PMID- 34867163
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211207
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 15
DP  - 2021
TI  - The Impact of Multimorbidity Burden, Frailty Risk Scoring, and 3-Directional 
      Morphological Indices vs. Testing for CSF Responsiveness in Normal Pressure 
      Hydrocephalus.
PG  - 751145
LID - 10.3389/fnins.2021.751145 [doi]
LID - 751145
AB  - Objective: Multimorbidity burden across disease cohorts and variations in 
      clinico-radiographic presentations within normal pressure hydrocephalus (NPH) 
      confound its diagnosis, and the assessment of its amenability to interventions. 
      We hypothesized that novel imaging techniques such as 3-directional linear 
      morphological indices could help in distinguishing between hydrocephalus vs. 
      non-hydrocephalus and correlate with responsiveness to external lumbar drainage 
      (CSF responsiveness) within NPH subtypes. Methodology: Twenty-one participants 
      with NPH were recruited and age-matched to 21 patients with Alzheimer's Disease 
      (AD) and 21 healthy controls (HC) selected from the Alzheimer's Disease 
      Neuroimaging Initiative (ADNI) database. Patients with NPH underwent testing via 
      the NPH programme with external lumbar drainage (ELD); pre- and post-ELD MRI 
      scans were obtained. The modified Frailty Index (mFI-11) was used to stratify the 
      NPH cohort, including Classic and Complex subtypes, by their comorbidity and 
      frailty risks. The quantitative imaging network tool 3D Slicer was used to derive 
      traditional 2-dimensional (2d) linear measures; Evans Index (EI), Bicaudate Index 
      (BCI) and Callosal Angle (CA), along with novel 3-directional (3d) linear 
      measures; z-Evans Index and Brain per Ventricle Ratio (BVR). 3-Dimensional (3D) 
      ventricular volumetry was performed as an independent correlate of 
      ventriculomegaly to CSF responsiveness. Results: Mean age for study participants 
      was 71.14 +/- 6.3 years (18, 85.7% males). The majority (15/21, 71.4%) of 
      participants with NPH comprised the Complex subtype (overlay from vascular risk 
      burden and AD); 12/21 (57.1%) were Non-Responders to ELD. Frailty alone was 
      insufficient in distinguishing between NPH subtypes. By contrast, 3d linear 
      measures distinguished NPH from both AD and HC cohorts, but also correlated to 
      CSF responsiveness. The z-Evans Index was the most sensitive volumetric measure 
      of CSF responsiveness (p = 0.012). Changes in 3d morphological indices across 
      timepoints distinguished between Responders vs. Non-Responders to lumbar testing. 
      There was a significant reduction of indices, only in Non-Responders and across 
      multiple measures (z-Evans Index; p = 0.001, BVR at PC; p = 0.024). This was due 
      to a significant decrease in ventricular measurement (p = 0.005) that correlated 
      to independent 3D volumetry (p = 0.008). Conclusion. In the context of 
      multimorbidity burden, frailty risks and overlay from neurodegenerative disease, 
      3d morphological indices demonstrated utility in distinguishing hydrocephalus vs. 
      non-hydrocephalus and degree of CSF responsiveness. Further work may support the 
      characterization of patients with Complex NPH who would best benefit from the 
      risks of interventions.
CI  - Copyright (c) 2021 Soon, Kumar, Tan, Lo, Lock, Kumar, Kwok and Keong.
FAU - Soon, Shereen X Y
AU  - Soon SXY
AD  - Department of Neurosurgery, National Neuroscience Institute, Singapore, 
      Singapore.
FAU - Kumar, A Aravin
AU  - Kumar AA
AD  - Department of Neurosurgery, National Neuroscience Institute, Singapore, 
      Singapore.
FAU - Tan, Audrey J L
AU  - Tan AJL
AD  - Department of Neurosurgery, National Neuroscience Institute, Singapore, 
      Singapore.
FAU - Lo, Yu Tung
AU  - Lo YT
AD  - Department of Neurosurgery, National Neuroscience Institute, Singapore, 
      Singapore.
FAU - Lock, Christine
AU  - Lock C
AD  - Department of Neurosurgery, National Neuroscience Institute, Singapore, 
      Singapore.
FAU - Kumar, Sumeet
AU  - Kumar S
AD  - Department of Neuroradiology, National Neuroscience Institute, Singapore, 
      Singapore.
FAU - Kwok, Janell
AU  - Kwok J
AD  - Department of Neurosurgery, National Neuroscience Institute, Singapore, 
      Singapore.
FAU - Keong, Nicole C
AU  - Keong NC
AD  - Department of Neurosurgery, National Neuroscience Institute, Singapore, 
      Singapore.
AD  - Duke-NUS Medical School, Singapore, Singapore.
LA  - eng
PT  - Journal Article
DEP - 20211116
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC8636813
OTO - NOTNLM
OT  - ADNI database
OT  - external lumbar drainage
OT  - normal pressure hydrocephalus
OT  - ventricular morphology
OT  - ventricular volume
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/12/07 06:00
MHDA- 2021/12/07 06:01
PMCR- 2021/01/01
CRDT- 2021/12/06 09:03
PHST- 2021/07/31 00:00 [received]
PHST- 2021/10/21 00:00 [accepted]
PHST- 2021/12/06 09:03 [entrez]
PHST- 2021/12/07 06:00 [pubmed]
PHST- 2021/12/07 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2021.751145 [doi]
PST - epublish
SO  - Front Neurosci. 2021 Nov 16;15:751145. doi: 10.3389/fnins.2021.751145. 
      eCollection 2021.