Clinical Study Received: October 21, 2013 Accepted after revision: June 13, 2014 Published online: January 21, 2015
Stereotact Funct Neurosurg 2015;93:25–29 DOI: 10.1159/000365223
Globus Pallidus Internus Deep Brain Stimulation as Rescue Therapy for Refractory Dyskinesias following Effective Subthalamic Nucleus Stimulation Raymond J. Cook a Lyndsey Jones a George Fracchia a Nathan Anderson a Jenny Miu a Linton J. Meagher a Peter A. Silburn a, b Paul Silberstein a
Sydney DBS, North Shore Private Hospital, St. Leonards, N.S.W., and b Asia-Pacific Centre for Neuromodulation, Brisbane, Qld., Australia
Key Words Deep brain stimulation · Parkinsonism · Subthalamic nucleus · Globus pallidus · Dyskinesia
Abstract Background: Deep brain stimulation (DBS) at the subthalamic nucleus (STN) or globus pallidus internus (GPi) can effectively treat the motor symptoms of Parkinson’s disease, but dual implantation is rare. We report the first cases of additional GPi stimulation as rescue therapy for disabling dyskinesias following successful STN stimulation. Methods: Two patients, initially treated with bilateral STN DBS, underwent subsequent bilateral GPi DBS after the development of refractory dyskinesias within 1 and 6 years of STN surgery. Patients were evaluated with the Unified Parkinson’s Disease Rating Scale (UPDRS) before and after surgeries for STN and GPi DBS. Results: GPi DBS effectively suppressed dyskinesias in these patients and improved their quality of life, as demonstrated by their videos and UPDRS scores. Conclusions: Additional bilateral GPi DBS may be considered in the rare instance of patients who develop refractory dyskinesias early or late after bilateral STN DBS. © 2015 S. Karger AG, Basel
© 2015 S. Karger AG, Basel 1011–6125/15/0931–0025$39.50/0 E-Mail [email protected] www.karger.com/sfn
Introduction
Deep brain stimulation (DBS) is an effective treatment for medication-refractory motor fluctuations and dyskinesias in Parkinson’s disease. Stimulation at the subthalamic nucleus (STN) or the globus pallidus internus (GPi) has been shown to be equally effective when comparing primary outcomes of motor scores of the Unified Parkinson’s Disease Rating Scale-III (UPDRS-III) [1–4]. Selection of the surgical target in any individual is generally based on their profile of motor and non-motor symptoms. STN DBS has been shown to be more effective for tremor and gait disorders, with greater improvements in off-phase motor symptoms [5], whereas GPi DBS has a direct anti-dyskinetic effect and lower neuropsychiatric morbidity [4]. While dual implantation is rare, two previous openlabel studies of patients with both STN and GPi implanted suggest only a small additive effect when examining the individual and combined efficacy of these targets [6, 7]. Others have used STN DBS as a rescue therapy following long-term failure of GPi stimulation, where removal of GPi electrodes and reimplantation in the STN have anecdotally led to improved parkinsonian control [8–10]. There has been 1 reported case where STN DBS was used Dr. Paul Silberstein North Shore Medical Centre Level 5, Suite 2, 66 Pacific Highway St. Leonards, NSW 2065 (Australia) E-Mail paul @ silberstein.com.au
Downloaded by: UCSF Library & CKM 169.230.243.252 - 3/5/2015 8:57:49 PM
a
to augment functional GPi DBS in a young-onset Parkinson’s disease patient [11], 1 case where targeting the GPi successfully treated recurring dystonia in an atypical levodopa-responsive dystonia-parkinsonism patient who also had recently received STN DBS [12], and 1 case where additional GPi DBS improved dyskinesia and akinesia after failure of STN DBS [13]. Dyskinesias can occur after STN DBS, particularly in the early post-operative period [14–18], but usually resolve spontaneously, or with medication or stimulation adjustment. Here, we describe 2 rare cases where dyskinesias developed following effective STN DBS that were refractory to standard treatment. Additional bilateral GPi DBS significantly reduced these troublesome dyskinesias.
a
b
Fig. 1. Position of bilateral STN and GPi electrodes in patient 1, as shown by a post-implant CT scan (a), and a three-dimensional reconstruction after bilateral GPi implantation (b).
