Gene and Cell-Based Therapies for Parkinson’s Disease: Where Are We?

Symptom Control ◽

Great Promise ◽

Cell Therapies ◽

Current State ◽

Current Therapies ◽

The Right ◽

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder that carries large health and socioeconomic burdens. Current therapies for PD are ultimately inadequate, both in terms of symptom control and in modification of disease progression. Deep brain stimulation and infusion therapies are the current mainstay for treatment of motor complications of advanced disease, but these have very significant drawbacks and offer no element of disease modification. In fact, there are currently no agents that are established to modify the course of the disease in clinical use for PD. Gene and cell therapies for PD are now being trialled in the clinic. These treatments are diverse and may have a range of niches in the management of PD. They hold great promise for improved treatment of symptoms as well as possibly slowing progression of the disease in the right patient group. Here, we review the current state of the art for these therapies and look to future strategies in this fast-moving field.

Visual Effects of Deep Brain Stimulation in a Patient with Parkinson’s Disease

Vision Development & Rehabilitation ◽

10.31707/vdr2019.5.3.p158 ◽

2019 ◽

pp. 158-173

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Visual System ◽

Brain Stimulation ◽

Initial Examination ◽

Before And After ◽

Deep Brain ◽

Cover Test

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by a dopamine deficiency that presents with motor symptoms. Visual disorders can occur concomitantly but are frequently overlooked. Deep brain stimulation (DBS) has been an effective treatment to improve tremors, stiffness and overall mobility, but little is known about its effects on the visual system. Case Report: A 75-year-old Caucasian male with PD presented with longstanding binocular diplopia. On baseline examination, the best-corrected visual acuity was 20/25 in each eye. On observation, he had noticeable tremors with an unsteady gait. Distance alternating cover test showed exophoria with a right hyperphoria. Near alternating cover test revealed a significantly larger exophoria accompanied by a reduced near point of convergence. Additional testing with a 24-2 Humphrey visual field and optical coherence tomography (OCT) of the nerve and macula were unremarkable. The patient underwent DBS implantation five weeks after initial examination, and the device was activated four weeks thereafter. At follow up, the patient still complained of intermittent diplopia. There was no significant change in the manifest refraction or prism correction. On observation, the patient had remarkably improved tremors with a steady gait. All parameters measured were unchanged. The patient was evaluated again seven months after device activation. Although vergence ranges at all distances were improved, the patient was still symptomatic for intermittent diplopia. OCT scans of the optic nerve showed borderline but symmetric thinning in each eye. All other parameters measured were unchanged. Conclusion: The case found no significant changes on ophthalmic examination after DBS implantation and activation in a patient with PD. To the best of the authors’ knowledge, there are no other cases in the literature that investigated the effects of DBS on the visual system pathway in a patient with PD before and after DBS implantation and activation.

THREE DAYS MONITORING OF ACTIVITIES OF DAILY LIVING AMONG YOUNG HEALTHY ADULTS AND PARKINSON’S DISEASE PATIENTS

Biomedical Sciences Instrumentation ◽

10.34107/yhpn9422.04177 ◽

2021 ◽

Vol 57 (2) ◽

pp. 177-183

Author(s):

Seong Hyun Moon ◽

◽

Rahul Soangra ◽

Christopher F. Frames ◽

Thurmon E. Lockhart ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Activities Of Daily Living ◽

Daily Living ◽

Healthy Subjects ◽

Activity Level ◽

Measurement Unit ◽

Great Promise ◽

Butterworth Filters

Parkinson’s Disease (PD) is a neurodegenerative disorder affecting the substantia nigra, which leads to more than half of PD patients are considered to be at high risk of falling. Recently, Inertial Measurement Unit (IMU) sensors have shown great promise in the classification of activities of daily living (ADL) such as walking, standing, sitting, and laying down, considered to be normal movement in daily life. Measuring physical activity level from longitudinal ADL monitoring among PD patients could provide insights into their fall mechanisms. In this study, six PD patients (mean age=74.3±6.5 years) and six young healthy subjects (mean age=19.7±2.7 years) were recruited. All the subjects were asked to wear the single accelerometer, DynaPort MM+ (Motion Monitor+, McRoberts BV, The Hague, Netherlands), with a sampling frequency of 100 Hz located at the L5-S1 spinal area for 3 days. Subjects maintained a log of activities they performed and only removed the sensor while showering or performing other aquatic activities. The resultant acceleration was filtered using high and low pass Butterworth filters to determine dynamic and stationary activities. As a result, it was found that healthy young subjects performed significantly more dynamic activities (13.2%) when compared to PD subjects (7%), in contrast, PD subjects (92.9%) had significantly more stationary activities than young healthy subjects (86.8%).

Case Report: Bilateral Deep Brain Stimulation Implantation on Different Targets for a Parkinson's Disease Patient With a Bullet in the Brain

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.808231 ◽

2022 ◽

Vol 15 ◽

Author(s):

Yu Tian ◽

Jiaming Wang ◽

Xin Shi ◽

Zhaohai Feng ◽

Lei Jiang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Right Hemisphere ◽

Disease Patient ◽

Long Term Effects ◽

History Of ◽

The Right ◽

Patients requiring deep brain stimulation due to intracerebral metallic foreign substances have not been reported elsewhere in the world. Additionally, the long-term effects of metallic foreign bodies on deep brain stimulation (DBS) are unknown. A 79-year-old man with a 5-year history of Parkinson's disease (PD) reported that, 40 years ago, while playing with a pistol, a metallic bullet was accidentally discharged into the left brain through the edge of the left eye, causing no discomfort other than blurry vision in the left eye. DBS was performed due to the short duration of efficacy for oral medication. Because the bullet was on the left subthalamic nucleus (STN) electrode trajectory and the patient's right limb was primarily stiff, the patient received globus pallidus interna (GPi)-DBS implantation in the left hemisphere and STN-DBS implantation in the right hemisphere. During a 6-month postoperative follow-up, the patient's PD symptoms were effectively managed with no noticeable discomfort.

14 Pathological oscillatory activity in Parkinson’s disease; what does it mean and how should we treat it?

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-bnpa.14 ◽

2020 ◽

Vol 91 (8) ◽

pp. e6.1-e6

Author(s):

Peter Brown

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Basal Ganglia ◽

Side Effects ◽

Brain Stimulation ◽

Neural Circuit ◽

Symptom Control ◽

Oscillatory Activity ◽

Professor Peter Brown is Professor of Experimental Neurology and Director of the Medical Research Council Brain Network Dynamics Unit at the University of Oxford. Prior to 2010 he was a Professor of Neurology at University College London.For decades we have had cardiac pacemakers that adjust their pacing according to demand and yet therapeutic adaptive stimulation approaches for the central nervous system are still not clinically available. Instead, to treat patients with advanced Parkinson’s disease we stimulate the basal ganglia with fixed regimes, unvarying in frequency or intensity. Although effective, this comes with side-effects and in terms of sophistication this treatment approach could be compared to having central heating system on all the time, regardless of temperature. This talk will describe recent steps being taken to define the underlying circuit dysfunction in Parkinson’s and to improve deep brain stimulation by controlling its delivery according to the state of pathological activity.Evidence is growing that motor symptoms in Parkinson’s disease are due, at least in part, to excessive synchronisation between oscillating neurons. Recordings confirm bursts of oscillatory synchronisation in the basal ganglia centred around 20 Hz. The bursts of 20 Hz activity are prolonged in patients withdrawn from their usual medication and the dominance of these long duration bursts negatively correlates with motor impairment. Longer bursts attain higher amplitudes, indicative of more pervasive oscillatory synchronisation within the neural circuit. In contrast, in heathy primates and in treated Parkinson’s disease bursts tend to be short. Accordingly, it might be best to use closed-loop controlled deep brain stimulation to selectively terminate longer, bigger, pathological beta bursts to both save power and to spare the ability of underlying neural circuits to engage in more physiological processing between long bursts. It is now possible to record and characterise bursts on-line during stimulation of the same site and trial adaptive stimulation. Thus far, this has demonstrated improvements in efficiency and side-effects over conventional continuous stimulation, with at least as good symptom control in Parkinsonian patients.

