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Review Article
Deep brain stimulation: Current status Sanjay Pandey, Neelav Sarma Department of Neurology, Govind Ballabh Pant Postgraduate Institute of Medical Education and Research, New Delhi, India
ABSTRACT In the last two decades, applications of deep brain stimulation (DBS) have expanded rapidly in the field of neurosciences. The most common indications for DBS are Parkinson’s disease, medically refractory seizures, essential tremors, and primary dystonia. This device has also been used as an investigational tool in patients having Tourette’s syndrome, tardive dyskinesia, and refractory seizures. In the field of psychiatry, DBS has been used for the treatment of refractory obsessive compulsive disorder and depression. The complications are mainly related to surgery, the device, and its stimulation. This article provides an overview of the current status and recent advances in the field of DBS. Key words: Parkinson’s disease; dystonia; tremor; device; surgery
Introduction Deep brain stimulation (DBS) is a safe and effective treatment modality for certain neurological and psychiatric disorders. In the 1960s, ablative stereotactic surgery was employed for a variety of movement disorders including Parkinson’s disease (PD), but was largely abandoned in the 1970s because of introduction of highly effective drugs like levodopa. In due course, however, it became obvious that levodopa and other anti‑Parkinsonian drugs produced complications such as motor fluctuations, dyskinesias, hallucination, and psychosis, thereby limiting their utility. This led to a resurgence of surgical modalities as treatment options. Surgeons initially utilized ablative procedures; more recently, DBS has largely replaced the ablative methods as the procedure of choice as it is much less invasive. It is also reversible and adjustable. The turning point for the utilisation of DBS in the management of movement disorders was the publication by Benabid et al. in 1987 on the efficacious stimulation of ventral intermediate Access this article online Website: www.neurologyindia.com DOI: 10.4103/0028-3886.152623 PMID: xxxxx
Quick Response Code
nucleus of the thalamus for treatment of PD.[1] Subsequently, Bergman et al. in 1990 and Aziz et al. in 1992 demonstrated the efficacy of selective bilateral subthalamic nuclear (STN) lesioning in the treatment of primates in whom Parkinsonism had been artificially developed with the help of the neurotoxin, 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP).[2,3] Since its approval by the Food and Drug Administration (FDA) for PD in 2002, DBS has become a viable therapeutic modality for patients suffering from neurological and psychiatric disorders.
Technique In the DBS procedure, the stimulation electrodes are implanted into specific regions of the brain. An implanted, externally programmable pulse generator delivers continuous high-frequency electrical stimulation akin to a cardiac pacemaker.[4] The aim of DBS is to alter the physiology of a group of neurons within the basal ganglia or the thalamus. The localization is done by radiological and physiological landmarks. The radiological localization is performed by identifying the anterior commissure (AC), posterior commissure (PC), and the border between the internal capsule (IC) and the thalamus by using both computed tomography (CT) and magnetic resonance imaging (MRI) scans through a CT/MRI fusion technique. Stereotactic ventriculography provides a better localization, but is not the
Address for correspondence: Dr. Sanjay Pandey, Department of Neurology, Govind Ballabh Pant Postgraduate Institute of Medical Education and Research, New Delhi ‑ 110 001, India. E‑mail: [email protected].
