The source of this article is the August 2005 of Arch Neurol: 
http://tinyurl.com/bvbfw

Management of Referred Deep Brain Stimulation Failures
A Retrospective Analysis From 2 Movement Disorders Centers

Michael S. Okun, MD; Michele Tagliati, MD; Michael Pourfar, MD; Hubert H. 
Fernandez, MD; Ramon L. Rodriguez, MD; Ronald L. Alterman, MD; Kelly D. 
Foote, MD


Arch Neurol. 2005;62:(doi:10.1001/archneur.62.8.noc40425).


Since the Food and Drug Administration approved deep brain stimulation 
(DBS) for Parkinson disease (PD), essential tremor (ET), and dystonia, 
there has been a surge in the number of centers providing the operative 
procedure. There remains no consensus in several important areas concerning 
DBS therapy. These areas include (1) appropriate patient screening 
procedures, (2) the training of health care professionals performing DBS 
surgery, (3) the training of personnel providing DBS programming, (4) 
access to DBS programming, (5) the need for an interdisciplinary team 
approach, and (6) education to identify and treat complications of DBS.1-2 
With increasing frequency, patients are coming to experienced movement 
disorders centers complaining of suboptimal results from DBS surgery. In 
this article, we review 41 such cases to identify common reasons for DBS 
failure and make recommendations to improve overall DBS outcomes.

Forty-one patients complaining of poor outcomes from DBS surgery visited 
the University of Florida Movement Disorders Center, Gainesville, or Beth 
Israel Movement Disorders Center, New York, NY, over a 24-month period. All 
patients were implanted with DBS devices at other medical centers and 
sought specialist management for DBS-related problems. Each patient was 
seen and examined by a movement disorders neurologist. Their complete 
medical records were reviewed. Their DBS devices were interrogated to 
assess thresholds for adverse effects at each contact, and the devices were 
programmed for maximal benefit. Documenting the preoperative selection 
process included noting the diagnosis and indication for surgery, the 
cognitive status, and medication trials. Preoperative indication for 
surgery was based on what the referring physician documented in the medical 
record. The movement disorders neurologist at the experienced DBS center 
then reassessed each patient and assigned a diagnosis. These diagnoses 
adhered to strict criteria.3-9 Preoperative cognitive status was based on a 
detailed interview with the patient and family, medical-record review, and 
the neurological examination. Medication trials were documented using the 
medical records as well as interviews of the patients and families. An 
inadequate medication trial for this study was defined by the movement 
disorders neurologist as the failure to administer, for a reasonable period 
of time, appropriate combinations of medications for PD, ET, or dystonia. 
Whether referred patients consulted a movement disorders neurologist prior 
to surgery was verified by medical-record review and by patient interview. 
Surgical targets were confirmed by medical-record data and postoperative 
imaging (when available). Lead location was judged quantitatively either by 
reconstructing the lead with a computed tomography/magnetic resonance 
imaging (MRI) fusion technique or by estimating the mediolateral and 
anteroposterior aspects of the lead using coronal MRIs. Lead location was 
also assessed functionally by checking thresholds for adverse effects and 
benefits during programming (eg, number of volts needed to induce a 
capsular/sensory or other response). The neurologist and neurosurgeon 
decided whether a lead was misplaced after examining all the imaging and 
clinical data. Information on hardware complications and programming was 
obtained from patient history, examination, medical-record review, and 
device interrogation. The device interrogation included an impedance and 
battery check. Extensive and systematic DBS programming was performed for 
adverse effects, threshold mapping, and maximal clinical benefit at each of 
the 4 contacts on the lead. The movement disorders specialist subjectively 
judged overall outcome. Patients in this study may have had 1 or more of 
several problems leading to a DBS failure (eg, poor patient selection and 
electrode misplacement).


DEMOGRAPHICS

The average age of patients was 63.4 years (range, 49-84 years). 
Preoperative indications for surgery included 9 patients with ET, 31 with 
PD, and 1 with dystonia. The patients underwent the following DBS 
implantations: 8 unilateral ventralis intermedius, 8 unilateral subthalamic 
nucleus, 1 unilateral globus pallidus interna, 1 bilateral ventralis 
intermedius, 21 bilateral subthalamic nucleus, and 1 bilateral globus 
pallidus interna. The movement disorders neurologist agreed with the 
preoperative indication for surgery in 32 of 41 patients. The diagnosis was 
revised in 9 cases, including PD and dementia,3 multiple system atrophy,2 
corticobasal degeneration,1 progressive supranuclear palsy,1 and myoclonus.1

SCREENING AND MEDICATION TRIALS

Thirty (73%) of 41 patients were evaluated by a movement disorders 
specialist prior to DBS implantation. Fourteen patients (34%) underwent 
documented preoperative neuropsychological testing, 4 (10%) did not have 
testing, and in the remaining 23 (56%) patients, it could not be 
ascertained whether or not they were tested. Five (12%) patients had an 
inadequate medication trial, and 5 (12%) patients had significant 
preoperative cognitive dysfunction.

MISPLACED LEADS AND HARDWARE COMPLICATIONS

Nineteen (46%) of 41 patients had misplaced leads (Figure 1). Seven leads 
(17%) were replaced with marked improvement, and 3 others (7%) were 
replaced with partial improvement (partial improvement was defined as 
symptom improvement but not to the level expected by the movement disorders 
neurologist and neurosurgeon). Three patients had problems with the 
battery, 2 had infections, and 1 had a lead fracture.

DBS PROGRAMMING

Seven (17%) of 41 patients had no or poor access to programming; 2 patients 
(5%) and 2 physicians (5%) moved away from their centers, resulting in an 
access problem. Eight patients (20%) required local follow-up (patients 
flew to a remote center to have the surgery performed). Fifteen patients 
(37%) were inadequately programmed, and 21 leads (51%) could not be 
reprogrammed. Fifteen patients (37%) were reprogrammed successfully, and 6 
more patients (15%) had partial improvement (partial improvement was 
defined as symptom improvement but not to the level expected by the 
movement disorders neurologist). These programming sessions took more than 
twice as long as typical DBS evaluations by the movement disorders 
neurologists.

POSTOPERATIVE MEDICATION CHANGES

Thirty (73%) of 41 patients required medication changes in parkinsonian 
drugs, 4 (10%) had antidepressants added to their regimens, and 1 (2%) 
received donepezil hydrochloride. One patient’s carbidopa/levodopa (2%) was 
restarted, having previously been stopped following the initial surgery.

PATIENT OUTCOMES

Twenty-one (51%) of 41 patients citing "failure" of DBS therapy ultimately 
had good outcomes with additional medical or surgical management, 6 (15%) 
had modest clinical improvement, and 14 (34%) failed to improve (Table).


DETERMINING THE DIAGNOSIS

Thirty (73%) of the 41 patients in this study were evaluated by a movement 
disorders neurologist prior to DBS implantation. Despite this high 
percentage, problems related to incorrect initial diagnosis, or 
inappropriate indication for surgery, were not uncommon. Arguably, the most 
important predictor of success or failure of DBS therapy is appropriate 
patient selection. Deep brain stimulation therapy has been shown to 
consistently provide significant benefit in the treatment of idiopathic PD, 
ET, and dystonia. These 3 disorders have been extensively studied and are, 
to date, the only indications for DBS approved by the Food and Drug 
Administration. The DBS practitioners who initially treated the patients in 
this case series believed they had identified 41 patients, all of whom had 
1 of these 3 diagnoses. Careful review revealed that 36 (88%) of the 41 
patients did have 1 of these 3 diagnoses, but 12% of the patients had other 
disorders that would not be expected to respond to DBS therapy. Also 
concerning was the observation that 20% of the patients had significant 
preoperative dementia. Patients with multiple system atrophy (n = 2), 
progressive supranuclear palsy (n = 1), corticobasal degeneration (n = 1), 
and myoclonus (n = 1) were misdiagnosed as either PD or ET. The multiple 
system atrophy and progressive supranuclear palsy cases had parkinsonian 
features, but the patients failed to demonstrate a significant response to 
levodopa. In the corticobasal degeneration and myoclonus cases, which were 
mistaken for ET, the phenomenologic analysis of the tremor and the presence 
of other signs (apraxia in the case of corticobasal degeneration) were 
presumably missed in preoperative evaluations.