Doença de Parkinson: Revisão Clínica e Atualização

Acta Médica Portuguesa ◽

10.20344/amp.11978 ◽

2019 ◽

Vol 32 (10) ◽

pp. 661

Author(s):

Verónica Cabreira ◽

João Massano

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Clinical Findings ◽

Disease Biomarkers ◽

The Past ◽

Non Motor Symptoms ◽

Parkinson’s disease is the second most common neurodegenerative disorder, and a significant increase in its prevalence in the past three decades has been documented. Environmental and genetic factors contribute to the pathophysiology of this disease, and 5% – 10% of cases have a monogenic cause. The diagnosis relies on clinical findings, supported by adequate testing. There is no absolute method to diagnose Parkinson’s disease in vivo, except for genetic testing in specific circumstances, whose usefulness is limited to a minority of cases. New diagnostic criteria have been recently proposed with the aim of improving diagnostic accuracy, emphasizing findings that might point to other causes of parkinsonism. The available therapeutic options are clinically useful, as they improve the symptoms as well as the quality of life of patients. After the introduction of levodopa, deep brain stimulation emerged as the second therapy with an important symptomatic impact in the treatment of Parkinson’s disease. Non-motor symptoms and motor complications are responsible for a large proportion of disability, so these should be identified and treated. Current scientific research is focused on the identification of disease biomarkers allowing correct and timely diagnosis, and on creating more effective therapies, thus fulfilling current clinical unmet needs. This paper presents an updated review on Parkinson’s disease, guiding the readership through current concepts, and allowing their application to daily clinical practice.

Syncope Associated with Subthalamic Nucleus Deep Brain Stimulation in a Patient with Parkinson’s Disease

Case Reports in Neurological Medicine ◽

10.1155/2013/371929 ◽

2013 ◽

Vol 2013 ◽

pp. 1-2

Author(s):

Dursun Aygun ◽

Ersoy Kocabicak ◽

Onur Yildiz ◽

Musa Kazim Onar ◽

Hatice Guz ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Early Period ◽

Motor Symptoms ◽

The Right ◽

Stn Dbs ◽

In advanced Parkinson's disease (PD), deep brain stimulation (DBS) may be an alternative option for the treatment of motor symptoms. Side effects associated with subthalamic nucleus (STN) DBS in patients with PD are emerging as the most frequent sensory and motor symptoms. DBS-related syncope is reported as extremely rare. We wanted to discuss the mechanisms of syncope associated with STN DBS in a patient with Parkinson's disease.Case report.Sixty-three-year-old female patient is followed up with diagnosis of idiopathic Parkinson's disease for 6 years in our clinic. The patient has undergone STN DBS due to painful dystonia and drug resistant tremor. During the operation, when the left STN was stimulated at 5 milliampere (mAmp), the patient developed presyncopal symptoms. However, when the stimulation was stopped symptoms improved. During the early period after the operation, when the right STN was stimulated at 1.3 millivolts (mV), she developed the pre-yncopal symptoms and then syncope. Our case shows that STN DBS may lead to directly autonomic symptoms resulting in syncope during stimulation-on (stim-on).

