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Background: Lumbar drain (LD) trials are used to temporarily divert CSF in order to predict clinical improvement prior to definitive CSF diversion in patients with a diagnosis of normal pressure hydrocephalus. New technology has improved clinical detection of subtle pupillary changes that may occur during CSF diversion trials. The aim of this study was to determine whether pupillary light response as recorded by automated pupillometry could be used to predict response during lumbar drain trials., Methods: The authors prospectively gathered quantitative pupillometry data on admission and following each CSF diversion in a cohort of 30 consecutive patients with a presumptive diagnosis of normal pressure hydrocephalus admitted to a university hospital for elective LD trial between January 1, 2020 and March 30, 2021. The value of pupillometry in predicting success of lumbar drainage in alleviating symptoms was correlated to clinical improvement during lumbar drainage., Results: Of the 29 patients undergoing a 4-day LD trial, 16 (55.2%) demonstrated clinical improvement. Pre-drainage pupillometry values did not differ between patients who had clinical improvement or no clinical improvement. Constriction velocity improved compared to baseline in patients who had a successful lumbar drain trial (LD +). There was a non-significant trend towards improved constriction velocity and improved dilation velocity found in patients even after the first aliquot drainage., Discussion: Baseline pupillary function by automated pupillometry did not predict clinical improvement during lumbar drain trials. Improvement in constriction and dilation velocity may be useful to monitor at the outset, after the initial drainage, and at completion of lumbar drain trials., (© 2022. Fondazione Società Italiana di Neurologia.)

Objective: Normal pressure hydrocephalus (NPH) is characterized by pathologically enlarged ventricles without elevated cerebrospinal fluid (CSF) pressure along with a triad of clinical symptoms including gait disturbances, urinary incontinence, and cognitive impairment. NPH is evaluated with lumbar drain trials (LDTs) where CSF is removed over several days to determine if patients would benefit from ventricular shunting. Candidate selection and success for these surgeries remains challenging because other diseases such as Alzheimer's disease (AD) share common features with NPH in cognitive impairment and enlarged ventricles. Prior research has found that 20%-40% of presumed NPH cases have AD pathology as determined by brain biopsy or autopsy. CSF biomarkers of AD can be altered in NPH and are not always conclusive, complicating the interpretation of results when formulating diagnoses and prognoses. Studies to refine the analyses of AD CSF biomarkers in NPH are needed. We aimed to examine the frequency of CSF biomarker results among patients presenting for NPH evaluations with LDTs. Participants and Methods: 62 patients presented for LDTs upon physician recommendations. CSF specimens were sent to Mayo Clinic Laboratories for Alzheimer Disease Evaluation (ADEVL) that utilizes Elecsys (Lenexa, KS) CSF electrochemiluminescence immunoassays (Roche Diagnostics, Basel, Switzerland) to measure levels of amyloid-beta 42 (Aβ42), total tau (t-tau), and phosphorylatedtau (p-tau), and p-tau:Aβ42 ratio. Results were classified based on interpretation through the Amyloid/Tau/Neurodegeneration (ATN) framework1: 1) AD - biomarker profile consistent with AD pathologic change, 2) non-AD profile - biomarker levels normal or inconsistent with AD pathologic change, or 3) indeterminate - biomarkers were incongruous with only one or two abnormal levels of Aβ42, t-tau, p-tau, or ptau: Aβ42. Indeterminate cases may represent altered protein levels due to CSF dynamics or AD-related pathologic change. In reviewing recent research on CSF dynamics and AD biomarkers in NPH2 a p-tau threshold of 15 pg/mL was derived and implemented such that cases with Aß42 <=1026 pg/mL and p-tau <15 pg/mL were designated as suspected non-AD, and those with Aß42 <=1026 pg/mL and p-tau >15 pg/mL were designated suspected AD. Results: Of the 62 LDT cases, 12 (19.35%) were classified as AD, 31 (50%) were indeterminate and 22 (35.48%) were non-AD. Of the 31 indeterminate cases, 21 (33.87% of the overall sample) were suspected non-AD and 7 (11.29% of the full sample) were categorized as suspected AD. Conclusions: Our findings show that 20%-30% of patients presenting for LDT showed evidence for AD-type pathologic change, consistent with prior reports of AD pathology in cases of possible NPH. Half of all LDT cases had indeterminate AD CSF biomarker results, the interpretations of which were confounded by the potential alterations of CSF biomarkers levels due to NPH independent of AD. Our findings emphasize the need to establish better approaches to interpreting CSF AD biomarkers in evaluating NPH. Future research should examine the discriminative utility of CSF AD biomarkers and the selected p-tau threshold in indeterminate cases for predicting response to LDT and shunting. [ABSTRACT FROM AUTHOR]

