measured with visual analogue scale (VAS) in recovery room. Sixty-three percent of patients receiving methylprednisolone had a VAS score <30 mm compared with 42% of those receiving ketoprofen (P = 0.04), with no difference in the consumption of morphine. We observed only marginal difference between methylprednisolone and ketoprofen to relieve pain after this surgery.     

Incidence of low central venous oxygen saturation during unplanned admissions in a multidisciplinary intensive care unit: an observational study

Introduction  

It has been shown that early central venous oxygen saturation (ScvO₂)-guided optimization of hemodynamics can improve outcome in septic patients. The early ScvO₂ profile of other patient groups is unknown. The aim of this study was to characterize unplanned admissions in a multidisciplinary intensive care unit (ICU) with respect to ScvO₂ and outcome.     

Impact of a goal-directed therapy protocol on postoperative fluid balance in patients undergoing liver transplantation: A retrospective study

Objective

Liver transplantation carries major risks during the perioperative period. Few studies focused on the hemodynamics of patients undergoing liver transplantation. The present study was aimed to evaluate the impact of the implementation of a protocol including goal-directed therapy in patients undergoing liver transplantation. Our first goal was to determine its impact on the fluid balance. Secondarily, we evaluated possible improvements in the patient outcomes.

Study design

A before and after study.

Patients and methods

Fifty patients undergoing liver transplantation were included during two successive six-month periods. During the first period, the management of the patients was left at the discretion of the senior physicians (control group, n = 25). During the second period, the patients were treated according to a predetermined protocol including a specific hemodynamic monitoring (protocol group, n = 25).

Results

The fluid balance was negative in the protocol group and positive in the control group at 24 h (−606 mL vs. +3445 mL, P < 0.01) and 48 h (−2315 mL vs. +1170 mL, P < 0.01) after liver transplantation. The volume of the crystalloid administration was lower in the protocol group than in the control group (5000 mL vs. 8000 mL, P < 0.01, and 1500 mL vs. 6000 mL, P < 0.01, during surgery and 48 h after liver transplantation, respectively). The duration of mechanical ventilation and postoperative ileus were significantly reduced in the protocol group, as compared with the control group, 20 h vs. 94 h (P < 0.01) and 4 days vs. 6 days (P < 0.01), respectively.

Conclusion

For patients undergoing liver transplantation, the implementation of a protocol aiming to optimize hemodynamics was associated with reduced fluid balance and decreased requirement for mechanical ventilation and postoperative ileus duration.     

Different effects of high and low shear stress on platelet-derived growth factor isoform release by endothelial cells: consequences for smooth muscle cell migration

In the present study, we analyzed the effect of conditioned media (CM) from bovine aortic endothelial cells exposed to laminar shear stress (SS) of 5 dyne/cm2 (SS5) or 15 dyne/cm2 (SS15) for 16 hours on smooth muscle cell (SMC) migration. In response to CM from bovine aortic endothelial cells exposed to SS5 (CMSS5) and SS15 (CMSS15), migration was 45 +/- 5.5 and 30 +/- 1.5 cells per field, respectively (P<0.05). Similar results were obtained with SS of 2 versus 20 dyne/cm2 and also when SS of 5 and 15 dyne/cm2 lasted 24 hours. Platelet-derived growth factor (PDGF)-AA levels in CMSS5 and CMSS15 were 9 +/- 7 and 18 +/- 5 ng/10(6) cells for 16 hours, respectively (P<0.05); PDGF-BB levels in CMSS5 and CMSS15 were 38 +/- 10 and 53 +/- 10 ng/10(6) cells for 16 hours, respectively (P<0.05). PDGF receptor alpha (PDGFRalpha) and PDGF receptor beta (PDGFRbeta) in SMCs were phosphorylated by CMSS15>CMSS5. In response to CMSS15, a neutralizing antibody against PDGF-AA enhanced SMC migration to a level comparable to that of CMSS5; in contrast, antibodies against PDGF-BB abolished SMC migration. Transfection of SMCs with a dominant-negative PDGFRalpha or PDGFRbeta increased or inhibited, respectively, SMC migration in response to CMSS15. Overexpression of wild-type PDGFRalpha inhibited SMC migration in response to CMSS5, CMSS15, or recombinant PDGF-BB (P<0.001). These results suggest that the ability of high SS to inhibit arterial wall thickening in vivo may be related to enhanced activation of PDGFRalpha in SMCs by PDGF isoforms secreted by the endothelium.