LAUSR

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. 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. 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.” 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, confirming overall what was seen in non-DBS patients of the Sydney cohort. Because retrospective studies have shown that the motor scores off medication (usually for 12 hours) and OFF stimulation (usually for only 30 minutes) are not different than the preoperative scores, it has been argued that STN DBS might have a disease-modifying effect. There are a handful of experimental papers suggesting that DBS exerts disease-modifying effects mostly based on animal models and the appealing theory that a supposed excitotoxic effect of STN (the only glutamatergic nucleus of the basal ganglia) is mitigated by DBS. However, although large, randomized, and prospective trials are lacking— and probably not even ethical—studies using nuclear tracers of dopaminergic function have shown that STN DBS does not halt the underlying neurodegenerative processes. Clinical evolution of PD can be subdivided into early, moderate, and advanced phases, the latter characterized by the development of clinical milestones such as visual hallucinations, cognitive deterioration, recurrent falls, and admission in a long-term care facility. After the development of those milestones, independently from age or disease duration, all patients share a similar survival time, with cognitive disability milestone as the main survival predictor. Whether STN DBS is able to delay the development of these milestones and therefore survival have not been definitively answered. There are only a few uncontrolled longterm studies reporting frequencies of key disability milestones in DBS patients and a handful of controlled studies yielding conflicting findings. In this issue of Movement Disorders Clinical Practice, 2 elegant papers addressed whether STN DBS effects wear off and whether DBS patients acquire disability milestones earlier than non-DBS patients. Although driven by different objectives, these studies are complementary and challenged by the unavoidable confounder of evaluating the long-term outcome of a surgical technique adopted in a highly variable and progressive disorder. Thomsen and colleagues compared the total intake of dopaminergic medication to baseline and found it to be significantly reduced by 44% at the long-term follow-up (8.5– 15 years after surgery), in line with the findings by Mahlknecht and colleagues in patients on STN DBS for 15 years. These latter authors found that DBS patients carry a lower risk of experiencing recurrent falls and psychosis compared with control patients extracted from a registry study (EuroPa), supposedly through an improved motor status and dopaminergic therapy reduction.