- Open Access
Deep brain stimulation in Parkinson’s disease
© Mehanna and Lai; licensee BioMed Central Ltd. 2013
- Received: 7 August 2013
- Accepted: 11 November 2013
- Published: 18 November 2013
For the last 50 years, levodopa has been the cornerstone of Parkinson’s disease management. However, a majority of patients develop motor complications a few years after therapy onset. Deep brain stimulation has been approved by the FDA as an adjunctive treatment in Parkinson disease, especially aimed at controlling these complications. However, the exact mechanism of action of deep brain stimulation, the best nucleus to target as well as the best timing for surgery are still debatable. We here provide an in-depth and critical review of the current literature on this topic.
- Deep brain stimulation
- Parkinson’s disease
- Subthalamic nucleus
- Globus pallidus
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the clinical tetrad of motor dysfunction, including tremor, rigidity, akinesia (or bradykinesia) and postural instability (TRAP). It has a prevalence of 1 to 2% above the age of 60 years  and typically develops between the ages of 55 and 65 years. The tremor typically starts asymmetrically and is present at rest, usually involving hands, legs, jaw, lips, but sparing the head. Pathologically, PD is classified as a synucleinopathy, associated predominantly with the loss of dopaminergic neurons in the substantia nigra, but other brainstem neurons have been found to degenerate in PD, possibly contributing to not only motor but also non-motor impairment . Indeed, PD is now considered to be a complex syndrome, and is no longer regarded as a pure motor system disorder . For example, neurobehavioral abnormalities are frequent in advanced PD and include depression, dementia, bradyphrenia, apathy, fearfulness, anxiety, emotional lability, social withdrawal, visual–spatial impairment, sleep disturbance and psychosis. Autonomic involvement leads to constipation, bladder and sphincter dysfunction and orthostatic hypotension. Dermatological problems such as seborrhea, sensory problems such as pain and tingling, and special sense disorders such as hyposmia and vestibular dysfunction are also well described .
Five years after initiation of therapy, a majority of patients develop medication related motor complications, namely levodopa induced dyskinesias (LID) and motor fluctuations. LID are choreic, stereotypic, and dystonic movements affecting any part of the body  and occurring either at peak dose or when the medication is kicking in or wearing off (dyskinesia-improvement-dyskinesia effect). Motor fluctuations occur when the duration of each medication dose is too short and the symptoms of PD recur sooner that initially. This weaning off the medication effect can occur suddenly and unexpectedly, leaving the patient with markedly decreased mobility and/or severe tremor [4, 5]. Deep brain stimulation (DBS) has been developed primarily to address these treatment related motor complications and therapeutic failures.
The estimated annual health care cost of PD ranges from $2,000 to more than $20,000 per patient , with an estimated global economic burden of $4.63 billion , the greatest part of which being represented by nursing homes and personal care-giving [8–10] which are much higher in the later stage PD .
To better understand the hypothesized mechanism of action of DBS in PD, we will first briefly review the motor circuitry of the basal ganglia. Different motor and non-motor cortical areas project primarily to the striatum which has two major projections: the direct pathway to the globus pallidus pars interna (GPi) and the indirect projection to the GPi via the globus pallidus pars externa and the subthalamic nucleus (STN). The GPi serves as the major output nucleus, which connects back to the cortex via the thalamus. Modulated by the substantia nigra pars compacta, the indirect pathway exerts surround inhibition and thus facilitates an excitatory drive to muscles responsible for a given movement and suppresses unwanted motor activity not relevant to the primary movement. Thus, PD is thought to result from over-activation of the indirect pathway leading to an increased output from the GPi and a decrease in spontaneous movement . This model of the basal ganglia and its connections is, of course, an oversimplification of a complex network that, when disrupted, can result in a range of motor abnormalities . For example, a hyperdirect pathway, projecting directly from the cortex to the STN, and from there to the GPi has recently been added to this model .
The loss of dopaminergic neurons in the substantia nigra, the main functional characteristic of PD, affects the circuit described above and leads to the cardinal motor symptoms of PD. While the exact mechanism of this process is unknown, animal research as well as human recordings have provided functional and biochemical evidence that bradykinesia in PD results from excessive activity in the STN and the GPi [3, 15–17]. This leads to an exaggerated beta (10-30 Hz) synchronization within and between structures in the basal ganglia circuitry  that could also contribute to rigidity and akinesia [18, 19].
The pathophysiology of rest tremor in PD is less clear and probably more complicated. The existence of a unique pacemaker driving the tremor in the thalamus or the GPi has been suggested and then rejected . This symptom most likely results from a dysfunction of both the striato-pallidal-thalamocortical and the cerebello-dentato-thalamocortical circuits , with hyperactivity and hypersynchronization between central oscillators . However, contrary to bradykinesia, tremor does not seem to be dependent on beta oscillatory synchronization [22, 23].
DBS acts through delivering an electrical current in a specific target area of the brain. This current can be modulated through modification of voltage, frequency and duration of each electrical pulse delivered. The delivered energy creates an electrical field of variable size and shape according to the parameters used for stimulation. Although initially believed to stimulate the target, thus the name of the whole process, it seems that DBS actually excites the neuronal fibers, but inhibits the neural cells [24, 25]. In fact, GPi DBS decreases the GPi mean firing rate back to a normal range in animal models as well as PD patients , and high frequency DBS has a similar effect as dopamine replacement therapies, and promotes faster (about 70 Hz) non-hypersynchronous activity in the basal ganglia, correlated with clinical improvement [27–30]. This might be achieved through stimulation of bypassing inhibitory pathways, synaptic inhibition, depolarizing blockade, synaptic depression, and simulation-induced disruption of pathological network activity [26, 31]. Overall, this leads to modifications of the firing rate and pattern of neurons  in the basal ganglia, as well as local release of neurotransmitters such as glutamate and adenosine [33–35]. In addition, it seems that DBS also increases blood flow and stimulates neurogenesis .
Over the last few years, functional imaging, specifically functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and single-photon emission computed tomography (SPECT), has been used in an attempt to clarify the mechanism of action of DBS. In fMRI, blood-oxygen-level-dependent (BOLD) signals are acquired, and oxygenated blood marks areas of neural stimulation or inhibition [37–39]. On the other hand, PET and SPECT allow for imaging of multiple activity markers, such as blood flow, glucose and oxygen metabolism [40, 41]. While fMRI is less powerful than nuclear medicine techniques, it provides a much better spatial and temporal resolution.
Because of the suspected inhibitory DBS effects in electrophysiological studies, reduced STN blood flow or glucose metabolism would have been expected on functional imaging. However, the opposite has been found to be true in an overwhelming majority of imaging studies to date [42–49]. In addition, BOLD activation in the area surrounding the electrode has been reported [48, 49], despite the electrode imaging artifact preventing direct observation of the STN around the electrode. This discrepancy between apparent STN inhibition in single-cell studies and activation in imaging studies might be explained by a few hypotheses . First, electrophysiological recordings identify short neuronal modulation (in the order of milliseconds) while neuroimaging methods may reflect the summed activity changes over seconds to minutes. Second, non-neuronal contributions to the change in blood flow and/or glucose metabolism cannot be excluded, and could confound the results of neuroimaging. Finally, it is possible that PET and fMRI actually detect the increased activity in the axons, rather than in the cell bodies. Complicating matters further, some imaging studies after STN DBS have showed increased activity in the GPi [47, 48, 51] while others reported decreased activity in that nucleus [42, 52].
In summary, it is still unclear how exactly DBS affects the firing rate and pattern of neurons and how these changes actually modify the symptoms of Parkinson’s disease. DBS is presently more of an empirically proven treatment in search of physiological explanation.
Randomized controlled trial comparing DBS to optimal medical management
Number of patients
Results (primary outcome)
Deuschl et al., 2006 
-Quality of life better with DBS
-Motor symptoms better with DBS.
