Deep brain stimulation for the treatment of Parkinson's disease

Deep brain stimulation for the treatment of Parkinson's disease in Turkey is an effective and successful treatment method that helps improve symptoms and can reduce the dose of medications needed by the patient. And it could be a reason to treat Parkinson's disease once and for all.

An introduction to Parkinson's disease and its stages of development

Prepare Parkinson's disease Parkinson's disease (PD) is the second most common chronic neurodegenerative disease after Alzheimer's disease the first, with a high incidence and is seen in 1-3% of all people over 65 years of age. Men are affected 1.5 times more frequently than women. [1]⁽¹⁾

Research studies have linked theories regarding the outbreak of PD to both environmental and genetic circumstances. These theories propose associations between PD and chemical reactions, neurotoxins, and genetic susceptibility or predisposition. [2]⁽²⁾

The main cause of PD is the loss of nigrostriatal dopaminergic neurons, disruption of dopamine and acetylcholine balance in the basal ganglia is also effective in the development of the disease. [1]⁽¹⁾

The main and early symptoms of PD include bradykinesia /akinesia, rigidity, rest tremor; later findings are postural instability and walking and balance disorders and it is a progressive movement disorder. [1]⁽¹⁾

It is considered Diagnosis in Parkinson's disease Clinically and can be performed using the UK Parkinson's Disease Society (UKPDS) Brain Bank criteria, the primary clinical features in Parkinson's disease are bradykinesia (without which the diagnosis cannot be made) and a combination of muscular rigidity, tremor (tremor) and/or instability Postural (which is not explained by visual, cerebellar, vestibular or proprioceptive impairment). ⁽³⁾

Deep Brain Stimulation for Parkinson's Disease (DBS) in Türkiye

Though the exact cause of Parkinson’s disease has not been identified, treatment discoveries have been progressive. There is no known cure for the disease, so treatments seek to manage symptoms rather than prevent or slow the progression of the disease. Treatments can vary from drugs, surgeries, behavioral therapy, or a combination of different treatments. [2]⁽²⁾

The main surgical techniques in the treatment of Parkinson's disease are: resection surgery, deep brain stimulation parkinson's method, and transfer of embryonic mesenchymal cells to the striatum of the brain.⁽²⁾

Despite optimal medical therapy, many patients with moderate to advanced disease have a poor quality of life because of fluctuating response, troublesome dyskinesia or levodopa-unresponsive symptoms. [4]⁽⁴⁾

The main advantage of deep brain stimulation for the treatment of Parkinson's disease (DBS) is that the stimulation parameters can be adjusted based on the needs of the patient in order to improve the results. Those with primary fibrillation.⁽⁴⁾

Deep brain stimulation for Parkinson's disease (DBS) applied to the hypothalamic nucleus (STN) or applied inside the globus pallidus (GPi) are the most common target sites for DBS treatment in those with disabling fibrillation and/or complications Kinetics associated with levodopa.⁽⁴⁾

Although deep brain stimulation for Parkinson's disease (DBS) is a proven treatment strategy, its success depends on the appropriate selection of cases and the experience and skill of the surgeon in order to increase the quality of results and reduce complications.⁽⁴⁾

Age itself does not seem to be a predictor of outcome in terms of motor function, since similar improvement in that domain can be detected in both younger and older PD patients. However, age was identified to be a relevant factor to predict beneficial effects on quality of life. [5]⁽⁵⁾

Technologies have been developed Deep brain stimulation for the treatment of Parkinson's disease DBS over the past 40 years has opened the door for the development of treatment in this way in other areas outside of movement disorders such as pain, cognition and psychiatric conditions.⁽⁶⁾

Brain stimulation therapy can help people with Parkinson's disease improve symptoms of tremor, stiffness and slowness of movement, and can reduce the drug dose people need to manage the disease.

Researchers who have followed patients after DBS have found that many patients continue to have improvements in their symptoms for several years after the procedure and are able to eat, use the bathroom and feed themselves. Patients being treated with DBS for movement disorders may or may not experience changes in memory, thinking or mood.

Deep brain stimulation for Parkinson's disease (DBS) is reversible and does not result in permanent damage to brain tissue. In addition, deep brain stimulation can be customized or programmed to better match the patient's symptoms.

