Unilateral subthalamotomy in Parkinson's disease: Cognitive, psychiatric and, neuroimaging changes

Unilateral subthalamotomy is an effective treatment for the cardinal motor features of Parkinson's disease (PD). However, non-motor changes possibly associated with right or left subthalamotomy remain unknown. Our aim was to assess cognitive, psychiatric and neuroimaging changes after treatment with unilateral subthalamotomy. Fourteen medicated patients with PD were evaluated before and after (mean 6 months after operation) unilateral subthalamotomy (5 right, 9 left). In addition to motor assessments, cognitive (global cognition and executive functions), psychiatric (apathy, depression, anxiety, mania, hypo- and hyperdopaminergic behaviours, impulsivity), quality of life evaluations and volume of lesions were obtained. After surgery, significant improvement of motor signs was observed. Unilateral subthalamotomy improved general cognitive status, but left subthalamotomy reduced semantic verbal fluency compared to the pre-operative state. Depression and quality of life were improved with both right and left subthalamotomy. However, hyper-emotionality was present after surgery and right subthalamotomy increased impulsivity and disinhibition (on NeuroPsychiatric Inventory and Ardouin Scale for Behaviour in PD), a result linked to larger lesion volumes. We conclude that unilateral subthalamotomy is effective for treating the cardinal motor features of PD and improves mood. Right subthalamotomy is associated with greater risk of impulsivity and disinhibition, while left subthalamotomy induces further impairment of semantic verbal fluency

Effects of Gestational Intermittent Hypoxia on Placental Morphology and Fetal Development in a Murine Model of Sleep Apnea

Obstructive sleep apnea (OSA) during pregnancy is characterized by episodes of intermittent hypoxia (IH) during sleep, resulting in adverse health outcomes for mother and offspring. Despite a prevalence of 8-20% in pregnant women, this disorder is often underdiagnosed.We have developed a murine model of gestational OSA to study IH effects on pregnant mothers, placentas, fetuses, and offspring. One group of pregnant rats was exposed to IH during the last 2 weeks of gestation (GIH). One day before the delivery date, a cesarean section was performed. Other group of pregnant rats was allowed to give birth at term to study offspring's evolution.Preliminary results showed no significant weight differences in mothers and fetuses. However, the weight of GIH male offspring was significantly lower than the controls at 14 days (p < 0.01). The morphological study of the placentas showed an increase in fetal capillary branching, expansion of maternal blood spaces, and number of cells of the external trophectoderm in the tissues from GIH-exposed mothers. Additionally, the placentas from the experimental males were enlarged (p < 0.05). Further studies are needed to follow the long-term evolution of these changes to relate the histological findings of the placentas with functional development of the offspring in adulthood.Ayudas para la realización de proyectos de investigación UVa 2021 (PROYEMER 57-E.O.

Theta burst magnetic stimulation over the pre-supplementary motor area improves motor inhibition

BACKGROUND: Stopping an ongoing motor response or resolving conflict induced by conflicting stimuli are associated with activation of a right-lateralized network of inferior frontal gyrus (IFG), pre-supplementary motor area (pre-SMA) and subthalamic nucleus (STN). However, the roles of the right IFG and pre-SMA in stopping a movement and in conflict resolution remain unclear. We used continuous theta burst stimulation (cTBS) to examine the involvement of the right IFG and pre-SMA in inhibition and conflict resolution using the conditional stop signal task. METHODS: We measured stop signal reaction time (SSRT, measure of reactive inhibition), response delay effect (RDE, measure of proactive action restraint) and conflict induced slowing (CIS, measure of conflict resolution). RESULTS: Stimulation over the pre-SMA resulted in significantly shorter SSRTs (improved inhibition) compared to sham cTBS. This effect was not observed for CIS, RDE, or any other measures. cTBS over the right IFG had no effect on SSRT, CIS, RDE or on any other measure. CONCLUSIONS: The improvement of SSRT with cTBS over the pre-SMA suggests its critical contribution to stopping ongoing movements

Slow oscillatory activity and levodopa-induced dyskinesias in Parkinson’s disease

The pathophysiology of levodopa-induced dyskinesias (LID) in Parkinson’s disease is not well understood. We have recorded local field potentials (LFP) from macroelectrodes implanted in the subthalamic nucleus (STN) of 14 patients with Parkinson’s disease following surgical treatment with deep brain stimulation. Patients were studied in the ‘Off’ medication state and in the ‘On’ motor state after administration of levodopa– carbidopa (po) or apomorphine (sc) that elicited dyskinesias in 11 patients. The logarithm of the power spectrum of the LFP in selected frequency bands (4–10, 11–30 and 60–80 Hz) was compared between the ‘Off’ and ‘On’ medication states. A peak in the 11–30 Hz band was recorded in the ‘Off’ medication state and reduced by 45.2% (P < 0.001) in the ‘On’ state. The ‘On’ was also associated with an increment of 77. 6% (P < 0.001) in the 4–10 Hz band in all patients who showed dyskinesias and of 17.8% (P < 0.001) in the 60–80 Hz band in the majority of patients. When dyskinesias were only present in one limb (n = 2), the 4–10 Hz peak was only recorded in the contralateralSTN. These findings suggest that the 4–10 Hz oscillation is associated with the expression of LID in Parkinson’s disease

