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Bilateral Deep Brain Stimulation (Dbs) Of The Subthalamic Nucleus (Stn) Or The Globus Pallidus Interna (Gpi) For Treatment Of Advanced Parkinson's Disease

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Deep brain stimulation involves the stereotactic placement of an electrode in the brain for the treatment of certain disorders associated with Parkinson's syndrome. The Food and Drug Administration (FDA) has approved the Medtronic ActivaTM Tremor Control Therapy device for unilateral thalamic stimulation for the suppression of tremor in the upper extremity for patients who are diagnosed with essential tremor or Parkinsonian tremor not controlled by medication and where the tremor constitutes a significant functional disability. Subsequently, bilateral stimulation in the subthalamic nucleus has been used for multiple symptoms of Parkinson's disease.

Currently, FDA is reviewing the safety and effectiveness of the bilateral use of this device in the subthalamic nucleus. Section 35-20 of the Medicare Coverage Issues (CIM) Manual states that "Medicare coverage of deep brain stimulation by implantation of a stimulator device is not prohibited. Therefore, coverage of deep brain stimulation provided by an implanted deep brain stimulator is at the carrier's discretion."

Requestor has asked that CMS issue a national coverage decision for the bilateral use of this device in the subthalamic nucleus. CMS will review the scientific evidence and determine if this procedure would be a reasonable and necessary service for Medicare beneficiaries.

The studies for inclusion as part of the evidence for unilateral thalamic stimulation were selected in the following ways:

  • Studies reviewed as part of the Blue Cross Blue Shield’s technology assessment entitled, Deep Brain Stimulation of the Thalamus for Tremor1.
  • Studies found in a Pubmed database search using the keywords “deep brain stimulation” and “Parkinson*.” The search was restricted to publications in English about human subjects.
  • The reference lists of retrieved publications were also reviewed.

Studies were excluded if there were less than 10 subjects. In reviewing the retrieved evidence, it was noted that several studies seemed to evaluate patients who had been included in previously published literature. We have included all the relevant articles for review. However, the study summary table is restricted to only the most recently published studies.

Study Descriptions of Unilateral Thalamic Stimulation for Essential Tremor or Parkinsonian Tremor

Study/Year Study design Patients/Treatment Diagnosis Results Comments

Koller et al, 2001

Clinical series

N=49 enrolled

N=25 analyzed

Mean age = 72.3 yrs ± 8.9

19 men 6 women

Unilateral in VIM

Selection criteria:

Tremor had to cause significant disability despite pharmacological treatment

Tremor had to be 3 or 4 in severity utilizing the Fahn-Tolosa-Marin Tremor Rating Scale – (0) none to (4) severe

25/49 ET pts completed at least 24 month follow-up

Mean disease duration = 33.3 yrs ± 15.4

24/49 ET pts without 24 mo follow-up were excluded from analysis:

* 7/24 explants

* 11/24 lost to follow-up

* 3/24 unrelated deaths

* 3/24 never implanted due to subdural hematoma and asymptomatic hemorrhage in operating room

Tremor Rating Scale with stimulation on and off (N=25)

Blindly evaluated only at 3 months; with open evaluation at baseline, 12 mo post-op and then yearly (average post-op follow-up 40.2 ± 14.7 mo)

Statistical analysis included Wilcoxon signed rank comparison of tremor scores for baseline and the stim on and off conditions at follow-up

Histogram of tremor scores (questions 1-10 on tremor rating scale) sign. improved with stim on at long-term follow-up (3, 12 and 40 mo) as compared to baseline (p<.001)

* 25 adverse surgical events including 3 asymptomatic bleeds and 1 seizure

* 70 stimulation complications

* 19 device complications

* 18 pts received additional surgical procedures

Likely includes the 38 patients above in Koller et al (1999)

Selection criteria for study inclusion not fully described

Lacks intention to treat analysis for all pts initially enrolled

Krauss et al, 2001

Clinical

series

N = 94

Mean age = 68.7 yrs (31-83)

68 men 26 women

65 unilateral implants

29 bilateral implants

Selection criteria:

“Tremor was disabling or a source of social embarrassment in all patients and was not controlled satisfactorily by medication”

45 PD

42 ET

7 Other (including multiple sclerosis, head injury, stroke,

degenerative disease)

Mean duration of disease not reported

Prior surgery not reported

Symptomatic outcome of tremor at last available formal follow-up evaluation summarized as excellent (complete or almost complete suppression of tremor), marked improvement (70-90%), moderate improvement (30-70%), minor improvement (0-30%), unchanged, or worse

Symptomatic improvement of tremor in PD pts:

* 23/45 excellent

* 16/45 marked

* 5/45 moderate

* 1/45 minor

Symptomatic improvement of tremor in ET pts:

* 24/42 excellent

* 15/42 marked

* 2/42 moderate

* 1/42 minor

Adverse events:

40/94 patients experienced stimulation-related side effects, generally mild and reversible, and more frequent in bilateral DBS pts

Includes 33 pts (14 ET; 19 PD) published by Ondo et al (1998)

Data pooled across centers; results and complications not stratified by age or center; no description of any center effects

Selection criteria for study inclusion not fully described, e.g., regarding degree of functional disability, social embarrassment or refractoriness to medications

No stratification for unilateral versus bilateral implants in PD and ET patients

No statistical analysis of results for subjective symptomatic improvement or interoperative test stimulation

Identity of the person making assessment of symptomatic improvement not stated

Lyons et al, 2001

Clinical Series

N = 12, analysis done on 9

Mean age = 67.8 yrs (SD 5.2)

8 men 1 woman

Unilateral in VIM

9 PD with medication resistant tremor

Mean duration of disease – 8.1 yrs (SD 3.5)

No surgery outside of the study

Evaluation using the motor section (part III) of the UPDRS performed with meds on at baseline, 3 months, 12 months, and yearly

Motor scores did not change from baseline to long-term follow-up.

Tremor scores on the targeted side were significantly improved with stimulation on at long-term follow-up compared to baseline

7 patients (58%) reported global improvement, 1 indicated no change (8%) and 3 reported good long term tremor control

Adverse events:

* 3 patients with asymptomatic bleeds and one patient with hematoma at the implantable generator site

* Stimulation events included paresthesias (12), headache (5), dysarthria (3), disequilibrium (3) and visual disturbances (2)

Device complications included lead repositioning (2), lead extension wire replacement (1), implantable generator replacement due to battery depletion (2), full system explant and subsequent pallidotomy due to loss of benefit (1)

1 unrelated death at 1 year (possible MI), and 2 unrelated deaths at 2 years (sepsis and respiratory arrest)

Suggestive that the patients selected are also reported in Koller, 2001

Analysis was only done on 9 of 12 patients due to loss of follow-up (25%)

Inclusion/exclusion criteria were not well defined

Obwegeser et al, 2001

Clinical series

N = 45, 4 excluded from study analysis

Mean age = 71 yrs ± 8

29 men 12 women

Implantation in VIM :

4 right side

22 left side

15 bilateral (1 simultaneous)

10 PD

31 ET

Mean duration of illness= 8 ± 3 yrs for patients with PD; 12 yrs ± 8 for patients with ET.

Previous pallidotomy in 3 patients

Tremor was evaluated 1-2 days before surgery and 3 months surgery using the Fahn-Tolosa-Marin rating scale, with stimulation on/off

Unilateral:

* Significant reductions in midline tremor and upper-extremity tremor contralateral to surgery. Significant reduction of upper-extremity tremor in ipsilateral arm

* Contralateral lower limb tremor also improved significantly with stimulator on/off

* ADLs improved for eating, drinking hygiene, writing, and working, but not speaking

* Pegboard evaluations were not significantly different

Bilateral:

* Tremors contralateral and ipsilateral were significantly decreased

* ADL measurements improved after bilateral implantation

Adverse events:

No perioperative or postoperative hemorrhaging episodes or infections

* 1 focal seizure intraoperatively, 1 tonic-clonic seizure 12 hours after surgery

* 3 cases of broken leads (one led to loss of tremor control).

  • 1 patient experienced dysarthria, emotional problems and dystonic movements in the right shoulder after bilateral placement, all alleviated by replacement and repositioning of the left electrode

Follow-up period (3 months) short

Limited description of patient selection criteria

Ondo et al, 2001

Clinical series

N = 78

Mean age =

71.2 yrs ± 7.1 (ET)

70.5 yrs ± 9.0 (PD)

ET: 27 men 13 women

PD: 27 men 5 women

Unilateral in VIM

Selection criteria:

ET- dx by guidelines of Tremor Investigation Group.

PD – 2/3 (tremor, rigidity, bradykinesia)

Excludes dementia, prior brain surgery, comorbid disease, > age 80

32 PD

41 ET

5 not included:

3 previous thalamotomy

2 not assessed prior to bilateral implantation

Prior surgery and disease duration not reported

73 patients assessed

Unblinded:

Testing at 7 days preoperative and 3-6 months postoperative

Blinded:

62 randomized to postoperative testing in either stimulator ON or stimulator OFF

Patients evaluated using questions similar to Tremor Rating Scale and UPDRS

ET:

Unblinded: Tremor/handwriting/pouring/ADL all significantly improved contralaterally

Blinded: Tremor/handwriting improved contralaterally

PD:

Unblinded: Tremor/Brady/Rigidity/ADL significantly improved contra; gait & balance didn’t improve

Blinded: Tremor/Rigidity sig. improved; Brady/gait didn’t improve

ET: slight improvement in ipsilateral tremors

PD: no ipsilateral improvement

Adverse events:

11 disequilibruim

6 dysarthria

Potentially includes same patients as Ondo et al, 1998 and Kraus 2001

Lacks intention to treat analysis for all pts initially enrolled

Schuurman et al, 2000

RCT

N=70, 2 not treated

Mean age:

Thalamotomy (n = 34):

64 yrs ± 11.0

Thalamic stimulation (n = 34):

59 yrs ± 14.2

Thalamotomy:

17 men 17 women

Thalamic stimulation:

27 men 7 women

Patients for each condition were randomly assigned to undergo thalamotomy or thalamic stimulation.

Patients with unilateral tremor underwent either unilateral thalamotomy or unilateral DBS

Patients with bilateral tremor underwent either thalamotomy followed by contralateral DBS or bilateral DBS

Selection criteria:

Unilateral or bilateral tremor of arm due to PD, ET, or MS > 1 yr

Exclude: <18, cognitive dysfunction (<24 on MMSE), contraindications to surgery; no evidence cerebral atrophy on CT; no previous thalamotomy

PD:

*23 thalamotomy

*22 thalamic stimulation

ET:

*6 thalamotomy

*7 thalamic stimulation

MS:

*5 thalamotomy

*5 thalamic stimulation

Mean duration of illness: *Thalamotomy: 12.6 yrs ± 12.5 yrs

*Thalamic stimulation: 10.9 yrs ± 7.9

Patients were assessed at baseline and 6 months after surgery as measured by the Frenchay Activities Index (FAI), severity of tremor, number of adverse events, and patients' assessment of the outcome

FAI results listed as ‘change in score from baseline’ and ‘difference between groups. No p values given. Those who underwent DBS consistently had greater changes in scores than those that received a thalamotomy. This was the case for all groups except for MS

Tremor:

Thalamotomy: disappeared in all pts immediately after & 20/26 at 6 months

DBS: disappeared in all post-op and 20/28 at 6 months

Adverse events:

Thalamotomy: 16 at 6 months

DBS: 6 at 6 months (1 death due to intracerebral hematoma)

Statistical analyses not used

Hariz et al, 1999

Clinical series

N=58 (of 60 consecutively operated pts)

Mean age:

66 yrs (24-79) ET

66 yrs (45-79) PD

ET: 26 men 10 women

PD: 16 men 6 women

Unilateral in VIM

Selection criteria not described

22 PD

36 ET

2 excluded from analysis: lack of effect during trial stimulation (1) and refusal of post-op follow-up (1)

Mean duration of symptoms for PD pts = 10 yrs (range 2-17 years)

Mean duration of symptoms for ET pts = 18 yrs (range 2-55 years

Prior surgeries of PD pts:

* 5 contralateral thalamotomy

* 9 contralateral

pallidotomy

* 3 ipsilateral pallidotomy

Prior surgeries of ET pts:

* 4 contralat thalamotomy

* 2 ipsilateral pallidotomy

At 1 yr, with 18/22 PD pts completing follow-up, motor portion of UPDRS improved from 37.2 to 26.6 (p<0.01)

At 1 yr, with 27/36 ET pts completing follow-up, total score of Essential Tremor Rating Scale (ETRS) improved from 53.9 to 27.8 (p<0.0001)

Adverse events:

2 PD pts experienced previously undescribed and non-adjustable side effect of stimulation-induced ataxia, and their disability was unchanged/worsened compared to pre-op

5/58 pts hardware complications

10/58 pts non-adj and permanent long-term complication, include upper limb ataxia with stimulation (2), balance problems (2) and dysarthria (6)

4/9 pts with prior thalamotomy, DBS contralateral VIM provoked some dysarthria with stimulation on

No related deaths, hematoma, paresis or infection

No description of selection

Incomplete analysis and variable follow-up of all pts operated

Multiple patients had previous surgeries include either ipsilateral or contralateral thalamotomy or pallidotomy

Unable to differentiate degree to which study outcomes represent benefit from stimulation and/or prior surgery

Authors noted decline in stimulation efficacy over time

Kumar et al, 1999

Clinical series

N = 20

Mean age:

69 ± 10 yrs ET

71 ± 8 yrs PD

Implantation in VIM

Selection criteria:

Tremor-dominant PD or ET, both unresponsive to medical therapy and causing severe disruption of ADLs

Unilateral VIM DBS:

7 PD

4 ET

Bilateral VIM DBS:

4 PD

5 ET

Mean duration of illness= 26 yrs ± 15

No previous surgeries

Evaluation by a third-party neurologist pre-op, 1 week post-op, every 3 months for the first year and every 6 months thereafter using the UPDRS, Schwab and England, Hoehn and Yahr, and the Clinical Rating Scale for Tremor (CRST)

PD: Schwab and England and total UPDRS score improved at 1 week post-op, but not at long-term follow-up

Contralateral arm and leg rest tremor and ipsilateral resting leg tremor were significantly improved at all time points

No statistically significant improvements were seen in rigidity, bradykinesia, gait speech, posture or postural instability

ET: Significant improvement in the total CRST score, total tremor score, and contralateral arm postural and action tremor at all time points

Significant improvement in the Benabid scoring system when applied to tremor

Adverse events:

* 2 seizures

* 1 patient with mild facial droop

* 1 intra-op confusion which resolved

* 2 ET patients developed mild persistent paresthesias in the contralateral jaw and fingertips

* 2 PD patients had mild dystonia

* 1 ET patient developed dysarthria, resolved with a decreased voltage and pulse width

Inclusion/exclusion criteria were not well defined

Patient selection criteria not described

Although mean follow-up time provided, no break down by time period given in results

Limousin et al, 1999

Clinical series

N = 111, 110 patients implanted at 13 centers in Europe

Mean age:

63.1 yrs (SD 12.7) ET

61.5 yrs (SD 10.8) PD

ET: 24 men 13 women

PD: 47 men 26 women

Unilateral (57) and bilateral (53) in VIM

Selection criteria:

Idiopathic or essential tremor with pharmacotherapy resistant tremor and tremor rating scale of at least 3

Ability to abide by protocol. Patients were excluded if the had previous thalamotomy on the side of implantation; sig. brain atrophy; or “other disorders that may interfere with efficacy of treatment of tremor”

73 PD

37 ET

Mean duration of disease:

PD: 10.0 yrs (SD 5.6)

ET: 26.6 yrs (SD 14.5)

PD patients assessed using the UPDRS, ET assessed according to the essential tremor rating scale (ETRS) at less than 1 month pre-op, 1 week pre-op, and 3, 6, and 12 months post-op both on/off stimulation

PD: at 3 and 12-month follow-up, both upper and lower limb tremor were significantly reduced. Pts receiving unilateral stimulation had a significant reduction of contralateral tremor at both time points

Motor score of the UPDRS was significantly reduced during “on” stimulation. Other symptoms reported as “very mild” before surgery

Schwab and England score improved after surgery

Number of patients taking medications and was not changed and the mean doses were not significantly reduced 12 months after surgery

ET: At 3 and 12 month follow-up, stimulation significantly reduced postural and action tremor of the upper limb and lower limb

Head tremor was significantly improved by stimulation at 3-month follow-up only

Voice tremor was not reduced.

In patients receiving unilateral stimulation, stimulation and the procedure significantly reduced contralateral but not ipsilateral tremor

The number of patients using meds was not changed, and the reduction in mean doses was not significant

Adverse events:

* 1 patient developed respiratory difficulty in the OR and was not implanted

* 4 patients had major adverse events unrelated to surgery, including 3 deaths from unrelated causes and 1 stroke in the contralateral hemisphere 3 months after surgery

* 3 patients had subdural hematomas which resolved

* 2 patients had subcutaneous hematomas which were evacuated

* 2 patients had infections

* 5 patients required electrode replacement

Other events were described as mild and resolved with changes in stimulation parameters

Well-described patient selection criteria and inclusion/exclusion criteria

Effect of unilateral vs. bilateral implantation not clearly stated

Troster et al, 1999

Clinical series

N=40

Mean age: 72 yrs ± 8.5

Gender not reported

Unilateral in VIM

Selection criteria:

Postural and/or kinetic hand tremor, in the absence of other neurological signs, inadequately controlled by medication for > 3 mo. and notable limitations of daily living

Excluded were patients with prior thalamotomy or neuropsychological evaluations carried out in another institution

Those with unstable medical problems, pacemakers, dementia, ect.

40 ET

Mean age of onset = 55 yrs ± 13.8

Tests:

Neuropsychological test battery (not defined in methods but included all tests in results)

Sickness Impact Profile (SIP)

Parkinson's Disease Questionnaire (PDQ-39)

Dementia rating scale: sig improved

Hooper Visual Organization Tests: sig improved

Grooved Pegboard Test: sig improved

California Verbal Learning Test: sig improved except decrease in letter fluency

Wechsler Memory Scale-Revised: sig improved

Profile of Mood States: sig Improved

SIP: sig.improved total & psychosocial but not physical

PDQ-39: sig.improved

Adverse events not reported

Outcomes were focused on quality of life indicators

Hubble et al, 1997*

Clinical series

N=29

Mean age and gender distribution not reported

Unilateral in VIM

Selection criteria:

Diagnosis of ET or PD

Age 18-80 years with disabling medication- refractory upper extremity tremor and no other evidence of supraspinal CNS disease or injury

Patients were excluded if they had unstable intercurrent medical problems or if they had a cardiac pacemaker, prior thalamotomy, required MRI, dementia, substance abuse, or botulinum toxin injections 6 mo. prior

19 ET

10PD

Mean disease duration not reported

Blinded rating of randomized tremor scores by CRST and disability rating at 3 month follow-up when the stimulation was “on” and “off” via videotaped footage

Statistically significant improvement in blinded rater CTRS videotape tremor scores (p< 0.01 **) for rest, kinetic, distal postural, and proximal tremor at 3 months

One subject had no improvement in tremor

Improvement of tremor was for most part the same between ET and PD

Improvement in disability ratings (p<0.01**)

Improvement of disability rating was the same between ET and PD

Adverse events:

No serious or unexpected DBS-related events

No other cardinal symptom of Parkinson’s disease was assessed.

Side effects:

All patients reported transient paresthesias when the device is first turned on

A subset of these patients was previously reported in Hubble et al, 1996

This study provides additional information on patients with PD

Relatively brief follow-up period (3 months)

Koller et al, 1997*

Clinical series

N=59 enrolled

Mean Age:

66.8 ± 11.5 yrs ET

65.4 ± 9.2 yrs PD

ET: 24 men 5 women

PD: 19 men 5 women

53/59 implantation in VIM

6/59 pts attempted surgery, but were not implanted, followed or analyzed:

* 2/6 with tremor not suppressed by intraoperative stimulation

* 1/6 with intercranial hemorrhage during surgery

* 1/6 with persistent micro-thalamotomy effect

* 1/6 with subdural hemorrhage during placement of burr hole

* 1/6 with withdrawal of consent on operating table

Selection criteria:

Dx of ET or PD with tremor of marked severity resulting in significant functional disability despite pharmacological treatment

ET dx’d by postural or kinetic tremors of hands w/out other neurologic signs

PD dx’d by presence of 2 of 3 cardinal signs (tremor, bradykinesia, rigidity) plus sustained responsiveness to L-dopa and absence of signs of other parkinsonian syndromes

29 ET

24 PD

6 not followed

Mean duration of disease not reported

However, mean age of tremor onset for ET pts = 34.9 yrs ± 16.9

Mean age of disease onset for PD pts = 55.6 yrs ± 9.5

Prior surgical procedures not described

At 3 months, Pts randomly assigned to either stimulation on or off; one-half of pts evaluated blindly with stimulation on or off; and after blinded evaluation, all pts re-evaluated with stimulation on

Follow-up evaluations at 6, 9, and 12 mo performed nonblinded with stimulation on and off

Tremor evaluated utilizing UPDRS for PD patients and the Tremor Rating Scale for ET pts

