6 2 experienced many technological advancements, includ- ing the introduction of multiple independent current controls, directional electrodes, a greater stimulation parameter space, image-guided programming, and adap- tive DBS, all of which may lead to reduced side effects and better long-term outcomes. However, the contin- ued deterioration of some motor and many non-motor domains and related progressive disability highlights the great need for other novel PD interventions and thera- peutics for these aspects of PD.” The dilemma isn’t much different from what has faced neurologists treating Parkinson’s disease for some 60 years. Now, however, new pharmaceutical products to combine extended and immediate release of levodopa/carbidopa to reduce off times have become available. L-DOPA, a precursor of dopamine that can pass through the blood-brain barrier, was celebrated as a wonder drug when its clinical use for Parkinson’s disease became widespread in the 1960s. It certainly seemed miraculous when patients who had been immobilized for years suddenly regained some critical functions. But the drug also had some downsides, however, such as dyskinesias and puzzling on–-off effects in which the drug almost instantly wears off—an issue that has persisted. The problem is that L-DOPA has a short plasma half- life of about 60-90 minutes, even when combined with peripheral decarboxylase inhibitors like carbidopa. That can result in a duration of action of only 3-4 hours.2 Still, L-DOPA remains the gold-standard for Parkinson’s treatment. Neurologists are constantly bal- ancing medications to avoid the so-called off periods, which affect about half of patients taking levodopa and more than 70% of long-term users. In a recent survey from the Michael J. Fox Foundation, about 70% of the respondents reported at least two “off” periods a day, with the accompanying stiffness, tremor and anxiety. In the survey, about 25% of affected patients said they experienced 3 to 6 hours of “off” time daily, while 52% reported 1 to 3 hours daily. Yet, while surgical device aided therapies (DAT) for Parkinson’s disease receive a lot of hype, their use tends to be quite low. A study last year led by Icahn School of Medicine at Mount Sinai in New York noted that 22% of Medicare Change From Baseline in Good On-Time, Least Squares Mean. Good on-time was defined as on-time without troublesome dyskinesia. EOS indicates end of study; IR CD-LD, immediate- release carbidopa-levodopa. Source: Aquino CC, Fox SH. Clinical spectrum of levodopa-induced complications. Mov Disord. 2015;30(1):80-89. doi: 10.1002/mds.26125
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