Neurology India / January 2015 / Volume 63 / Issue 1
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currently preferred technique because it is invasive and may not always be successful due to the difficulty encountered in cannulating an undilated ventricle.[5] Physiological localization helps in identifying different basal ganglia and thalamic nuclei on the basis of their electrophysiological properties. These properties include spontaneous activity, neuronal response to passive and active movements, and sensory responses to natural or electrical stimulation. Microelectrodes are used to isolate single action potentials.[6‑8] These microelectrodes have a high impedance, facilitating isolation of single frequencies.[9] The STN is localized by its typical firing patterns (bursting pattern characterized by asymmetrical spikes at high frequency which shows proprioceptive response to passive movements). Since substantia nigra pars reticularis is immediately below the STN, it is important to recognize the neuronal activity of substantia nigra also (symmetrical spikes having a large amplitude with no response to external stimuli).[5] The electrode implantation is preferably performed under local anesthesia. Occasionally, this may also be done under general anesthesia, but the beneficial effects of DBS on the patient’s symptoms will not be apparent during surgery. After establishing multiple tracks using physiological localization, the neurophysician directly assesses the effects of DBS at various locations. This is the most important step in deciding the site of microelectrode placement and is pivotal for the success of the DBS procedure. Testing for rigidity of movements at the wrist is the easiest way to assess the beneficial effects of surgery as it does not require the active participation of the patient. Tremor may also be assessed during surgery; however, intraoperative assesment of speech and bradykinesia is difficult. Once the best track with maximal beneficial and minimal side effects has been established, the microelectrode is replaced by a lead that is fixed to the skull. Following the successful intracranial lead placement, a pulse generator is placed at the subclavian region in a subcutaneous pouch under general anesthesia. However, some groups prefer to perform this step a week after the insertion of the electrode. A postoperative MRI helps in ensuring proper placement of the electrodes within the brain. The next important step is the programming of the device in which the neurophysician adjusts the voltage, frequency, and polarity settings to achieve the best possible outcome [See Table 1].
Mechanism of Action The exact mechanism by which DBS exerts its action is still not clear. It has been proposed that its effects depends on stimulation rather than creation of a lesion. Mechanisms by which it produces a functional inhibition include 1) neuronal message jamming (that is transmitted through the stimulated 10
Table 1: Post procedural programming of the deep brain stimulation (DBS) hardware[97] Patient Usually 3–4 weeks after the surgery (so that any micro‑lesional effects may be over by that time) Initial stimulation is done in the ‘off’ state Electrode configuration Use pseudo‑monopolar configuration to assess effect and side‑effect threshold, and gradually increase the amplitude Decide whether bipolar versus monopolar configuration is more useful using microelectrode recording data obtained during surgery Frequency, pulse duration, and voltage setting depend on the indications and may be different for each individual patient Effect Easiest effect to monitor is tremor Rigidity is a close second Bradykinesia is unreliable Effect on dystonia may take weeks to months Associated problems during the initial stimulation Dyskinesia may worsen transiently, which is considered as a good prognostic marker Rapid tapering of dopaminergic drugs may be considered in such patients DBS - Deep brain stimulation
structure) and desynchronization of abnormal oscillations;[10‑12] (2) inhibition of neuronal firing;[13,14] (3) combined induction and excitation of high-frequency bursts; and, (4) inhibition of neurotransmitter release.[15] DBS in PD The preferred targets for DBS in PD patients are the bilateral subthalamic nuclei. The response to DBS is quantified by a unified PD rating scale (UPDRS). It is divided into part I, II, III, and IV that assess non‑motor experiences, motor experiences, motor examination, and drug-induced dyskinesias (including motor fluctuations), respectively. Patients with PD who have cardinal symptoms of the disease are likely to improve significantly.[16‑18] Patients showing significant improvement with the optimum adjustment of anti‑PD drugs are likely to show a similar improvement after proper placement of the electrodes within the STN.[19,20] Studies have shown unequivocal improvement in patients in part II and III UPDRS.[21‑24] DBS alleviates the same symptoms of PD that are relieved by levodopa. In addition, DBS also helps in reducing dyskinesias and non‑dopa‑responsive tremors. The contraindications to its usage include the presence of dementia and cognitive deficits. These features may get exacerbated after a DBS procedure. Stimulation of either the STN or the globus pallidus internus (Gpi) has shown statistically significant improvement in the UPDRS scores.[25] Comparison between the effects of the two stimulation sites have not shown any superiority of one over the other.[26] In a study, 159 patients were randomly assigned to Gpi (n = 89) and STN (N = 70) DBS. At a follow-up after 36 months, the motor symptoms were
Neurology India / January 2015 / Volume 63 / Issue 1
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stable and did not differ in the two groups.[27] However, one study has found that STN stimulation achieves a greater improvement in the UPDRS and the other disability scores and also ensures a more sustained benefit through medicines for PD.[28] A high baseline score on section III (motor) of the UPDRS and good baseline levodopa responsiveness are independent predictors of a greater improvement in the motor score after surgery.[5] The other candidates in whom DBS shows a sustained benefit include those with motor fluctuations and dyskinesias who do not respond well to medical therapy.[29,30] In a recent study, neurostimulation was studied in patients with PD with early motor fluctuation. STN stimulation was found to be superior to the medical therapy in them.