Weaver et al., 2009 
BL STN or GPi
Dyskinesia- free ON time 4.6 hours longer with DBS
Williams et al., 2010 
BL STN or GPi
-Quality of life better with DBS
The first trial was conducted in Germany and Austria on 156 patients with PD and persistent motor symptoms despite optimal medical therapy . These patients were randomly assigned to DBS of the STN (STN DBS) or optimal medical management. DBS assigned patients had a statistically better quality of life, as measured by the Parkinson’s Disease Questionnaire-39 (PDQ-39), as well as motor symptoms control, as measured by the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS, Part III). Another trial conducted in the United States as a double-blinded randomized study and involving 255 patients showed that DBS in either the STN or GPi increased the amount of dyskinesia free ON time at 6 months by 4.6 hours compared to the optimally managed medical group . The statistically significant improvement in quality of life after DBS compared to optimal medical management was reproduced in a third trial on 366 patients followed for 1 year in the United Kingdom .
Summary of benefits and side effects of DBS
Reported side effects
Decreased OFF time
Intra cranial hemorrhage
Reduced OFF symptoms
Muscle twitches or tonic contractions
Can also improve:
Impulse control disorders,
DBS is a reasonable option to consider when medication adjustments do not control disabling symptoms anymore [6, 66, 68]. However, not all such PD patients are candidates for DBS, and a thorough multidisciplinary screening process is required to determine those who are good candidates [69, 70]. In the current context of reducing unnecessary expenses, this screening process can be staged to help reduce costs and improve its efficiency. Patients should first undergo a thorough clinical evaluation from the neurologist to ascertain the diagnosis and exclude other causes of parkinsonism, such as vascular parkinsonism or Parkinson Plus Syndromes that are refractory to DBS. The neurologist should optimize medical management before offering DBS. Patients should then discuss at length with the neurologist and neurosurgeon to assess their understanding of the risk/benefits ratio of the surgery. If the patients then clearly understand this commitment and wish to proceed, the ON levodopa/OFF levodopa motor testing can be performed. In the ON/OFF testing, the patient is asked to withhold all PD medications for 12 hours before undergoing examination with the UPDRS. The patient is then given his regular dose of levodopa and the UPDRS is administered again after the patient reports feeling the full effect of this dose. ON and OFF UPDRS scores are compared and an improvement of at least 30% after medication intake is typically recommended to proceed to the next step. Indeed, only the symptoms that improve with levodopa are expected to improve with DBS, with the notable exception of medication refractory tremor that can still improve after surgery. DBS should thus be offered to patients with levodopa-responsive symptoms . At that point, if the patient is still considered a good candidate for surgery, brain MRI, neuropsychological testing and psychiatry evaluation would be pursued.
Animal models of PD have suggested that STN DBS might prevent further neuronal loss and thus have a neuroprotective effect [72–77]. The mechanisms of such effect are unknown, but could include a reduction in excitotoxic induced damage . However, these results have not yet been reproduced in the few human studies evaluating DBS for a neuroprotective effect [78, 79].
Similar to the medical management of PD, DBS is thus a symptomatic treatment and has not been shown to slow the progression of the disease. The duration of the therapeutic benefit has not been clearly established, but modifying the parameters of the stimulation allows the healthcare provider to tailor delivered energy to the patient’s symptoms and evolution, and sustained clinical improvement had been reported up to 10 years after implant [80–84]. However, the greatest sources of disability in late-stage PD, including drug-resistant axial motor features and non-motor symptoms, especially psychiatric disorders and cognitive decline, are not significantly modified by DBS .
Occasionally, patients might have a suboptimal response to DBS. In a series of 41 such patients, 31 of whom initially diagnosed with PD, Okun et al.  reported poor patient screening and selection as the main causes for DBS failure. Other causes included improper electrode location as well as suboptimal DBS programming and medication management. 51% of these patients markedly improved with appropriate management adjustments . Occasionally, patients might require surgical lead repositioning or even the addition of another lead in another brain structure .
While DBS related expenses such as the hardware, surgery, post-surgical programming visits and personal care-giving are relevant , STN DBS seems economically more beneficial than optimal medical management through a decrease in drug requirement and cost as well as a reduction in nursing care cost [58, 89–91]. No such data exist for GPi DBS.
Like all surgeries, DBS implant is not deprived of potential complications (Table 2). The rate of post-operative wound or hardware infection varies from 1.2% to 15.2% in different series [92–94], and most often such incidences require removal of the hardware in addition to an antibiotic course [6, 94]. Intracranial hemorrhage has been reported in 5% of cases, but was symptomatic only in 2.1% of implanted patients and caused a permanent deficit or death in 1.1% . Another larger study reported 1% of intracranial hemorrhage and stroke respectively, in 299 patients after DBS placement . Older age and a history of hypertension have been associated with an increased risk of hemorrhage . Post-operative seizures were reported in 2.4% of patients in one review , but these do not increase the risk of epilepsy. Prophylactic anticonvulsive therapy before and around surgery is currently unjustified.
Because the energy delivered to the target can spread to nearby structures and alter their function as well, DBS can induce cognitive and speech impairment, visual complaints, mood disorders including suicidal ideation [97, 98], dysphagia, paresthesia and muscle twitches or tonic contractions. These are most frequently due to a lead positioned too close to the medial STN, optic tract, oculomotor nerve, internal capsule or lemniscal tract. Ideally, these side effects could be reduced or avoided by optimal placement of the lead, with a combined use of anatomic localization and intraoperative microelectrode recording. In addition, using bipolar stimulation settings will create a smaller field with less spreading to adjacent structures, and consequently fewer side effects. The most frequent cognitive side effect to DBS seems to be a decrease in verbal fluency, especially when the STN is targeted , although some authors argue this to be a consequence of the implant rather than the stimulation . In a trial comparing 123 patients randomized to bilateral STN DBS or optimal medical management with neuropsychological and psychiatric evaluations at baseline and at 6 months, there was a selective decrease in frontal cognitive function, especially verbal fluency and naming in the DBS group. However, overall cognition was preserved and anxiety was more improved in that group . Other reported neuropsychiatric adverse effects include anxiety, apathy [101, 102], decreased frontal cognitive function , decreased executive function , impulse control disorders, obsessive-compulsive disorder and aggression [104–108]. Poor pre-operative affective state may predict continued depression post DBS , highlighting the need for appropriate pre-surgical patient screening. Finally, DBS can also lead to weight gain .
These side effects are more frequent in bilateral procedures , and a unilateral implantation can also have bilateral benefits [111–113]. The decision to implant unilaterally or bilaterally needs to be tailored to the patient’s needs.
Randomized controlled trials comparing STN and GPi DBS
Number of patients
Differences in results
Anderson et al., 2005 
-Greater decrease in dopaminergic drug dosage with STN.
-Cognitive and behavioral complications exclusively with STN.
Okun et al., 2009 
-Worse verbal fluency with STN.
-Side effects including mood and cognition.
-Greater improvement in QOL with GPi .
-Higher risk to require controlateral DBS implant in STN group .
Follett et al., 2010 
-Greater decrease in dopaminergic drug dosage with STN.
-Side effects profile.
-Worse decline in visuomotor processing with STN
-Depression improved with GPi but worsened with STN.
Weaver et al., 2012 
-Greater decrease in dopaminergic drug with STN.
-Side effects profile.
-Worse cognitive performance with STN
Odekerken et al., 2013 
-Quality of life.
-Greater decrease in dopaminergic drug dosage with STN.
-Cognitive, psychiatric and behavioral side effects
-Greater improvement in the OFF phase motor score with STN
- Greater improvement in disability with STN
Anderson et al.  conducted the first randomized controlled trial comparing STN DBS and GPi DBS. This trial included only 20 patients followed for 12 months and showed both targets to be equally effective for improving PD motor symptoms and dyskinesia. It also showed a greater decrease in dopaminergic medication use in the STN group (p = 0.08) as well as cognitive and behavioral complications exclusively in that group.
