Monday, September 26, 2022

Journal Of Parkinson’s Disease

Opportunities For Input From Pharmacy Professionals

Deep Brain Stimulation (DBS)

As there is no cure for PD, medication management is crucial in managing the disease. Pharmacy professionals can play a significant role in both primary and secondary care. It is important that pharmacy professionals are familiar with PD symptoms and are aware of which referral pathway is most suitable for the patient. Many of the symptoms are straightforward to manage for example, constipation, and simple interventions can make a big difference to the patients quality of life.

Pharmacy professionals should also be aware of local services that are available to both patients and themselves. The Parkinsons UK website provides support and resources for healthcare professionals, patients and their family or carers.

Dysfunctional Protein Clearance Systems

There are two central protein clearance systems within cells responsible for the removal of dysfunctional proteins: the ubiquitin-proteasome system and the autophagy-lysosome pathway. The UPS is primarily responsible for breaking down abnormal proteins, and it does so by tagging them with ubiquitin and transporting them to the proteasome for degradation. The autophagy-lysosome pathway is divided into three constituents: macroautophagy, microautophagy, and chaperone-mediated autophagy . Briefly, in macroautophagy, intracellular components, including cytosolic proteins, are engulfed by the autophagosome, which then fuses with the lysosome, leading to the breakdown of its contents. On the other hand, in microautophagy, the lysosome alone engulfs and destroys cytoplasmic components. CMA is a more selective process, whereby molecular chaperones target specific proteins and transport them to the lysosome for degradation . Monomeric -synuclein is generally cleared by both the UPS and the autophagy-lysosome pathway , and damage in either of their machineries is implicated in the pathogenesis of PD by contributing to the accumulation of defective proteins, in particular soluble misfolded -synuclein .

Toxic Protein Accumulation Causes Nerve Damage In Parkinsons Disease

Parkinsons disease is a neurological illness that causes tremors, slow movement, and joint stiffness and can lead to significant cognitive impairments. It has a high global prevalence. The occurrence of Parkinsons may rise as people live longer lives. The illness can cause movement abnormalities and several psychological and physiological issues.

Illustration Showing How -Syn monomers Form Aggregates Inside Neurons Inducing Cell Toxicity. Credit: Nature Neuroscience

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Parkinsons disease occurs due to the death of neurons in some brain areas. A protein known as alpha-synuclein misfolds and joins together into damaging aggregates in afflicted nerve cells. The mechanics behind the cause of the protein pathology are not fully understood. The scientists in this new study created a new sensitive way of studying what occurs to alpha-synuclein throughout the early stages of sickness. The scientists discovered how an accumulation of toxic protein begins within nerve cells in Parkinsons disease, eventually leading to neuronal cell death. The study gives fresh insight into a critical physiological mechanism underlying Parkinsons disease by investigating how, where, and why this build-up occurs.

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Symptomatic Treatment Of Levodopa

Levodopa-resistant symptoms

There are many levodopa-resistant motor symptoms such as dysarthria and dysphagia, freezing of gait, postural instability and dysautonomia. Freezing, sudden immobility of the feet when attempting to walk, often associated with falls, may be seen in either the off or the on period. Although off-period freezing may improve with optimisation of medications, on-period freezing is usually resistant to pharmacologic treatment.

Physical therapy, including strategies that utilise sensory cues, such as stepping over a horizontal laser beam, may be helpful. Dysarthria and dysphagia are often treated by speech and voice therapists. Injection of botulinum toxin has been found to be effective in controlling high-amplitude rest and postural hand tremor which may be resistant to levodopa. Botulinum toxin may be also beneficial in the treatment of a variety of other non-levodopa responsive parkinsonian symptoms such as blepharospasm, apraxia of eyelid opening, anterocollis, camptocormia, bruxism, sialorrhea, seborrhea, hyperhidrosis, overactive bladder and constipation.

Non-motor symptoms

Neurosurgery For Pd: The Lesional Era

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Both performing pallidotomy and making thalamotomy lesions could be done safely only unilaterally on one brain hemisphere because performing bilateral lesions increased the risks of dysarthria, dysphonia and disturbances of balance . It was the advent of DBS that paved the way for performing bilateral surgery safely and for enabling the discovery of new brain targets that provided more efficient control of symptoms of PD.

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Rapid Eye Movement Sleep Behaviour Disorder

REM sleep behaviour is associated with PD and is a prodromal symptom in many cases. Patients with REM sleep disorder often physically act out vivid dreams during REM sleep, which can affect their quality of life and that of their family and carers. NICE recommends the off-label use of clonazepam or melatonin . Benzodiazepines are cautioned in the elderly population therefore, this patient cohort must be monitored closely by their care team if started on clonazepam.

Tanya Simuni Jurg L Jaggi Heather Mulholland Howard I Hurtig Amy Colcher Andrew D Siderowf Bernard Ravina Brett E Skolnick Reid Goldstein Matthew B Stern And Gordon H Baltuch

Object. Palliative neurosurgery has reemerged as a valid therapy for patients with advanced Parkinson disease that is complicated by severe motor fluctuations. Despite great enthusiasm for long-term deep brain stimulation of the subthalamic nucleus , existing reports on this treatment are limited. The present study was designed to investigate the safety and efficacy of bilateral stimulation of the STN for the treatment of PD.

Methods. In 12 patients with severe PD, electrodes were stereotactically implanted into the STN with the assistance of electrophysiological conformation of the target location. All patients were evaluated preoperatively during both medication-off and -on conditions, as well as postoperatively at 3, 6, and 12 months during medication-on and -off states and stimulation-on and -off conditions. Tests included assessments based on the Unified Parkinson’s Disease Rating Scale and timed motor tests.

The stimulation effect was significant in patients who were in the medication-off state, resulting in a 47% improvement in the UPDRS Part III score at 12 months, compared with preoperative status. The benefit was stable for the duration of the follow-up period. Stimulation produced no additional benefit during the medication-on state, however, when compared with patient preoperative status. Significant improvements were made in reducing dyskinesias, fluctuations, and duration of off periods.

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Symptomatic Treatment Of Motor Symptoms

Levodopa

A majority of patients with PD require levodopa therapy within 2 years of symptom onset. Levodopa, the most effective drug in the treatment of PD, is almost always combined with carbidopa or benserazide, aromatic acid decarboxylase inhibitors that prevent its peripheral metabolism and markedly reduce the risk of nausea. Increasing the ratio of carbidopa:levodopa from the current standard 1:4 has been shown to increase on time without dyskinesia and reduce off time.

The global antiparkinsonian efficacy of levodopa is so predictable that a positive therapeutic response is used to support the diagnosis of PD. Adverse effects of levodopa include nausea and vomiting, orthostatic hypotension, sedation, confusion, sleep disturbance, hallucinations and dyskinesias. There are many different types of dyskinesia but peak-dose chorea or stereotypy and wearing off dystonia are most common. About half of the patients experience wearing off, and a third experience dyskinesias within 2 years after initiation of levodopa therapy. Latency from ingestion of levodopa to observable therapeutic benefit can be shortened by taking levodopa on an empty stomach , avoiding or reducing protein intake, or by crushing the levodopa tablet and mixing it with a carbonated beverage.

Other drugs

Besides levodopa, there are many other types of medications available for the treatment of PD-related motor symptoms: anticholinergics, amantadine, MAOIs, COMTIs, dopamine agonists and istradefylline.

A New Explanation For Nerve Injury In Parkinsons Disease

Cinpanemab in Early Parkinson’s Disease | NEJM

The exact method of how Parkinsons disease occur has been elusive to scientists for years. These limitations have prevented a better understanding of the illness and ways to address therapy.

The present research comprised a multi-team of scientists. The research team of neurologists, chemists, and structural biologists discovered that alpha-synuclein interacts with the membranes, or linings, of structures within neuronal cells. When it comes into contact with the membrane wall of the mitochondria, the part of the cell involved in energy production, it causes alpha-synuclein to misfold and clump.

The protein joins then accumulate heavily on the surface of the mitochondria, causing damage to the surface, causing holes to form on the membrane, and interfering with the mitochondrias ability to generate energy. These changes cause the mitochondria to release signals that cause the nerves to die. While there are several types of Parkinsons disease, this protein is known to misfold and join together in various forms. However, these misfolded proteins are cleaned and eliminated from the cell while neurons are healthy. The elimination process of this dangerous protein slows down as people age. The scientists hope to continue investigating how protein pathology inside cells impacts cell function and health.

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Management Of Parkinsons Disease

Overall treatment is specific to the patient and the symptoms they experience. Symptoms can be variable from day to day or even hour to hour therefore, it is important that patients have a good understanding of their treatment, disease, coping mechanism, support system and regular reviews. Life expectancy can be normal however, more advanced symptoms can lead to increased disability and poor health, which may make someone more vulnerable to complications .

Emmanuel Cuny Dominique Guehl Pierre Burbaud Christian Gross Vincent Dousset And Alain Rougier

Object. The goal of this study was to determine the most suitable procedure to localize the optimal site for high-frequency stimulation of the subthalamic nucleus for the treatment of advanced Parkinson disease.

Methods. Stereotactic coordinates of the STN were determined in 14 patients by using three different methods: direct identification of the STN on coronal and axial T2-weighted magnetic resonance images and indirect targeting in which the STN coordinates are referred to the anterior commissureposterior commissure line, which, itself, is determined either by using stereotactic ventriculography or reconstruction from three-dimensional MR images. During the surgical procedure, electrode implantation was guided by single-unit microrecordings on multiple parallel trajectories and by clinical assessment of stimulations. The site where the optimal functional response was obtained was considered to be the best target. Computerized tomography scanning was performed 3 days later and the scans were combined with preoperative 3D MR images to transfer the position of the best target to the same system of stereotactic coordinates. An algorithm was designed to convert individual stereotactic coordinates into an all-purpose PC-referenced system for comparing the respective accuracy of each method of targeting, according to the position of the best target.

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Pathogenesis Of Parkinsons Disease

A number of mechanisms have been implicated in PD pathogenesis, with -synuclein aggregation central to the development of the disease. Multiple other processes are thought to be involved, with several studies suggesting that abnormal protein clearance, mitochondrial dysfunction, and neuroinflammation play a role in the onset and progression of PD. However, the relationship between these pathways remains unclear.

Effects Of An Aquatic Physical Exercise Program On Ventilatory Parameters In People With Parkinsons Disease

New symptoms of early

Problems in the respiratory system are the main cause of death in Parkinsons disease . Ventilatory limitations can also be part of a vicious cycle involving physical-functional limitations and the patients perception of fatigue. The objective of this study was to analyze the effects of an aquatic physical exercise intervention program on ventilatory parameters, perception of fatigue, and gait capacity in participants with PD. This quasi-experimental study had a single group with repeated measures in four assessments, proposing an aquatic physical exercise intervention program. The inclusion criteria encompassed being in levels 1 to 4 on the Hoehn and Yahr scale and having a medical certificate for the activities. Assessments took place at 3-month intervals between themthe first period was the control, the second following the intervention, and the third period was the follow-up. The intervention had 25 biweekly sessions over 3 months. A total of 13 people participated in the intervention, without significant differences in the control period. Between the intervention assessments, they had statistically significant differences in MIP, MEP, FVC, Tiffeneau index, MVV, and fatigue. The study demonstrated that the aquatic physical exercise intervention was effective for ventilatory outcomes and fatigue in people with PD.

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Joachim K Krauss Thomas J Loher Ralf Weigel H Holger Capelle Sabine Weber And Jean

Object. The authors studied the long-term efficacy of deep brain stimulation of the posteroventral lateral globus pallidus internus up to 2 years postoperatively in patients with primary non-DYT1 generalized dystonia or choreoathetosis. The results are briefly compared with those reported for DBS in DYT1 dystonia , which is caused by the DYT1 gene.

Methods. Enrollment in this prospective expanded pilot study was limited to adult patients with severely disabling, medically refractory non-DYT1 generalized dystonia or choreoathetosis. Six consecutive patients underwent follow-up examinations at defined intervals of 3 months, 1 year, and 2 years postsurgery. There were five women and one man, and their mean age at surgery was 45.5 years. Formal assessments included both the Burke-Fahn-Marsden dystonia scale and the recently developed Unified Dystonia Rating Scale. Two patients had primary generalized non-DYT1 dystonia, and four suffered from choreoathetosis secondary to infantile cerebral palsy. Bilateral quadripolar DBS electrodes were implanted in all instances, except in one patient with markedly asymmetrical symptoms. There were no adverse events related to surgery.

Neuropathology Of Parkinsons Disease

Macroscopically, the brain in idiopathic PD is often unremarkable with mild atrophy of the frontal cortex and ventricular dilation in some cases. The main distinctive morphological change in the PD brain is observed in transverse sections of the brainstem, where almost all cases present with loss of the darkly pigmented area in the substantia nigra pars compacta and locus coeruleus. This pigmentation loss directly correlates with the death of dopaminergic neuromelanin-containing neurons in the SNpc and noradrenergic neurons in the locus coeruleus . Cell death in the SNpc is mostly restricted to a specific group of neuromelanin-containing dopaminergic neurons, namely the A9 neurons, while other neuronal and glial cell types are largely spared .

Coronal section at the level of the substantia nigra pars compacta in a control and a PD brain stained by hematoxylin and eosin. In both sections, the dark brown cells are the neuromelanin-containing dopaminergic neurons.

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Philip A Starr Chadwick W Christine Philip V Theodosopoulos Nadja Lindsey Deborah Byrd Anthony Mosley And William J Marks Jr

Object. Chronic deep brain stimulation of the subthalamic nucleus is a procedure that is rapidly gaining acceptance for the treatment of symptoms in patients with Parkinson disease , but there are few detailed descriptions of the surgical procedure itself. The authors present the technical approach used to implant 76 stimulators into the STNs of patients with PD and the lead locations, which were verified on postoperative magnetic resonance images.

Methods. Implantation procedures were performed with the aid of stereotactic MR imaging, microelectrode recording in the region of the stereotactic target to define the motor area of the STN, and intraoperative test stimulation to assess the thresholds for stimulation-induced adverse effects. All patients underwent postoperative MR imaging, which was performed using volumetric gradient-echo and T2-weighted fastspin echo techniques, computational reformatting of the MR image into standard anatomical planes, and quantitative measurements of lead location with respect to the midcommissural point and the red nucleus. Lead locations were statistically correlated with physiological data obtained during MER and intraoperative test stimulation.

Editors Of Clinical Trials Highlights

Possible link between vitamin B12 levels and dementia in Parkinsons disease

Kevin McFarthingParkinsons Advocate, Innovation Fixer Ltd, OxfordUnited Kingdom

Parkinson’s Disease and Movement Disorders Center, Northwestern University Feinberg School of Medicine, ChicagoUSA

Case Western Reserve University, ClevelandUSA

Case Western Reserve University, ClevelandUSA

Columbia University College of Physicians & Surgeons, New YorkUSA

École Polytechnique Fédérale de Lausanne, LausanneSwitzerland

Institut du Cerveau et de la Moelle épinière, ParisFrance

National Neurological Hospital Carlo Besta, MilanItaly

Harvard School of Public Health, BostonUSA

University of Ulm, Ulm, Germany

Jose Bras

Pierre and Marie Curie UniversityParis

Policlinico Gemelli, Catholic University, RomeItaly

Beijing Institute of Geriatrics, BeijingChina

University of California Los Angeles, Los AngelesUSA

Rush University Medical Center, ChicagoUSA

Johns Hopkins University School of Medicine, BaltimoreUSA

Johns Hopkins University School of Medicine, BaltimoreUSA

Connecticut Advocates for Parkinson’s, New Preston Marble DaleUSA

University of California San Francisco, San FranciscoUSA

The Feinstein Institute for Medical Research, New YorkUSA

United Arab Emirates University, Al-AinUnited Arab Emirates

Columbia University College of Physicians & Surgeons, New YorkUSA

University of British Columbia, VancouverCanada

Hospital de Santa Maria, LisbonPortugal

Tel Aviv University, Tel AvivIsrael

Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière, ParisFrance

Olle Lindvall

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Jrgen Voges Jens Volkmann Niels Allert Ralph Lehrke Athanasios Koulousakis Hans

Object. The goal of this study was to relate the degree of clinical improvement and that of energy consumption to the anatomical position of electrode poles used for long-term stimulation.

Methods. The authors conducted a retrospective analysis of 15 consecutive patients in whom targeting of the subthalamic nucleus had been performed using ventriculography, three-dimensional magnetic resonance imaging, and 3D computerized tomography, together with macrostimulation and teleradiographic control of the electrode position. In these patients the follow-up period ranged from 6 to 12 months. Postoperative improvement in contralateral motor symptoms, which was assessed by assigning a lateralized motor subscore of the Unified Parkinson’s Disease Rating Scale , and stimulus intensity required for optimal treatment results were correlated with the intracerebral position of the active electrode pole.

This observation makes blocking or activation of large fiber connections arising in the STN or running nearby more likely than electrical interference with cell bodies inside the STN. Anatomical correlates may be the pallidothalamic bundle , the pallidosubthalamic tract, and/or the zona incerta.

Aims & Scope Of The Journal

Journal of Parkinson’s Disease publishes scientific articles examining recent vital contributions in the areas of Clinical Neurology and General Neuroscience. The main research topics published in this journal consist of Disease, Internal medicine, Neuroscience, Physical therapy and Physical medicine and rehabilitation. The publication process for Journal of Parkinson’s Disease is to publish novel original articles that have been appropriately reviewed by skilled scientific experts. The journal encourages submissions from the research community where the priority will be on the innovativeness and the practical importance of the published findings.Journal of Parkinson’s Disease is covered by various abstracting/indexing services including Scopus, Journal Citation Reports and Research.com. A number of leading scientists considered this journal to publish their scholarly documents including Bastiaan R. Bloem, K. Ray Chaudhuri, Patrik Brundin, Bastiaan R. Bloem and Daniel Weintraub.For further information on the guidelines and submission requirements for authors, please visit the official website for the journal for Journal of Parkinson’s Disease at .

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