Patient 2 A 26-year-old man presented with a young-onset parkinsonian syndrome and underwent bilateral STN DBS a year later with symptomatic improvement. Motor fluctuations and dyskinesia returned over the next 2 years. These initially improved with adjustments in stimulation parameters and the introduction of intermittent apomorphine, but with progressive loss of symptomatic control, lead position was re-evaluated and the patient underwent repositioning of his STN leads (fig. 2). The patient improved to the extent that all Parkinson’s disease medications ceased. Worsening parkinsonism necessitated the re-introduction of dopaminergic medication after 1.5 years. A range of medications were trialled, including combinations of L-dopa, entacapone, amantadine and pramipexole. Prior to GPi implantation, the medication regime was pramipexole (Sifrol 500 mg nocte), sustained-release L-dopa/ carbidopa (Sinemet CR 200/50 mg ½ mane), L-dopa/benserazide (Madopar 125 mg ½ tablet ×5) and entacapone (Comtan 200 mg ×5). Whilst initially effective, there was a gradual narrowing of the therapeutic window with re-emergence of motor fluctuations and
26
Stereotact Funct Neurosurg 2015;93:25–29 DOI: 10.1159/000365223
b
a
c
Fig. 2. Position of bilateral STN and GPi electrodes (arrows) in patient 2, as shown by a post-implant CT scan (a) and the post-
operative GPi CT scan fused back to the pre-operative GPi MRI scan, in the coronal (b) and axial (c) plane, showing localisation of the GPi (thin arrows) and STN (thick arrows).
dyskinesias, and the patient ultimately elected for additional bilateral GPi DBS, 5.5 years after STN lead repositioning. This improved L-dopa tolerance, reduced off severity, as well as the severity and duration of dyskinesias.
Methods Surgical Procedure and Clinical Evaluation Quadripolar DBS electrodes (3387, Medtronic) were implanted bilaterally initially in the STN and then GPi (in two separate surgeries) using frame-based Cosman-Roberts-Wells stereotactic techniques [19]. Optimal positioning of STN leads was confirmed
Cook/Jones/Fracchia/Anderson/Miu/ Meagher/Silburn/Silberstein
Downloaded by: UCSF Library & CKM 169.230.243.252 - 3/5/2015 8:57:49 PM
Patient 1 A 70-year-old woman with a 20-year history of essential tremor developed tremulous parkinsonian features over a 12-month period. Treatment with levodopa/carbidopa was satisfactory for 5 years before she developed treatment-refractory motor fluctuations and dyskinesias and elected to undergo bilateral STN DBS. Despite appropriate positioning of leads (fig. 1) and suppression of tremor, she developed persistent disabling and painful lower limb dyskinesias in the weeks following surgery. These could not be controlled by adjusting stimulation parameters without losing stimulation-related tremor control. With STN stimulation set to off, dyskinesias were still disabling. A variety of medication combinations were trialled, including L-dopa/carbidopa, amantadine, apomorphine, clonazepam and levetiracetam. None were effective and the patient became wheelchair-dependent due to persistent lower limb dyskinesias. Prior to surgery she was not taking any oral anti-parkinsonian therapy. One year following STN DBS, the patient elected to undergo additional bilateral GPi DBS.
