Precision Of Temporal Interference Stimulation
One important requirement of DBS is high spatial precision . Stimulating brain regions unrelated to the disease might reduce the effectiveness of treatment or cause undesired side effects. In their study, the authors both built computer models to simulate the stimulation effects and demonstrated their spatial precision via two sets of experiments in anaesthetised mice.
In the first set of experiments, the researchers selectively targeted a small region found deep in the brain called the hippocampus, and they proved that stimulation of this area does not affect an overlaying brain region called the cortex. The stimulation effect was validated with two laboratory techniques. The first method was an electrical recording technique called in vivo whole cell patch clamp, which uses a glass tube called a patch pipette to acquire signals from neurons in the brains of live animals. This method requires open-skull surgery on mice to place the patch pipette deep into the stimulated brain region, and it demonstrated the stimulation effect with single-cell precision. The second method was a technique called c-fos labeling, which can reveal neurons that have recently been stimulated. After the noninvasive stimulation experiment, the authors dissected the mouses brain and found that the only neurons that had been activated resided in the hippocampus region and not in the overlaying cortex region.
Side Effects Of The Treatment
Despite the success of Deep Brain Stimulation on many patients, it has the potential for numerous side effects such a hallucinations, depression, cognitive dysfunction, and apathy. These side effects are associated with the placement of the electrode and can be corrected by proper placement. The risk of infection, bleeding or the body rejecting the electrode is also apparent before, during and after the procedure.
The benefits of Deep Brain Stimulation far surpass its negative effects and the procedure is highly recommended for those whose Parkinsons Disease symptoms interfere with their daily activities.
What To Expect After Dbs
Surgery to implant the leads generally entails an overnight stay, while the IPG is usually implanted as same-day surgery. During recovery, your surgeon will talk to you about caring for your wounds, when you can shower, and any activity restrictions. Its usually recommended that any heavy lifting be avoided for a few weeks.
After another two to four weeks, youll return to have your device programmed. This process will continue for several weeks to ensure the stimulation settings are optimal to control your symptoms. During these visits, you will be shown how to turn the device on and off with the handheld device and check the battery level.
Once the programming has been completed, you will have regular follow-up visits to check and adjust the stimulation to maintain the most benefit for your symptoms.
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Etiology And Risk Factors
Parkinsonian symptoms can arise from either the neuropathologic condition of PD or other forms of parkinsonism. For neuropathologic PD, about 90% of cases are sporadic, with no clear etiology an additional 10% have a genetic origin, and at least 11 different linkages with 6 gene mutations have been identified Genetic forms of PD are seen more frequently in young-onset PD. A combination of environmental factors or toxins, genetic susceptibility, and the aging process may account for many sporadic cases Secondary forms of parkinsonism can be caused by medications, the sequelae of central nervous system infection, toxins, or vascular/metabolic disorders . The only proven risk factor for PD is advancing age . Other environmental or lifestyle risk factors associated with development of PD are rural living, exposure to pesticides and herbicides, well-water drinking, and working with solvents . However, none of these factors unequivocally has been demonstrated to cause iPD .
Deep Brain Stimulation For Parkinsons Disease
Neurons, a type of brain cell, communicate with each other via electrical signals to control functions in the brain and throughout the body. In Parkinsons disease patients, these signals become abnormal and irregular, leading to major movement disorders, tremors, stiffness, and impairment of balance. About 7 to 10 million people worldwide are living with Parkinsons disease. Parkinsons disease cannot be cured, but its symptoms can be controlled by two common treatments: taking medication or having a long metal wire called an electrode surgically implanted into the brain. When the disease cannot be controlled by drugs, as is often the case with late-stage patients, the inserted electrode can effectively mitigate symptoms the moment its turned on.
Electrode stimulation treatment, or deep brain stimulation , requires open-skull surgery to place the electrode into the specific regions deep in the brain that control movement, such as the subthalamic nucleus . After implantation, the electrode is connected to a battery-powered stimulator that can precisely deliver a continuous flow of electricity. Similar to the way that pacemakers regulate heartbeats, this electrical current controls how neurons communicate with each other.
