Is there a spinal tap responder in progressive supranuclear palsy?: The first prospective study

Objective Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disease, and sometimes shows idiopathic normal pressure hydrocephalus (iNPH)-like presentations. We aimed to evaluate spinal tap responsiveness in patients with PSP, including the effect of sham spinal tap. Methods Eleven patients with PSP, ten with probable/definite iNPH, and eight control patients were prospectively enrolled. All participants underwent sham spinal tap and spinal tap procedures. Gait was evaluated using wearable inertial sensors. We defined “tap responders” as individuals with a 10% or more improvement from baseline in any of the gait parameters (timed up-and-go test total time, stride length, and velocity during straight walking under single-task and cognitive dual-task conditions). We compared the ratio of tap responders in patients with PSP to patients with iNPH and controls. Results The ratio of tap responders in patients with PSP was significantly higher than that in control patients, but not different from patients with iNPH. The ratio of sham tap responders was significantly higher in PSP patients than that in control patients, but not that in patients with iNPH. Notably, one patient with PSP responded to the spinal tap beyond the effect of sham spinal tap, and even to the shunt operation. Interpretation This is the first prospective study to demonstrate tap and shunt responsiveness in patients with PSP while highlighting the placebo effects of the spinal tap in patients with PSP and iNPH. Our findings suggest that some PSP patients have impaired cerebrospinal fluid circulation, contributing to a distinct component of the clinical spectrum. ### Competing Interest Statement T.H. has received speaker honoraria from Daiichi Sankyo Company, Limited; Sumitomo Dainippon Pharma Co., Ltd.; and Kyowa Kirin Co., Ltd. The other authors declare no competing interests. ### Clinical Trial UMIN000033026 ### Funding Statement This research was supported by the Nakayama Foundation for Human Science and Taiju Life Social Welfare Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Boards of Tokyo Medical and Dental University Hospital gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes