Understanding the Collection of Cerebrospinal Fluid

CSF Biomarkers are Part of a Comprehensive Analysis Cerebrospinal fluid (CSF) biomarker data can be used as supplemental information to cognitive evaluations and mental exams to help clinicians decipher their patient’s neurological symptoms. Amyloid PET (Positron Emission Tomography) is another method to detect for the presence of amyloid deposits in the brain, however this technology is associated with patient exposure to radiation, high cost, long turnaround times, and limited access for patients. CSF biomarker testing could offer a safe, fast, inexpensive method to provide clinicians with supplemental and valuable biomarker data by utilizing the current blood testing workflow and network of laboratories.

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What is CSF • Cerebrospinal fluid (CSF) is a clear, colorless liquid surrounding the brain and spinal cord1,2 • It protects the brain from trauma, supplies nerve cells with nutrients, and clears waste away from the brain • The total volume in adults is approximately 150 mL • It is produced continuously in large quantities at approximately 20 mL per hour

CSF Collection Procedure • CSF is collected by inserting a needle in the subarachnoid space located below the end of the spinal cord between the third and fourth or fourth and fifth lumbar vertebrae • The collection procedure is referred to as CSF collection or lumbar puncture (LP) • It is a safe and standard medical procedure performed by trained health care providers for diagnosis of suspected meningitis, subarachnoid hemorrhage, and multiple sclerosis. LPs are performed for spinal anesthesia and for treatment purposes using intrathecal drug administration3, 4, 5 • Explain the procedure and value of CSF biomarkers to the patient • Position the patient in either a sitting position or lateral recumbent position (recommended) • Disinfect the site using standard procedures • LP may be performed with or without local anesthetics • Introduce the needle with the bevel parallel to dura fibers • Collect in recommended polypropylene tubes • Once the fluid is collected, remove needle and apply sterile dressing • Send CSF to a diagnostic testing site

Lumbar Puncture

LATERAL RECUMBENT POSITION

SITTING POSITION

Benefits of CSF Biomarkers to the Patient They may help to determine the cause of memory complaints. Doctors may use this information to determine abnormal levels of β-amyloid and tau. These proteins may help distinguish AD from normal aging or other brain conditions.7

Potential Patient Objections Regarding CSF Collection REFUSAL DUE TO CONCERNS REGARDING COMPLICATIONS FROM LP • Explain the procedure and the prognostic value of CSF biomarkers and AD • Refer patient to a center that performs LPs routinely • Describe the procedure as a safe technique with minimal side effects3, 6

“LP IS A DIFFICULT TECHNIQUE” • LP is performed routinely to diagnose other neurological conditions and is performed by highly trained health care professionals

LP REQUIRES A SPECIALIZED FACILITY AND EQUIPMENT • LP can be performed in any outpatient center or hospital using standard medical equipment4, 5

COST MAY BE OF CONCERN • The cost of LP is low in comparison to other diagnostic procedures, such as PET imaging1

“THE PROCEDURE WILL BE PAINFUL” • Local anesthetics can be given at the collection area during the procedure3

POTENTIAL SIDE EFFECTS • Doctors are trained to use special techniques to lower the risk of side effects • The most common is a headache. Typically mild in most cases and usually resolves without treatment, and is usually resolved by lying down3, 6

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1. Blennow K, Winblad B, Andreasen N. Cerebrospinal Fluid Biomarkers as Diagnostic Tools in Alzheimer’s Disease. High Wycombe, UK: Alpha-Plus Medical Communications Ltd; 2010. 2. Sakka L, Coll G, Chazal J. Anatomy and physiology of cerebrospinal fluid. Eur Ann Otorhinolaryngol Head Neck Dis. 2011; 128(6):309-316. 3. Engelborghs S, Niemantsverdriet E, Struyfs H, et al. Consensus guidelines for lumbar puncture in patients with neurological diseases. Alzheimer’s Dement (Amst). 2017; 8:111-126. 4. Wright BL, Lai JT, Sinclair AJ. Cerebrospinal fluid and lumbar puncture: A practical review. J Neurol. 2012; 259(8):1530-1545. 5. Mayo Clinic. Tests and procedures: lumbar puncture (spinal tap). http://www.mayoclinic.org/tests-procedures/ lumbar-puncture/basics/definition/prc-20012679. Accessed May 1, 2017. 6. Duits FH, Martinez-Lage P, Paquet C, et al. Performance and complications of lumbar puncture in memory clinics: results of the multicenter lumbar puncture feasibility study. Alzheimer’s Dement. 2016; 12(2):154-163. 7. Lewczuk P, et al. Clinical significance of fluid biomarkers in Alzheimer’s Disease. Pharmacological Reports (2020); 72:528-542.

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