Gamma Knife Radiosurgery (GKRS) in the Management of Parkinson's Disease and Essential Tremor: Long-term Follow-up Report of 192 Cases

Reviewer: Samuel Swisher-McClure, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 31, 2010

Share article


Authors: C. Frentress, R.J Mark, H. Smith, D. Jacques, R. Young, B. Copcutt, C. Chen, P.J. Anderson, M. Nair.

Background

Tremor secondary to Parkinson's disease (PD) and Essential Tremor (ET) are often progressive in nature and without effective treatment may result in significant disability for affected patients.

  • Medication is typically used as first line therapy for tremor secondary to PD and ET. In patients for whom tremor becomes refractory to medication, additional management options include:
    • Deep Brain Stimulation (DBS)
    • Radiofrequency (RF)
    • Gamma Knife Stereotactic Radiosurgery (GKSRS).
  • When Lars Leksell originally presented stereotactic radiosurgery (SRS) in 1951, one of the original intentions was to use the technique in the treatment of functional disorders such as Parkinson's Disease (PD).
  • SRS has been used in the treatment of tremor secondary to PD and ET for over 25 years and several authors have published results that compare favorably with other available treatments with respect to relief and complications.
  • One of the larger previously published experiences was by Young et al. in the Journal of Neurosurgery in 2000
    • The authors reported 8 year outcomes in 102 patients with PD and 52 patients with ET treated with GKRS using 4 mm collimator and maximum dose of 120-160 Gy directed at the Ventralis Inter-medius nucleus within the thalamus.
    • In 88% of patients with PD or ET, there was long term relief of symptoms after GKRS that was determined to be statistically significant using a validated rating scale before and after therapy.
    • Complication rates were relatively low (1.9%) and were generally transient.
  • The authors of the current study have also previously reported their experience with shorter follow-up using GK SRS (Median Dose 130 Gy) for tremor related to PD or ET (Duma et al. Journal of Neurosurgery 1998).
  • In that prior publication, the authors reported results for 34 treated patients with a median follow-up of 28 months and found that 79% of patient experienced at least “good response” to treatment with respect to improved tremor.
  • The authors now report updated long-term results with GKRS in the treatment of tremors.

Methods

  • Between 1991 and 2010, 192 patients underwent MRI Scan targeted GKRS thalamotomy for medically refractory tremors secondary to PD (n = 118) and ET (n = 74).
  • The target was the Ventralis Inter-Medius (VIM) nucleus which received a median dose of 140 Gy in a single shot prescribed to Dm using a 4 mm collimator.
  • Treatment planning was accomplished thru the Leksell Treatment Planning System.
  • Pre-operative and post-operative blinded assessments were performed by a team of independent examiners.
  • The Unified Parkinson's Disease Rating Scale and Clinical Rating Scale for Tremors were used to score tremors before and after treatment.

Results

  • The median follow-up for the current study was 7 years (Range 2-19 years)
  • Among patients receiving GKRS for tremor refractory to medical therapy, 83.3% (160/192) of patients had significant or complete resolution of tremors.
  • In patients with PD, 83.0% (98/118) had near or complete tremor resolution, vs. 83.8% (62/74) with ET. There was no statistically significant difference between results observed in patients with PD vs. ET (Fisher's Test p = 1.0).
  • Reported toxicity rates were low
  • Four patients (2.1 %) experienced MRI proven edema and transient hemiparesis and speech difficulty.
    • In three patients, the deficits resolved with high dose steroids.
    • The 4th patient was treated with high dose steroids, and hyperbaric oxygen, with eventual resolution of paresis and edema.
  • There were no cases of hemorrhage, infection, or death.

Conclusions

  • GKRS thalamotomy to the VIM nucleus provides favorable results, both with respect to tremor relief and complications, for patients with medically refractory tremors secondary to PD or ET.
  • These long term results are comparable to those reported from other institutions that have published experience using GKRS for tremor secondary to PD and ET.
  • The observed results with GKRS compare favorably to DBS and RF, with regard to tremor relief, complications, and cost.
    • GKRS allows avoidance of risk of infection and anesthesia that is associated with the invasive nature of DBS.
    • In addition, GKSRS is approximately ½ the cost of DBS.
  • In view of these long-term tremor resolution results, low complication risks, and cost savings, GKRS should be considered as a primary initial treatment option in medically refractory tremors.

Clinical Implications

  • This study provides long-term follow-up of outcomes in a large group patients treated with GK SRS for medically refractory tremors secondary to PD and ET.
  • The authors used validated metrics (Unified Parkinson's Disease Rating Scale and Clinical Rating Scale for Tremors) to measure changes in tremor severity as a response to treatment.
  • The majority of patients (83.3%) had significant or complete resolution of tremor symptoms.
  • The treatment was found to be well tolerated with relatively low complication rates (2.1%) that were temporary in all patients.
  • Potential limitations of the study include:
    • Limited information regarding methods of patient follow-up such as interval of assessment of tremor severity.
    • Limited information with respect to the frequency of development of recurrent tremor among patients or the number of patients who required additional treatment after GKRS.
  • This study represents one of the larger reported series of patients receiving GKSRS for tremor secondary to PD or ET.
  • Based upon the results reported by the authors as well as other published experience, GKRS represents an effective and safe treatment and should be considered as a first-line treatment option for medically refractory tremor secondary to PD and ET.


News
FDA is reviewing long-term trial data but has not issued new recommendations on use of the drug

Apr 2, 2010 - Patients who take the Parkinson's disease medication Stalevo (entacapone/carbidopa/levodopa) may be at increased risk for developing prostate cancer, according to a safety announcement released March 31 by the U.S. Food and Drug Administration.



I Wish You Knew

How cancer patients have changed my life

View More



Blogs and Web Chats

OncoLink Blogs give our readers a chance to react to and comment on key cancer news topics and provides a forum for OncoLink Experts and readers to share opinions and learn from each other.




OncoLink OncoPilot

Facing a new cancer diagnosis or changing the course of your current treatment? Let our cancer nurses help you through!

Learn More