Suboccipital Puncture

Earn CME/CE in your profession:


Continuing Education Activity

Suboccipital puncture is a procedure that was developed at the beginning of the last century. It was designed to obtain cerebrospinal fluid for diagnostic and therapeutic purposes as an alternative to lumbar puncture. This activity describes suboccipital puncture and explains the role of the interprofessional team in managing patients who undergo a suboccipital puncture. The lateral C1-C2 cervical puncture technique is also described in this activity as it serves the same purpose.

Objectives:

  • Identify the indications for suboccipital puncture and lateral C1-C2 cervical puncture.
  • Describe the technique for suboccipital puncture and lateral C1-C2 cervical puncture.
  • Outline the most common adverse events associated with a suboccipital puncture and lateral C1-C2 cervical puncture.
  • Summarize the risks associated with a suboccipital puncture and lateral C1-C2 cervical puncture.

Introduction

Suboccipital puncture is a procedure that was developed at the beginning of the last century. It was designed to obtain cerebrospinal fluid (CSF) for diagnostic and therapeutic purposes as an alternative to lumbar puncture. It was performed through a midline puncture below the occipital bone. Many years later, the puncture was modified, and it was performed as a lateral C1-C2 cervical puncture. Recently, the suboccipital puncture was popularized but using a lateral trajectory.

In 1908, Obregia performed the first in vivo midline suboccipital puncture.[1][2] His idea was utilized in 1919 by Ionescu to inject general anesthetics. It was also used by Wegeforth, Ayer, and Essick during 1919-1920, which they called a cisterna magna puncture.[1][2][3] On its origins, the suboccipital puncture had many indications, but most of them are out of date. Still, it can be used when the lumbar puncture can not be performed or is contraindicated.[3] It still is currently used for animal experiments to obtain CSF or inject drugs.[4][5][6][7][8][9]

A lateral C1-C2 cervical puncture technique was developed to do percutaneous cervical cordotomy by Mullan et al. in 1962, and by Rosomof et al. in 1965.[10][11][12] The technique was later used in 1975 by Skalpe and Amundsen to perform myelography, and in 1979 by Rice and Bathia.[13][14] With its safer use to obtain CSF and the capacity to perform cervical myelogram, it almost replaced the use of the suboccipital puncture.[15]

Cervical myelography led to the widespread use of the lateral cervical puncture in appropriate cases. Several years later, a controversy was commenced arguing that a cervical injection was not needed to perform a cervical myelogram recognizing that if enough contrast were injected in the lumbar spine by a lumbar puncture, there would be adequate visualization of the entire spine making a lateral cervical puncture or a suboccipital puncture unnecessary.[16] Therefore, the procedure was also forgotten and only used for those cases where there was no lumbar access, or there were contraindications. Although lateral C1–C2 puncture was previously preferred for cervical myelography, most radiologists now prefer a lumbar puncture approach. In 2009, a survey showed that over 85% of neuroradiologists still performed C1-C2 lateral punctures and that over 95% still consider it to be the standard of care for cervical myelography.[17]

In 2017, Gong et al. described a lateral atlantooccipital space puncture (also called lateral cisterna magna puncture), where he performed 1008  procedures in 667 patients.[18] This procedure is similar to the original midline suboccipital puncture, but it is executed using a lateral approach. The method avoids the midline suboccipital puncture and the risks of medulla oblongata puncture. This technique will probably revive the use of the suboccipital puncture.

Both techniques are described in this review; the suboccipital puncture and the cervical C1-C2 puncture. Both should be well known, and on some occasions, one procedure can be used as an alternative to the other.

Anatomy and Physiology

The cisterna magna is formed by the enlarging and expanding subarachnoid space located between the cerebellum and medulla oblongata. It connects directly with the fourth ventricle. The traditional midline cisterna magna puncture is potentially dangerous because the puncture needle directly faces the medulla oblongata.

In most patients, the dorsal subarachnoid space widens at C1–C2 providing a target for access. The cervical spinal cord expands inferior to C2, decreasing the ratio of the cervical spinal canal to the cervical spinal cord area, and making this region suboptimal for obtaining access. The extraspinal vertebral artery V3 segment courses through the C2 transverse foramen ascending through the C1 transverse foramen, and travels posteromedially within a groove on the superior surface of the posterior arch of C1 around the atlantooccipital junction. It then turns anterosuperiorly to enter the dura at the foramen magnum.

