Parkinson's disease is characterized by the progressive loss of midbrain dopamine neurons. Dopamine replacement therapy with levodopa alleviates parkinsonian motor symptoms but is complicated by the development of involuntary movements, termed levodopa-induced dyskinesia (LID). Aberrant activity in the striatum has been hypothesized to cause LID. Here, to establish a direct link between striatal activity and dyskinesia, we combine optogenetics and a method to manipulate dyskinesia-associated neurons, targeted recombination in active populations (TRAP). We find that TRAPed cells are a stable subset of sensorimotor striatal neurons, predominantly from the direct pathway, and that reactivation of TRAPed striatal neurons causes dyskinesia in the absence of levodopa. Inhibition of TRAPed cells, but not a nonspecific subset of direct pathway neurons, ameliorates LID. These results establish that a distinct subset of striatal neurons is causally involved in LID and indicate that successful therapeutic strategies for treating LID may require targeting functionally selective neuronal subtypes.

Objectives

While a minimalist transcatheter aortic valve replacement (TAVR) approach has shown safety and efficacy at civilian hospitals, limited data exist regarding developing this approach at Veterans Affairs (VA) medical centers (VAMCs). We implemented TAVR with minimalist approach (MA) using conscious sedation (CS) with transthoracic echocardiography (TTE) and compared safety and outcomes with general anesthesia (GA) with transesophageal echocardiography (TEE) at a university-affiliated VAMC.

Methods

A total of 258 patients underwent transfemoral TAVR at a VAMC between November 2013 and October 2019. Ninety-three patients underwent GA/TEE and 165 patients underwent CS/TTE with dexmedetomidine and remifentanil. Propensity-score matching with nearest-neighbor matching was used to account for baseline differences, yielding 227 participants (81 GA, 146 CS).

Results

MA-TAVR had no effect on 30-day mortality or paravalvular leakage. No differences were found in permanent pacemaker implantation, major vascular complications, or postoperative hemodynamics. In this population, MA-TAVR did not reduce procedural time, hospital length of stay, or intensive care unit length of stay.

Conclusions

Unlike civilian hospitals, MA with CS/TTE did not reduce overall length of stay in the veteran population; however, it was safe and effective for transfemoral TAVR without impacting clinical outcomes of mortality, major vascular complications, and paravalvular leakage.