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|Year : 2013 | Volume
| Issue : 4 | Page : 345-348
Deep brain stimulation: Lessons learned in 25 years and future ahead
Department of Neurology, GB Pant Hospital, New Delhi, India; Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, MD, USA
|Date of Submission||01-Apr-2013|
|Date of Decision||02-Apr-2013|
|Date of Acceptance||30-Jun-2013|
|Date of Web Publication||4-Sep-2013|
Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, MD, USA
Source of Support: Indo.US Science Technology Forum (IUSTTF), Conflict of Interest: None
Deep brain stimulation (DBS) is a major advancement in the field of functional neurosurgery in the last century. This treatment option is now utilized for many hyperkinetic and hypokinetic movement disorders and certain disorders in the field of psychiatry. The basis of treatment is a by-product of excellent advancement made in the field of basic neuroscience and technology. Due to the improvement in the field of neuroimaging, brain structures are now better localized leading to a better outcome. Newer sites of stimulations are being recognized, which may further improve the clinical outcome in patients. However, it is very important to stick to stringent inclusion and exclusion criteria while selecting patients for DBS to get the best results.
Keywords: Deep brain stimulation, essential tremor, functional neurosurgery, movement disorder, Parkinson′s disease
|How to cite this article:|
Pandey S. Deep brain stimulation: Lessons learned in 25 years and future ahead. Neurol India 2013;61:345-8
| » Introduction|| |
Twenty six years back in 1987, Benabid et al. first documented the safety and efficacy of thalamic stimulation in a patient with tremor.  Since then there has been much advancement in the field of deep brain stimulation (DBS). High frequency stimulation of sub-thalamic nucleus was first done in a patient with an advanced Parkinson's disease (PD) in the year 1993.  There was marked improvement in dyskinesias and motor fluctuation in this patient. It was also noted that patient was able to decrease his dopaminergic medications following the procedure. In the year 2000, Coubes et al. first reported the outcome of stimulation of globus pallidus interna (GPi) in early onset primary dystonia (DYT-1) patients.  The safety and efficacy of DBS has been well-documented in several studies. At present DBS is a proven therapy for PD and essential tremor (ET). Many additional neurological and psychiatric indications are emerging rapidly.
| » Electrodes, Pulse Generator and Programming|| |
DBS surgery has two important steps. In the first step, the electrode lead is implanted at the desired part of the brain parenchyma through a burr hole. Electrode lead is then connected with implanted pulse generator (IPG) through a wire. IPG is fixed below the clavicle and runs on a battery device. Life of the battery is 3-5 years and depends on the stimulation parameters. Recently, rechargeable batteries have been introduced, which lasts for around 9 years and may be a good choice in dystonia patients where high frequency consumption is a major issue.  Usually, IPG is a voltage controlled device where amount of stimulation depends on brain impedance. There is a growing interest in shifting from voltage controlled device to current controlled device as the latter is expected to provide fixed stimulation leading to better results.
After the surgery, patient is sent back home and 2-3 weeks later patient comes for the programming of the DBS. Usually, patient is asked to be off medications for 12 h when called for programming. Different stimulation parameters are checked for the optimal benefit. Patient is assessed off medication off stimulation, off medication on stimulation, on medication off stimulation and on medication on stimulation. In majority of the patients programming of DBS parameters is an evolving process, which is completed over a period of time depending upon the clinical response. Patients can change some of the parameters at home on their own as per the device setting.
| » Different Sites of Stimulation|| |
Different areas of brain have been stimulated for different indications [Table 1]. The most common site of stimulation is sub-thalamic nucleus (STN) in PD patients. GPi is another alternative site of stimulation.  There is a growing debate about the preferred site of stimulation in PD patients. In a recently published study motor improvement was similar in both (STN and Gpi) the groups, but there were worsening of non-motor features in STN group over a period of time.  Another evolving area of stimulation is pedunculopontine nucleus (PPN) for freezing of gait in PD patients. Ventral intermediate nucleus (Vim) of thalamus is the ideal area for stimulation in Essential tremor (ET) patients.  This area has also been tried in Parkinson's disease (PD) patients having tremor as dominant symptom and multiple sclerosis patients with drug refractory tremor. Ventral striatum (VS) and nucleus accumbens (NAcc) are the major areas of stimulation in psychiatric disorders. 
| » Mechanisms of Deep Brain Stimulation|| |
Pathogenesis of PD includes degeneration of dopaminergic neurons and changes in basal ganglia-thalamus-cortex loop resulting in different symptom complexes. Effect of DBS on this loop is local and remote.  Local effect improves blood supply and promotes neuronal regeneration by stimulation of axons. Remote effects are mainly on different components of basal ganglia-thalamus-cortex loop resulting in symptom improvement. The mechanism of effect is electrical and chemical. By electrical mechanism DBS inhibits the abnormal neuronal activity leading to inactivation of excitatory neurotransmission and activation of inhibitory neurotransmission leading to overall motor improvement in patients. Simultaneously, there is release and synthesis of new neurotransmitters. Following STN stimulation there is some effect on cerebellothalamic tract also leading to response in tremor in PD patients. Effect on cerebellothalamic tract and thalamocortical tract following Vim stimulation are important in relief of ET symptoms. In obsessive compulsive disorders (OCDs) the good effect is mainly due to the activation of interconnections in the cortical - subcortical network and restoration of frontostriatal network. There are additional chronic changes including synaptic plasticity and neuroprotective effects.  Effect of DBS in dystonia patients are delayed due to the neuronal plasticity and cortical modeling.