Several studies and a meta‑analysis have indicated that there was a significant improvement in the UPDRS part II and part III scores and also reduction in the medication administered in the “off period” following the DBS when compared to the pre‑surgery medication being administered for the same state.[16,17,31] The reduction (43–57%) in part III UPDRS was also found to be sustained in studies where patients were followed up for 2–4 years.[32‑38] Tremor and rigidity were found to have an improvement of 70–75%, while akinesia improved by 50% in a study.[16] The mean reduction in the postoperative levodopa requirement was in the range of 50–56%.[17,31] There was a reduction of levodopa-induced dyskinesias and in their duration by 69% and 71%, respectively.[17,37] One
Table 2: Recent studies of deep brain stimulation in Parkinson’s disease Study
Study type
Target
Tir 2007
Prospective study
STN
100 PD
1
in UPDRS (III) 43%,(II) 34% and dyskinesia-related disability by 61%
Romito 2009
Prospective study
STN
20 PD
5
Weaver 2009
Multi‑center RCT
STN=60 Gpi=61
Okun 2009
Prospective blinded study for mood and cognition
Unilateral GPi (23), STN (22)
45 PD
7 months
UPDRS 54.2% LED by 61.9% DBS group gained 4.6 h/d without troubling dyskinesia and non DBS 0 h/d ê in UPDRS motor score same in two groups
Moro 2010
Multi‑center prospective
Bilateral STN (35) Gpi‑16
51 PD
5‑6
William 2010
PD‑SURG trial at 13 centres randomized, open‑label 13 centers RCT
STN surgery and Medical (183) vs. Medical alone (183)
366 PD
1
STN‑147 GPi‑152
299 PD
2
No difference in UPDRS (III) in STN, GPi groups (P=0.50). STN patients required less dopaminergic drugs
Kishore 2010
Single blind and open‑label
All bilateral STN
45 PD
5
Benefits of simulation substantial on motor complications and QOL
Okun 2012
Prospective multi‑centric RCT Multi‑center RCT
STN CC
136 STNCC 159 PD
1
UPDRS (III) improved by 39%
3
Odekerken 2012
NSTAPS study : RCT
STN‑63 GPi‑65
128 APD
1
Schuepbach 2013
EARLYSTIM RCT
Bilateral STN
251 PD
2
UPDRS (III) improvement from baseline almost similar in STN and GPi STN>GPi in UPDRS (III) mean change, ALDS score, medication reduction ê in PDQ (39%), UPDRS‑II, III and medication
Follett 2010
Weaver et al. 2012
Number
Follow‑up Results (years)
255 APD
Bilateral STN (70) GPi (89)
ê in UPDRS (III). In both groups, dyskinesias and ADL improved. Anti-PD medications ê in STN group only Mean improvement in PDQ‑summary index score more in surgical group
Complications Infection (7), intracerebral hematoma (5), electrode failure (4), incorrect lead placement (8) Data not available 39 AEs and 1 death
No effect on mood, cognition on optimal stimulation. Ventral stimulation caused less energy, less happy disposition. Verbal fluency worse in 3 STN DBS Adverse events were more frequent in the STN group
36 (19%) patients had serious surgery‑related AEs
Visuomotor processing speed decline (P=0.03), depression (P=0.02) more in STN group. Serious AEs more in STN (56%) than GPi (51%) procedure-related AEs (9), device related AE (5) and stimulation related AE (57) Infection (5), ICH (4) Mattis dementia rating scale declined faster for STN than GPi (P=0.01) No differences in AEs
AE similar in neurostimulation and medication group
DBS - Deep brain stimulation, STN - Subthlamic nucleus, Vim - Ventral intermediate nucleus, PD - Parkinson’s disease patients, APD - Advanced PD patients, - Decrease, UPDRS - Unified Parkinson’s disease rating scale, LED - Levodopa equivalent dose, AE - Adverse events, GPi - Globus pallidus internus, QOL - Quality of life, ALDS - Academic Medical Center Linear Disability Scale, PDQ - Parkinson’s Disease Questionnaire, ICH - Intracerebral hemorrhage, STNCC - STN constant current