Color version available online
Clinical Histories
Results
Patient 1 Prior to STN surgery, UPDRS-III scores were 78 and 28 off and on medication, respectively. She reported feeling off 26–50% of her waking day (UPDRS-IV Q39). Tremor (essential and parkinsonian) suppression was incomplete even in the on-medication state. She also reported dyskinesias but these were graded as mild (Q33) and slightly painful (Q34), present 1–25% of her waking day (Q32). Following STN DBS there was significant improvement in parkinsonian control, particularly tremor. However, over the following weeks, her dyskinesias worsened, increasing in duration to 51–75% of her waking time (Q32), and grading to completely disabling (Q33) and markedly painful (Q34) (online suppl. video, segment 1; for all online suppl. material, see www.karger. com/doi/10.1159/000365223). Following GPi DBS, the dyskinesias were suppressed (UPDRS-IV) and her mobility restored (online suppl. video, segment 2). Dyskinesias returned when GPi stimulation was turned off (online suppl. video, segment 3). Her UPDRS-III scores were 47 (on medication, on STN, off GPi) and 25 (on medication, on STN, on GPi). Ongoing STN stimulation was required to achieve tremor suppression. Current stimulation parameters are: left STN, 1-C+, 3.1 V, 60 μs, 130 Hz; right STN, 9-C+, 2.8 V, 60 μs, 130 Hz; left GPi, 0-1-C+, 3.5 V, 60 μs, 130 Hz; right GPi, 9-10-C+, 3.8 V, 60 μs, 130 Hz. STN/GPi Dual Stimulation in Parkinson’s Disease
Patient 2 In the ensuing 6 years after STN DBS, the patient experienced gradual recurrence of parkinsonism and increasingly severe motor fluctuations and dyskinesias. Prior to GPi surgery, symptomatic off time was reported as 26–50% (UPDRS-IV Q39) and dyskinesias 51–75% of his waking time (Q32). Dyskinesias were scored as severely disabling (Q33) and moderately painful (Q34), with left foot dystonia being his major off symptom (L-dopa equivalent dose 440 mg) [20]. GPi DBS led to improved dyskinesia control and facilitated an increase in dopaminergic medication (L-dopa equivalent dose 505 mg), in total resulting in a reduction in the severity of off-medication severity (online suppl. video, segment 4). GPi stimulation without STN activation was not effective in providing relief of cardinal parkinsonian features, necessitating activation of both systems for optimal symptom control (online suppl. video, segment 5). UPDRS-III score (on STN, on GPi, on medication) was 33. The patient experiences severe dyskinesia when GPi is off (online suppl. video, segment 6). Current stimulation parameters are: left STN, 2-C+, 4.4 V, 60 μs, 180 Hz; right STN, 5-6-C+, 4.4 V, 60 μs, 180 Hz; left GPi, 2-C+, 4.3 V, 90 μs, 130 Hz; right GPi, 9-10-C+, 4.4 V, 60 μs, 130 Hz. Neither patient has experienced surgical or hardwarerelated complications.
Discussion
Loss of GPi DBS efficacy over time, with subsequent, successful STN implantation [8–10] has been reported in the literature; however, little data exists regarding the converse. Wohrle et al. [12] have described GPi DBS as a rescue therapy for the control of recurring dystonia in a case of atypical parkinsonian dystonia following STN DBS, while Allert et al. [13] report on 1 case where additional GPi DBS was used to control dyskinesia and akinesia following STN DBS. We present 2 unique cases where troublesome dyskinesias occurring subsequent to bilateral STN DBS were effectively treated with additional bilateral GPi DBS. While STN DBS provided excellent control of motor symptoms, dyskinesias were induced immediately (patient 1), or recurred over time (patient 2); both were refractory to further medical treatment or to stimulation adjustment at the STN. Dyskinesias are a recognised complication following STN DBS [14–18]. The phenomenology is similar to lesion-induced [15] and levodopa-induced [21] dyskineStereotact Funct Neurosurg 2015;93:25–29 DOI: 10.1159/000365223
27
Downloaded by: UCSF Library & CKM 169.230.243.252 - 3/5/2015 8:57:49 PM
prior to GPi insertion using 1.5-tesla MRI. For GPi implantation, the patient was anaesthetised and placed in a Cosman-RobertsWells stereotactic headframe. A CT scan was performed and fused to the 1.5-tesla MRI scan with identification of the posteroventral part of the GPi bilaterally. The patient was taken into the operating room, and the coronal skin incision was made with careful dissection of the previously inserted STN DBS electrodes from the underlying scalp. Entry points for the GPi were lateral to the entry points for the STN. The fused target obtained from the CT/MRI image was then placed into the Cosman-Roberts-Wells stereotactic frame. A microelectrode recording was made of the pallidum through to the base of the pallidum followed by insertion of DBS electrodes, with the final position being checked with the intraoperative image intensifier. The leads were then secured to the skull with StimLock caps (Medtronic). The patient underwent a CT scan post-operatively, and this image was then refused back to the preoperative MRI scan (fig. 1, 2). The position of the pallidal leads was then checked against the anatomy of the pre-operative 1.5-tesla MRI to ascertain correct lead placement. Implantable pulse generators (IPG; Kinetra, Activa RC, Activa PC, Medtronic) were implanted under general anaesthesia and stimulation parameters adjusted as required. Clinical evaluation included pre-operative and post-operative UPDRS scores, as well as video documentation.