The COMPARE trial  included 45 patients with unilateral GPI or STN DBS who were followed for 7 months. The 2 targets were similar in motor control improvement and side effects profiles including mood and cognition, except for worsening of verbal fluency in the STN DBS group. However, GPi DBS patients had a bigger improvement in their quality of life compared to STN patients (38 vs. 14%, respectively; P = 0.03) with decrease in verbal fluency potentially contributing to less improvement in the STN patients . In a follow up to the COMPARE trial including 52 patients, unilateral STN DBS implant carried a 5.2 times increased risk to require a contralateral DBS implant at 3 years, when compared to unilateral GPi DBS implant .
In a large multicenter randomized control trial, Follett et al.  followed 299 patients for 2 years. GPi and STN DBS were similar in motor control improvement and side effects profiles, except for more severe decline in visuomotor processing as well as requiring lower doses of dopaminergic medications in STN DBS patients (p = 0.03 and 0.02 respectively). In addition, the level of depression improved in the GPi DBS group while it worsened in STN DBS patients (p = 0.02). At the 3-year follow-up of the same group, including 159 patients, Weaver et al.  showed that the 2 targets were similar in motor control improvement and side-effect profiles, except for worse cognitive performance in the STN group at 3 years (p = 0.01). This study also confirmed the greater reduction in dopaminergic drugs in the STN group.
The most recent double blinded randomized controlled trial comparing STN and GPi DBS  included 128 patients and reproduced the lack of significant difference in quality of life improvement between the 2 targets at 1 year. However, there was greater improvement in the OFF phase motor score and disability in STN DBS patients (p = 0.03). This study also confirmed a greater decrease in dopaminergic medication doses in the STN group (p = 0.01). However, there was no difference in cognitive, psychiatric and behavioral side-effects between the 2 groups.
It is unclear why STN DBS might have a higher rate of cognitive decline and/or depression in some studies. These finding first need to be reproduced, but both current spreading to limbic regions as well as the decreased dose of dopaminergic drugs might be contributory . Taking all these data into consideration, the current tendency is to prefer targeting the STN because of a greater improvement in the OFF phase motor symptoms as well as a higher chance to decrease the medication dosage and a lower battery consumption linked to the use of lower voltage in the STN compared to the GPi DBS. Lower battery consumption correlates with longer battery life and thus less frequent surgery to replace it . On the other hand, GPi DBS has a direct anti-dyskinestic effect when stimulation is delivered to the ventral part of the nucleus, while decrease in LID after STN DBS can be achieved through the decrease in medication dose. For that reason, GPi can be the preferred target if LID is the main complaint. As most studies showed that STN DBS resulted in more cognitive and behavioral deficits [57, 115, 116, 118], GPi DBS might be preferred for patients with mild cognitive impairment and psychiatric symptoms.
Because of its role in locomotion, the pedunculopontine nucleus (PPN) has been suggested as a DBS target to address gait difficulty and freezing of gait, which are typically resistant to STN or GPi DBS. A few small observational or open labeled studies have been conducted, evaluating PPN DBS as an add-on to STN DBS [82, 121–126]. Precise anatomical lead locations as well as results were controversial, and PPN DBS cannot be recommended at this point.
Currently, patients are not considered for DBS unless they do not tolerate levodopa, become resistant to medications or have complications from medical therapy, while still being medically and psychologically fit for surgery. Some authors suggest that exhausting all pharmacological options before considering DBS can delay the surgery to a time when the patient is no longer fit because of disease progression [58, 127, 128].
A small randomized trial of bilateral STN DBS in 10 patients with early PD (mean duration of 7 years) compared to 10 matched medically treated controls  showed a significant benefit from DBS on quality of life, motor control and decrease in levodopa doses. More recently, Schuepbach et al.  conducted a randomized controlled trial comparing bilateral STN DBS to optimal medical management in 251 PD patients aged less than 60 years, with PD for more than 4 years but with motor fluctuations and dyskinesia for 3 years or less. This study demonstrated improvement in quality of life, motor control, as well as mood at 24 months in the DBS group compared to the medical group. Mild side effects were more frequent in the DBS group, but the incidence of moderate to severe side effect was comparable between the 2 groups. With a mean age of onset of 52 years as compared with 59 to 62 years in other trials [55–57, 80, 119] and a mean duration of PD of 7.5 years, as compared with 10.8 to 13.8 years [53, 55–57, 119], this study demonstrated the added benefit of early DBS in PD symptoms control, when medical treatment is still effective. However, these results have yet to be confirmed.
Another ongoing trial comparing DBS early in the course of PD to optimal medical management, EARLYSTIM [58, 131], involves 247 patients implanted a mean of 7.5 years after diagnosis and within 3 years of development of treatment induced motor complications. Preliminary results report a mean age of 52 years, levodopa therapy duration of 4.9 years and fluctuations and/or dyskinesias present for 1.5 or 1.7 years respectively. At 2 years follow up, quality of life and motor control were superior in the DBS group. Side effects were more frequent in the medical group, and surgical complications resolved entirely.
In addition, an analytic model of STN DBS, defined by off time and applied at an early versus delayed stage, concluded that early DBS increases quality-adjusted life years and reduces treatment costs . However, further studies in this area are warranted before recommending early DBS placement in PD patients. In addition, it would be wise to wait 5 years after the onset of symptoms before performing the surgery, in order to rule out any Parkinson Plus Syndrome.
For the last 50 years, levodopa has been the cornerstone of PD management. However, a majority of patients develop motor fluctuations and/or LID about 5 years after the initiation of therapy. DBS of the STN or the GPi grant to patients with PD improved quality of life and decreased motor complications, and has been approved as such by the Food and Drug Administration in the US in 2002. We reviewed the experience and available literature on DBS for Parkinson’s disease over the last decade and arrive at the following suggestions. (1) The success of DBS surgery depends on the accurate placement of the leads and meticulous programming of the stimulation. Therefore, it is best accomplished by an experienced team of neurosurgeon, neurologist, and support staff dedicated to the treatment. (2) Reports of surgical complication rates and long-term side-effects of DBS are very variable, so benefits and potential adverse results should not be under- or over-emphasized. (3) While essentially equal in improving the motor symptoms of PD, STN and GPi might have their own benefits and risks, and the choice of the target should be individualized and adapted to the patient’s situation. (4) Knowledge to further improve DBS treatment for Parkinson’s disease, such as a more scientific and reliable protocol on programming, strategies to minimize cognitive and psychiatric complications, and the better long-term maintenance of the implanted device, are still lacking. (5) Data on the impact of DBS on non-motor symptoms affecting the quality of life of PD patients, such as pain, speech or gastro-intestinal complaints, are still scarce. Further research in these areas will help make this useful treatment even more beneficial.
