Deep brain stimulation of the Cuneiform nucleus for levodopa-resistant freezing of gait in Parkinson’s disease: study protocol for a prospective, pilot trial

Abstract Background Freezing of gait (FOG) is a particularly debilitating motor deficit seen in subset Parkinson’s disease (PD) patients that poorly responsive to standard levodopa therapy or deep brain stimulation (DBS) established PD targets such as the subthalamic nucleus and globus pallidus interna. The proposal DBS target midbrain, known pedunculopontine (PPN) address FOG, was based on its observed pathology hypothesized involvement locomotor control part mesencephalic region, functionally defined area midbrain elicits locomotion both intact animals decerebrate animal preparations with electrical stimulation. Initial reports PPN were met much enthusiasm; however, subsequent studies produced mixed results, recent meta-analysis results have been far less convincing than initially expected. A closer review extensive region (MLR) preclinical literature, including optogenetics studies, strongly suggests closely related cuneiform (CnF), just dorsal PPN, may be superior promote initiation. Methods We will conduct prospective, open-label, single-arm pilot study assess safety feasibility CnF levodopa-refractory FOG. Four receive assessments without during 6-month follow-up. Discussion This paper presents design rationale for investigating novel dysfunction, targeting considerations. intended support future larger scale clinical trials this target. Trial registration ClinicalTrials.gov identifier: NCT04218526 (registered January 6, 2020)