sias, although in our experience the distribution of postoperative dyskinesias can differ from pre-operative levodopa-induced dyskinesias in the same patient. Whilst post-operative or stimulation-induced dyskinesias generally habituate [14–18], prolonged hyperkinesias that last weeks or months can occur. Treatment options include cessation or rapid reduction of anti-parkinsonian medications, or alternative stimulation configurations [16, 17]. Stimulation of a more rostral contact can suppress dyskinesias. This ‘pseudopallidotomy effect’ likely relates to stimulation of pallidofugal fibres which course rostral to the STN [16]. Given the rapidity with which dyskinesia developed after surgery in patient 1, we must assume that this was an effect of bilateral subthalamotomy. The patient’s small brain, together with the relatively long STN passes (5 mm, 6 mm) and our standard technique of using a 1.8-mm thermistor rod to create the track for the DBS electrode prior to implantation of the permanent stimulating electrode, may have been contributing factors. In patient 2, dyskinesias occurred years after effective STN DBS and only after the re-emergence of parkinsonism, despite optimal stimulation, necessitated the re-introduction of L-dopa. In this case, dyskinesias likely recurred due to a further narrowing of the therapeutic window, which led to the consideration of STN DBS in the initial instance. Progression of motor symptoms in the years following DBS is well documented [1, 22–24], although this is generally considered to relate to progression of parkinsonian pathology in non-dopamine-related neuronal circuitry [25]. Whilst it is common practice to re-introduce or increase dopamimetic medication as a therapeutic trial in this context, the benefits of escalating dose are generally modest and consequently it is unusual to see this level of recurrence of motor fluctuations
after initially effective STN DBS. The severe re-emergence of motor fluctuations and dyskinesias with re-introduction of medical therapy in this case likely relates to a multifactorial substrate including young-onset disease, rapid progression of persistently dopa-responsive rigidity and bradykinesia, marked dopa sensitivity and relative absence of progressive non-dopamine-responsive pathology. Dyskinesias have been associated with reduced pallidal firing rates and altered firing patterns [26, 27] as well as increased pallidal neuronal synchronisation at low frequencies (
Stereotact Funct Neurosurg 2015;93:25–29 DOI: 10.1159/000365223
Globus Pallidus Internus Deep Brain Stimulation as Rescue Therapy for Refractory Dyskinesias following Effective Subthalamic Nucleus Stimulation Raymond J. Cook a Lyndsey Jones a George Fracchia a Nathan Anderson a Jenny Miu a Linton J. Meagher a Peter A. Silburn a, b Paul Silberstein a
Sydney DBS, North Shore Private Hospital, St. Leonards, N.S.W., and b Asia-Pacific Centre for Neuromodulation, Brisbane, Qld., Australia
Key Words Deep brain stimulation · Parkinsonism · Subthalamic nucleus · Globus pallidus · Dyskinesia
Abstract Background: Deep brain stimulation (DBS) at the subthalamic nucleus (STN) or globus pallidus internus (GPi) can effectively treat the motor symptoms of Parkinson’s disease, but dual implantation is rare. We report the first cases of additional GPi stimulation as rescue therapy for disabling dyskinesias following successful STN stimulation. Methods: Two patients, initially treated with bilateral STN DBS, underwent subsequent bilateral GPi DBS after the development of refractory dyskinesias within 1 and 6 years of STN surgery. Patients were evaluated with the Unified Parkinson’s Disease Rating Scale (UPDRS) before and after surgeries for STN and GPi DBS. Results: GPi DBS effectively suppressed dyskinesias in these patients and improved their quality of life, as demonstrated by their videos and UPDRS scores. Conclusions: Additional bilateral GPi DBS may be considered in the rare instance of patients who develop refractory dyskinesias early or late after bilateral STN DBS. © 2015 S. Karger AG, Basel
© 2015 S. Karger AG, Basel 1011–6125/15/0931–0025$39.50/0 E-Mail [email protected] www.karger.com/sfn