Figure 1:DBS electrode targeting the subthalamic nucleus for Parkinsons disease treatment.
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Indications And Presurgical Assessment
Criteria for selecting patients for GPi DBS for dystonia remain ambiguous.In general, surgical referral for all types of dystonia can be considered inpatients who have failed trials with anticholinergic drugs, benzodiazepines,and levodopa in generalized/segmental dystonia, or had no benefit or failurewith botulinum toxin injections in cranial and cervical dystonia. There iscurrently no widely accepted consensus about which type of medication, whichdose, or how many trials are needed before surgery. In general, it is notmandatory to have tried all available medications.
Symptoms should be disabling enough to justify the surgical risk. TheBurke-Fahn-Marsden Dystonia Rating ScaleReference Burke, Fahn, Marsden, Bressman, Moskowitz and Friedman17 and the Toronto Western Spasmodic Torticollis Rating ScaleReference Consky, Basinski, Belle, Ranawaya and Lang18 are two validated and widely used scales used to measure dystoniadisability and compare pre- and postoperatory outcomes. However, there is noagreement about which scales to use to assess symptoms, or which thresholdscores for disability, dystonia, and pain severity are needed for surgery.During the preoperatory assessment, it is generally important to considerusing quality of life scales, as this is often the main reason forsurgery.
Coordinates Of Active Electrode Contacts
Retrospective analysis of the stereotactic position of the active electrode contacts was done in 25 patients for whom postoperative T1 weighted MRI of sufficient quality or stereotactic radiographic examinations were available. Such analyses could not be undertaken in other patients implanted with subthalamic nucleus electrodes during the same period because of motion artefacts in the postoperative MRI, missing postoperative T1 weighted MRI, or missing postoperative stereotactic x rays. For the 25 patients evaluated, the mean and median coordinates of all active contacts are summarised in table 3. The mean laterality of all active electrode contacts mm median 12.7 mm) correlated well with the laterality of the subthalamic nucleus, as determined 3 mm ventral to the intercommissural plane in T2 weighted MRI of 35 patients mm). However, in the dorso-ventral direction the mean and median z coordinate of all active contacts do not project within the subthalamic nucleus proper, but suggest an area between the dorsal margin of the subthalamic nucleus and the subthalamic region according to different stereotactic brain atlases. Moreover, 12 of 49 active contacts were located within 0.5 mm of the intercommissural plane or further dorsal they were thus most probably in the subthalamic area.
Active electrode contacts relative to the mid-commissural point
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Testing Before Deep Brain Stimulation
For patients with Parkinsons disease, the doctor must confirm that the PD is levodopa-responsive and determine which symptoms are most likely to respond to DBS and discuss these with the patient.
To accomplish these two objectives, the movement disorders neurologist will examine the patient in the absence of his or her PD medications, then again after having taken them. Seeing the effect of PD medications on the movement and non-motor symptoms helps the physician and patient identify good target symptoms for DBS.
A cognitive assessment can help determine a persons ability to participate in the procedure, which involves providing feedback to the doctor during surgery and throughout the neurostimulator adjustment process. This assessment also informs the team of the risk of having worsened confusion or cognitive problems following the procedure.
Some hospitals also perform an occupational therapy review or speech, language and swallowing assessment. A psychiatrist may examine the person to determine if a condition such as depression or anxiety requires treatment before the DBS procedure.
Stereotactic Dbs Vs Interventional Image
Stereotactic DBS surgery requires the patient to be off their medication. During the procedure, a frame stabilizes the head and provides coordinates to help the surgeons guide the lead to the correct location in the brain. The patient gets local anesthesia to keep them comfortable throughout each step along with a mild sedative to help them relax.
During image-guided DBS surgery, such as with interventional MRI or CT scan, the patient is often asleep under general anesthesia while the surgeon uses images of the brain to guide the lead to its target.
