Fading of Deep Brain Stimulation Efficacy Versus Disease Progression: Untangling a Gordian Knot

Abstract

Parkinson’s disease (PD) is a relentlessly progressive neurodegenerative disorder leading to increasingly motor and nonmotor disabling symptoms with a substantial risk of functional decline and reduced life expectancy. Since its approval for treating PD, deep brain stimulation (DBS) of the subthalamic nucleus (STN) has gained a place as an effective treatment for the cardinal signs of the disease and—more important—for PD-related motor complications, that is, motor fluctuations and levodopa-induced dyskinesias. Several articles have shown significant improvement of motor symptoms and quality of life up to 5 years after DBS.1 Few others with follow-up periods ranging from 8 to 11 years have confirmed a persistent effect on motor complications and appendicular levodopa-responsive motor signs.2,3 The patients of these long-term prospective series had, however, declined in terms of axial motor signs (speech, postural stability, and gait) as well as nonmotor symptoms, cognition in particular, thus presenting the typical features of the “long-term DBS syndrome.”4 Subsequent cohorts with follow-up up to 15 years after surgery have instead focused on disease milestones, such as psychosis, urinary incontinence, and death rate,5 confirming overall what was seen in non-DBS patients of the Sydney cohort.6