Drug-Refractory Tardive Dyskinesia Improves with Deep-Brain Stimulation

VBCN - April 2016 Volume 3, No 1

Patients with drug-refractory tardive dyskinesia had significant and durable symptomatic improvement after bilateral deep-brain stimulation, a small clinical study showed (Pouclet-Courtemanche H, et al. Neurology. 2016;86:651-659).

All 19 evaluable patients had a decrease of more than 40% in the Extrapyramidal Symptom Rating Scale (ESRS) score at 6 months. The improvement increased at 12 months, and was maintained during follow-up for as long as 11 years.

All subscores of the ESRS and the Abnormal Involuntary Movement Scale (AIMS) improved. No patient had cognitive decline, and the majority of patients had improvement in mood. However, symptoms returned when deep-brain stimulation was stopped, the investigators reported.

“In our series, pallidal DBS [deep-brain stimulation] improved dystonic and choreic-like abnormal movements to the same extent,” reported Hélène Pouclet-Courtemanche, MD, a neurologist at the Centre d’Investigation Cli­nique, Department of Neurology, CHU de Nantes, France, and colleagues. “It also improved to a similar extent oro-buccal-lingual, axial, as well as limb abnormal movements. Based on these results, pallidal DBS should not be restricted to severe dystonic presentations but should be proposed in severe TD [tardive dyskinesia] refractory to medical treatment, regardless of its semiology,” the researchers noted.

These findings add to and extend the data from the first 10 patients included in the series and published in 2007 (Damier P, et al. Arch Gen Psychiatry. 2007;64:170-176). The series increased to 19 patients who received treatment from 2003 to 2007 at 6 university hospitals in France. One additional patient was excluded from the study after a diagnosis of Huntington’s disease.

All the patients were adults with severe tardive dyskinesia (item 5 of the ESRS score >4) that had not responded to at least a 3-month trial of a dopamine receptor antagonist. Eligible patients had normal brain magnetic resonance imaging results and a normal neurologic examination (except for abnormal movements), ineffective medical therapy, stable psychiatric symptoms without recent medication modification, and a Mini-Mental State Examination score of ≥24.

Stimulation leads were implanted bilaterally in the posteroventral area of the internal globus pallidus. The leads were connected to an external subcutaneous programmable pulse generator several days after surgery. Treatment was adapted and reduced according to response to stimulation.

The patients were evaluated using the ESRS and AIMS scores at baseline, and then 3, 6, and 12 months after surgery. The primary objective was the change in the ESRS score at 6 months, assessed by means of a double-blind ESRS evaluation with stimulation on and off.

All 19 patients had >40% improvement in their baseline ESRS scores at the 6-month evaluation. The mean improvement from baseline in the total ESRS score had increased to 58% (range, 21%-81%; P <.0001) at the 12-month evaluation. In addition, the total AIMS score had decreased by 50% from baseline (P <.0001).

Study Findings

At 12 months, all ESRS and AIMS subscales had improved significantly from baseline, including ESRS-Parkinsonism (51%; P <.0001), ESRS-dystonia (64%; P <.0001), ESRS-chorea (57%; P <.0001), AIMS-facial and oral movements (39%; P <.001), AIMS-extremities movements (28%; P <.001), and AIMS-trunk movements (49%; P <.001).

The double-blind assessment at 6 months demonstrated a mean improvement in the total ESRS score of 49% (range, 9%-84%; P <.0001). Similar improvement was observed for all the ESRS subscales.

The investigators observed no clear association between the efficacy of deep-brain stimulation and the specific positioning of the electrodes.

At 12 months, 8 of 16 patients receiving antidyskinetic drugs at baseline had stopped the medication, or decreased its frequency or dosage.

Assessments of cognitive function and psychiatric symptomatology provided no evidence of deterioration, and showed some improvement in specific subscales at the different time points. The mean depression score at 12 months had improved by nearly 50% from baseline, but did not reach significance.

Adverse Events

Overall, 3 patients had serious side effects related to surgery; 2 of these cases involved inappropriate lead placement, which was corrected. The third resulted from connection cable traction, which was corrected by the reattachment of the lead. A total of 5 patients had falls, with traumatic consequences in 3 cases, and 8 patients had psychiatric events that were managed with medication or psychotherapy.

Among 14 patients with long-term follow-up (6-11 years), the mean total ESRS score remained 60% below the baseline, and the mean total AIMS score was 63% lower than the baseline. Overall, 9 patients had recurrence of symptoms within days or weeks of when deep-brain stimulation was stopped (usually because of a depleted pulse generator battery).

Related Items

Subscribe to
Value-Based Care in Neurology

Stay up to date with personalized medicine by subscribing to recieve the free VBCN e‑Newsletter.

I'd like to recieve: