A protocol to reduce self-reported pain scores and adverse events following lumbar punctures in older adults

Nobuhara, Chloe K.; Bullock, W. Michael; Bunning, Thomas; Colin, Brian J.; Cooter, Mary; Devinney, Michael J.; Ferrandino, Michael N.; Gadsden, Jeff; Garrigues, Grant E.; Habib, Ashraf S.; Moretti, Eugene W.; Moul, Judd W.; Ohlendorf, Brian; Sandler, Adrian D.; Scheri, Randall P.; Sharma, Bharat; Thomas, John P.; Young, Christopher C.; Mathew, Joseph P.; Berger, Miles; Madco-Pc,; Teams, Intuit Investigators

doi:10.1007/s00415-020-09797-1

Cited by 17 publications

(20 citation statements)

References 20 publications

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“…Other studies have reported moderate to severe headache rates ranging from 2.5% –9% and overall adverse event rates up to 22.3%, much of which were mild [ 3–5, 7, 27 ]. A recent analysis of LP techniques and associated symptoms found a low total adverse event rate of 2.72% (0.49% post-LP headache; 0.74% low back pain; 1.48% vasovagal response or mild headache) when following much of the current evidence-based methodology (seated position, use of L4-5 interspace, standardized atraumatic needle use, aspiration method) in addition to use of topical benzocaine prior to lidocaine injection, timed waiting period following lidocaine injection and benzocaine application, and ultrasound use for select patients [ 8 ]. Other studies have also indicated use of ultrasound to assist LP is associated with less pain and an increase in the number of successful procedures [ 28, 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, LPs are less expensive, less time-consuming to perform, can be readily obtained in clinical settings, and provide information regarding both amyloid and tau, as well as other features of the AD pathological cascade such as neurodegeneration and gliosis [2]. Further, LPs have been established as a safe, well-tolerated procedure with minimal risk and adverse side effects, especially when performed with atraumatic, smaller-gauge Sprotte needles to collect less than 30 mL of CSF with the participant in a seated position [3][4][5][6][7][8].…”

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confidence: 99%

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Factors Associated with Lumbar Puncture Participation in Alzheimer’s Disease Research

Blazel¹,

Lazar²,

Hulle³

et al. 2020

JAD

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Background: Cerebrospinal fluid (CSF) provides insight into the spectrum of Alzheimer’s disease (AD) pathology. While lumbar punctures (LPs) for CSF collection are generally considered safe procedures, many participants remain hesitant to participate in research involving LPs. Objective: To explore factors associated with participant willingness to undergo a research LP at baseline and follow-up research study visit. Methods: We analyzed data from 700 participants with varying cognition (unimpaired, mild cognitive impairment, and dementia) in the Wisconsin Alzheimer’s Disease Research Center. We evaluated the relationship of demographic variables (age, sex, race, ethnicity, and years of education) and clinical variables (waist-to-hip ratio, body mass index, AD parental history, cognitive diagnosis) on decision to undergo baseline LP1. We evaluated the relationship of prior LP1 experience (procedure success and adverse events) with the decision to undergo follow-up LP2. The strongest predictors were incorporated into regression models. Results: Over half of eligible participants opted into both baseline and follow-up LP. Participants who underwent LP1 had higher mean education than those who declined (p = 0.020). White participants were more likely to choose to undergo LP1 (p < 0.001); 33% of African American participants opted in compared to 65% of white participants. Controlling for age, education, and AD parental history, race was the only significant predictor for LP1 participation. Controlling for LP1 mild adverse events, successful LP1 predicted LP2 participation. Conclusion: Race was the most important predictor of baseline LP participation, and successful prior LP was the most important predictor of follow-up LP participation.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Factors Associated with Lumbar Puncture Participation in Alzheimer’s Disease Research

Blazel¹,

Lazar²,

Hulle³

et al. 2020

JAD

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“…CSF samples were obtained at a baseline study visit ≤ 1 month prior to surgery, and 24 h and 6 weeks after surgery. Lumbar punctures were performed as described 19 , 20 using a 25-gauge pencil point spinal needle. A 10-mL polypropylene syringe was used to aspirate CSF from the spinal needle prior to placing the CSF into a 15-mL centrifuge tube (VWR, Radnor, PA, USA; catalog No 10025-686) pre-chilled to 4 °C.…”

Section: Methodsmentioning

confidence: 99%

Immunomodulatory lipid mediator profiling of cerebrospinal fluid following surgery in older adults