Objective: Ventriculoperitoneal (VP) shunting is commonly used to treat normal pressure hydrocephalus (NPH). Assessment of cognition and balance pre- and post-lumbar drain (LD) can be used to provide objective metrics which may help determine the potential benefit of VP shunting. The aim of this investigation was to determine which measures identify clinical change as a result of a LD trial and to develop recommendations for standard NPH clinical assessment procedures. Methods: The Berg Balance Scale (BBS) and a brief battery of commonly used neuropsychological tests pre- and post-LD (MMSE, trail making test, animal fluency, Hopkins Verbal Learning Test – Revised, and digit span) were administered to 86 patients with a diagnosis of NPH. Subjects were divided into groups based on whether or not clinical change was present, and thus, VP shunting was recommended post-LD, and predictors of group membership were examined. Results: Significant improvements (p < 0.05) were seen on the BBS and Trail Making Part B in the VP shunt-recommended group, with no other significant changes over time in either group. Regression analyses found that VP shunt recommendation was accurately predicted for 80% of the sample using the BBS score alone, with accuracy increasing to 85% when Trails B was added. Conclusions: Scores from the BBS and Trails B were most likely to change in those chosen to undergo VP shunting post-LD. Given that the typical clinical presentation of NPH includes gait disturbance and cognitive impairment, it is recommended that a standard pre-/post-LD evaluation include the BBS and trail making test. [ABSTRACT FROM AUTHOR]

Objective: Distinguishing normal pressure hydrocephalus (NPH) from Alzheimer's disease (ad) would aid patient selection for lumbar drain trials (LDT). Cerebrospinal fluid (CSF) ad biomarkers are altered in NPH, limiting interpretation. This study examines the utility of CSF ad biomarkers in predicting gait and cognitive outcomes in patients undergoing LDT. Methods: 127 patients underwent LDT. CSF ad biomarkers from Mayo Clinic Laboratories (MCL) or Athena Diagnostics were used to classify patients as ad, non-ad, or indeterminate. MCL indeterminate results were further classified as suspected ad, non-ad, or suspected NPH (sNPH) using a derived p-tau threshold (>15 pg/mL & Aß42 <=1026 pg/mL)1. Cognitive improvement was determined using reliable change indices for Trail Making Test A&B and Hopkins Verbal Learning Test-Revised. Physical therapists (PT) utilized the Berg Balance Scale and/or the Timed Up and Go to determine gait improvements. Chi-square tests investigated relationships between diagnostic groups, PT and cognitive improvements, and eventual shunting for the whole sample and then stratified by the two laboratory assays. Results: The sNPH group had the highest percentage of PT (63%–70%) and cognitive (9% -11%) improvement (see Table 1), while the ad group had the lowest (50% and 3%, respectively). The sNPH group underwent shunting more (56%–68%) compared to the ad and non-ad groups (47%). Relationships, however, were not statistically significant (p > 0.05). Conclusion: Patients with sNPH CSF ad biomarker profiles demonstrated clinically meaningful physical improvements and underwent shunting more frequently than those with ad or non-ad biomarker profiles. This highlights the potential for CSF ad biomarkers in predicting NPH treatment response. [ABSTRACT FROM AUTHOR]