Parkinsonism caused by adverse drug reactions: a case series

<p>Abstract</p> <p>Introduction</p> <p>Parkinsonism puts a high direct cost burden on both patient and caregiver. Several reports of drug-induced parkinsonism have been published, but to the best of our knowledge, there has not been any report of quinine or halothane inducing parkinsonism.</p> <p>Case presentation</p> <p>We describe two cases of parkinsonism possibly caused by adverse drug reaction to quinine in a 29-year-old black Nigerian woman and to halothane in a 36-year-old black Hausa (Nigerian) man who received it as general anaesthesia for appendicectomy in our teaching hospital.</p> <p>Conclusion</p> <p>These are two unusual cases of parkinsonism caused by adverse drug reactions to high-dose quinine and to halothane as general anaesthesia. We consider that these two cases are important in bringing this potential side-effect to the attention of both pharmacologists and primary care physicians as these are two of the most commonly used medications in our clinics. We conclude that parkinsonism should be included among the adverse drug reactions to high-dose quinine and halothane general anaesthetic.</p

Update of the MDS research criteria for prodromal Parkinson's disease

The MDS Research Criteria for Prodromal PD allow the diagnosis of prodromal Parkinson's disease using an evidence‐based conceptual framework, which was designed to be updated as new evidence becomes available. New prospective evidence of predictive values of risk and prodromal markers published since 2015 was reviewed and integrated into the criteria. Many of the predictive values (likelihood ratios, LR) remain unchanged. The positive likelihood ratio notably increase for olfactory loss and decreased for substantia nigra hyperechogenicity. Negative likelihood ratio remained largely unchanged for all markers. New levels of diagnostic certainty for neurogenic and symptomatic orthostatic hypotension have been added, which substantially differ in positive likelihood ratio from the original publication. For intermediate strength genetic variants, their age‐related penetrance is now incorporated in the calculation of the positive likelihood ratio. Moreover, apart from prospective studies, evidence from cross‐sectional case‐control genome‐wide association studies is also considered (given their likely lack of confounding and reverse causation), and to account for the effect of multiple low‐penetrance genetic variants polygenic risk scores are added to the model. Diabetes, global cognitive deficit, physical inactivity, and low plasma urate levels in men enter the criteria as new markers. A web‐based prodromal PD risk calculator allows the calculation of probabilities of prodromal PD for individuals. Several promising candidate markers may improve the diagnostic accuracy of prodromal PD in the future

New MRI, 18F-DOPA and 11C-(+)-alpha-dihydrotetrabenazine templates for Macaca fascicularis neuroimaging: advantages to improve PET quantification

Normalization of neuroimaging studies to a stereotaxic space allows the utilization of standard volumes of interest (VOIs) and voxel-based analysis (SPM). Such spatial normalization of PET and MRI studies requires a high quality template image. The aim of this study was to create new MRI and PET templates of 18F-DOPA and 11C-(+)-α-dihydrotetrabenazine (11C-DTBZ) of the Macaca fascicularis brain, an important animal model of Parkinson's disease. MRI template was constructed as a smoothed average of the scans of 15 healthy animals, previously transformed into the space of one representative MRI. In order to create the PET templates, 18F-DOPA and 11C-DTBZ PET of the same subjects were acquired in a dedicated small animal PET scanner and transformed to the created MRI template space. To validate these templates for PET quantification, parametric values obtained with a standard VOI-map applied after spatial normalization to each template were statistically compared to results computed using individual VOIs drawn for each animal. The high correlation between both procedures validated the utilization of all the templates, improving the reproducibility of PET analysis. To prove the utility of the templates for voxel-based quantification, dopamine striatal depletion in a representative monkey treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was assessed by SPM analysis of 11C-DTBZ PET. A symmetric reduction in striatal 11C-DTBZ uptake was detected in accordance with the induced lesion. In conclusion, templates of M. fascicularis brain have been constructed and validated for reproducible and automated PET quantification. All templates are electronically available via the internet

Ecological implications of a flower size/number trade-off in tropical forest trees

Peer reviewedPublisher PD

Elevated Pontine and Putamenal GABA Levels in Mild-Moderate Parkinson Disease Detected by 7 Tesla Proton MRS

Background: Parkinson disease (PD) is characterized by the degeneration of nigrostriatal dopaminergic neurons. However, postmortem evidence indicates that the pathology of lower brainstem regions, such as the pons and medulla, precedes nigral involvement. Consistently, pontomedullary damage was implicated by structural and PET imaging in early PD. Neurochemical correlates of this early pathological involvement in PD are unknown. Methodology/Principal Finding: To map biochemical alterations in the brains of individuals with mild-moderate PD we quantified neurochemical profiles of the pons, putamen and substantia nigra by 7 tesla (T) proton magnetic resonance spectroscopy. Thirteen individuals with idiopathic PD (Hoehn &amp; Yahr stage 2) and 12 age- and gender-matched healthy volunteers participated in the study. c-Aminobutyric acid (GABA) concentrations in the pons and putamen were significantly higher in patients (N = 11, off medications) than controls (N = 11, p,0.001 for pons and p,0.05 for putamen). The GABA elevation was more pronounced in the pons (64%) than in the putamen (32%). No other neurochemical differences were observed between patients and controls. Conclusion/Significance: The GABA elevation in the putamen is consistent with prior postmortem findings in patients with PD, as well as with in vivo observations in a rodent model of PD, while the GABA finding in the pons is novel. The more significant GABA elevation in the pons relative to the putamen is consistent with earlier pathological involvement of th

II Congrés Internacional sobre Traducció : abril 1994 : actes

Machine learning-based approach unravels distinct pathological signatures induced by patient-derived α-synuclein seeds in monkeys. Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)-rich protein aggregates [termed "Lewy bodies" (LBs)], is a well-established characteristic of Parkinson's disease (PD). Much evidence, accumulated from multiple experimental models, has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning-based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneratio