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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