Terrando

Park

Devinney

et al. 2021

Sci Rep

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Arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) derived lipids play key roles in initiating and resolving inflammation. Neuro-inflammation is thought to play a causal role in perioperative neurocognitive disorders, yet the role of these lipids in the human central nervous system in such disorders is unclear. Here we used liquid chromatography–mass spectrometry to quantify AA, DHA, and EPA derived lipid levels in non-centrifuged cerebrospinal fluid (CSF), centrifuged CSF pellets, and centrifuged CSF supernatants of older adults obtained before, 24 h and 6 weeks after surgery. GAGE analysis was used to determine AA, DHA and EPA metabolite pathway changes over time. Lipid mediators derived from AA, DHA and EPA were detected in all sample types. Postoperative lipid mediator changes were not significant in non-centrifuged CSF (p > 0.05 for all three pathways). The AA metabolite pathway showed significant changes in centrifuged CSF pellets and supernatants from before to 24 h after surgery (p = 0.0000247, p = 0.0155 respectively), from before to 6 weeks after surgery (p = 0.0000497, p = 0.0155, respectively), and from 24 h to 6 weeks after surgery (p = 0.0000499, p = 0.00363, respectively). These findings indicate that AA, DHA, and EPA derived lipids are detectable in human CSF, and the AA metabolite pathway shows postoperative changes in centrifuged CSF pellets and supernatants.

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“…Repeat CSF samples were obtained 24 ± 2 hours after the start of surgery and 6 ± 3 weeks after surgery [34,44]. CSF was collected using our protocol for minimizing pain and adverse events associated with lumbar puncture [41,45]. Brie y, participants' lower backs were scrubbed with sterile iodine, and 20% benzocaine was applied by spray canister.…”

Section: Csf and Blood Sample Collectionmentioning

confidence: 99%

“…Subsequently, a 25-gauge spinal needle was inserted through 20-gauge introducers at the same interspace to extract approximately 10 mL of CSF using aseptic techniques. The puncture site was then covered with a bandage, and the patient was instructed to remain supine for at least 30 minutes to minimize the risk of post-dural puncture headache [45].…”

Section: Csf and Blood Sample Collectionmentioning

confidence: 99%

Cerebrospinal Fluid Proteomic Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction

VanDusen

et al. 2020

Preprint

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Background: Postoperative cognitive dysfunction (POCD) is a syndrome of cognitive deficits that occurs in 10-40% of patients age > 60 within 1-12 months after surgery, hypothesized to be caused in part by neuroinflammation. However, the specific neuroinflammatory pathways involved remain unclear. Unbiased mass spectrometry-based proteomic analyses have been used to identify neuro-inflammatory pathways in multiple neurologic diseases and syndromes but have not yet been used in the POCD field. Thus, we used unbiased mass spectrometry-based proteomics to compare cerebrospinal fluid (CSF) samples from patients with and without POCD to identify potential neuroinflammatory pathways for further investigation in future studies. Methods: We performed unbiased LC-MS/MS proteomics on immunodepleted CSF samples obtained before, 24 hours, and 6 weeks after major non-cardiac surgery in older adults who developed (n=8) or did not develop POCD (n=6). General linear mixed models were used to identify peptides and proteins with intensity differences between groups or over time by groups. Kyoto Encyclopedia of Genes and Genomes analysis was used to identify pathways containing proteins/peptides with q values < 0.25 in the mixed model. Results: Mass spectrometry quantified 8258 peptides from 1222 proteins in >50% of patient samples at all three time points. Twelve peptides from 11 proteins showed differences in expression over time between groups (POCD vs non-POCD) at q < 0.05, including several from proteins previously implicated in neurodegenerative disease pathophysiology. Additionally, 283 peptides from 182 proteins were identified with trend-level differences (q < 0.25) in expression over time between these patient groups. Of these 283 peptides with trend-level significance, pathway analysis revealed that 50 of them were from 17 proteins that mapped to the complement and coagulation pathways (q=2.44*10-13).Conclusions: These data demonstrate the feasibility of performing unbiased mass spectrometry on perioperative CSF samples to identify peptides, proteins, and pathways associated with POCD. Additionally, they provide hypothesis-generating evidence for CSF complement and coagulation pathway changes in patients with POCD.

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A protocol to reduce self-reported pain scores and adverse events following lumbar punctures in older adults

Cited by 17 publications

References 20 publications

Factors Associated with Lumbar Puncture Participation in Alzheimer’s Disease Research

Factors Associated with Lumbar Puncture Participation in Alzheimer’s Disease Research

Immunomodulatory lipid mediator profiling of cerebrospinal fluid following surgery in older adults

Cerebrospinal Fluid Proteomic Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction

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