Using kinematics to re-define the pull test as a quantitative biomarker of the postural response in normal pressure hydrocephalus patients

Daly, Samuel; Hanson, Jacob; Mavanji, Vibha; Gravely, Amy; Jean, James; Jonason, Alec; Lewis, Scott M.; Ashe, James; Looft, John M.; McGovern, Robert A.

doi:10.1007/s00221-021-06292-5

Cited by 9 publications

(20 citation statements)

References 34 publications

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“…While the plethora of recent articles can be retrieved as one uses the search keyword of ‘biomarker and hydrocephalus’ ( Nakajima et al, 2010 ; Miyajima et al, 2013 ; Pyykko et al, 2014 ; Jingami et al, 2015 ; Kazui et al, 2016 ; Nagata et al, 2017 ; Abu-Rumeileh et al, 2019 ; Niermeyer et al, 2020 ; Nakajima et al, 2021 ; Torretta et al, 2021 ; Daly et al, 2022 ; Jeppsson et al, 2022 ; Mazzeo et al, 2022 ), we have not yet found literature focusing on ‘mRNA biomarker and hydrocephalus’. Instead, there were two recent articles related to ‘mRNA biomarker and Alzheimer’s ( Fiala et al, 2011 ; Isik and Beydemir, 2022 ), suggesting that most biomarker studies on iNPH and/or sNPH might be designed through fluid or CSF assays ( Nakajima et al, 2010 ; Miyajima et al, 2013 ; Pyykko et al, 2014 ; Jingami et al, 2015 ; Kazui et al, 2016 ; Nagata et al, 2017 ; Abu-Rumeileh et al, 2019 ; Niermeyer et al, 2020 ; Nakajima et al, 2021 ; Torretta et al, 2021 ; Daly et al, 2022 ; Jeppsson et al, 2022 ; Mazzeo et al, 2022 ). This highlights the novelty and utility of tissue assays in which mRNA markers were pursued with the caudate nucleus.…”

Section: Discussionmentioning

confidence: 99%

TRPV4 mRNA is elevated in the caudate nucleus with NPH but not in Alzheimer’s disease

et al. 2022

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Symptoms of normal pressure hydrocephalus (NPH) and Alzheimer’s disease (AD) are somewhat similar, and it is common to misdiagnose these two conditions. Although there are fluid markers detectable in humans with NPH and AD, determining which biomarker is optimal in representing genetic characteristics consistent throughout species is poorly understood. Here, we hypothesize that NPH can be differentiated from AD with mRNA biomarkers of unvaried proximity to telomeres. We examined human caudate nucleus tissue samples for the expression of transient receptor potential cation channel subfamily V member 4 (TRPV4) and amyloid precursor protein (APP). Using the genome data viewer, we analyzed the mutability of TRPV4 and other genes in mice, rats, and humans through matching nucleotides of six genes of interest and one house keeping gene with two factors associated with high mutation rate: 1) proximity to telomeres or 2) high adenine and thymine (A + T) content. We found that TRPV4 and microtubule associated protein tau (MAPT) mRNA were elevated in NPH. In AD, mRNA expression of TRPV4 was unaltered unlike APP and other genes. In mice, rats, and humans, the nucleotide size of TRPV4 did not vary, while in other genes, the sizes were inconsistent. Proximity to telomeres in TRPV4 was <50 Mb across species. Our analyses reveal that TRPV4 gene size and mutability are conserved across three species, suggesting that TRPV4 can be a potential link in the pathophysiology of chronic hydrocephalus in aged humans (>65 years) and laboratory rodents at comparable ages.

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Section: Discussionmentioning

confidence: 99%

TRPV4 mRNA is elevated in the caudate nucleus with NPH but not in Alzheimer’s disease

et al. 2022

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“…In order to fully assess the entire spectrum of balance dysfunction, clinical discretion was used to unpredictably vary the pull force intensities throughout the trials. 6 However, the patient's pull test was scored solely on the first trial after the instructional trial, which was always "brisk," as required by the MDS-UPDRS PT scale. 7…”

Section: Task Detailsmentioning

confidence: 99%

“…Conversely, "abnormal" pull test responses are typically characterized by slower rises to peak V COM as the patient reacts more slowly, followed by slower decreases to zero as the patient takes more steps to recover (Figure 1A, Patients). 6 Pull test step length (PTSL) was defined as the difference in foot position between the first step onset and first step land, and reaction time was defined as the time between the perturbation onset and the initiation of the first step (Supplemental Fig. 2).…”

Section: Data Collection and Variable Definitionmentioning

confidence: 99%

“…When varying the pull intensity over a series of pulls, a "normal" recovery is characterized by the ability to appropriately scale initial step length and reaction time to perturbation intensity. 6 Additional details on variable definitions can be found in our supplemental material.…”

Section: Data Collection and Variable Definitionmentioning

confidence: 99%

“…Our previous work has demonstrated that the clinical gold standard assessment of PI -the pull test (Movement Disorder Society-Unified Parkinson's Disease Rating Scale item 3.12; MDS-UPDRS PT ) -can be instrumented and quantified with inertial measurement units (IMUs) in these patients. 6 The goal of this study was to quantify the long-term effects of VPS on gait and PI compared to patients who did not undergo VPS using prospective kinematics collected during clinical visits.…”

Section: Introductionmentioning

confidence: 99%

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Longitudinal improvement in postural instability is distinct from gait in treated adult hydrocephalus

Wacek

Jean

Jonason

et al. 2022

Preprint

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Background: Ventriculoperitoneal shunting improves gait in patients with normal pressure hydrocephalus. Postural instability is a major concern, but mostly ignored in the evaluation and treatment of these patients. This study quantified postural instability using kinematics via a prospective cohort design. Methods: Seventeen patients with suspected normal pressure hydrocephalus and twenty age-matched, healthy controls underwent quantitative pull test and gait examinations while wearing inertial measurement units at baseline. Patients with suspected normal pressure hydrocephalus who were shunted (n=13) and not shunted (n=4) underwent further testing after a lumbar drain trial and at follow-up visits 6 and 12 months post-operatively. Results: While most gait improvement in patients who were shunted was seen immediately after the lumbar drain trial, measures of their postural response continued to improve after the lumbar drain trial through one year of follow-up. Patients who were not shunted showed no statistically significant changes in gait and postural instability measures. Conclusions: After shunting, postural instability improves continuously over one year. In contrast, a large improvement in gait is seen immediately with minimal change over the subsequent year. This difference in timing may implicate two distinct neurophysiological mechanisms of recovery and provides novel evidence that postural instability improves in response to long-term CSF diversion.

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Postural instability in Parkinson’s disease assessed with clinical “pull test” and standardized postural perturbations: effect of medication and body weight support

Louie

Stutz

et al. 2022

J Neurol

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Using kinematics to re-define the pull test as a quantitative biomarker of the postural response in normal pressure hydrocephalus patients

Cited by 9 publications

References 34 publications

TRPV4 mRNA is elevated in the caudate nucleus with NPH but not in Alzheimer’s disease

TRPV4 mRNA is elevated in the caudate nucleus with NPH but not in Alzheimer’s disease

Longitudinal improvement in postural instability is distinct from gait in treated adult hydrocephalus

Postural instability in Parkinson’s disease assessed with clinical “pull test” and standardized postural perturbations: effect of medication and body weight support

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