New insights from a Malaysian real-world deep brain stimulation cohort

BACKGROUND: The availability of deep brain stimulation (DBS), a highly efficacious treatment for several movement disorders, remains low in developing countries, with scarce data available on utilization and outcomes.

OBJECTIVE: We characterized the DBS cohort and outcomes at a Malaysian quaternary medical center.

METHODS: A retrospective chart review was done on DBS-related surgery at the University of Malaya, including clinico-demographic, genetics, and outcomes data focusing on post-operative medication reduction and complications.

RESULTS: 149 Parkinson's disease (PD) patients underwent DBS targeting the subthalamic nucleus. Six had globus pallidus internus DBS (primarily for dystonia). Only 16.1% of patients were government-funded. Of the 133 PD patients operated in the past decade (2013-2022), 25 (18.8%) had disease duration <5 years. At 6-12 months post-DBS, median levodopa-equivalent daily dose (LEDD) reduction was 440.5 [418.9] mg/day, corresponding to a reduction of ≥50% and ≥30% in 42.2% and 69.8% of patients, respectively. LEDD reductions were larger in the early-onset and short-duration subgroups. Three patients (1.9% of 155) had symptomatic intracranial hemorrhage, resulting in stroke in two. Pathogenic monogenic or GBA1 variants were detected in 12/76 (16%) of patients tested, mostly comprising the "severe" GBA1 variant p.L483P (12%).

CONCLUSIONS: This is the largest report on DBS from Southeast Asia. The procedures were effective, and complication rates on par with international norms. Our study found a high frequency of GBA1-PD; and included a substantial number of patients with short-duration PD, who had good outcomes. It also highlights regional inequities in access to device-aided therapy.

PLAIN LANGUAGE SUMMARY: Deep brain stimulation (DBS) is a highly effective treatment for several movement disorders, including Parkinson's disease (PD). However, there is very limited published information about DBS in developing countries, and on "real-life" outcomes when DBS is performed earlier in the course of PD. Here, we describe a relatively large cohort of patients who underwent DBS at a major hospital in Kuala Lumpur, Malaysia. DBS was effective with low complication rates, and at 6-12 months after surgery, the PD medication dosage was reduced by at least one-half in 4 out of 10 patients and by at least one-third in 7 out of 10 patients. Patients with PD who underwent DBS early in their disease course (within 5 years from diagnosis, comprising one-fifth of the patients), and those diagnosed at age 50 years or younger (comprising one-half of the patients), appeared to have larger reductions in their PD medications. A significant proportion of patients with PD (16%) who had genetic testing done were found to harbor monogenic (causative) gene variants or GBA1 risk gene variants, which have been associated with worse disease progression, and these patients had lesser medication reduction compared to GBA1 variant-negative patients. Less than two out of 10 patients (16%) had their DBS funded via the public health system. To our knowledge, this is the largest report on DBS from Southeast Asia and documents good outcomes overall, including in PD patients operated on early in their disease course, but highlights limited government funding for this potentially life-changing therapy as a significant barrier in developing countries.