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

Subthalamic Nucleus Deep Brain Stimulation: An Invaluable Role for MER

10.1017/s0317167100014682 ◽

2013 ◽

Vol 40 (4) ◽

pp. 572-575 ◽

Cited By ~ 8

Author(s):

F. A. Zeiler ◽

M. Wilkinson ◽

J. P. Krcek

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Localization And Mapping ◽

Stereotactic Atlas ◽

The Right ◽

Stn Dbs ◽

Abstract:Introduction:Subthalamic nucleus (STN) deep brain stimulation (DBS) is currently the main surgical procedure for medically refractory Parkinson's disease. The benefit of intra-operative microelectrode recording (MER) for the purpose of neurophysiological localization and mapping of the STN continues to be debated.Methods:A retrospective review of the charts and operative reports of all patients receiving STN DBS implantation for Parkinson's disease at our institution from January 2004 to March 2011 was done.Results:Data from 43 of 44 patients with Parkinson's disease treated with STN DBS were reviewed. The average number of tracts on the left was 2.4, versus 2.3 on the right. The average dorsal and ventral anatomical boundaries of the STN based on Schaltenbrand's Stereotactic Atlas were estimated to be at -5.0 mm above and +1.4 mm below target respectively. The average dorsal and ventral boundaries of the STN using MER were -2.6 mm above and +2.0 mm below target respectively. The average dorsal-ventral distance of the STN as predicted by Stereotactic Atlas was 6.4 mm, compared to 4.6 mm as determined by MER. MER demonstrated the average dorsal and ventral boundaries on the left side were -2.6 mm and +2.2 mm from target respectively, while the average dorsal and ventral boundaries on the right side were -2.5 mm and +1.8 mm from target respectively with MER.Conclusions:MER in STN DBS surgery demonstrated measurable difference between stereotactic atlas/MRI STN target and neurophysiologic STN localization.

Outcome of Deep Brain Stimulation (DBS) for the Treatment of Parkinson’s Disease in Terms of Improvement in MDS-UPDRS Scale Over 5 Years

Pakistan Journal Of Neurological Surgery ◽

10.36552/pjns.v24i4.498 ◽

2021 ◽

Vol 24 (4) ◽

pp. 305-314

Author(s):

Khalid Mahmood ◽

Omair Afzal Ali ◽

Adeeb-ul- Hassan ◽

Imran Ali

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Rating Scale ◽

Disease Rating ◽

The Mean ◽

Updrs Part ◽

Background & Objective: Parkinson’s disease (PD) is the second most common Neurodegenerative disorder after Alzheimer’s disease. There are several surgical procedures for advanced PD, but amongst all deep brain stimulation has proven to be safest and effective. The objective of this study was to see the outcome of DBS for the treatment of PD in terms of improvement in MDS UPDRS over 5 years. Material and Methods: 44 patients were included in study from Oct 2014 to Sep 2019. History, examination was carried out, and preoperative MDS-UPDRS (Movement Disorder Society Unified Parkinson’s Disease Rating Scale) was recorded. Postoperative improvement in MDS-UPDRS score was assessed at first Programming, 2nd week, and 6th week and at 3rd month. Results: At baseline the mean, the MDS – UPDRS (Part-I) score was 14.20 ± 0.61 and at the end of 3rd month, the mean score was 11.18 ± 0.47 respectively. At baseline the mean, the MDS – UPDRS (part-II) score was 18.99 ± 0.70 and at the end of 3rd month, the mean score was 13.01 ± 0.57, respectively. At baseline the mean, the MDS – UPDRS (part-III) score was 45.19 ± 0.90 and at the end of 3rd month, the mean score was 25.15 ± 1.20 respectively. At baseline the mean, the MDS – UPDRS (part-IV) score was 10.18 ± 0.87 and at the end of 3rd month, the mean score was 3.85 ± 1.03, respectively. Conclusion: The Deep Brain Stimulation (DBS) is safe and effective in the management of PD.