Some advanced centers offer both the stereotactic and iMRI-guided options for DBS surgery. In this case, the doctor and patient will discuss which procedure is better based on a number of factors.
For instance, the doctor may recommend an image-guided procedure for children, patients who have extreme symptoms, those who are especially anxious or fearful or those whose leads are going into certain parts of the brain.
Generally, DBS surgery follows this process:
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Epilepsy Medication Use Weighs On Patients Quality Of Life Study Finds
Scientists at the University of Ottawa, in Canada, tested whether providing an electrical signal to the SMA might ease patients bradykinesia symptoms. The electricity was administered through electrodes placed on their scalp, a process called transcranial direct current stimulation .
The experiments purpose was to investigate whether applying anodal tDCS over the SMA for 10 minutes would lead to improvements in patients premotor reaction time and movement kinematics during a simple reaction time task performed by the upper limb.
Researchers hypothesized that tDCS would lead to increased cortical excitability and result in a reduction in premotor RT and improved kinematic features related to bradykinesia symptoms, such as movement time, displacement and velocity.
They enrolled 13 right-handed people with Parkinsons, 12 men and one woman with a mean age of 63 all had a mean disease duration of eight years, and were tested while in an on treatment state.
In the experiments, participants waited with their right arm in a fixed position then, upon being cued, extended their elbow in a specific manner as quickly and accurately as possible. The scientists recorded these movements done in two blocks of 20 cued extensions alongside accompanying electrical activity in patients muscles.
tDCS did not significantly affect participants reaction times, findings showed.
How Does Deep Brain Stimulation Work
Movement-related symptoms of Parkinsons disease and other neurological conditions are caused by disorganized electrical signals in the areas of the brain that control movement. When successful, DBS interrupts the irregular signals that cause tremors and other movement symptoms.
After a series of tests that determines the optimal placement, neurosurgeons implant one or more wires, called leads, inside the brain. The leads are connected with an insulated wire extension to a very small neurostimulator implanted under the persons collarbone, similar to a heart pacemaker. Continuous pulses of electric current from the neurostimulator pass through the leads and into the brain.
A few weeks after the neurostimulator has been in place, the doctor programs it to deliver an electrical signal. This programming process may take more than one visit over a period of weeks or months to ensure the current is properly adjusted and providing effective results. In adjusting the device, the doctor seeks an optimal balance between improving symptom control and limiting side effects.
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Who May Benefit From Deep Brain Stimulation
A number of criteria can help identify people who are good candidates for deep brain stimulation. This includes people who:
- Have been living with Parkinsons disease for at least five years, though the procedure was approved for early symptoms in 2016 and is now being evaluated to see if it offers benefits for people earlier in the disease
- Have symptoms that are not well controlled on medications
- Are responding to Parkinsons medications : The procedure should only be done for people who are responding to this treatment, but the medication effects fluctuate during the day and the effectiveness of the medication is getting shorter.
- Find that the uncontrolled symptoms are lowering their quality of life
- Are doing relatively well cognitively
At the current time, there is no set age limit for DBS, but the effectiveness may be lower in older people.
What Are The Risks
No surgery is without risks. General complications of any surgery include bleeding, infection, blood clots, and reactions to anesthesia. Complications related to placement of the DBS lead include seizures, infection, and a 1% chance of bleeding in the brain.
Reasons for which you might need additional surgery include breakage of the extension wire in the neck parts may wear through the skin and removal of the device due to infection or mechanical failure. If you have a non-rechargeable DBS system, the battery will need to be replaced every 3 to 5 years. Rechargeable DBS systems have a battery that lasts 10 to 15 years.
DBS may also cause worsening of some symptoms such as speech and balance impairments. In some patients with Parkinson’s, DBS may cause or worsen depression. If you develop any side effects from a stimulation adjustment, you need to return to the office for further programming.