- Tanner CM, Aston DA: Epidemiology of Parkinson’s disease and akinetic syndromes. Curr Opin Neurol 2000, 13: 427-430.PubMedView ArticleGoogle Scholar
- Mehanna R, Jankovic J: Respiratory problems in neurologic movement disorders. Parkinsonism Relat Disord 2010, 16: 628-638.PubMedView ArticleGoogle Scholar
- Jankovic J, Mehanna R: Pathophysiology and clinical assessment. In Handbook of Parkinson’s Disease. 5th edition. Edited by: Pahwa R, Lyons K. Florida: CRC press; 2013:61-91.View ArticleGoogle Scholar
- Fahn S: The spectrum of levodopa-induced dyskinesias. Ann Neurol 2000, 47(1):S2-S9.PubMedView ArticleGoogle Scholar
- Fahn S: Description of Parkinson’s disease as a clinical syndrome. Ann N Y Acad Sci 2003, 991: 1-14.PubMedView ArticleGoogle Scholar
- Okun M: Deep brain stimulation for Parkinson’s disease. N Engl J Med 2012, 367: 1529-1538.PubMedView ArticleGoogle Scholar
- Findley LJ: The economic impact of Parkinson’s disease. Parkinsonism Relat Disord 2007, 13(Suppl):S8-S12.PubMedView ArticleGoogle Scholar
- Vossius C, Nilsen OB, Larsen JP: Parkinson’s disease and nursing home placement: the economic impact of the need for care. Eur J Neurol 2009, 16: 194-200.PubMedView ArticleGoogle Scholar
- Winter Y, Balzer-Geldsetzer M, Spottke A, Reese JP, Baum E, Klotsche J, Rieke J, Simonow A, Eggert K, Oertel WH, Dodel R: Longitudinal study of the socioeconomic burden of Parkinson’s disease in Germany. Eur J Neurol 2010, 17: 1156-1163.PubMedView ArticleGoogle Scholar
- Weintraub D, Comella CL, Horn S: Parkinson’s Disease. Part 1: pathophysiology, symptoms, burden, diagnosis, and assessment. Am J Manag Care 2008, 14: S40-S48.PubMedGoogle Scholar
- Chen JJ: Parkinson’s disease: health-related quality of life, economic cost, and implications of early treatment. Am J Manag Care 2010, 16: S87-S93.PubMedGoogle Scholar
- Mehanna R, Jankovic J: Movement disorders in cerebrovascular disease. Lancet Neurol 2013, 12: 597-608.PubMedView ArticleGoogle Scholar
- Diederich NJ, Parent A: Parkinson’s disease: acquired frailty of archaic neural networks? J Neurol Sci 2012, 314: 143-151.PubMedView ArticleGoogle Scholar
- Brunenberg EJ, Moeskops P, Backes WH, Pollo C, Cammoun L, Vilanova A, Janssen ML, Visser-Vandewalle VE, ter Haar Romeny BM, Thiran JP, Platel B: Structural and resting state functional connectivity of the subthalamic nucleus: identification of motor STN parts and the hyperdirect pathway. PLoS One 2012, 7(6):e39061. doi: 10.1371/journal.pone.0039061. Epub 2012 Jun 29PubMed CentralPubMedView ArticleGoogle Scholar
- Bergman H, Wichmann T, DeLong MR: Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 1990, 249: 1436-1438.PubMedView ArticleGoogle Scholar
- Lintas A, Silkis IG, Albéri L, Villa AE: Dopamine deficiency increases synchronized activity in the rat subthalamic nucleus. Brain Res 2012, 1434: 142-151.PubMedView ArticleGoogle Scholar
- Dostrovsky JO, Hutchinson WD, Lozano AM: The globus pallidus, deep brain stimulation and Parkinson’s disease. Neuroscientist 2002, 8: 284-290.PubMedGoogle Scholar
- Brown P: Abnormal oscillatory synchronisation in the motor system leads to impaired movement. Curr Opin Neurobiol 2007, 17: 656-664.PubMedView ArticleGoogle Scholar
- Hammond C, Bergman H, Brown P: Pathological synchronization in Parkinson’s disease: networks, models and treatments. Trends Neurosci 2007, 30: 357-364.PubMedView ArticleGoogle Scholar
- Boecker H, Brooks DJ: Resting tremor in Parkinson disease: is the pallidum to blame? Ann Neurol 2011, 69: 229-231.PubMedView ArticleGoogle Scholar
- Bartolic´ A, Pirtosek Z, Rozman J, Ribaric S: remor amplitude and tremor frequency variability in Parkinson’s disease is dependent on activity and synchronisation of central oscillators in basal ganglia. Med Hypotheses 2010, 74: 362-365.PubMedView ArticleGoogle Scholar
- Kühn AA, Kupsch A, Schneider GH, Brown P: Reduction in subthalamic 8–35 Hz oscillatory activity correlates with clinical improvement in Parkinson’s disease. Eur J Neurosci 2006, 23: 1956-1960.PubMedView ArticleGoogle Scholar
- Ray NJ, Jenkinson N, Wang S, Holland P, Brittain JS, Joint C, Stein JF, Aziz T: Local field potential beta activity in the subthalamic nucleus of patients with Parkinson’s disease is associated with mprovements in bradykinesia after dopamine and deep brain stimulation. Exp Neurol 2008, 213: 108-113.PubMedView ArticleGoogle Scholar
- McIntyre CC, Hahn PJ: Network perspectives on the mechanisms of deep brain stimulation. Neurobiol Dis 2010, 38: 329-337.PubMed CentralPubMedView ArticleGoogle Scholar
- Vitek JL: Mechanisms of deep brain stimulation: excitation or inhibition. Mov Disord 2002, 17(Suppl 3):S69-S72.PubMedView ArticleGoogle Scholar
- Goldberg J, Boraud T, Bergman H: Microrecording in the primate MPTP model. In Microelectrode recording in movement disorder surgery. Edited by: Israel Z, Burchiel K. New York: Thieme; 2004:46-62.Google Scholar
- Farmer S: Neural rhythms in Parkinson’s disease. Brain 2002, 125: 1175-1176.PubMedView ArticleGoogle Scholar
- Levy R, Ashby P, Hutchison WD, Lang AE, Lozano AM, Dostrovsky JO: Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson’s disease. Brain 2002, 125: 1196-1209.PubMedView ArticleGoogle Scholar
- Priori A, Foffani G, Pesenti A, Tamma F, Bianchi AM, Pellegrini M, Locatelli M, Moxon KA, Villani RM: Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson’s disease. Exp Neurol 2004, 189: 369-379.PubMedView ArticleGoogle Scholar
- Silberstein P, Pogosyan A, Kühn AA, Hotton G, Tisch S, Kupsch A, Dowsey-Limousin P, Hariz MI, Brown P: Cortico-cortical coupling in Parkinson’s disease and its modulation by therapy. Brain 2005, 128: 1277-1291.PubMedView ArticleGoogle Scholar
- McIntyre CC, Savasta M, Kerkerian-Le Goff L, Vitek JL: Uncovering the mechanism(s) of action of deep brain stimulation: activation, inhibition, or both. Clin Neurophysiol 2004, 115: 1239-1248.PubMedView ArticleGoogle Scholar
- Wichmann T, DeLong MR, Guridi J, Obeso JA: Milestones in research on the pathophysiology of Parkinson’s disease. Mov Disord 2011, 26: 1032-1041.PubMed CentralPubMedView ArticleGoogle Scholar
- Tawfik VL, Chang SY, Hitti FL, Roberts DW, Leiter JC, Jovanovic S, Lee KH: Deep brain stimulation results in local glutamate and adenosine release: investigation into the role of astrocytes. Neurosurgery 2010, 67: 367-375.PubMed CentralPubMedView ArticleGoogle Scholar
- Lee KH, Chang SY, Roberts DW, Kim U: Neurotransmitter release from high-frequency stimulation of the subthalamic nucleus. J Neurosurg 2004, 101: 511-517.PubMedView ArticleGoogle Scholar
- Lee KH, Hitti FL, Chang SY, Lee DC, Roberts DW, McIntyre CC, Leiter JC: High frequency stimulation abolishes thalamic network oscillations: an electrophysiological and computational analysis. J Neural Eng 2011, 8: 046001.PubMed CentralPubMedView ArticleGoogle Scholar
- Vedam-Mai V, van Battum EY, Kamphuis W, Feenstra MG, Denys D, Reynolds BA, Okun MS, Hol EM: Deep brain stimulation and the role of astrocytes. Mol Psychiatry 2012, 17: 124-131.PubMedView ArticleGoogle Scholar
- Bandettini PA, Wong EC, Hinks RS, Tikofsky RS, Hyde JS: Time course EPI of human brain function during task activation. Magn Reson Med 1991, 25: 390-397.View ArticleGoogle Scholar
- Kwong KK, Belliveau JW, Chesler DA, Goldberg IE, Weisskoff RM, Poncelet BP, Kennedy DN, Hoppel BE, Cohen MS, Turner R, et al.: Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proc Natl Acad Sci 1992, 89: 5675-5679.PubMed CentralPubMedView ArticleGoogle Scholar
- Ogawa S, Lee T, Kay A, Tank D: Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A 1990, 87: 9868-9872.PubMed CentralPubMedView ArticleGoogle Scholar
- Phelps ME: PET: the merging of biology and imaging into molecular imaging. J Nucl Med 2000, 41: 661-681.PubMedGoogle Scholar
- Heiss W-D, Herholz K: Brain receptor imaging. J Nucl Med 2006, 47: 302-312.PubMedGoogle Scholar
- Asanuma K, Tang C, Ma Y, Dhawan V, Mattis P, Edwards C, Kaplitt MG, Feigin A, Eidelberg D: Network modulation in the treatment of Parkinson’s disease. Brain 2006, 129: 2667-2678.PubMed CentralPubMedView ArticleGoogle Scholar
- Boertien T, Zrinzo L, Kahan J, Jahanshahi M, Hariz M, Mancini L, Limousin P, Foltynie T: Functional imaging of subthalamic nucleus deep brain stimulation in Parkinson’s disease. Mov Disord 2011, 26: 1835-1843.PubMedView ArticleGoogle Scholar
- Geday J, Ostergaard K, Johnsen E, Gjedde A: STN-stimulation in Parkinson’s disease restores striatal inhibition of thalamocortical projection. Hum Brain Mapp 2009, 30: 112-121.PubMedView ArticleGoogle Scholar
- Haslinger B, Kalteis K, Boecker H, Alesch F, Ceballos-Baumann AO: Frequency-correlated decreases of motor cortex activity associated with subthalamic nucleus stimulation in Parkinson’s disease. Neuroimage 2005, 28: 598-606.PubMedView ArticleGoogle Scholar
- Hilker R, Voges J, Weisenbach S, Kalbe E, Burghaus L, Ghaemi M, Lehrke R, Koulousakis A, Herholz K, Sturm V, Heiss WD: Subthalamic nucleus stimulation restores glucose metabolism in associative and limbic cortices and in cerebellum: evidence from a FDG-PET study in advanced Parkinson’s disease. J Cereb Blood Flow Metab 2004, 24: 7-16.PubMedView ArticleGoogle Scholar
- Hilker R, Voges J, Weber T, Kracht LW, Roggendorf J, Baudrexel S, Hoevels M, Sturm V, Heiss WD: STN-DBS activates the target area in Parkinson disease An FDG-PET study. Neurology 2008, 71: 708-713.PubMedView ArticleGoogle Scholar
- Jech R, Urgosík D, Tintera J, Nebuzelský A, Krásenský J, Liscák R, Roth J, Růzicka E: Functional magnetic resonance imaging during deep brain stimulation: a pilot study in four patients with Parkinson’s disease. Mov Disord 2001, 16: 1126-1132.PubMedView ArticleGoogle Scholar
- Jech R: Functional imaging of deep brain stimulation: fMRI, SPECT, and PET. In Deep Brain Stimulation in Neurological and Psychiatric Disorders. Edited by: Tarsy D, Vitek JL, Starr P, Okun M. Springer; 2008:179-201.View ArticleGoogle Scholar
- Albaugh DL, Shih YY: Neural circuit modulation during deep brain stimulation at the subthalamic nucleus for Parkinson’s disease: what have we learned from neuroimaging studies? Brain Connect 2013. Oct 22. [Epub ahead of print]Google Scholar
- Ceballos-Baumann AO, Boecker H, Bartenstein P, von Falkenhayn I, Riescher H, Conrad B, Moringlane JR, Alesch F: A positron emission tomographic study of subthalamic nucleus stimulation in Parkinson disease: enhanced movement-related activity of motor-association cortex and decreased motor cortex resting activity. Arch Neurol 1999, 56: 997.PubMedView ArticleGoogle Scholar
- Scherfler C, Seppi K, Mair KJ, Donnemiller E, Virgolini I, Wenning GK, Poewe W: Left hemispheric predominance of nigrostriatal dysfunction in Parkinson’s disease. Brain 2012, 135: 3348-3354.PubMedView ArticleGoogle Scholar
- Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schäfer H, Bötzel K, Daniels C, Deutschländer A, Dillmann U, Eisner W, Gruber D, Hamel W, Herzog J, Hilker R, Klebe S, Kloss M, Koy J, Krause M, Kupsch A, Lorenz D, Lorenzl S, Mehdorn HM, Moringlane JR, Oertel W, Pinsker MO, Reichmann H, Reuss A, Schneider GH, Schnitzler A, Steude U, et al.: A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med 2006, 355: 896-908.PubMedView ArticleGoogle Scholar
- Weaver FM, Follett K, Stern M, Hur K, Harris C, Marks WJ Jr, Rothlind J, Sagher O, Reda D, Moy CS, Pahwa R, Burchiel K, Hogarth P, Lai EC, Duda JE, Holloway K, Samii A, Horn S, Bronstein J, Stoner G, Heemskerk J, Huang GD, CSP 468 Study Group: Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA 2009, 301: 63-73.PubMed CentralPubMedView ArticleGoogle Scholar
- Williams A, Gill S, Varma T, Jenkinson C, Quinn N, Mitchell R, Scott R, Ives N, Rick C, Daniels J, Patel S, Wheatley K, PD SURG Collaborative Group: Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson’s disease (PD SURG trial): a randomized, open-label trial. Lancet Neurol 2010, 9: 581-591.PubMed CentralPubMedView ArticleGoogle Scholar
- Okun MS, Gallo BV, Mandybur G, Jagid J, Foote KD, Revilla FJ, Alterman R, Jankovic J, Simpson R, Junn F, Verhagen L, Arle JE, Ford B, Goodman RR, Stewart RM, Horn S, Baltuch GH, Kopell BH, Marshall F, Peichel D, Pahwa R, Lyons KE, Tröster AI, Vitek JL, Tagliati M, SJM DBS Study Group: Subthalamic deep brain stimulation with a constant-current device in Parkinson’s disease: an open-label randomized controlled trial. Lancet Neurol 2012, 11: 140-149.PubMedView ArticleGoogle Scholar
- Follett KA, Weaver FM, Stern M, Hur K, Harris CL, Luo P, Marks WJ Jr, Rothlind J, Sagher O, Moy C, Pahwa R, Burchiel K, Hogarth P, Lai EC, Duda JE, Holloway K, Samii A, Horn S, Bronstein JM, Stoner G, Starr PA, Simpson R, Baltuch G, De Salles A, Huang GD, Reda DJ, CSP 468 Study Group: Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. N Engl J Med 2010, 362: 2077-2091.PubMedView ArticleGoogle Scholar
- Desouza R, Moro E, Lang A, Schapira A: Timing of deep brain stimulation in Parkinson’s disease: a need for reappraisal? Ann Neurol 2013, 73: 565-575.PubMed CentralPubMedView ArticleGoogle Scholar