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of the symptoms that improves less when compared to the other ones is speech.[16] As a result of involvement of the cortico‑bulbar fibres the patients may have increased dysarthria.[38] In terms of quality of life, a multicentric trial compared the impact of DBS along with optimal medical therapy versus optimal medical therapy alone and found greater improvement in mobility, activities of daily living, emotional well‑being, stigma, and bodily discomfort in the former group when compared to the medical therapy alone.[17] Factors that predict response to DBS include the age of the patient and his/her response to levodopa therapy.[19,39] An age of less than 65 years predicts an improvement in the quality of life; good results, however, have also been reported in patients in a more advanced age.[23] Factors such as freezing of gait that do not respond to levodopa also respond poorly to DBS therapy [Tables 2 and 3].[40]
Table 3: DBS in Parkinson’s disease: Recommendations (EFNS) 2014[98]
DBS in dystonia Before DBS, apart from botulinum toxin, there were hardly any options available for patients with dystonia (especially generalized dystonias). The preferred site for DBS in dystonic patients is the GPi in the basal ganglia; however, STN stimulation has also been successfully used.[40‑43] DBS produces a good response in patients having a primary dystonia, especially generalized dystonia. The other types of dystonia where it is also effective include the cervical dystonias and tardive dystonia.[44‑46] Results are better in young patients with a shorter disease duration.[47] Moreover, unlike other diseases, the beneficial effect of DBS in dystonia is delayed by weeks or months after the procedure.[48] The target localization of GPi for DBS in dystonic patients is difficult to achieve as compared to the STN localization in patients with PD. This is because younger patients manifesting a dystonia have difficulty in cooperating during the awake surgery; no definite thumbprint of the neurophysiological target is available; and, no intraoperative changes occur on stimulating the target site. Nevertheless, studies have demonstrated a 50% reduction in the disability of patients suffering from primary generalized dystonia.[49] Similarly, patients having a cervical or tardive dystonia improve by 40–90%.[50] The Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) for evaluating generalized dystonia, and the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) for assessing cervical dystonia, are useful tools to grade the severity of the disease and the response to treatment.[51‑54] DBS has also been found to have long-term beneficial effects.[55‑58] Results in secondary dystonia have also been encouraging. In a study of 13 consecutive patients (that included 9 patients having a secondary dystonia), 11 had global subjective gains and notable objective improvement, but the benefits were variable and not completely predictable.[59] In another study, bilateral Gpi DBS was performed in adults
with dystonic‑choreoathetotic cerebral palsy. There was a significant improvement in pain, functional disability, and mental health‑related quality of life.[60] In a multicentric (16 centers) study, 23 patients having neurodegeneration due to iron accumulation in the brain were treated with bilateral GPi DBS. At a follow up of 9–15 months, 66.7% of patients had 20% or more improvement in the severity of dystonia and 31.3% had 20% or more improvement from their pretreatment disability status.[61] In another multicentric study of 15 patients of choreoacanthocytosis who underwent DBS of the GPi, the short- and long-term outcomes were analyzed. These patients had a significant improvement in their unified Huntington’s disease motor and functional capacity scores [Tables 4 and 5].[62]