Introduction
Deep brain stimulation (DBS) is an effective treatment for medication-refractory motor fluctuations and dyskinesias in Parkinson’s disease. Stimulation at the subthalamic nucleus (STN) or the globus pallidus internus (GPi) has been shown to be equally effective when comparing primary outcomes of motor scores of the Unified Parkinson’s Disease Rating Scale-III (UPDRS-III) [1–4]. Selection of the surgical target in any individual is generally based on their profile of motor and non-motor symptoms. STN DBS has been shown to be more effective for tremor and gait disorders, with greater improvements in off-phase motor symptoms [5], whereas GPi DBS has a direct anti-dyskinetic effect and lower neuropsychiatric morbidity [4]. While dual implantation is rare, two previous openlabel studies of patients with both STN and GPi implanted suggest only a small additive effect when examining the individual and combined efficacy of these targets [6, 7]. Others have used STN DBS as a rescue therapy following long-term failure of GPi stimulation, where removal of GPi electrodes and reimplantation in the STN have anecdotally led to improved parkinsonian control [8–10]. There has been 1 reported case where STN DBS was used Dr. Paul Silberstein North Shore Medical Centre Level 5, Suite 2, 66 Pacific Highway St. Leonards, NSW 2065 (Australia) E-Mail paul @ silberstein.com.au
Downloaded by: UCSF Library & CKM 169.230.243.252 - 3/5/2015 8:57:49 PM
a
to augment functional GPi DBS in a young-onset Parkinson’s disease patient [11], 1 case where targeting the GPi successfully treated recurring dystonia in an atypical levodopa-responsive dystonia-parkinsonism patient who also had recently received STN DBS [12], and 1 case where additional GPi DBS improved dyskinesia and akinesia after failure of STN DBS [13]. Dyskinesias can occur after STN DBS, particularly in the early post-operative period [14–18], but usually resolve spontaneously, or with medication or stimulation adjustment. Here, we describe 2 rare cases where dyskinesias developed following effective STN DBS that were refractory to standard treatment. Additional bilateral GPi DBS significantly reduced these troublesome dyskinesias.
a
b
Fig. 1. Position of bilateral STN and GPi electrodes in patient 1, as shown by a post-implant CT scan (a), and a three-dimensional reconstruction after bilateral GPi implantation (b).
Patient 2 A 26-year-old man presented with a young-onset parkinsonian syndrome and underwent bilateral STN DBS a year later with symptomatic improvement. Motor fluctuations and dyskinesia returned over the next 2 years. These initially improved with adjustments in stimulation parameters and the introduction of intermittent apomorphine, but with progressive loss of symptomatic control, lead position was re-evaluated and the patient underwent repositioning of his STN leads (fig. 2). The patient improved to the extent that all Parkinson’s disease medications ceased. Worsening parkinsonism necessitated the re-introduction of dopaminergic medication after 1.5 years. A range of medications were trialled, including combinations of L-dopa, entacapone, amantadine and pramipexole. Prior to GPi implantation, the medication regime was pramipexole (Sifrol 500 mg nocte), sustained-release L-dopa/ carbidopa (Sinemet CR 200/50 mg ½ mane), L-dopa/benserazide (Madopar 125 mg ½ tablet ×5) and entacapone (Comtan 200 mg ×5). Whilst initially effective, there was a gradual narrowing of the therapeutic window with re-emergence of motor fluctuations and
26
Stereotact Funct Neurosurg 2015;93:25–29 DOI: 10.1159/000365223
b
a
c
Fig. 2. Position of bilateral STN and GPi electrodes (arrows) in patient 2, as shown by a post-implant CT scan (a) and the post-
operative GPi CT scan fused back to the pre-operative GPi MRI scan, in the coronal (b) and axial (c) plane, showing localisation of the GPi (thin arrows) and STN (thick arrows).
dyskinesias, and the patient ultimately elected for additional bilateral GPi DBS, 5.5 years after STN lead repositioning. This improved L-dopa tolerance, reduced off severity, as well as the severity and duration of dyskinesias.