SCREENING FOR SURGERY

There is currently no standard screening for DBS surgery.1-2 There are no 
accepted guidelines that recommend patients undergo an on-off levodopa 
challenge, medication optimization, or neuropsychological screening. The 
Florida Surgical Questionnaire for PD is 1 screening tool that was designed 
to aid referring physicians in identifying potential candidates for DBS. 
This questionnaire examines several domains, including appropriate 
diagnosis, potential contraindications, favorable and unfavorable patient 
characteristics, medication trial, and refractory tremor.2 Many of the DBS 
failures in this series may have been avoidable if such a systematic 
patient screening approach had been employed. The results from the current 
study support the need for more thoughtful screening to identify 
appropriate surgical candidates. Additionally, the use of 
neuropsychological screening may be helpful in many if not all cases. 
Ongoing efforts to improve the screening of surgical candidates by all DBS 
practitioners will likely improve overall outcomes. Despite the best 
screening procedures, a small number of patients will "convert" from what 
appears to be idiopathic PD to another parkinsonian syndrome. Many of these 
patients who convert from one diagnosis to another have seen highly 
qualified specialists.10-12

MISPLACED LEADS

Many techniques can be used effectively for DBS implantation, and the 
necessity for microelectrode recording continues to be a controversial 
issue.13-14 One point that is not controversial, however, is that 
regardless of the implantation technique, appropriate electrode placement 
is absolutely necessary to achieve optimal results from DBS. No amount of 
expert DBS programming can compensate for a poorly placed electrode. In 
this series of patients with suboptimal results, 19 (46%) of 41 patients 
had a misplaced DBS electrode. This alarmingly large number should be 
interpreted with caution because there was clearly a significant selection 
bias. One may hypothesize that electrodes were misplaced because of the use 
of inadequate localization techniques or equipment or because of inadequate 
training for DBS implanters. On the other hand, these patients with 
misplaced electrodes may represent a small minority of patients with DBS 
implanted in the region, but their poor outcomes led them to congregate at 
a tertiary care­level movement disorders center. We suspect there was a 
wide spectrum of reasons for electrode misplacement.

Although this case series cannot answer the question as to why there were 
so many misplaced electrodes, it does suggest that better follow-up and 
evaluation procedures can help identify and potentially correct 
electrode-misplacement problems. Centers managing "DBS failures" should 
obtain imaging to determine as accurately as possible the location of the 
DBS electrode (relative to midline and the midcommissural point). 
Programming should also be performed to assess thresholds for adverse 
effects and benefits at each electrode contact. This information is quite 
useful when judging the appropriateness of an electrode’s location and when 
making decisions about a potential lead revision. Given the importance of 
electrode location and the apparently significant incidence of electrode 
misplacement, a strong case may be made for recommending routine 
postoperative imaging in all DBS cases. Certainly imaging is indicated to 
assess the electrode location in any patient who does not derive the 
expected benefits from DBS programming.

HARDWARE FAILURES

The number of hardware complications seen in this series is likely not 
representative of all implanting centers. These numbers may again be 
partially explained by the selection bias in this patient cohort. Because 
we included only patients with poor DBS outcomes, we obviously expected to 
see a high complication rate in this cohort. It is important, however, when 
evaluating a DBS device that is not performing effectively, to test 
electrode impedances during programming. If abnormally high or infinite 
impedances are found, a series of plain x-rays should be obtained to look 
for fractures or disconnections. End of battery life, lead fractures or 
short circuits, tissue erosions, and infections are all potentially 
correctable reasons for poor DBS outcomes.

PROGRAMMING

Only 15 (37%) of 41 patients in this series could be successfully improved 
by reprogramming the DBS device. Reasons for the difficulties in 
reprogramming likely included (1) diagnoses that do not respond well to 
DBS, (2) electrode misplacement, (3) hardware failure, and (4) issues with 
the DBS programmer (eg, inadequate experience, lack of time commitment).

Ideally, patients treated with DBS should receive programming at the same 
institution and by the same team that implanted their devices. Programming 
at the implanting center provides continuity among caregivers, immediate 
access, direct knowledge of the preoperative history and examination, 
availability of imaging studies, information on initial programming and 
thresholds, and information about electrode placement from the operating room.

Inadequate access to DBS programming was a significant problem uncovered by 
this small study. Appropriate access to postoperative care will continue to 
be an important determinant of the overall success or failure of DBS in 
general, and global outcomes should improve as expert postoperative care 
becomes more readily available. Access can be hampered not only by a lack 
of trained local physicians available to program devices, but also by 
physicians and patients moving from one area to another. Patients who have 
their devices implanted at remote institutions also have the added burden 
of seeking local follow-up, not only for programming but also for potential 
complications.

Many surgeons implant DBS devices but do not participate in programming or 
follow-up. This creates an unfortunate disconnection between the procedure 
and the outcome. For surgeons to responsibly monitor the effectiveness of 
their DBS interventions, they must have feedback regarding the measured 
benefits to the patient or the difficulties encountered in programming. 
Surgeons who are unaware of poor outcomes are unlikely to make appropriate 
corrections in technique, and suboptimal results may be unnecessarily 
propagated. Extensive DBS programming and in-depth assessment of the effect 
of DBS on the patient’s neurological function and quality of life by the 
implanting neurosurgeon may be impractical, but close communication with a 
multidisciplinary DBS treatment team, including specialists in movement 
disorders neurology and DBS programming (at a minimum), can provide the 
necessary outcomes data to the implanting surgeon.


POSTOPERATIVE MEDICATION CHANGES

Patients with movement disorders, with and without DBS, require frequent 
medication adjustments. Thirty (73%) of 41 patients in our series required 
medication changes. Three patients in our series improved markedly from 
medication changes alone, 1 from DBS programming alone, and 17 after a 
combination of DBS programming and medication changes. As evidenced by the 
numbers in this series, surgery does not replace appropriate medical 
management. In many cases, simultaneous adjustment of medications and 
stimulation parameters is difficult, and a greater effort should be made to 
educate DBS practitioners regarding the concurrent management of DBS and 
medical therapy.


Ultimately, with diligent reprogramming, medication adjustments, and in 
some cases electrode replacement, 21 (51%) of the 41 DBS failures in our 
study were successfully salvaged. Many patients, however, had persistently 
poor outcomes despite our interventions. This case series provides 
important insight into the common reasons for "DBS failures" and proposes 
some effective strategies for their management.

Future studies will be designed to more adequately assess patient and 
physician perceptions of postoperative outcomes relative to their 
preoperative expectations.

As the prevalence of DBS therapy increases, implanting centers are becoming 
more experienced. We are hopeful that this experience, along with ongoing 
efforts to educate DBS practitioners regarding effective practices, will 
result in global improvement in the outcomes of DBS surgery.


Correspondence: Michael S. Okun, MD, University of Florida Movement 
Disorders Center, 100 S Newell Dr, Room L3-101, Gainesville, FL 32610 
([log in to unmask]).

Accepted for Publication: February 2, 2005; published online, June 13, 2005.

Author Contributions: Study concept and design: Okun, Fernandez, and Foote. 
Acquisition of data: Okun, Tagliati, Pourfar, Fernandez, Alterman, and 
Foote. Analysis and interpretation of data: Okun, Tagliati, Pourfar, 
Fernandez, Rodriguez, and Foote. Drafting of the manuscript: Okun, 
Tagliati, and Fernandez. Critical revision of the manuscript for important 
intellectual content: Okun, Tagliati, Pourfar, Fernandez, Rodriguez, 
Alterman, and Foote. Administrative, technical, and material support: Okun, 
Tagliati, Pourfar, Fernandez, Rodriguez, Alterman, and Foote. Study 
supervision: Okun, Tagliati, and Foote.

Author Affiliations: Department of Neurology, University of Florida 
Movement Disorders Center, McKnight Brain Institute, Gainesville (Drs Okun, 
Fernandez, Rodriguez, and Foote); Department of Neurology (Dr Tagliati) and 
Department of Neurosurgery (Dr Alterman), Mount Sinai Medical Center, New 
York, NY.



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