| » Complications During and After DBS Surgery|| |
Complications may occur during the surgery or after the surgery [Table 2]. Life-threatening and serious complications include intracerebral hemorrhage, cerebrovascular accident (including venous infarct), infection, seizure and lead related problems (fracture or misplacements).  Following the surgery patients may have confusion and diplopia (due to gaze abnormalities). During follow-up patients may notice skin infection or local necrosis at the implant site on scalp. Obesity, weight gain and neuropsychiatric complications are also seen in DBS patients. Neuropsychiatric complications include decrease verbal fluency, worsening of non-motor features including cognitive decline and behavioral disorders such as sadness of mood, depression, anxiety and suicidal thoughts.
| » Use of DBS in Clinical Practice|| |
DBS has been used in different neurological and psychiatric disorders. Only approved indication for DBS are PD and ET [Table 3]. Dystonia and OCD patients may be treated by DBS as a part of research for which human device exemption has been granted. DBS may be a treatment option in Tourette syndrome, Huntington's disease, Holmes' tremor and medication resistant tremor in multiple sclerosis.  There are case reports of successful DBS use in epilepsy, depression, headache, pain and stroke recovery [Table 4]  .
| » Parkinson's disease|| |
PD patients showing consistent response to levodopa and evidence of motor fluctuation are good candidates for DBS treatment. The only major contraindication for this surgery is significant cognitive deficit in patient. Following DBS most likely symptoms to improve are bradykinesia and rigidity. STN and Gpi stimulations are effective in control of PD symptoms except postural instability and gait disturbances. PPN stimulation has been effective in PD patients having freezing of gait. Speech and non-motor symptoms are not likely to improve and in a small group of patients they may rather deteriorate following bilateral STN stimulation. Significant number of patients is able to decrease their dopaminergic drugs following the surgery. As risk of dyskinesia is high following levodopa in the majority of patient's dopa agonists is the drug of choice following surgery. In three different randomized controlled trials significant improvement in quality-of-life was seen in PD patients following STN stimulation.  However, it is important to compare the risk of surgery and benefit in quality-of-life before taking a decision regarding DBS surgery.
| » Essential tremor|| |
DBS of Vim of thalamus or surrounding sub-thalamic area is an effective treatment for ET, but still there is no consensus on the preferred site. More than 90% patients achieve significant reduction in their tremor following DBS. Improvement is consistent in contralateral limb tremor whereas inconsistent in head and voice tremor. However, still there is no clarity regarding the selection of patients for the surgery as there is no trial available comparing the efficacy of DBS versus medical management.  Bilateral stimulation may cause speech problem and cognitive decline in some patients so selection of candidate is very important.
| » Dystonia|| |
Ideal candidates for DBS in dystonia are primary generalized dystonia patients where adequate trial of medications has already been given. Bilateral Gpi is the most preferred site of stimulation for these patients. In a long-term follow-up study 40-60% patients had improvement in dystonia following stimulation.  Combined STN and Gpi stimulation has also been tried. In focal or segmental dystonia patients unilateral stimulation may be carried out if patients are not responding to botulinum toxin injections. Results are better with mobile dystonia patients in comparison to fixed dystonia patients. Long-term side-effects include mood disturbances and neurocognitive decline.
| » Psychiatric Disorders|| |
DBS have been used as a treatment option in OCD and treatment refractory depression. In OCD significant reduction (35-50%) in Yale-Brown obsessive compulsive score have been achieved. , Ventral portion of anterior internal capsule (VC) and VS have been traditionally used as a target in OCD. However, another area of stimulation is NAcc, which is a major component of vs0 . Significant antidepressant effects have been seen targeting NAcc and VC/VS as site of stimulation.
| » Ethical Concern|| |
Recently, there have been many publications on apprehensions and morality issues related to DBS. , There is a growing concern regarding the use of DBS for unproven indications beyond diseases such as cognitive enhancement, obesity and treatment for antisocial behavior. It will be fair to say that any technical advancement in the field of DBS will survive only if the indications and contraindications are identified using a very stringent criteria based on robust clinical trials rather than isolated case reports.
| » Future Issues|| |
In spite of considerable progress made in the field of DBS still there is no consensus on many issues. Still, we are searching for the ideal site of stimulation. It is not clear whether the unilateral stimulation is good or bilateral stimulation is better in a PD patient who is still having unilateral symptoms. Bilateral stimulation carries more risk for neurocognitive side-effects in comparison to unilateral stimulation. Another area, which is being strongly debated is the time of intervention in PD patients early or late. In a recent trial (EARLYSTIM), it was concluded that early stimulation was better in PD patients with early motor complications.  Another area of concern is the cost of the procedure and device. Cost is primarily due to the hardware device, which needs to be made available at lower rates as a large population in developing country like India is not able to afford it. There is a great degree of variability in reporting of complications during surgery, which may be improved by introducing standard reporting guidelines.
| » Conclusion|| |
DBS has revolutionized the functional neurosurgery in last 25 years. Significantly, large numbers of PD patients are benefitted by this technology, which has improved their quality-of-life. There are growing indications of DBS every day and better technology in future will lead to more indications with better results. However, we need to be cautious and not to use this important technology for unproven indications.
| » Acknowledgment|| |
Indo-US Science Technology Forum (IUSTTF), which has awarded the fellowship to the author to be conducted at Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, MD, USA in the field of Parkinson`s disease and movement disorder.
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[Table 1], [Table 2], [Table 3], [Table 4]