12
The procedure is only recommended for patients (
Review Article
Deep brain stimulation: Current status Sanjay Pandey, Neelav Sarma Department of Neurology, Govind Ballabh Pant Postgraduate Institute of Medical Education and Research, New Delhi, India
ABSTRACT In the last two decades, applications of deep brain stimulation (DBS) have expanded rapidly in the field of neurosciences. The most common indications for DBS are Parkinson’s disease, medically refractory seizures, essential tremors, and primary dystonia. This device has also been used as an investigational tool in patients having Tourette’s syndrome, tardive dyskinesia, and refractory seizures. In the field of psychiatry, DBS has been used for the treatment of refractory obsessive compulsive disorder and depression. The complications are mainly related to surgery, the device, and its stimulation. This article provides an overview of the current status and recent advances in the field of DBS. Key words: Parkinson’s disease; dystonia; tremor; device; surgery
Introduction Deep brain stimulation (DBS) is a safe and effective treatment modality for certain neurological and psychiatric disorders. In the 1960s, ablative stereotactic surgery was employed for a variety of movement disorders including Parkinson’s disease (PD), but was largely abandoned in the 1970s because of introduction of highly effective drugs like levodopa. In due course, however, it became obvious that levodopa and other anti‑Parkinsonian drugs produced complications such as motor fluctuations, dyskinesias, hallucination, and psychosis, thereby limiting their utility. This led to a resurgence of surgical modalities as treatment options. Surgeons initially utilized ablative procedures; more recently, DBS has largely replaced the ablative methods as the procedure of choice as it is much less invasive. It is also reversible and adjustable. The turning point for the utilisation of DBS in the management of movement disorders was the publication by Benabid et al. in 1987 on the efficacious stimulation of ventral intermediate Access this article online Website: www.neurologyindia.com DOI: 10.4103/0028-3886.152623 PMID: xxxxx
Quick Response Code
nucleus of the thalamus for treatment of PD.[1] Subsequently, Bergman et al. in 1990 and Aziz et al. in 1992 demonstrated the efficacy of selective bilateral subthalamic nuclear (STN) lesioning in the treatment of primates in whom Parkinsonism had been artificially developed with the help of the neurotoxin, 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP).[2,3] Since its approval by the Food and Drug Administration (FDA) for PD in 2002, DBS has become a viable therapeutic modality for patients suffering from neurological and psychiatric disorders.
Technique In the DBS procedure, the stimulation electrodes are implanted into specific regions of the brain. An implanted, externally programmable pulse generator delivers continuous high-frequency electrical stimulation akin to a cardiac pacemaker.[4] The aim of DBS is to alter the physiology of a group of neurons within the basal ganglia or the thalamus. The localization is done by radiological and physiological landmarks. The radiological localization is performed by identifying the anterior commissure (AC), posterior commissure (PC), and the border between the internal capsule (IC) and the thalamus by using both computed tomography (CT) and magnetic resonance imaging (MRI) scans through a CT/MRI fusion technique. Stereotactic ventriculography provides a better localization, but is not the
Address for correspondence: Dr. Sanjay Pandey, Department of Neurology, Govind Ballabh Pant Postgraduate Institute of Medical Education and Research, New Delhi ‑ 110 001, India. E‑mail: [email protected].