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How Do I Get Ready For Dbs
DBS requires a commitment to participate in evaluations, procedures, and consultations before and after the procedure. DBS is usually only available in large medical centers. If you do not live close to a medical center that offers DBS procedures, you may need to spend significant time traveling. The procedure and associated appointments can be expensive. It is also important for you to have realistic expectations. Although DBS can improve symptoms, it will not cure the condition.
Before DBS, you will have assessments to determine whether this is a good option for you. You will need tests to evaluate memory and thinking. A psychiatrist may examine you to determine if you have a condition such as depression or anxiety that requires treatment before the DBS procedure.
Ask your healthcare provider about what you might need to do in the days and weeks before your procedure, such as if there are any special dietary or medicine restrictions.
How Is The Surgery Performed
UPMC was one of the first centers to use ROSA robotic assistance for the placement of DBS electrodes. ROSA is similar to a GPS device for the brain. It provides the surgeon with a roadmap to reach the intended brain targets. The patient is sedated for the beginning of the surgery while we make a small opening in the skin and bone at the surgical site. The patient will not feel or remember this part of the surgery, but once these steps are complete, he is awoken for the remainder of the surgery.
Brain MappingWe use neurophysiology recordings from very thin electrodes inserted into the brain to map activity in the intended target and confirm the best spot for the DBS electrode. It is important for the patient to be awake during this part of the surgery so we can obtain the best recordings possible, which will aid in the most accurate placement of the DBS electrode. The brain mapping is not painful and the surgical team will be available to provide reassurance and feedback the entire time.
Intra-Operative Stimulation TestingWhen the best site is identified from the brain mapping, the DBS electrode is inserted and tested. We monitor the patient for improvement in his symptoms, for example tremor, and also ask him to report any new sensations he experiences. Again, this part of the procedure is not painful, but provides valuable feedback to the surgical team.
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Can I Use Electrical And Electronic Devices If I Have Dbs Devices Implanted
In general, electronic devices and appliances shouldnt cause any problems with the pulse generator. If they do, the most likely effect is that your pulse generator will switch off. This might not have an immediate effect, but sometimes youll notice that your symptoms get worse, or you’ll notice an unpleasant feeling or sensation.
In general, you should keep in mind the following:
- Your healthcare provider will give you two key items you should keep nearby whenever possible: an ID card and a patient programmer. The ID card can help you in situations with certain kinds of electronic devices like metal detectors or anti-theft scanners. The patient programmer allows you to turn the device on and off, plus adjust settings for the stimulation if needed.
- Home appliances, such as microwaves, computers, smartphones and other common electronics, shouldnt cause any kind of interference or problems with your pulse generator.
- Having one or more DBS leads and a pulse generator implanted in your body means you can’t have certain medical and diagnostic imaging procedures. The procedures you can’t have are magnetic resonance imaging scans, transcranial magnetic stimulation and diathermy.
Patient Selection Presurgical Assessment And Safety
Patient selection should be carried out in designated centres by amultidisciplinary team including a movement disorders specialist,neurosurgeon, neuropsychologist, psychiatrist, neuroradiologist, and nurses,all experienced in DBS. DBS candidacy is usually established according toinclusion and exclusion criteria proposed by the core assessment program forsurgical interventional therapies in PD .Reference Defer, Widner, Marie, Remy and Levivier1 The following factors should be carefully assessed before advocatingsurgery to a given patient: disease duration, age, levodopa responsiveness,type and severity of levodopa-unresponsive symptoms, cognitive andpsychiatric issues, comorbid disorders, and brain magnetic resonance imaging findings. In the present article, we review and summarize the currentrecommendations for each given aspect.
Patients with unstable severe health issues are commonly not consideredsurgical candidates thus, there are no data regarding this subset ofpatients. However, although formal studies are lacking, seriouscomorbidities should be regarded as a contraindication to DBS given thenegative influence on the risk-benefit ratio.Reference Pollak5
In conclusion, several factors should be taken into account when consideringsurgery in PD patients and a thorough evaluation of the risk-benefit by aspecialized multidisciplinary team is mandatory in all cases.
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