Reduction of Medicine of PD’s Patients to Reduce Side Effects of Medicine and Brain Disorder Effects Using Crashing of Precedence Relationship Process of Operational Research (Preprint)

10.2196/preprints.15993 ◽

2019 ◽

Author(s):

Mohammad Rashid Hussain

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Side Effects ◽

Analytical Treatment ◽

Brain Disorder ◽

Balanced Diet ◽

Normal Quantity ◽

The Right ◽

Critical Order

BACKGROUND Case of a Parkinson’s disease (PD’s). PD’s is caused by a decreased production of dopamine. It is progressive which means it develops gradually over a long period of time. It’s a neurodegenerative condition that’s caused by a loss of nerve cells in a certain part of the brain. People suffering from Parkinson’s disease can try something new, make a list of small tasks and complete them can help their body produce the dopamine it needs, and that reduce some symptoms of PD’s. There is no cure, so treatment focuses on managing symptoms. So while eating the right food and considering a lifestyle certainly cannot offset the effects of Parkinson’s disease entirely, a recommended diet and lifestyle can support their body’s ability to produce dopamine and combat symptoms of the disease. OBJECTIVE This study was undertaken with aim to investigate the effects of Crashing. The objective of study is to reduce the quantity of medicine while minimizing effect of neurodegenerative brain disorder. METHODS The concept of crashing is the method for minimizing the side effects by reducing one or more critical order of medicine to decrease their normal quantity of medicine. Critical order of medicine is an order of medicine in which the sequence of order of medicine which add up to longest overall quantity of medicine. This determines the less quantity of medicine possible to reduce the neurodegenerative disorder effect. RESULTS A medicine consists of interrelated relationship which is to be related in a certain order before the entire order of medicine is completed. The medicine is represented in a form of interrelated logical sequence which is known as precedence relationship diagram for the purpose of analytical treatment to get the solution for reducing the amount of medicine and controlling the side effects of distinct medicine. When we speedup the activity, the crash effect of medicine will be higher when compare to normal effect of medicine to find the optimal crashed quantity of medicine to reduce movement disorder. CONCLUSIONS When speedup the activity, the normal quantity of medicine can be reduced to crash quantity of medicine. People suffering from Parkinson’s disease can do the following activity to increase their dopamine levels: Try something new, Make a list of small tasks and complete them, Avoid foods with excess fat and sugar, try to maintain a balanced diet that contains adequate protein, vitamins and minerals, Listen to music you enjoy, get enough sleep , do yoga and Exercise regularly can help their body produce the dopamine it needs, and that reduce some symptoms of Parkinson’s disease. No food or diet can serve as a cure for Parkinson’s disease. But eating certain foods can help to minimize symptoms and help them to get the most out of their medication.

Subthalamic stimulation impairs stopping of ongoing movements

Brain ◽

10.1093/brain/awaa341 ◽

2020 ◽

Cited By ~ 1

Author(s):

Roxanne Lofredi ◽

Georg Cem Auernig ◽

Friederike Irmen ◽

Johanna Nieweler ◽

Wolf-Julian Neumann ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Right Hemisphere ◽

Inferior Frontal Gyrus ◽

Motor Area ◽

Subthalamic Stimulation ◽

The Right ◽

Abstract The subthalamic nucleus is part of a global stopping network that also includes the presupplementary motor area and inferior frontal gyrus of the right hemisphere. In Parkinson’s disease, subthalamic deep brain stimulation improves movement initiation and velocity, but its effect on stopping of ongoing movement is unknown. Here, we examine the relation between movement stopping and connectivity of stimulation volumes to the stopping network. Stop and go times were collected in 17 patients with Parkinson’s disease on and off subthalamic stimulation during visually cued initiation and termination of continuous, rotational movements. Deep brain stimulation contacts were localized; the stimulation volume computed and connectivity profiles estimated using an openly available, normative structural connectome. Subthalamic stimulation significantly increased stop times, which correlated with the connectivity of the stimulation volume to presupplementary motor area and inferior frontal gyrus of the right hemisphere. The robustness of this finding was validated using three separate analysis streams: voxel-wise whole-brain connectivity, region of interest connectivity and a tract-centred method. Our study sheds light on the role of the fronto-subthalamic inhibitory triangle in stopping of ongoing movements and may inspire circuit based adaptive stimulation strategies for control of stopping impairment, possibly reflected in stimulation-induced dyskinesia.