Tardive dyskinesia (TD) can be addressed by the right intervention even in severe, refractory cases.
These cases, characterized by involuntary muscle movements, are most often caused by antipsychotics, and addressing them often involves discontinuing use of the drug. Treatment with VMAT2 inhibitors like valbenazine (Ingrezza) and deutetrabenazine (Austedo) also is an option.
In rare cases of severe, medication-resistant TD, deep brain stimulation (DBS) might be considered as a treatment option, as noted in guidelines from the American Psychiatric Association.
“DBS significantly improves the symptoms of tardive dyskinesia and tardive dystonia through continuing stimulation of certain deep brain areas [or] targets,” explained Tao Xie, MD, PhD, director of the Parkinson’s Disease and Movement Disorder Clinic and DBS Program at the University of Chicago.
How DBS Works
Performed as an invasive neurosurgical procedure, DBS involves placing a probe for microelectrode recording (MER) wires and a stimulating lead into certain deep brain areas in each side of the brain. The lead is attached to a small, pacemaker-like device placed under the skin near the collarbone. The device then sends signals to the brain to help reduce involuntary muscle movements associated with TD.
“It is a very mature and largely safe procedure, as the technology has existed in clinical practice for more than 20 years,” Xie explained to MedPage Today.
DBS works by neuromodulating the cortico-basal ganglia-thalamo-cortical loop. The most common target to stimulate is the globus pallidus internus. Though less common, another area that may be targeted for stimulation is the subthalamic nucleus. The standard stimulation sites are typically the same for TD as for treating Parkinson’s disease, Xie pointed out.
“Most of the published cases, case serials, and clinical trials — though limited — on the effect of the DBS on improvement of TD and tardive dystonia are pretty effective, based on both short-term and long-term follow-up data, with the improvement on quality of life as well,” said Xie.
In a 2018 meta-analysis of patients who underwent DBS for TD or tardive dystonia, patients reported a 62% improvement in symptoms on the Abnormal Involuntary Movement Scale and 76% improvement on the Burke-Fahn-Marsden scale over about 2 years of follow-up. Of 117 patients included, surgery-related adverse events were reported in seven patients, stimulation-induced events in 12, and psychiatric events in three.
While DBS lead and impulse generator implantation is generally considered safe, there are risks associated with surgery. While uncommon, these can range from death, symptomatic stroke, intracranial infection and seizure, skin infection, and migration and breakage of the leads and connection cable.
Who Is a Candidate?
A patient with TD who is considering DBS should first be evaluated by an experienced movement disorder specialist, said Xie. “[They can] decide whether DBS is indicated, whether the patient is a good candidate without contraindications, what are the pros and cons of the surgery, and whether there is good family or caregiver support for periodical post-surgical follow-up for DBS programming and adjustment.”
TD patients who are candidates for DBS are typically those with severe symptoms who haven’t had a good response to treatment or can’t tolerate treatment, particularly with VMAT2 inhibitors. “[These patients] usually respond pretty well to DBS,” he said. Other features of a good candidate include a good support system and availability to periodically return for DBS adjustment or programming.
Patients with tonic dystonia could respond less well to DBS, Xie said. “Those with uncontrolled psychiatric symptoms such as depression or psychosis, significant cognitive impairment, and significant brain lesions or systemic diseases affecting the safe placement of DBS lead and quality of life would not be a good candidate,” he added.
Other Types of Neurostimulation
Though evidence is limited, two other neurostimulation methods — repetitive transcranial magnetic stimulation and transcranial direct current stimulation — may also help improve TD.
While these methods are non-invasive, Xie noted some reasons why DBS may be a better choice for TD.
DBS can lead to better success because of its precision, he noted. “We can verify the target not only just by its anatomy based on merged head CT and brain MRI and an atlas overlaid onto both images, but also by its signature electrophysiological pattern as detected by MER,” he said.
Responses to the stimulation can be tested intraoperatively “to ensure a good response without causing any side effects or complications, as otherwise we can adjust the position of the leads in the operating room to optimize the therapeutic effect,” Xie added.
“The DBS also can allow us to pick up the best active stimulating contact and parameters, given their various combinations allowed, to achieve the best therapeutic effect post-surgically,” he said.
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