- Fimm B, Heber IA, Coenen VA, Fromm C, Noth J, Kronenbuerger M: Deep brain stimulation of the subthalamic nucleus improves intrinsic alertness in Parkinson’s disease. Mov Disord 2009, 24: 1616-1620.View ArticleGoogle Scholar
- Nazzaro JM, Pahwa R, Lyons KE: The impact of bilateral subthalamic stimulation on nonmotor symptoms of Parkinson’s disease. Parkinsonism Relat Disord 2011, 17: 606-609.PubMedView ArticleGoogle Scholar
- Strutt AM, Simpson R, Jankovic J, York MK: Changes in cognitive-emotional and physiological symptoms of depression following STN-DBS for the treatment of Parkinson’s disease. Eur J Neurol 2012, 19: 121-127.PubMedView ArticleGoogle Scholar
- Halim A, Baumgartner L, Binder DK: Effect of deep brain stimulation on autonomic dysfunction in patients with Parkinson’s disease. J Clin Neurosci 2011, 18: 804-806.PubMedView ArticleGoogle Scholar
- Witjas T, Kaphan E, Régis J, Jouve E, Chérif AA, Péragut JC, Azulay JP: Effects of chronic subthalamic stimulation on nonmotor fluctuations in Parkinson’s disease. Mov Disord 2007, 22: 1727-1734.View ArticleGoogle Scholar
- Halpern CH, Rick JH, Danish SF, Grossman M, Baltuch GH: Cognition following bilateral deep brain stimulation surgery of the subthalamic nucleus for Parkinson’s disease. Int J Geriatr Psychiatry 2009, 24: 443-451.PubMedView ArticleGoogle Scholar
- Mehanna R, Ondo W: Sleep problems in Parkinson’s disease patients. Neurodegenerative dis manag 2011, 1: 307-321.View ArticleGoogle Scholar
- Amara AW, Standaert DG, Guthrie S, Cutter G, Watts RL, Walker HC: Unilateral subthalamic nucleus deep brain stimulation improves sleep quality in Parkinson’s disease. Parkinsonism Relat Disord 2012, 18: 63-68.PubMed CentralPubMedView ArticleGoogle Scholar
- Amara AW, Watts RL, Walker HC: The effects of deep brain stimulation on sleep in Parkinson’s disease. Ther Adv Neurol Disord 2011, 4: 15-24.PubMed CentralPubMedView ArticleGoogle Scholar
- Okun MS, Foote KD: Enough is enough: moving on to deep brain stimulation in patients with fluctuating Parkinson disease. Arch Neurol 2009, 66: 778-780.PubMedView ArticleGoogle Scholar
- Okun MS, Fernandez HH, Pedraza O, Misra M, Lyons KE, Pahwa R, Tarsy D, Scollins L, Corapi K, Friehs GM, Grace J, Romrell J, Foote KD: Development and initial validation of a screening tool for Parkinson disease surgical candidates. Neurology 2004, 63: 161-163.PubMedView ArticleGoogle Scholar
- Okun MS, Foote KD: Parkinson’s disease DBS: what, when, who and why? The time has come to tailor DBS targets. Expert Rev Neurother 2010, 10: 1847-1857.PubMed CentralPubMedView ArticleGoogle Scholar
- Okun MS, Fernandez HH, Rodriguez RL, Foote KD: Identifying candidates for deep brain stimulation in Parkinson’s disease: the role of the primary care physician. Geriatrics 2007, 62: 18-24.PubMedGoogle Scholar
- Spieles-Engemann AL, Behbehani MM, Collier TJ, Wohlgenant SL, Steece-Collier K, Paumier K, Daley BF, Gombash S, Madhavan L, Mandybur GT, Lipton JW, Terpstra BT, Sortwell CE: Stimulation of the rat subthalamic nucleus is neuroprotective following significant nigral dopamine neuron loss. Neurobiol Dis 2010, 39: 105-115.PubMed CentralPubMedView ArticleGoogle Scholar
- Maesawa S, Kaneoke Y, Kajita Y, Usui N, Misawa N, Nakayama A, Yoshida J: Long-term stimulation of the subthalamic nucleus in hemiparkinsonian rats: neuroprotection of dopaminergic neurons. J Neurosurg 2004, 100: 679-687.PubMedView ArticleGoogle Scholar
- Harnack D, Meissner W, Jira JA, Winter C, Morgenstern R, Kupsch A: Placebo-controlled chronic high-frequency stimulation of the subthalamic nucleus preserves dopaminergic nigral neurons in a rat model of progressive Parkinsonism. Exp Neurol 2008, 210: 257-260.PubMedView ArticleGoogle Scholar
- Zhao XD, Cao YQ, Liu HH, Li FQ, You BM, Zhou XP: Long term high frequency stimulation of STN increases dopamine in the corpus striatum of hemiparkinsonian rhesus monkey. Brain Res 2009, 1286: 230-238.PubMedView ArticleGoogle Scholar
- Wallace BA, Ashkan K, Heise CE, Foote KD, Torres N, Mitrofanis J, Benabid AL: Survival of midbrain dopaminergic cells after lesion or deep brain stimulation of the subthalamic nucleus in MPTP-treated monkeys. Brain 2007, 130: 2129-2145.PubMedView ArticleGoogle Scholar
- Shaw VE, Keay KA, Ashkan K, Benabid AL, Mitrofanis J: Dopaminergic cells in the periaqueductal grey matter of MPTP-treated monkeys and mice; patterns of survival and effect of deep brain stimulation and lesion of the subthalamic nucleus. Parkinsonism Relat Disord 2010, 16: 338-344.PubMedView ArticleGoogle Scholar
- Warnke PC: STN stimulation and neuroprotection in Parkinson’s disease-when beautiful theories meet ugly facts. J Neurol Neurosurg Psychiatry 2005, 76: 1186-1187.PubMed CentralPubMedView ArticleGoogle Scholar
- Hilker R, Portman AT, Voges J, Staal MJ, Burghaus L, van Laar T, Koulousakis A, Maguire RP, Pruim J, de Jong BM, Herholz K, Sturm V, Heiss WD, Leenders KL: Disease progression continues in patients with advanced Parkinson’s disease and effective subthalamic nucleus stimulation. J Neurol Neurosurg Psychiatry 2005, 76: 1217-1221.PubMed CentralPubMedView ArticleGoogle Scholar
- Krack P, Batir A, Van Blercom N, Chabardes S, Fraix V, Ardouin C, Koudsie A, Limousin PD, Benazzouz A, LeBas JF, Benabid AL, Pollak P: Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med 2003, 349: 1925-1934.PubMedView ArticleGoogle Scholar
- Fasano A, Romito LM, Daniele A, Piano C, Zinno M, Bentivoglio AR, Albanese A: Motor and cognitive outcome in patients with Parkinson’s disease 8 years after subthalamic implants. Brain 2010, 133: 2664-2676.PubMedView ArticleGoogle Scholar
- Moro E, Lozano AM, Pollak P, Agid Y, Rehncrona S, Volkmann J, Kulisevsky J, Obeso JA, Albanese A, Hariz MI, Quinn NP, Speelman JD, Benabid AL, Fraix V, Mendes A, Welter ML, Houeto JL, Cornu P, Dormont D, Tornqvist AL, Ekberg R, Schnitzler A, Timmermann L, Wojtecki L, Gironell A, Rodriguez-Oroz MC, Guridi J, Bentivoglio AR, Contarino MF, Romito L, et al.: Long-term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson’s disease. Mov Disord 2010, 25: 578-586.PubMedView ArticleGoogle Scholar
- Zibetti M, Merola A, Rizzi L, Ricchi V, Angrisano S, Azzaro C, Artusi CA, Arduino N, Marchisio A, Lanotte M, Rizzone M, Lopiano L: Beyond nine years of continuous subthalamic nucleus deep brain stimulation in Parkinson’s disease. Mov Disord 2011, 26: 2327-2334.PubMedView ArticleGoogle Scholar
- Castrioto A, Lozano AM, Poon YY, Lang AE, Fallis M, Moro E: Ten-year outcome of subthalamic stimulation in Parkinson disease: a blinded evaluation. Arch Neurol 2011, 68: 1550-1556.PubMedView ArticleGoogle Scholar
- Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG: The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord 2008, 23: 837-844.PubMedView ArticleGoogle Scholar
- Okun MS, Tagliati M, Pourfar M, Fernandez HH, Rodriguez RL, Alterman RL, Foote KD: Management of referred deep brain stimulation failures: a retrospective analysis from 2 movement disorders centers. Arch Neurol 2005, 62: 1250-1255.PubMedView ArticleGoogle Scholar
- Ellis TM, Foote KD, Fernandez HH, Sudhyadhom A, Rodriguez RL, Zeilman P, Jacobson CE 4th, Okun MS: Reoperation for suboptimal outcomes after deep brain stimulation surgery. Neurosurgery 2008, 63: 754-760.PubMedView ArticleGoogle Scholar
- McIntosh E: Perspective on the economic evaluation of deep brain stimulation. Front Integr Neurosci 2011, 5: 19.PubMed CentralPubMedView ArticleGoogle Scholar
- Valldeoriola F, Morsi O, Tolosa E, Rumia J, Marti MJ, Martinez-Martin P: Prospective comparative study on cost-effectiveness of subthalamic stimulation and best medical treatment in advanced Parkinson’s disease. Mov Disord 2007, 22: 2183-2191.PubMedView ArticleGoogle Scholar
- Spottke EA, Volkmann J, Lorenz D, Krack P, Smala AM, Sturm V, Gerstner A, Berger K, Hellwig D, Deuschl G, Freund HJ, Oertel WH, Dodel RC: Evaluation of healthcare utilization and health status of patients with Parkinson’s disease treated with deep brain stimulation of the subthalamic nucleus. J Neurol 2002, 249: 759-766.PubMedView ArticleGoogle Scholar
- Fraix V, Houeto JL, Lagrange C, Le Pen C, Krystkowiak P, Guehl D, Ardouin C, Welter ML, Maurel F, Defebvre L, Rougier A, Benabid AL, Mesnage V, Ligier M, Blond S, Burbaud P, Bioulac B, Destée A, Cornu P, Pollak P, SPARK Study Group: Clinical and economic results of bilateral subthalamic nucleus stimulation in Parkinson’s disease. Neurol Neurosurg Psychiatry 2006, 77: 443-449.View ArticleGoogle Scholar
- Voges J, Waerzeggers Y, Maarouf M, Lehrke R, Koulousakis A, Lenartz D, Sturm V: Deep-brain stimulation: long-term analysis of complications caused by hardware and surgery — experiences from a single centre. J Neurol Neurosurg Psychiatry 2006, 77: 868-872.PubMed CentralPubMedView ArticleGoogle Scholar
- Sillay KA, Larson PS, Starr PA: Deep brain stimulator hardware-related infections incidence and management in a large series. Neurosurgery 2008, 62: 360-366.PubMedView ArticleGoogle Scholar
- Fenoy AJ, Simpson RK: Management of device-related wound complications in deep-brain stimulation surgery. J Neurosurg 2012, 116: 1324-1332.PubMedView ArticleGoogle Scholar
- Zrinzo L, Foltynie T, Limousin P, Hariz MI: Reducing hemorrhagic complications in functional neurosurgery: a large case series and systematic literature review. J Neurosurg 2012, 116: 84-94.PubMedView ArticleGoogle Scholar
- Coley E, Farhadi R, Lewis S, Whittle IR: The incidence of seizures following deep brain stimulating electrode implantation for movement disorders, pain and psychiatric conditions. Br J Neurosurg 2009, 23: 179-183.PubMedView ArticleGoogle Scholar
- Voon V, Krack P, Lang AE, Lozano AM, Dujardin K, Schüpbach M, D’Ambrosia J, Thobois S, Tamma F, Herzog J, Speelman JD, Samanta J, Kubu C, Rossignol H, Poon YY, Saint-Cyr JA, Ardouin C, Moro E: A multicentre study on suicide outcomes following subthalamic stimulation for Parkinson’s disease. Brain 2008, 131: 2720-2728.PubMed CentralPubMedView ArticleGoogle Scholar
- Temel Y: Limbic effects of high-frequency stimulation of the subthalamic nucleus. Vitam Horm 2010, 82: 47-63.PubMedView ArticleGoogle Scholar
- Parsons TD, Rogers SA, Braaten AJ, Woods SP, Troster AI: Cognitive sequelae of subthalamic nucleus deep brain stimulation in Parkinson’s disease: a metaanalysis. Lancet Neurol 2006, 5: 578-588.PubMedView ArticleGoogle Scholar
- Witt K, Daniels C, Reiff J, Krack P, Volkmann J, Pinsker MO, Krause M, Tronnier V, Kloss M, Schnitzler A, Wojtecki L, Bötzel K, Danek A, Hilker R, Sturm V, Kupsch A, Karner E, Deuschl G: Neuropsychological and psychiatric changes after deep brain stimulation for Parkinson’s disease: a randomised, multicentre study. Lancet Neurol 2008, 7: 605-614.PubMedView ArticleGoogle Scholar
- Kirsch-Darrow L, Zahodne LB, Marsiske M, Okun MS, Foote KD, Bowers D: The trajectory of apathy after deep brain stimulation: from pre-surgery to 6 months post-surgery in Parkinson’s disease. Parkinsonism Relat Disord 2011, 17: 182-188.PubMed CentralPubMedView ArticleGoogle Scholar
- Porat O, Cohen OS, Schwartz R, Hassin-Baer S: Association of preoperative symptom profile with psychiatric symptoms following subthalamic nucleus stimulation in patients with Parkinson’s disease. J Neuropsychiatry Clin Neurosci 2009, 21: 398-405.PubMedView ArticleGoogle Scholar
- Smeding HM, Speelman JD, Koning-Haanstra M, Schuurman PR, Nijssen P, van Laar T, Schmand B: Neuropsychological eff ects of bilateral STN stimulation in Parkinson disease: a controlled study. Neurology 2006, 66: 1830-1836.PubMedView ArticleGoogle Scholar
- Péron J, Biseul I, Leray E, Vicente S, Le Jeune F, Drapier S, Drapier D, Sauleau P, Haegelen C, Vérin M: Subthalamic nucleus stimulation affects fear and sadness recognition in Parkinson’s disease. Neuropsychology 2010, 24: 1-8.PubMedView ArticleGoogle Scholar
- Demetriades P, Rickards H, Cavanna AE: Impulse control disorders following deep brain stimulation of the subthalamic nucleus in Parkinson’s disease: clinical aspects. Parkinsons Dis 2011, 2011: 658415.PubMed CentralPubMedGoogle Scholar
- Broen M, Duits A, Visser-Vandewalle V, Temel Y, Winogrodzka A: Impulse control and related disorders in Parkinson’s disease patients treated with bilateral subthalamic nucleus stimulation: a review. Parkinsonism Relat Disord 2011, 17: 413-417.PubMedView ArticleGoogle Scholar
- Appleby BS, Duggan PS, Regenberg A, Rabins PV: Psychiatric and neuropsychiatric adverse events associated with deep brain stimulation: A meta-analysis of ten years’ experience. Mov Disord 2007, 22: 1722-1728.PubMedView ArticleGoogle Scholar
- Heo JH, Lee KM, Paek SH, Kim MJ, Lee JY, Kim JY, Cho SY, Lim YH, Kim MR, Jeong SY, Jeon BS: The effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) on cognition in Parkinson disease. J Neurol Sci 2008, 273: 19-24.PubMedView ArticleGoogle Scholar
- Okun MS, Wu SS, Foote KD, Bowers D, Gogna S, Price C, Malaty I, Rodriguez RL, Jacobson CE, Ward H: Do stable patients with a premorbid depression history have a worse outcome after deep brain stimulation for Parkinson disease? Neurosurgery 2011, 69: 357-360.PubMed CentralPubMedView ArticleGoogle Scholar
- Videnovic A, Metman LV: Deep brain stimulation for Parkinson’s disease: prevalence of adverse events and need for standardized reporting. Mov Disord 2008, 23: 343-349.PubMedView ArticleGoogle Scholar
- Alberts JL, Hass CJ, Vitek JL, Okun MS: Are two leads always better than one: an emerging case for unilateral subthalamic deep brain stimulation in Parkinson’s disease. Exp Neurol 2008, 214: 1-5.PubMed CentralPubMedView ArticleGoogle Scholar
- Taba HA, Wu SS, Foote KD, Hass CJ, Fernandez HH, Malaty IA, Rodriguez RL, Dai Y, Zeilman PR, Jacobson CE, Okun MS: A closer look at unilateral versus bilateral deep brain stimulation: results of the National Institutes of Health COMPARE cohort. J Neurosurg 2010, 113: 1224-1229.PubMedView ArticleGoogle Scholar
- Alberts JL, Okun MS, Vitek JL: The persistent effects of unilateral pallidal and subthalamic deep brain stimulation on force control in advanced Parkinson’s patients. Parkinsonism Relat Disord 2008, 14: 481-488.PubMed CentralPubMedView ArticleGoogle Scholar
- Pedrosa DJ, Timmermann L: Review: management of Parkinson’s disease. Neuropsychiatr Dis Treat 2013, 9: 321-340.PubMed CentralPubMedView ArticleGoogle Scholar
- Anderson VC, Burchiel KJ, Hogarth P, Favre J, Hammerstad JP: Pallidal vs subthalamic nucleus deep brain stimulation in Parkinson disease. Arch Neurol 2005, 62: 554-560.PubMedView ArticleGoogle Scholar
- Okun MS, Fernandez HH, Wu SS, Kirsch-Darrow L, Bowers D, Bova F, Suelter M, Jacobson CE 4th, Wang X, Gordon CW Jr, Zeilman P, Romrell J, Martin P, Ward H, Rodriguez RL, Foote KD: Cognition and mood in Parkinson’s disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE trial. Ann Neurol 2009, 65: 586-595.PubMed CentralPubMedView ArticleGoogle Scholar
- Zahodne LB, Okun MS, Foote KD, Fernandez HH, Rodriguez RL, Wu SS, Kirsch-Darrow L, Jacobson CE 4th, Rosado C, Bowers D: Greater improvement in quality of life following unilateral deep brain stimulation surgery in the globus pallidus as compared to the subthalamic nucleus. J Neurol 2009, 256: 1321-1329.PubMed CentralPubMedView ArticleGoogle Scholar
- Weaver FM, Follett KA, Stern M, Luo P, Harris CL, Hur K, Marks WJ Jr, Rothlind J, Sagher O, Moy C, Pahwa R, Burchiel K, Hogarth P, Lai EC, Duda JE, Holloway K, Samii A, Horn S, Bronstein JM, Stoner G, Starr PA, Simpson R, Baltuch G, De Salles A, Huang GD, Reda DJ, CSP 468 Study Group: Randomized trial of deep brain stimulation for Parkinson disease: thirty-six month outcomes. Neurology 2012, 79: 55-65.PubMed CentralPubMedView ArticleGoogle Scholar
- Odekerken VJ, van Laar T, Staal MJ, Mosch A, Hoffmann CF, Nijssen PC, Beute GN, van Vugt JP, Lenders MW, Contarino MF, Mink MS, Bour LJ, van den Munckhof P, Schmand BA, de Haan RJ, Schuurman PR, de Bie RM: Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson’s disease (NSTAPS study): a randomised controlled trial. Lancet Neurol 2013, 12: 37-44.PubMedView ArticleGoogle Scholar
- Tagliati M: Turning tables: should GPi become the preferred DBS target for Parkinson disease? Neurology 2012, 79: 19-20.PubMedView ArticleGoogle Scholar
- Hamani C, Moro E, Lozano AM: The pedunculopontine nucleus as a target for deep brain stimulation. J Neural Transm 2011, 118: 1461-1468.PubMedView ArticleGoogle Scholar
- Stefani A, Lozano AM, Peppe A, Stanzione P, Galati S, Tropepi D, Pierantozzi M, Brusa L, Scarnati E, Mazzone P: Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson’s disease. Brain 2007, 130: 1596-1607.PubMedView ArticleGoogle Scholar
- Stefani A, Pierantozzi M, Ceravolo R, Brusa L, Galati S, Stanzione P: Deep brain stimulation of pedunculopontine tegmental nucleus (PPTg) promotes cognitive and metabolic changes: a target-specific effect or response to a low-frequency pattern of stimulation? Clin EEG Neurosci 2010, 41: 82-86.PubMedView ArticleGoogle Scholar
- Costa A, Carlesimo GA, Caltagirone C, Mazzone P, Pierantozzi M, Stefani A, Peppe A: Effects of deep brain stimulation of the peduncolopontine area on working memory tasks in patients with Parkinson’s disease. Parkinsonism Relat Disord 2010, 16: 64-67.PubMedView ArticleGoogle Scholar
- Ferraye MU, Debu B, Fraix V, Goetz L, Ardouin C, Yelnik J, Henry- Lagrange C, Seigneuret E, Piallat B, Krack P, Le Bas JF, Benabid AL, Chabardes S, Pollak P: Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson’s disease. Brain 2010, 133: 205-214.PubMedView ArticleGoogle Scholar
- Moro E, Hamani C, Poon YY, Al-Khairallah T, Dostrovsky JO, Hutchison WD, Lozano AM: Unilateral pedunculopontine stimulation improves falls in Parkinson’s disease. Brain 2010, 133: 215-224.PubMedView ArticleGoogle Scholar
- Moro E, Allert N, Eleopra R, Houeto JL, Phan TM, Stoevelaar H: A decision tool to support appropriate referral for deep brain stimulation in Parkinson’s disease. J Neurol 2009, 256: 83-88.PubMedView ArticleGoogle Scholar
- Wachter T, Minguez-Castellanos A, Valldeoriola F, Herzog J, Stoevelaar H: A tool to improve pre-selection for deep brain stimulation in patients with Parkinson’s disease. J Neurol 2011, 258: 641-646.PubMed CentralPubMedView ArticleGoogle Scholar
- Schüpbach WM, Maltête D, Houeto JL, du Montcel ST, Mallet L, Welter ML, Gargiulo M, Béhar C, Bonnet AM, Czernecki V, Pidoux B, Navarro S, Dormont D, Cornu P, Agid Y: Neurosurgery at an earlier stage of Parkinson disease: a randomized, controlled trial. Neurology 2007, 68: 267-271.PubMedView ArticleGoogle Scholar
- Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L, Hälbig TD, Hesekamp H, Navarro SM, Meier N, Falk D, Mehdorn M, Paschen S, Maarouf M, Barbe MT, Fink GR, Kupsch A, Gruber D, Schneider GH, Seigneuret E, Kistner A, Chaynes P, Ory-Magne F, Brefel Courbon C, Vesper J, Schnitzler A, Wojtecki L, Houeto JL, Bataille B, et al.: Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med 2013, 368: 610-622.PubMedView ArticleGoogle Scholar
- Deuschl G, Schüpbach M, Knudsen K, Pinsker MO, Cornu P, Rau J, Agid Y, Schade-Brittinger C: Stimulation of the subthalamic nucleus at an earlier disease stage of Parkinson’s disease: concept and standards of the EARLYSTIM-study. Parkinsonism Relat Disord 2013, 19: 56-61.PubMedView ArticleGoogle Scholar
- Espay AJ, Vaughan JE, Marras C, Fowler R, Eckman MH: Early versus delayed bilateral subthalamic deep brain stimulation for parkinson’s disease: a decision analysis. Mov Disord 2010, 25: 1456-1463.PubMedView ArticleGoogle Scholar
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