DBS Benefits in Dystonia May Linger After Device Shut-Off

Megan Brooks

February 22, 2013

Two patients with primary generalized dystonia successfully treated with bilateral pallidal deep brain stimulation (DBS) continued to experience relief of symptoms for at least 2 months after active stimulation was inadvertently turned off.

"These 2 accidental findings were extremely interesting and surprising," Michele Tagliati, MD, director of the Movement Disorders Program at Cedars-Sinai Medical Center, Los Angeles, California, noted in an interview with Medscape Medical News.

DBS is considered a symptomatic treatment, with symptoms returning within hours or days of device shut-off, which can sometimes be more severe than those present at baseline, he explained. But these 2 young patients continued to have clinical benefit despite interruption of DBS therapy for several months. And when symptoms did return, they were milder than before DBS.

Dr. Tagliati and colleagues describe the 2 patients in a paper online February 11 in Movement Disorders.

Dr. Michele Tagliati

Young Patients

One was a male who experienced initial symptoms of dystonia at age 11. Genetic testing revealed the DYT-1 mutation. By age 15, despite maximal medical therapy, his symptoms became disabling (Burke-Fahn-Marsden Dystonia Rating Scale [BFMDRS] motor score, 64).

The patient began bilateral pallidal DBS at a stimulation frequency of 60 Hz, which led to progressive improvement in motor function. At 6 months, his BFMDRS motor score had decreased to 2.5. At 1 year, the patient was essentially symptom-free, with a BFMDRS motor score of 0.

At a routine evaluation 5 years after implantation, it was discovered that the right neurostimulator had been inadvertently turned off for roughly 3 months. Because significant symptoms had not returned during this time, he was watched while receiving unilateral (left) stimulation.

At a planned follow-up visit 2 weeks later, he had developed mild involuntary movements of the left shoulder and his BFMDRS motor score was 4. A controlled 24-hour discontinuation of bilateral DBS did not result in further symptom recurrence on the right side. However, given the return of mild dystonic symptoms in his left upper extremity, both neurostimulators were restarted and dystonic movements quickly improved over the following day. The patient remains asymptomatic 7 years after DBS implantation.

At age 11, the other patient, also male, developed dystonia symptoms that evolved and failed to improve significantly with medications. Brain MRI evaluation and DYT-1 testing revealed no abnormalities. At age 18, he started bilateral pallidal DBS and over the first 6 months his BFMDRS motor scores decreased from 66 to 1.

About 19 months after DBS initiation, generalized mild twitches returned. It was discovered that his left neurostimulator had been off for about 7 months and the right stimulator had been off for 2 months. His symptoms resolved almost immediately after reactivation of the stimulators.

Dr. Tagliati said young age, short duration of disease and length of time on DBS, and a relatively low energy of stimulation seem to be factors in lingering motor benefits after prolonged DBS interruption.

These 2 cases build on a "small but emerging" body of evidence documenting persistent motor benefit in dystonia after interruption of therapeutic DBS, the authors note in their article. To their knowledge, these 2 patients represent the longest duration of such retention of benefit in primary generalized dystonia.

Rewiring the Brain

Reached for outside comment, Michael S. Okun, MD, co-director, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, told Medscape Medical News, "It has been noticed by several experts in the DBS field that occasionally when a battery drains, is depleted, or is inadvertently switched to the off condition, patients may enjoy brief or prolonged periods of improvement. This has been especially true in dystonia patients, who often initially take weeks to months of stimulation post-activation to observe the sometimes dramatic improvements in coordinated movement."

"Our best guess," Dr. Okun said, "is that the brain is remodeling and that neuroplasticity may underpin the improvements seen in dystonia.  It is very interesting to see more of these cases emerge, and this adds to mounting evidence that sustained improvements can be seen in these patients even when off DBS, lending support to the notion that the brain is remodeled in some unknown way as a response to the electricity."

Diane Ruge, MD, from the Institute of Neurology University College London, United Kingdom, agrees. Lingering DBS benefits after device shut-off "we think [are due] to neural reorganization and plastic changes induced by DBS," she told Medscape Medical News.  

Dr. Ruge has also seen patients with dystonia who have lingering DBS motor benefits after device shut-off, which she described in a report in the journal Brain in 2011.

Dr. Tagliati noted that the pathophysiology of dystonia is "not very well known, but one credited hypothesis is that it is a disease of connectivity, of abnormal plasticity, which basically means that the brain starts overreacting to certain stimulation leading to loss of control of certain movements."

Echoing Dr. Okun and Dr. Ruge, he said, "It's fascinating to hypothesize that in some of these particularly young patients who receive stimulation early in the disease process that stimulation might somewhat reverse this abnormal plasticity, it might rewire the abnormal connectivity of the brain."

Dr. Tagliati also noted that currently, the choice of doing DBS brain surgery is more linked to the severity of the disease than the duration of the disease. "People wait until they really have no other option, but as we learn more definitely it appears that the earlier we intervene the better it is. It is a difficult clinical decision," Dr. Tagliati said.

Dr. Tagliati has received speaker honoraria from Medtronic Inc and consultation fees from St. Jude Medical Inc, Abbott Laboratories, and Impax Laboratories Inc, unrelated to this study. Dr. Okun and Dr. Ruge have disclosed no relevant financial relationships.

Movement Disord. Published online February 11, 2013. Abstract