Neurology India / January 2015 / Volume 63 / Issue 1
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[Downloaded free from http://www.neurologyindia.com on Thursday, March 05, 2015, IP: 202.177.173.189] || Click here to download free Android application for this journal Pandey and Sarma: Deep brain stimulation
currently preferred technique because it is invasive and may not always be successful due to the difficulty encountered in cannulating an undilated ventricle.[5] Physiological localization helps in identifying different basal ganglia and thalamic nuclei on the basis of their electrophysiological properties. These properties include spontaneous activity, neuronal response to passive and active movements, and sensory responses to natural or electrical stimulation. Microelectrodes are used to isolate single action potentials.[6‑8] These microelectrodes have a high impedance, facilitating isolation of single frequencies.[9] The STN is localized by its typical firing patterns (bursting pattern characterized by asymmetrical spikes at high frequency which shows proprioceptive response to passive movements). Since substantia nigra pars reticularis is immediately below the STN, it is important to recognize the neuronal activity of substantia nigra also (symmetrical spikes having a large amplitude with no response to external stimuli).[5] The electrode implantation is preferably performed under local anesthesia. Occasionally, this may also be done under general anesthesia, but the beneficial effects of DBS on the patient’s symptoms will not be apparent during surgery. After establishing multiple tracks using physiological localization, the neurophysician directly assesses the effects of DBS at various locations. This is the most important step in deciding the site of microelectrode placement and is pivotal for the success of the DBS procedure. Testing for rigidity of movements at the wrist is the easiest way to assess the beneficial effects of surgery as it does not require the active participation of the patient. Tremor may also be assessed during surgery; however, intraoperative assesment of speech and bradykinesia is difficult. Once the best track with maximal beneficial and minimal side effects has been established, the microelectrode is replaced by a lead that is fixed to the skull. Following the successful intracranial lead placement, a pulse generator is placed at the subclavian region in a subcutaneous pouch under general anesthesia. However, some groups prefer to perform this step a week after the insertion of the electrode. A postoperative MRI helps in ensuring proper placement of the electrodes within the brain. The next important step is the programming of the device in which the neurophysician adjusts the voltage, frequency, and polarity settings to achieve the best possible outcome [See Table 1].
Mechanism of Action The exact mechanism by which DBS exerts its action is still not clear. It has been proposed that its effects depends on stimulation rather than creation of a lesion. Mechanisms by which it produces a functional inhibition include 1) neuronal message jamming (that is transmitted through the stimulated 10
Table 1: Post procedural programming of the deep brain stimulation (DBS) hardware[97] Patient Usually 3–4 weeks after the surgery (so that any micro‑lesional effects may be over by that time) Initial stimulation is done in the ‘off’ state Electrode configuration Use pseudo‑monopolar configuration to assess effect and side‑effect threshold, and gradually increase the amplitude Decide whether bipolar versus monopolar configuration is more useful using microelectrode recording data obtained during surgery Frequency, pulse duration, and voltage setting depend on the indications and may be different for each individual patient Effect Easiest effect to monitor is tremor Rigidity is a close second Bradykinesia is unreliable Effect on dystonia may take weeks to months Associated problems during the initial stimulation Dyskinesia may worsen transiently, which is considered as a good prognostic marker Rapid tapering of dopaminergic drugs may be considered in such patients DBS - Deep brain stimulation
structure) and desynchronization of abnormal oscillations;[10‑12] (2) inhibition of neuronal firing;[13,14] (3) combined induction and excitation of high-frequency bursts; and, (4) inhibition of neurotransmitter release.[15] DBS in PD The preferred targets for DBS in PD patients are the bilateral subthalamic nuclei. The response to DBS is quantified by a unified PD rating scale (UPDRS). It is divided into part I, II, III, and IV that assess non‑motor experiences, motor experiences, motor examination, and drug-induced dyskinesias (including motor fluctuations), respectively. Patients with PD who have cardinal symptoms of the disease are likely to improve significantly.[16‑18] Patients showing significant improvement with the optimum adjustment of anti‑PD drugs are likely to show a similar improvement after proper placement of the electrodes within the STN.[19,20] Studies have shown unequivocal improvement in patients in part II and III UPDRS.[21‑24] DBS alleviates the same symptoms of PD that are relieved by levodopa. In addition, DBS also helps in reducing dyskinesias and non‑dopa‑responsive tremors. The contraindications to its usage include the presence of dementia and cognitive deficits. These features may get exacerbated after a DBS procedure. Stimulation of either the STN or the globus pallidus internus (Gpi) has shown statistically significant improvement in the UPDRS scores.[25] Comparison between the effects of the two stimulation sites have not shown any superiority of one over the other.[26] In a study, 159 patients were randomly assigned to Gpi (n = 89) and STN (N = 70) DBS. At a follow-up after 36 months, the motor symptoms were
Neurology India / January 2015 / Volume 63 / Issue 1
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stable and did not differ in the two groups.[27] However, one study has found that STN stimulation achieves a greater improvement in the UPDRS and the other disability scores and also ensures a more sustained benefit through medicines for PD.[28] A high baseline score on section III (motor) of the UPDRS and good baseline levodopa responsiveness are independent predictors of a greater improvement in the motor score after surgery.[5] The other candidates in whom DBS shows a sustained benefit include those with motor fluctuations and dyskinesias who do not respond well to medical therapy.[29,30] In a recent study, neurostimulation was studied in patients with PD with early motor fluctuation. STN stimulation was found to be superior to the medical therapy in them.