The V3 segment often forms a dorsal curve as it emerges from the transverse foramen of C2 before inclining ventrally again to enter the transverse foramen of C1; therefore, it overlies the lateral side of the spinal canal between the first and second cervical vertebrae, usually the anteroinferior quadrant. At C1-2, 72.2% of vertebral arteries lay anterior to the spinal canal. Of the remainder, 19.0% overlay the anterior third, 7.3% the middle third, and 0.9% the posterior third of the canal.[19] The theoretical risk of producing significant vascular injury at lateral cervical puncture is very low, provided the posterior third of the spinal canal is approached. The anterior part of the canal near the superior border of the arch of C2 should particularly be avoided. Slight rotation of the patient away from the side of the puncture is suggested to minimize further the possibility of injuring the vertebral artery (because the artery lies lateral to the canal, it moves anteriorly when there is the rotation of the spine to the opposite side).[19] Anomalous intrathecal arteries at C1-2 lie anterior to the dentate ligament, and therefore will not be endangered by approaching the posterior third of the spinal canal.[14]

The posterior inferior cerebellar artery (PICA) caudal loop extends below the foramen magnum in 14.7%, and below the posterior arch of C1 in 0.6% of patients.[19][20] The PICA is far less likely to be encountered in lateral cervical than a cisternal puncture.[19]

Sometimes, during the development of the vertebral artery, there is the persistence of the first intersegmental artery, which causes the distal vertebral artery to enter the spinal canal between C2 and C1 rather than entering the transverse foramen of C1. This anomaly is called a C2 segmental type vertebral artery. Fenestration of the vertebral artery above and below C1 (duplicated vertebral artery), occurs when the first intersegmental artery persists in combination with the preservation of a distal vertebral artery that enters the C1 transverse foramen; however, this rarely happens.[19]

Indications

Suboccipital puncture and lateral C1-C2 cervical puncture have various therapeutic and diagnostic indications. Following are some important indications a provider may come across:

Suboccipital Puncture

  • Cervical myelography[21][22]
  • Cisternography[23]
  • Ventriculography[24]
  • Intrathecal chemotherapy[25]
  • Intrathecal antibiotics or antifungals
  • Stem cell transplantation[18]
  • Arachnoiditis at the lumbar area
  • Severe lumbar stenosis or ankylosis
  • Spinal dysraphism at the lumbar region, occult or manifest
  • Complete obstruction documented
  • For the definition of the superior margin in a complete block
  • Infection at the lumbar area

Lateral C1-C2 Cervical Puncture

  • Arachnoiditis at the lumbar area
  • Severe lumbar stenosis or ankylosis
  • Spinal dysraphism at the lumbar area, occult or manifest
  • Complete obstruction documented
  • For the definition of the superior margin in a complete block
  • Infection at the lumbar region
  • Intrathecal chemotherapy
  • Intrathecal antibiotics or antifungals
  • Better assessment of the cervical region during a myelogram

Contraindications

Suboccipital puncture is only used rarely. It has various contraindications that are either absolute or relative. Following are some important contraindications a provider must be aware of:

Suboccipital Puncture

  • Craniocervical anomalies
  • Chiari malformation
  • Down syndrome
  • Difficulty assuming head positioning for the procedure
  • Severe cardiopulmonary dysfunction
  • Intracranial space-occupying lesions
  • Evidence of herniation
  • Uncorrectable coagulopathy

Lateral C1-C2 Cervical Puncture

  • Chiari malformation
  • Mass at C1–C2
  • Cervical stenosis at C1–C2
  • Evidence of herniation
  • Uncorrectable coagulopathy
  • Vertebral or PICA variant with vessel crossing the posterior spinal canal at C1–C2
  • Obstructive hydrocephalus
  • Uncooperative patient and low-lying tonsils
  • Achondroplasia
  • C2 pannus with cord compression

