Pleiotrophin over-expression provides trophic support to dopaminergic neurons in parkinsonian rats

Background: Pleiotrophin is known to promote the survival and differentiation of dopaminergic neurons in vitro and is up-regulated in the substantia nigra of Parkinson's disease patients. To establish whether pleiotrophin has a trophic effect on nigrostriatal dopaminergic neurons in vivo, we injected a recombinant adenovirus expressing pleiotrophin in the substantia nigra of 6-hydroxydopamine lesioned rats. Results: The viral vector induced pleiotrophin over-expression by astrocytes in the substantia nigra pars compacta, without modifying endogenous neuronal expression. The percentage of tyrosine hydroxylase-immunoreactive cells as well as the area of their projections in the lesioned striatum was higher in pleiotrophin-treated animals than in controls. Conclusions: These results indicate that pleiotrophin over-expression partially rescues tyrosine hydroxylase-immunoreactive cell bodies and terminals of dopaminergic neurons undergoing 6-hydroxydopamine-induced degeneration

Six Action Steps to Address Global Disparities in Parkinson Disease: A World Health Organization Priority

Importance: The Global Burden of Disease study conducted between 1990 and 2016, based on a global study of 195 countries and territories, identified Parkinson disease (PD) as the fastest growing neurological disorder when measured using death and disability. Most people affected by PD live in low- and middle-income countries (LMICs) and experience large inequalities in access to neurological care and essential medicines. This Special Communication describes 6 actions steps that are urgently needed to address global disparities in PD. Observations: The adoption by the 73rd World Health Assembly (WHA) of resolution 73.10 to develop an intersectoral global action plan on epilepsy and other neurological disorders in consultation with member states was the stimulus to coordinate efforts and leverage momentum to advance the agenda of neurological conditions, such as PD. In April 2021, the Brain Health Unit at the World Health Organization convened a multidisciplinary, sex-balanced, international consultation workshop, which identified 6 workable avenues for action within the domains of disease burden; advocacy and awareness; prevention and risk reduction; diagnosis, treatment, and care; caregiver support; and research. Conclusions and Relevance: The dramatic increase of PD cases in many world regions and the potential costs of PD-associated treatment will need to be addressed to prevent possible health service strain. Across the board, governments, multilateral agencies, donors, public health organizations, and health care professionals constitute potential stakeholders who are urged to make this a priority

Does Parkinson's disease start in the gut?

ABSTRACT Current understanding of the pathophysiology of Parkinson's disease suggests a key role of the accumulation of alpha-synuclein in the pathogenesis. This critical review highlights major landmarks, hypotheses and controversies about the origin and progression of synucleinopathy in Parkinson's disease, leading to an updated review of evidence suggesting the enteric nervous system might be the starting point for the whole process. Although accumulating and compelling evidence favors this theory, the remaining knowledge gaps are important points for future studies

Dancing Dorsal Quadrilaterals: A Novel Peripherally Induced Movement Disorder

Recognized peripherally induced movement disorders include the painful legs moving toes syndrome, postamputation dyskinesias, and belly dancer dyskinesias. To introduce and characterize the dancing dorsal quadrilaterals, a novel peripherally induced movement disorder that predominantly affects dorsal quadrilateral muscles (trapezius and rhomboids) after upper spine instrumentation. Between 1990 and 2015, a total of 4 patients who developed abnormal movements of the dorsal quadrilateral muscles after upper spine instrumentation were referred to movement disorders clinics at 3 academic medical centers in the United States, Canada, and Argentina. A prospective and retrospective analysis of the clinical and electrophysiologic characteristics of their abnormal movements is presented in this brief report. Data were analyzed between July 2015 and January 2018. Extensive upper spine instrumentation complicated with misalignment and prolonged postsurgical neuropathic pain. Video documentation of clinical and electrophysiologic characteristics of dancing dorsal quadrilaterals. Four patients with upper spine disease (2 women and 2 men, ranging in age from early 30s to early 70s) required extensive surgical manipulation and instrumentation that was complicated by misalignment, prolonged dorsal neuropathic pain, and unusual abnormal movements. These movements consisted of semirhythmic, repetitive writhing, and jerky movements of the scapular region with distinctive rotatory motions. They are referred to as the dancing dorsal quadrilaterals because they predominantly affected the bilateral trapezius and rhomboids (dorsal quadrilateral muscles) but could spread to adjacent muscles, and they are similar in appearance and possibly pathogenesis to "belly dancer" dyskinetic movements. The movements of the dancing dorsal quadrilaterals occur when upright but not when lying down or during voluntary muscle activation. Sensory stimulation also diminishes the movements. Long-duration bursts of normal motor unit potentials with normal recruitment pattern were evidenced. The dancing dorsal quadrilaterals syndrome represents a further example of a peripherally induced movement disorder characterized by neuropathic pain preceding a regional movement disorder following soft-tissue or nerve injury