Several studies and a meta‑analysis have indicated that there was a significant improvement in the UPDRS part II and part III scores and also reduction in the medication administered in the “off period” following the DBS when compared to the pre‑surgery medication being administered for the same state.[16,17,31] The reduction (43–57%) in part III UPDRS was also found to be sustained in studies where patients were followed up for 2–4 years.[32‑38] Tremor and rigidity were found to have an improvement of 70–75%, while akinesia improved by 50% in a study.[16] The mean reduction in the postoperative levodopa requirement was in the range of 50–56%.[17,31] There was a reduction of levodopa-induced dyskinesias and in their duration by 69% and 71%, respectively.[17,37] One
Table 2: Recent studies of deep brain stimulation in Parkinson’s disease Study
Study type
Target
Tir 2007
Prospective study
STN
100 PD
1
in UPDRS (III) 43%,(II) 34% and dyskinesia-related disability by 61%
Romito 2009
Prospective study
STN
20 PD
5
Weaver 2009
Multi‑center RCT
STN=60 Gpi=61
Okun 2009
Prospective blinded study for mood and cognition
Unilateral GPi (23), STN (22)
45 PD
7 months
UPDRS 54.2% LED by 61.9% DBS group gained 4.6 h/d without troubling dyskinesia and non DBS 0 h/d ê in UPDRS motor score same in two groups
Moro 2010
Multi‑center prospective
Bilateral STN (35) Gpi‑16
51 PD
5‑6
William 2010
PD‑SURG trial at 13 centres randomized, open‑label 13 centers RCT
STN surgery and Medical (183) vs. Medical alone (183)
366 PD
1
STN‑147 GPi‑152
299 PD
2
No difference in UPDRS (III) in STN, GPi groups (P=0.50). STN patients required less dopaminergic drugs
Kishore 2010
Single blind and open‑label
All bilateral STN
45 PD
5
Benefits of simulation substantial on motor complications and QOL
Okun 2012
Prospective multi‑centric RCT Multi‑center RCT
STN CC
136 STNCC 159 PD
1
UPDRS (III) improved by 39%
3
Odekerken 2012
NSTAPS study : RCT
STN‑63 GPi‑65
128 APD
1
Schuepbach 2013
EARLYSTIM RCT
Bilateral STN
251 PD
2
UPDRS (III) improvement from baseline almost similar in STN and GPi STN>GPi in UPDRS (III) mean change, ALDS score, medication reduction ê in PDQ (39%), UPDRS‑II, III and medication
Follett 2010
Weaver et al. 2012
Number
Follow‑up Results (years)
255 APD
Bilateral STN (70) GPi (89)
ê in UPDRS (III). In both groups, dyskinesias and ADL improved. Anti-PD medications ê in STN group only Mean improvement in PDQ‑summary index score more in surgical group
Complications Infection (7), intracerebral hematoma (5), electrode failure (4), incorrect lead placement (8) Data not available 39 AEs and 1 death
No effect on mood, cognition on optimal stimulation. Ventral stimulation caused less energy, less happy disposition. Verbal fluency worse in 3 STN DBS Adverse events were more frequent in the STN group
36 (19%) patients had serious surgery‑related AEs
Visuomotor processing speed decline (P=0.03), depression (P=0.02) more in STN group. Serious AEs more in STN (56%) than GPi (51%) procedure-related AEs (9), device related AE (5) and stimulation related AE (57) Infection (5), ICH (4) Mattis dementia rating scale declined faster for STN than GPi (P=0.01) No differences in AEs
AE similar in neurostimulation and medication group
DBS - Deep brain stimulation, STN - Subthlamic nucleus, Vim - Ventral intermediate nucleus, PD - Parkinson’s disease patients, APD - Advanced PD patients, - Decrease, UPDRS - Unified Parkinson’s disease rating scale, LED - Levodopa equivalent dose, AE - Adverse events, GPi - Globus pallidus internus, QOL - Quality of life, ALDS - Academic Medical Center Linear Disability Scale, PDQ - Parkinson’s Disease Questionnaire, ICH - Intracerebral hemorrhage, STNCC - STN constant current
Neurology India / January 2015 / Volume 63 / Issue 1