Mechanism of effect of deep brain stimulation for the treatment of Parkinson's disease (DBS)

DBS is the application of electrical fields to stimulate neural element particularly axons around the electrode resulting in opening and closing of voltage-gated sodium channels, generating action potentials and controlling the release of neurotransmitters; however, it is still unclear if this is entirely an inhibitory or excitatory mechanism or whether the effects are predominantly local or network-wide. [6]⁽⁶⁾

There are four main theories to explain how brain stimulation works in the treatment of Parkinson's disease: 1) direct inhibition of neuronal activity, 2) direct excitation of neuronal activity, 3) information interruption, and 4) synaptic clearance.⁽⁶⁾

Although current theories about how deep brain stimulation works for Parkinson's disease generally focus on immediate effects, there is evidence that deep brain stimulation may lead to synaptic and neuronal plasticity, and there is also some evidence that it may lead to cell formation. Neurotransmitters and synapses and may protect brain cells.⁽⁶⁾

Criteria that qualifies a patient for deep brain stimulation surgery in Parkinson's disease (DBS)

Current German guidelines recommend that the following criteria are mandatory to consider DBS in PD:

1. 1. Presence of motor fluctuations including levodopa-sensitive off symptoms or treatment-induced dyskinesia.
2. 2. Tremor, which cannot be satisfactorily treated with medication.
3. 3. A levodopa-induced reduction of motor symptoms by >33% of the Unified Parkinson Disease Rating Scale (UPDRS), where tremor may be disregarded from the calculation as it may be refractory to levodopa treatment while still responding well to DBS.

Even more restrictive inclusion criteria are recommended for patients not older than 60 years and the presence of motor fluctuations for not longer than 3 years. [5]⁽⁵⁾

Ineligibility criteria for deep brain stimulation

• Unstable clinical comorbidities (e.g., coronary artery disease, active infection, other disabling cerebrovascular diseases, malignancy).
• Major psychiatric or neurobehavioral disorders (e.g., psychotic disorder, bipolar disorder, depressive disorder, severe personality disorder).
• Definitive dementia.
• Doubtful diagnosis of PD.
• Significant ventricular enlargement or cerebral atrophy in magnetic resonance imaging (MRI).
• Severe axial symptoms resistant to treatment with levodopa (dysarthria, dysphagia, postural instability or gait disturbances).
• Absence of functional disability.
• Inability to provide informed consent.
• Social or geographic difficulties in gaining access to the center, for follow-up visits and programming of the stimulator.
• Inadequate or fragile social support ( family or caregivers). [7]⁽⁷⁾

Surgical procedure in deep brain stimulation

As a prerequisite to define the target point and the trajectory for DBS electrode placement, the patient’s individual anatomy as provided by MRI of the brain has to be illustrated in stereotactic space. [5]⁽⁵⁾

Following a skin incision and the drilling of a burr hole allowing the entrance to the planned trajectory, microelectrodes are inserted and either stepwise (steps 0.5–1 mm) or continuously forwarded along the planned pathway. [5]⁽⁵⁾

Utilization of microelectrode recording (MER) may help identify target areas by distinct activity patterns, determined by spontaneous background firing, spike discharges, and changes of activity due to movement or sensory stimuli and therefore may increase the accuracy of the final electrode placement. [5]⁽⁵⁾

Relatively low thresholds for characteristic side effects, like tetanic contraction due to stimulation of the internal capsule, may help in estimating the proximity to adjacent anatomical areas, which mediate the side effects of DBS. In turn, low thresholds for beneficial effects without the development of side effects suggest a favorable position. Once the optimal target has been specified, the DBS electrode is eventually inserted. [5]⁽⁵⁾

Patients undergoing awake surgery may improve faster and have better results on axial symptoms like dysarthria, potentially since DBS-induced worsening of such symptoms can easily be detected during intraoperative testing stimulation in awake surgery, allowing for better decision making on the final electrode placement. [5]⁽⁵⁾

DBS involves the placement of three device parts into the body. They are all implanted below the skin. The first part is the wires that go into the brain, which are called leads or electrodes. The second part is the battery pack or called a generator, which is placed in the chest just below the collar bone. The third part is the wires that connect the leads to the generator.

Everyone responds to DBS differently. For most, results are noticed shortly after the initial programming of the DBS. However, it could take several visits to adjust the settings for maximal benefit. The parameter settings will be adjusted in order to find the optimal symptom control without side effects. These can continually be updated as your symptoms change over time.

The surgery itself to implant the electrodes takes a few hours. Implantation is done in two stages. During the first sage, the electrodes are placed in the brain, and the patient need to spend a night in the hospital. During the second stage, the internal pulse generator (which is the computer and battery) is implanted under the skin of the chest, and the patient usually go home the same day.

Depending on the disease, it may be possible to reduce medications. However, DBS is most helpful when used along with medications and other treatments. That's because using it and other treatments at the same time means it may be possible to lower medication doses, have fewer side effects and still get the same benefits.

Complications or risks of deep brain stimulation for the treatment of Parkinson's disease

Deep brain stimulation surgery carries inherent surgery- related risks and complications from treatment. The major surgical risk of DBS is intracerebral hemorrhage. The risk of intracerebral hemorrhage is approximately 1%–2% including minor hemorrhages. Seizures are a risk of any supratentorial procedure, and have a 1% incidence in DBS procedures. [6]⁽⁶⁾

Medical complications including deep venous thrombosis, phlebitis, pneumonia, urinary tract infections, and pulmonary embolism, which may also occur with any surgical procedure and have been reported in less than 2% of DBS cases. [6]⁽⁵⁾

Some complications are directly related to the DBS device itself, and can include lead migration and fracture in 3%-2 and infection in the 3%-3 device. Complications may also occur from electrical stimulation in DBS depending on the location targeted in the DBS and the anatomical location of the electrodes. These complications range from cranial nerve deficits and motor symptoms to psychiatric disorders and autonomic disorders.⁽⁶⁾

The death rate from deep brain stimulation surgery for Parkinson's disease is about 0.4% and is most often associated with postoperative myocardial infarction and pulmonary embolus.⁽⁶⁾

Rehabilitation after deep brain stimulation

Rehabilitation programs should not only aim to treat the functions that are impaired but also to prevent the problems that will arise. Beginning the physiotherapy program concurrently with the treatment of the disease from the early stages of the disease may help to avoid such problems that lead to dependence, inactivity, social isolation and reduced quality of life. [8]⁽⁸⁾

Rehabilitation phase before deep stimulation surgery in Türkiye

The first step of preoperative evaluation is to inform the patient and his/her family about the possible complications of the surgeon. The evaluation procedure to be performed before determining the appropriate rehabilitation program for the patient includes balance, mobility, tremor, rigidity, coordination, speech, evaluation of hand functions, activities of daily living, environmental assessment, assistive device selection. The goals of physical therapy program are;

• improve the respiratory function and to prevent respiratory complications
• decrease rigidity
• Reduce the pain
• Maintain independence
• Improve the flexibility
• Optimize gait
• Maximize gross motor coordination and balance
• Educate and guide care giving needs. [8]⁽⁸⁾

Postoperative phase

After surgery, patients are assessed at first 24 hours following the battery setting. Parkinson's disease has respiratory failure due to flexure posture, kyphosis and rigidity. After surgery, physiotherapy begins with breathing exercises. Respiratory exercises, postural alignment exercises, and thoracic extension exercises are effective for increasing respiratory capacity. [8]⁽⁸⁾

In order to reduce postural disturbance and balance problems, the patient should be taught the correct posture. Postural extension exercises and trunk rotation movements should be applied. [8]⁽⁸⁾

In order to prevent falls, the patient should be instructed to rotate around a large arc by correctly positioning the foot and increasing visual and verbal stimuli, while walking. Walking with a rhythm and proper walking with arm swings should be taught to prevent freezing. Frequent rest periods should be given during exercises, excessive fatigue should be avoided. [8]⁽⁸⁾

Recommendations for patient and family after deep brain stimulation

The activities that patients should not do after surgery are as follows:

• Cervical manipulation, massage and excessive cervical exercise should be avoided.
• Upper limb activities above the head level should not be done.
• Do not lift more than 3-4 kg in the first month.
• Some medical devices such as MRI should not be used.
• Do not pass-through electromagnetic gates (airport detectors)
• Wireless connections are dangerous for battery.
• Stay away from high-powered industrial machines.
• Simple sportive activities can be carried out, especially those that are not physically risky to crash and without contact with the tie or neurostimulator. [8]

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The price of deep brain stimulation for the treatment of Parkinson's disease in Türkiye

The price of deep brain stimulation for the treatment of Parkinson's disease in Turkey varies according to the type of center in which the operation will be performed, as the cost in the state hospital is about 22 thousand US dollars, while the cost in private hospitals is about 27 thousand dollars, while it may reach 33 thousand US dollars in the best Deep stimulation therapy center.

References

1. Ibrahimoğlu and Akyol. Early-term results of deep brain stimulation in Parkinson's disease: a case report. Cukurova Medical Journal 2019;44:1499-1505.
2.  Lee et al. A review on Parkinson's disease treatment. Neuroimmunology and Neuroinflammation 2021;8:222-244.
3. Esmail S. The Diagnosis and Management of Parkinson's Disease. Sch J Appl Sci Res 2018; 1: 13-19.
4. Jankovic J, Tan EK. Parkinson's disease: etiopathogenesis and treatment. J Neurol Neurosurgical Psychiatry 2020;91:795-808.
5. CJ Hartmann, S Fliegen et al. An update on best practice of deep brain stimulation in Parkinson's disease. Therapeutic Advances in Neurological Disorders 2019;12:1-20.
6. Lee et al. Current and future directions of deep brain stimulation for neurological and psychiatric disorders. J Neurosurg 2019;131:333-342.
7. Brandão P et al. DBS in Parkinson's disease: therapeutic decisions. Arq Neuropsiquiatr 2018;76(6):411-420.
8. Ünal A, Altug F. Clinical Experience from Turkey in Rehabilitation of Parkinson's Disease after Deep Brain Stimulation: What are we Doing?. Physiother Rehabil 2017;2:142.