Pleiotrophin over-expression rescues dopaminergic neurons in parkinsonian rats

Background: Pleiotrophin is known to promote the survival and differentiation of dopaminergic neurons in vitro and is up-regulated in the substantia nigra of Parkinson's disease patients. To establish whether pleiotrophin has a trophic effect on nigrostriatal dopaminergic neurons in vivo, we injected a recombinant adenovirus expressing pleiotrophin in the substantia nigra of 6-hydroxydopamine lesioned rats. Results: The viral vector induced pleiotrophin over-expression by astrocytes in the substantia nigra pars compacta, without modifying endogenous neuronal expression. The percentage of tyrosine hydroxylase-immunoreactive cells as well as the area of their projections in the lesioned striatum was higher in pleiotrophin-treated animals than in controls. Conclusions: These results indicate that pleiotrophin over-expression partially rescues tyrosine hydroxylase-immunoreactive cell bodies and terminals of dopaminergic neurons undergoing 6-hydroxydopamine-induced degeneration

Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease

Whether the treatment of Parkinson's disease has to be initiated with levodopa or a D2 agonist like pramipexole remains debatable. Levodopa is more potent against symptoms than D2 agonists, but D2 agonists are less prone to induce motor complications and may have neuroprotective effects. Although regulation of plastic changes in striatal circuits may be the key to their different therapeutic potential, the gene expression patterns induced by de novo treatments with levodopa or D2 agonists are currently unknown. By studying the whole striatal transcriptome in a rodent model of early stage Parkinson's disease, we have identified the gene expression patterns underlying therapeutically comparable chronic treatments with levodopa or pramipexole. Despite the overall relatively small size of mRNA expression changes at the level of individual transcripts, our data show a robust and complete segregation of the transcript expression patterns induced by both treatments. Moreover, transcripts related to oxidative metabolism and mitochondrial function were enriched in levodopa-treated compared to vehicle-treated and pramipexole-treated animals, whereas transcripts related to olfactory transduction pathways were enriched in both treatment groups compared to vehicle-treated animals. Thus, our data reveal the plasticity of genetic striatal networks possibly contributing to the therapeutic effects of the most common initial treatments for Parkinson's disease, suggesting a role for oxidative stress in the long term complications induced by levodopa and identifying previously overlooked signaling cascades as potentially new therapeutic targets. (C) 2015 Elsevier Ltd. All rights reserved

Screening for idiopathic REM sleep behavior disorder: usefulness of actigraphy

Abstract Study Objectives To evaluate the utility of multimodal low-cost approaches including actigraphy, a wrist-worn device monitoring rest/activity cycles, in identifying patients with idiopathic REM sleep behavior disorder (iRBD). Methods: Seventy patients diagnosed with sleep disorders causing different motor manifestations during sleep (iRBD, sleep apnea, restless legs syndrome) and 20 subjects without any relevant motor manifestation during sleep, underwent video-polysomnography (vPSG) and 2 week actigraphy, completed six validated RBD screening questionnaires, and sleep apps use was assessed. Actigraphy was analyzed automatically, and visually by seven blinded sleep medicine experts who rated as “no,” “possible,” and “probable” RBD. Results: Quantitative actigraphy analysis distinguished patients from controls, but not between patients with different types of motor activity during sleep. Visual actigraphy rating by blinded experts in sleep medicine using pattern recognition identified vPSG confirmed iRBD with 85%–95% sensitivity, 79%–91% specificity, 81%–91% accuracy, 57.7% ± 11.3% positive predictive value, 95.1% ± 3.3% negative predictive value, 6.8 ± 2.2 positive likelihood ratio, 0.14 ± 0.05 negative likelihood ratio and 0.874–0.933 area under the ROC curve (AUC). AUC of the best performing questionnaire was 0.868. Few patients used sleep apps; therefore, their potential utility in the evaluated patients’ groups is limited. Conclusions: Visual analysis of actigraphy using pattern recognition can identify subjects with iRBD, and is able to distinguish iRBD from other motor activities during sleep, even when patients are not aware of the disease in contrast to questionnaires. Therefore, actigraphy can be a reliable screening instrument for RBD potentially useful in the general population