Application of Deep Brain Stimulation in treating Parkinson’s Disease
By Ayesha Sachdev
This paper will explore the applications which Deep Brain Stimulation (DBS), a brain implant used to treat the symptoms of Parkinson’s Disease.
Parkinson’s Disease is a degenerative neurological disorder that causes uncontrollable or unintentional movements such as shaking and tremors, dystonia, bradykinesia, postural instability and stiffness of the muscles. In all cases, it leads to a progressing loss in motor function and control, due to the decay of the dopaminergic neurons (Louise Morales-Brown), which are located in the substantia nigra region of the brain. The function of dopamine within the cerebrum is to act as a neurotransmitter - a chemical messenger that carries chemical signals from one neuron to another - therefore it has a vital role in neurological function.
Deep Brain Stimulation is a therapeutic tool which is typically used to help treat chronic symptoms of Parkinson’s disease, namely: essential tremors, dystonia, epilepsy and obsessive-compulsive disorder by regulating abnormal electrical impulses or stimulating specific cells, tissues and chemicals within the brain (Mayo Clinic Staf ). Additionally, research has shown a correlation between stimulation in the thalamus, pedunculopontine nucleus and cortex, and an improvement in nocturnal complications like sleep-wake disturbances (Sharma et al.).
Implantation of the DBS mechanism requires surgery for the placement of the electrodes within the brain, as well as a neurostimulator which tends to be implanted within the chest wall of the patient. A lead wire is run down from the brain within the skin to connect the electrodes to the neurostimulator (The Editors of Encyclopaedia Britannica).
Even though the mechanisms of DBS are still not understood thoroughly (Guma), its stimulations show inspired and hopeful results as it tackles the biggest disorders and illnesses in our modern society. A common misconception about DBS is that its mechanisms can stunt and delay the progression of neurodegenerative processes that arise as a byproduct of certain diseases (for example, the loss of motor function in patients who may suffer from Parkinson’s).
In standard cases, the symptoms of Parkinson’s are typically treated in 3 ways (“Parkinson’s Disease Treatment”):
Firstly, ablative surgery - the process of destroying targeted areas of the brain that produces abnormal chemicals or electrical impulses, which may be the cause of tremors and other common symptoms. An example of this is a procedure known as a bilateral thalamotomy, which makes the chance of swallowing and speech impairments highly likely as it creates lesions within the thalamus region of the brain.
Secondly, restorative surgery is when dopamine-producing cells are ingrained into certain parts of the brain. However, this surgery is still highly experimental but is being explored in the direction of utilising stem cells. This may indicate a possible new option for treating Parkinson's Disease in the near future and allow patients to embrace a higher quality of life.
The third option, DBS, is seen as highly controversial due to common misconceptions. However, it is an established and well-known treatment and has been approved by the food and drug administration (FDA) since 2002 (Miocinovic et al., “History, Applications, and Mechanisms of Deep Brain Stimulation”). Globally, more than 160,000 patients have used the DBS mechanism for a variety of conditions and this statistic is seen to be growing at a progressing pace (Lozano et al.). The process of DBS allows patients who suffer from Parkinson's Disease to experience a decrease in uncontrollable and involuntary movements and an increase in the speed of various motions. Moreover, it also reduces the dosage of the drug, Levodopa which has historically caused involuntary, drug-induced movement (dyskinesia). Furthermore, it doesn’t require the formation of lesions within the cerebrum. This is an irreversible effect generated during ablative surgery. On the contrary, DBS has a ‘reversible effect’ (to an extent) as the stimulation can be terminated or the entirety of the DBS mechanism can be removed from the cerebrum and the chest wall when required.
The first area that needs to be stimulated is the subthalamic nucleus (STN) in the basal ganglia, which includes a large number of glutaminergic neurons, which controls the regulation of movement (Basinger and Joseph). Next, the globus pallidus (internus) which is still in the basal ganglia and functions to control consciousness and kinesthesia (Javed and Cascella). Lastly, the ventral intermediate nucleus of the thalamus receives signals from the cerebellum, cortex and striatum and reflects these signals into the primary motor cortex in the precentral gyrus (Tlamsa and Brumberg, “Organization and Morphology of Thalamocortical Neurons of Mouse Ventral Lateral Thalamus”). These are the three main areas which are mainly affected by Parkinson's Disease, so the stimulation is operated to attempt to partly restore prior function.
Additionally, there’s significance in the realm of biophysics in order to control the stimulation parameters to optimise clinical outcomes. This is achieved by varying the parameters of pulse width, amplitude, polarity and frequency of the signals. Reducing damage to neural tissue can also be achieved by varying the electrode contact to target precise areas of the cerebrum. In a prior study generated by the Genrobe team, 130 Hz frequency is the conventional value for stimulation, specifically with Parkinson's Disease patients (Frey et al.). Be that as it may, most parameters require alteration in order to be tailored to the specific needs of the patient. Therefore, this process is to be described as a process of ‘trial and error’. Finding suitable parameters for individuals is a strenuous process as it involves trying different combinations to maximise benefits and minimise the harmful effects on the patient (Miocinovic et al., “History, Applications, and Mechanisms of Deep Brain Stimulation”). Hence implantation of the electrodes is usually done with a local anaesthetic, meaning that the patient is awake during the procedure so immediate side effects of improper placement can be detected and the electrode can be placed in a different position (The Editors of Encyclopaedia Britannica).
However, DBS involves surgical procedures, which come with a list of feasible side effects. Moreover, if there’s a failure in certain parts within the DBS system, surgery is required to restore the components (such as running out of battery power). The unlikely event of the lead wire shifting leads to the misplacement of the electrodes in the brain, which causes misfiring electrical impulses to healthy areas of the brain which can lead to other major complications. In rare cases, the lead wire can be seen emerging from the surface of the skin, causing an infection in the opening wound. A brain haemorrhage can arise as one of the most severe side effects and can lead to a stroke or possibly even death (The Editors of Encyclopaedia Britannica). In addition to these side effects, DBS has also been proven to alter the behavioural attributes of patients. Specifically, alterations of decision-making behaviours and increased impulsivity. The reason behind this is that the STN is associated with regulating decision-making in the cerebrum.
The future of DBS is very promising as it continues to advance at a rapid rate. Advances to the various components of the DBS system such as that its battery will have a longer lasting battery span, so replacements will be less frequent. Additionally, the progression of metameric lead wires will increase effectiveness and reduce damage to the closeby areas where the electrode is positioned. There are also advances in targeting the stimulation by new imaging sequences and new research on the brain's structural and functional connections between cells, known as connectomics; this research enables a boost in accuracy for the positioning of the electrodes and the parameters of the stimulation. In recent years, DBS has been applied in greater values of various disorders, providing scientists and physicians with a deeper and more comprehensive understanding of its systems. This has allowed and will continue to allow a greater application of DBS to other disorders (Frey et al.). For example, the implementation of DBS in epilepsy and certain psychiatric disorders was founded using this method.
In summary, since the early experimental endeavours of DBS in the 19th century by Alim Benabid (Oliveria), many scientists and researchers have taken different standpoints in experimenting with DBS mechanisms in a clinical setting. Both sides have been researched comprehensively, which has provided the 21st century with a greater understanding of this protocol and the science that surrounds it. Although all of the information has not been revealed, it is important to not lose sight of the full picture, and what it could potentially become. Scientists are constantly finding information to crack the code of this deeply complex apparatus. This is why society should remain hopeful and support researchers and scientists as they continue to maximise benefits and minimise adverse effects to the patients of the world.
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