Methods Surgical Procedure and Clinical Evaluation Quadripolar DBS electrodes (3387, Medtronic) were implanted bilaterally initially in the STN and then GPi (in two separate surgeries) using frame-based Cosman-Roberts-Wells stereotactic techniques [19]. Optimal positioning of STN leads was confirmed
Cook/Jones/Fracchia/Anderson/Miu/ Meagher/Silburn/Silberstein
Downloaded by: UCSF Library & CKM 169.230.243.252 - 3/5/2015 8:57:49 PM
Patient 1 A 70-year-old woman with a 20-year history of essential tremor developed tremulous parkinsonian features over a 12-month period. Treatment with levodopa/carbidopa was satisfactory for 5 years before she developed treatment-refractory motor fluctuations and dyskinesias and elected to undergo bilateral STN DBS. Despite appropriate positioning of leads (fig. 1) and suppression of tremor, she developed persistent disabling and painful lower limb dyskinesias in the weeks following surgery. These could not be controlled by adjusting stimulation parameters without losing stimulation-related tremor control. With STN stimulation set to off, dyskinesias were still disabling. A variety of medication combinations were trialled, including L-dopa/carbidopa, amantadine, apomorphine, clonazepam and levetiracetam. None were effective and the patient became wheelchair-dependent due to persistent lower limb dyskinesias. Prior to surgery she was not taking any oral anti-parkinsonian therapy. One year following STN DBS, the patient elected to undergo additional bilateral GPi DBS.
Color version available online
Clinical Histories
Results
Patient 1 Prior to STN surgery, UPDRS-III scores were 78 and 28 off and on medication, respectively. She reported feeling off 26–50% of her waking day (UPDRS-IV Q39). Tremor (essential and parkinsonian) suppression was incomplete even in the on-medication state. She also reported dyskinesias but these were graded as mild (Q33) and slightly painful (Q34), present 1–25% of her waking day (Q32). Following STN DBS there was significant improvement in parkinsonian control, particularly tremor. However, over the following weeks, her dyskinesias worsened, increasing in duration to 51–75% of her waking time (Q32), and grading to completely disabling (Q33) and markedly painful (Q34) (online suppl. video, segment 1; for all online suppl. material, see www.karger. com/doi/10.1159/000365223). Following GPi DBS, the dyskinesias were suppressed (UPDRS-IV) and her mobility restored (online suppl. video, segment 2). Dyskinesias returned when GPi stimulation was turned off (online suppl. video, segment 3). Her UPDRS-III scores were 47 (on medication, on STN, off GPi) and 25 (on medication, on STN, on GPi). Ongoing STN stimulation was required to achieve tremor suppression. Current stimulation parameters are: left STN, 1-C+, 3.1 V, 60 μs, 130 Hz; right STN, 9-C+, 2.8 V, 60 μs, 130 Hz; left GPi, 0-1-C+, 3.5 V, 60 μs, 130 Hz; right GPi, 9-10-C+, 3.8 V, 60 μs, 130 Hz. STN/GPi Dual Stimulation in Parkinson’s Disease
Patient 2 In the ensuing 6 years after STN DBS, the patient experienced gradual recurrence of parkinsonism and increasingly severe motor fluctuations and dyskinesias. Prior to GPi surgery, symptomatic off time was reported as 26–50% (UPDRS-IV Q39) and dyskinesias 51–75% of his waking time (Q32). Dyskinesias were scored as severely disabling (Q33) and moderately painful (Q34), with left foot dystonia being his major off symptom (L-dopa equivalent dose 440 mg) [20]. GPi DBS led to improved dyskinesia control and facilitated an increase in dopaminergic medication (L-dopa equivalent dose 505 mg), in total resulting in a reduction in the severity of off-medication severity (online suppl. video, segment 4). GPi stimulation without STN activation was not effective in providing relief of cardinal parkinsonian features, necessitating activation of both systems for optimal symptom control (online suppl. video, segment 5). UPDRS-III score (on STN, on GPi, on medication) was 33. The patient experiences severe dyskinesia when GPi is off (online suppl. video, segment 6). Current stimulation parameters are: left STN, 2-C+, 4.4 V, 60 μs, 180 Hz; right STN, 5-6-C+, 4.4 V, 60 μs, 180 Hz; left GPi, 2-C+, 4.3 V, 90 μs, 130 Hz; right GPi, 9-10-C+, 4.4 V, 60 μs, 130 Hz. Neither patient has experienced surgical or hardwarerelated complications.