Motor performance also assessed by pt’s writing and pouring liquids; and pts asked to subjectively assess change from baseline as un-changed, mild, moderate or marked

Total tremor resolution:

9/29 (31%) ET

14/24 (58.3%) PD

Stimulation “on” produced significant decrease in contralateral tremor at 3 month blinded evaluation, and at 6, 9, and 12 month open label evaluation

Motor performance skills (ADLs) improved at 3 mo only in ET pts. PD pts unchanged, and no change in functional measures from 3 mo to 1 yr

At 3 months moderate to marked subjective improvement in 90% of ET pts and 71% of PD pts

10% of all pts thought they were unchanged or mildly worse

Adverse events:

* Surg complications among patients undergoing implantation: 1 lead dislodgment requiring reimplantation, 1 ischemic changes on EKG, and 1 generalized post-op motor seizures

* Stimulation-related complications (esp paraesthesias, headache, disequilibrium and paresis of contralateral limb): 66 pts at 3 mo, 28 pts at 6 mo, and 22 pts and 12 mo

* “Long-term” device complications during first year: 2 skin infections, 1 pulse generator malfunction requiring replacement, and 1 extension wire erosion requiring replacement

10 ET patients previously reported by Hubble et al (1996)

Subset of 19 ET and 10 PD pts also reported separately by Hubble et al (1997)

Selection criteria incompletely described

Data pooled across centers; results and complications not stratified by age or center

Analysis did not include all pts with surg complications (see 6 pts not implanted or subsequently followed in study)

Benabid et al, 1996*

Clinical series

N = 117

Mean age and sex of patients were not reported

Implantation in 177 thalami

80 PD

20ET

17 Miscellaneous

Mean duration of illness not reported.

59 patients - bilateral VIM stimulation

(38 PD 13 ET)

14 patients stimulated contralateral to a previous thalamotomy

A total of 74 patients received bilateral surgery

Patients were evaluated pre-operatively and between the 3rd and 6th months after surgery and were followed for as long as 8 years

Tremor suppression for as long as 8 years in PD but no suppression of bradykinesia or rigidity

Satisfactory results in essential tremor, with deterioration with time in 18.5%

Much less favorable results for other dyskinesias (except MS: 2 of 4 have good to fair benefit)

Adverse events:

* No operative mortality.

* No permanent morbidity.

* Paresthesias (9%) usually induced at intensities of stimulation higher than those that suppressed tremor

* Foot dystonia (9%) seen after 12 months of stimulation, reversible when stimulation discontinued dysarthria in 23 patients (19.6%), 4 of whom had previous contralateral thalamotomy, and 14 of whom had bilateral stimulation

Side effects:

37 patients (31.6%) experienced minor side effects, always immediately after surgery

It is suggestive that the patients included in this study were included in Benabid et al, 1991 and 1993

No information on selection criteria for inclusion into the study

No statistical analysis of results

Alesch et al, 1995*

Clinical series

N=27

Mean age = 65 yrs (41-77)

25 men 8 women

27 patients received unilateral implantation (total 33 thalami)

6 patients received bilateral implantation

23 PD

4ET

Mean duration of illness = 13 yrs

Previous thalamotomy in 5 patients

Evaluation of the patients occurred pre-operatively and after 3, 6, and 12 months

The Tremor Rating Scale was used to assess tremor:

* Complete suppression of tremor seen in 21/33 (64%) implanted thalami

* Major improvement occurred in 6/33 sides (18%)

* Marked tremor remained in 4 sides (12%) a minor improvement

* No improvement in 2/33 sides (6%).

Patients under stimulation showed a mean improvement of 45% during ADL and 43% for motor performance test measured by the UPDRS.

No significant effect on any other exiting symptoms of Parkinson’s disease, such as rigidity and akinesia, as measured by the UPDRS.

Adverse effects:

* In 27 cases, turning on the IPG led to paresthesias which lasted about 5 seconds and disappeared;

* In 2 cases, paresthesias were permanent;

* Mild dysarthria in two patients implanted bilaterally

* Marked dysarthria in 1 patient implanted bilaterally

* Disequilibrium- one case

Complications one patient suffered subdural hematoma at time of drilling of the burr hole

36 patients were screened for inclusion in the study and 27 were selected. However, there is no information as to what criteria was used to select these patients for inclusion

Patients severely impaired in most routine activities due to persistent tremor refractory to conservative treatment

All side effects reversed by turning off stimulator

No statistical analysis of results

Caparros-LeFebvre et al, 1993*

Clinical series

N=14

Mean age = 62.5 yrs

Distribution by sex not reported

Implantation in VIM

10PD

Mean duration of illness = 10.4 yrs.

Group1:

5 patients without levodopa-induced dyskinesia

Group 2:

5 patients with levodopa-induced dyskinesia

Tremor was assessed by 3 neurologists according to the UPDRS before and after thalamic stimulation on videotape recordings

Dyskinesia was rated on a 4-point scale before surgery and after implantation and with and without stimulation

Follow-up was for average of 27 months.

Group 1:

Tremor suppression in 4/5 (one patient, with previous thalamotomy, not controlled by stimulation)

Group 2:

Tremor suppression and suppression of levodopa induced dyskinesia in 4/5 patients (one patient with previous thalamotomy derived only transient tremor relief and no dyskinesia relief)

No effect on other cardinal symptom of Parkinson’s was reported

Peak-dose dyskinesia was improved in all 5 cases where L-dopa induced dyskinesia was observed

No neuropsychological side effects were noted

There was no effect on L-dopa dosing before and after implantation

Adverse events:

Mild dystonic hand posture related to stimulation observed in one case

Patients included in this study were part of the selection of patients previously reported in Blond et al, 1992

This article provides additional information on the differences in effect of stimulation for patients with and without L-dopa induced dyskinesia

No statistical analysis of results

Only a brief description of the patient selection method was included

Blond et al, 1992*

Clinical series

N = 14

Mean age:

62.5 yrs (54-74) ET

62.2 yrs (42-76) PD

Distribution by sex not reported

Implantation in VIM

10 PD 4 ET

Mean duration of illness = 10.4 yrs PD and 36.8 yrs ET

3/10 PD cases had previous contralateral thalamotomy

Tremor was assessed before and after stimulation by means of clinical evaluation, surface electromyography, accelerometer, and video tape recordings

PD patients were followed on average for 19.4 months

ET patients were followed on average for 11 months

Complete suppression of tremor in 9/14 patients (64%)

Marked functional improvements in 11 patients (78%)

L-dopa induced dyskinesia improved in 5 PD patients

Akinesia was not changed by stimulation.

Residual rigidity was difficult to assess, but seemed to improve

No postoperative memory, speech, or praxis skill disorders with neurophysiological testing a few days after surgery

Adverse events:

Tonic posture of fingers during stimulation in one patient with PD

Persistent slight paresthesias during stimulation in one patient with ET

Patient selection method was described and stated that age was not part of the criteria because of the presumed safety of the procedure

Description of the assessment and results of all other cardinal symptoms of Parkinson’s, except tremor, were vague and inadequate.

No statistical analysis of results

Notes:
* These summaries included text from a Blue Cross Blue Shield review of these articles in their technology assessment, Deep Brain Stimulation of the Thalamus for Tremor (1997).

Abbreviations:
ET- Essential tremor
PD- Parkinson’s disease
MS- Multiple sclerosis
CRST-Clinical Rating Scale for Tremor
DBS – Deep brain stimulation
UTRA - Unified Tremor Rating Assessment.
UPDRS - Unified Parkinson's Disease Rating Scale
MMSE - Mini-Mental State Examination

Unilateral Reference Articles Bibliography

Alesch, F., Pinter, M. M., Helscher, R. J., Fertl, L., Benabid, A. L., & Koos, W. T. (1995). Stimulation of the ventral intermediate thalamic nucleus in tremor dominated Parkinson's disease and essential tremor. Acta Neurochir, 136(1-2), 75-81.

Benebid, A., Pollak, P., & Gervason, C. et al. (1991). Long-term suppresion of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet, 337(8738), 403-6.

Benebid, A., Pollak, P., & Seigneuret, E. et al. (1993). Chronic VIM thalamic stimulation in Parkinson's disease, essential tremor and extra-pyramidal dysinkesias. Acta Neurochir Suppl, 58, 39-44.

Benebid, A., Pollak, P., & Gao, D. et al. (1996). Chronic electric stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders. J Neurosurg, 84(2), 203-14.

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1 Blue Cross Blue Shield Association (1997) Deep Brain Stimulation of the Thalamus for Tremor. Assessment Program. Volume 12, No. 20. December, 1997

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