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of the symptoms that improves less when compared to the other ones is speech.[16] As a result of involvement of the cortico‑bulbar fibres the patients may have increased dysarthria.[38] In terms of quality of life, a multicentric trial compared the impact of DBS along with optimal medical therapy versus optimal medical therapy alone and found greater improvement in mobility, activities of daily living, emotional well‑being, stigma, and bodily discomfort in the former group when compared to the medical therapy alone.[17] Factors that predict response to DBS include the age of the patient and his/her response to levodopa therapy.[19,39] An age of less than 65 years predicts an improvement in the quality of life; good results, however, have also been reported in patients in a more advanced age.[23] Factors such as freezing of gait that do not respond to levodopa also respond poorly to DBS therapy [Tables 2 and 3].[40]
Table 3: DBS in Parkinson’s disease: Recommendations (EFNS) 2014[98]
DBS in dystonia Before DBS, apart from botulinum toxin, there were hardly any options available for patients with dystonia (especially generalized dystonias). The preferred site for DBS in dystonic patients is the GPi in the basal ganglia; however, STN stimulation has also been successfully used.[40‑43] DBS produces a good response in patients having a primary dystonia, especially generalized dystonia. The other types of dystonia where it is also effective include the cervical dystonias and tardive dystonia.[44‑46] Results are better in young patients with a shorter disease duration.[47] Moreover, unlike other diseases, the beneficial effect of DBS in dystonia is delayed by weeks or months after the procedure.[48] The target localization of GPi for DBS in dystonic patients is difficult to achieve as compared to the STN localization in patients with PD. This is because younger patients manifesting a dystonia have difficulty in cooperating during the awake surgery; no definite thumbprint of the neurophysiological target is available; and, no intraoperative changes occur on stimulating the target site. Nevertheless, studies have demonstrated a 50% reduction in the disability of patients suffering from primary generalized dystonia.[49] Similarly, patients having a cervical or tardive dystonia improve by 40–90%.[50] The Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) for evaluating generalized dystonia, and the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) for assessing cervical dystonia, are useful tools to grade the severity of the disease and the response to treatment.[51‑54] DBS has also been found to have long-term beneficial effects.[55‑58] Results in secondary dystonia have also been encouraging. In a study of 13 consecutive patients (that included 9 patients having a secondary dystonia), 11 had global subjective gains and notable objective improvement, but the benefits were variable and not completely predictable.[59] In another study, bilateral Gpi DBS was performed in adults
with dystonic‑choreoathetotic cerebral palsy. There was a significant improvement in pain, functional disability, and mental health‑related quality of life.[60] In a multicentric (16 centers) study, 23 patients having neurodegeneration due to iron accumulation in the brain were treated with bilateral GPi DBS. At a follow up of 9–15 months, 66.7% of patients had 20% or more improvement in the severity of dystonia and 31.3% had 20% or more improvement from their pretreatment disability status.[61] In another multicentric study of 15 patients of choreoacanthocytosis who underwent DBS of the GPi, the short- and long-term outcomes were analyzed. These patients had a significant improvement in their unified Huntington’s disease motor and functional capacity scores [Tables 4 and 5].[62]
12
The procedure is only recommended for patients (