Discussion
Loss of GPi DBS efficacy over time, with subsequent, successful STN implantation [8–10] has been reported in the literature; however, little data exists regarding the converse. Wohrle et al. [12] have described GPi DBS as a rescue therapy for the control of recurring dystonia in a case of atypical parkinsonian dystonia following STN DBS, while Allert et al. [13] report on 1 case where additional GPi DBS was used to control dyskinesia and akinesia following STN DBS. We present 2 unique cases where troublesome dyskinesias occurring subsequent to bilateral STN DBS were effectively treated with additional bilateral GPi DBS. While STN DBS provided excellent control of motor symptoms, dyskinesias were induced immediately (patient 1), or recurred over time (patient 2); both were refractory to further medical treatment or to stimulation adjustment at the STN. Dyskinesias are a recognised complication following STN DBS [14–18]. The phenomenology is similar to lesion-induced [15] and levodopa-induced [21] dyskineStereotact Funct Neurosurg 2015;93:25–29 DOI: 10.1159/000365223
27
Downloaded by: UCSF Library & CKM 169.230.243.252 - 3/5/2015 8:57:49 PM
prior to GPi insertion using 1.5-tesla MRI. For GPi implantation, the patient was anaesthetised and placed in a Cosman-RobertsWells stereotactic headframe. A CT scan was performed and fused to the 1.5-tesla MRI scan with identification of the posteroventral part of the GPi bilaterally. The patient was taken into the operating room, and the coronal skin incision was made with careful dissection of the previously inserted STN DBS electrodes from the underlying scalp. Entry points for the GPi were lateral to the entry points for the STN. The fused target obtained from the CT/MRI image was then placed into the Cosman-Roberts-Wells stereotactic frame. A microelectrode recording was made of the pallidum through to the base of the pallidum followed by insertion of DBS electrodes, with the final position being checked with the intraoperative image intensifier. The leads were then secured to the skull with StimLock caps (Medtronic). The patient underwent a CT scan post-operatively, and this image was then refused back to the preoperative MRI scan (fig. 1, 2). The position of the pallidal leads was then checked against the anatomy of the pre-operative 1.5-tesla MRI to ascertain correct lead placement. Implantable pulse generators (IPG; Kinetra, Activa RC, Activa PC, Medtronic) were implanted under general anaesthesia and stimulation parameters adjusted as required. Clinical evaluation included pre-operative and post-operative UPDRS scores, as well as video documentation.
sias, although in our experience the distribution of postoperative dyskinesias can differ from pre-operative levodopa-induced dyskinesias in the same patient. Whilst post-operative or stimulation-induced dyskinesias generally habituate [14–18], prolonged hyperkinesias that last weeks or months can occur. Treatment options include cessation or rapid reduction of anti-parkinsonian medications, or alternative stimulation configurations [16, 17]. Stimulation of a more rostral contact can suppress dyskinesias. This ‘pseudopallidotomy effect’ likely relates to stimulation of pallidofugal fibres which course rostral to the STN [16]. Given the rapidity with which dyskinesia developed after surgery in patient 1, we must assume that this was an effect of bilateral subthalamotomy. The patient’s small brain, together with the relatively long STN passes (5 mm, 6 mm) and our standard technique of using a 1.8-mm thermistor rod to create the track for the DBS electrode prior to implantation of the permanent stimulating electrode, may have been contributing factors. In patient 2, dyskinesias occurred years after effective STN DBS and only after the re-emergence of parkinsonism, despite optimal stimulation, necessitated the re-introduction of L-dopa. In this case, dyskinesias likely recurred due to a further narrowing of the therapeutic window, which led to the consideration of STN DBS in the initial instance. Progression of motor symptoms in the years following DBS is well documented [1, 22–24], although this is generally considered to relate to progression of parkinsonian pathology in non-dopamine-related neuronal circuitry [25]. Whilst it is common practice to re-introduce or increase dopamimetic medication as a therapeutic trial in this context, the benefits of escalating dose are generally modest and consequently it is unusual to see this level of recurrence of motor fluctuations
after initially effective STN DBS. The severe re-emergence of motor fluctuations and dyskinesias with re-introduction of medical therapy in this case likely relates to a multifactorial substrate including young-onset disease, rapid progression of persistently dopa-responsive rigidity and bradykinesia, marked dopa sensitivity and relative absence of progressive non-dopamine-responsive pathology. Dyskinesias have been associated with reduced pallidal firing rates and altered firing patterns [26, 27] as well as increased pallidal neuronal synchronisation at low frequencies (
