User:Jessica Kurf/sandbox

Assigned Article: Management of Parkinson's disease

1.DBS: More to Come

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Deep brain stimulation
Deep brain stimulation (DBS) is presently the most used method of surgical treatment because it does not destroy brain tissue, it is reversible, and it can be tailored to individuals at their particular stage of disease. DBS employs three hardware components: a neurostimulator, also called an implanted pulse generator (IPG), which generates electrical impulses used to modulate neural activity, a lead wire which directs the impulses to a number of metallic electrodes towards the tip of the lead near the stimulation target, and an extension wire that connects the lead to the IPG. The IPG, which is battery-powered and encased in titanium, is traditionally implanted under the collarbone, and is connected by the subcutaneous extension to the lead, which extends from outside the skull under the scalp down into the brain to the target of stimulation. The IPG, or the entire three-component system, are sometimes referred to as a brain pacemaker, due to the precedence and renown of cardiac pacemakers and similarities in the components of both types of systems.

The preoperative targeting of proper implantation sites can be accomplished by the indirect and direct methods. The indirect method uses computer tomography, magnetic resonance imaging, or ventriculography to locate the anterior and posterior commissures and then employs predetermined coordinates and distances from the intercommissural line to define the target area. Subsequent histologically defined atlas maps can also be used to verify the target area. The direct method provides visualization and targeting of deep nuclei by applying stereotactic preoperative MRI, which unlike the indirect method, takes into account the anatomic variation of the nuclei’s size, position, and functional segregation amongst individuals.

Electrophysial functional mapping, a tool used in both methods to verify the target nuclei, has come under scrutiny due to its associated risks of hemorrhages, dysarthria or tetanic contractions. Recently, susceptibility-weighted imaging, a type of MRI, has shown incredible power in its ability to distinguish these deep brain nuclei and is being used in DBS to reduce the overuse of EFM.

DBS is recommended to PD patients without important neuropsychiatric contraindications who suffer motor fluctuations and tremor badly controlled by medication, or to those who are intolerant to medication.

DBS is effective in suppressing symptoms of PD, especially tremor. A recent clinical study led to recommendations on identifying which Parkinson's patients are most likely to benefit from DBS.

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Deep brain stimulation (DBS) can be categorized as personalized medicine because it requires a personal-tailored surgery for individual PD patient’s anatomy. There are different DBS approaches such as subthalamic nucleus DBS (STN-DBS), globus pallidus DBS (GPi-DBS), ventralis intermedius DBS (Vim-DBS) and pedunculopontine nucleus DBS (PPN-DBS). The challenges for STN or GPi-DBS is the deficiency of the battery-life. As for Vim or PPN-DBS, the efficacy varies for different PD patients. However, these adaptive DBS offer an accurate and individualized treatment for PD patients through automatically adjusting parameters based on the real-time brain/body response. Moreover, an advanced option by adopting spontaneous stimulation parameters can be used to meet further needs for each PD patient in the near future.

2.Rehabilitation: More to come

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Rehabilitation
Partial evidence indicates speech or mobility problems can improve with rehabilitation, although studies are scarce and of low quality. Regular physical exercise and/or therapy can be beneficial to maintain and improve mobility, flexibility, strength, gait speed, and quality of life. Exercise may also improve constipation. Exercise interventions have been shown to benefit patients with Parkinson’s disease in regards to physical functioning, health-related quality of life, and balance and fall risk. In a review of 14 studies examining the effects of exercise on persons with Parkinson’s disease, no adverse events or side effects occurred following any of the exercise interventions. Five proposed mechanisms by which exercise enhances neuroplasticity are known. Intensive activity maximizes synaptic plasticity; complex activities promote greater structural adaptation; activities that are rewarding increase dopamine levels and therefore promote learning/relearning; dopaminergic neurones are highly responsive to exercise and inactivity (“use it or lose it”); and where exercise is introduced at an early stage of the disease, progression can be slowed. One of the most widely practiced treatments for speech disorders associated with Parkinson's disease is the Lee Silverman voice treatment (LSVT), which focuses on increasing vocal loudness and has an intensive approach of one month. Speech therapy and specifically LSVT may improve voice and speech function. Occupational therapy (OT) aims to promote health and quality of life by helping people with the disease to participate in as many activities of their daily living as possible. Few studies have been conducted on the effectiveness of OT and their quality is poor, although some indication shows it may improve motor skills and quality of life for the duration of the therapy.

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Neurohabilitation is a non-pharmaceutical treatment for PD and the core of it is to help PD patients control their motor and non-motor symptoms by the training of behavioral adaptations. There are four relatively new fields in neurohabilitation, which are visual rehabilitation because optimal vision is crucial to PD patients, cueing delivered by wearable devices in an on-demand manner because it can be used to objectively, continuously and quantitatively detect PD patients’ mobility difficulties, exergamin which combines physical exercise with cognitive games, and telemedicine that can deliver the professional neurohabilitation advice to PD patients directly. Even though collecting robust scientific evidence on the cost-effectiveness for these four new neurohabilitation approaches has been challenging, positive results and good clinical trials show that these new developments of neurohabilitation can potentially improve PD patients’ quality of life.

3.Research Direction: More to come

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8.5 Biomarker

In the modern time, large amounts of biomarkers could be used in various neurological practices to provide better decision for patient prognosis or in prediction of treatment affects. Although future validation of these biomarkers is needed before utilizing them into standard clinical diagnose algorithms, the importance of personalized medicine will be considered significantly to achieve more effective, cheaper and better-tailored treatment for different neurological diseases in the future. In Parkinson’s disease, there is no validated diagnostic biomarker for PD as late of 2016. However, like Alzheimer’s disease, perspective biomarkers are such as dopamine metabolism, oxidative stress, α-synuclein, auto antibodies against α synuclein and inflammatory markers. The reliable results are obtained from studies of α synuclein, the major component of lewy bodies, and it can be found in saliva, serum, plasma and cerebrospinal fluid (CSF). In addition, inflammatory markers such as higher level of interleukin 6 (IL-6) and soluble tumor necrosis factor (TNF) receptor-1 are associated with PD or early onset of disease. More than 25 genetic factors have been reported to affect the risk factor for PD and the major risk factor is shown to be homozygous and heterozygous mutations of the glucocerebrosidase gene. For PD, one biomarker and a single measure are not efficient to provide useful information. The combination of different biomarkers with clinical relevant patient’s characteristics can be considered to offer better and integrated information on disease.