Equipment

Suboccipital puncture is a specialized procedure that requires some specialized equipment as follow:

  • Fluoroscopic machine
  • Needle 20-22 gauge needle
  • Local anesthetic medication
  • CSF collection tray (lumbar puncture tray)
  • Myelographic dye (if myelogram indicated)

Personnel

Suboccipital puncture requires a collaborative effort or the following personnel in order to achieve the best outcomes:

  • Neuroradiologist
  • Neurosurgeon
  • Radiation technologist
  • Nurse

Preparation

  1. Review the medical record for indications and contraindications.
  2. Review the current medications and history of contrast agent allergy.
  3. Head imaging must be performed before the procedure in all cases. A head computed tomographic (CT) scan with bone window views is obtained to exclude cervical-occipital junction and problematic skull base bone variants. CT angiography (CTA) or magnetic resonance angiography (MRA) of the neck is performed before deciding whether the procedure is safe to perform. A preliminary CTA or MRA with 3D reconstruction including the skull base, atlantooccipital junction, and upper cervical spine will visualize the vertebral artery V3 segment to exclude arterial variants crossing in the spinal canal at the C1–C2 level at the puncture location.
  4. Coagulation tests performed.
  5. Anticoagulation and antiplatelet medications are withheld according to established guidelines.
  6. Determine if the patient can maintain a cervical extension position.
  7. Determine if the patient can maintain a sitting, supine, prone, or lateral decubitus position.
  8. Local sterilization of the area.

Technique or Treatment

Suboccipital Puncture

The classical technique used by Ayer in 1929 is positioning the patient in lateral decubitus, with slight cervical flexion and inserting the needle in the midline above the posterior spinal arch of the C1 cervical vertebra with a slight cranial inclination until the dura is perforated.[2] In 2004, Pachmann et al. used a prone position with an extended neck fluoroscopic x-ray guidance.[25] A long 21-gauge needle is inserted midline above the posterior spinal arch of the C1 cervical vertebra and aimed at the anterior surface of the dorsal arches of C1. The needle tip is advanced until clear fluid is obtained.

To avoid using the midline puncture, in 2017, Gong et al. developed a lateral technique called lateral atlantooccipital space puncture (also called lateral cisterna magna puncture) with the patient in a supine position.[18] The puncture site is identified 1 cm inferior and 1 cm posterior to the highest point of the mastoid (between the lower edge of the occipital bone and atlas). It does not require fluoroscopic assistance or navigation; however, fluoroscopic guidance can be used while learning the technique. After the sterilization of the area and application of local anesthesia, a 20-gauge needle is entered in the skin at the puncture site. The direction of the puncture is perpendicular to the neck, parallel to a line between both sides of the external auditory canal, and below the occipital bone.

When the needle is advanced, the atlantooccipital posterior membrane is entered first, followed by the perforation of the dura. The puncture depth for adults is 5.5 to 6.5 cm. After the dura is entered, an additional 1 to 2 mm is introduced, and the needle stylet is removed to see if there is CSF outflow or advance slowly until CSF flow is obtained. As needed, CSF is drained or collected, therapeutic drugs are injected, or myelographic dye is injected. When the procedure ends, the needle is withdrawn, and pressure is applied on the puncture site for one minute. During lateral atlantooccipital space puncture, the needle remains just underneath the occipital bone, and no vessels are located in the area. The vertebral artery runs in the sulcus located more posteriorly and medially.

Lateral Cervical C1-C2 Puncture

The lateral C1-C2 technique is performed under fluoroscopic control with the patient in the prone, supine, or lateral decubitus position with the head extended to increase the width of the dorsal subarachnoid space at C1–C2. If the patient is in the supine position, the head must be flexed to prevent the intracranial flow of contrast material. The entry point is marked at the posterior one-third of the spinal canal, approximately 2-5 mm anterior to the spinolaminar line and 4-6 mm inferior to the arch of C1. After area sterilization and application of local anesthesia, a 20 or 22-gauge long spinal needle is entered at the skin at the puncture site. The needle is advanced under intermittent fluoroscopic guidance with the bevel facing dorsally. An anteroposterior image is obtained to check the needle position. When the needle is up to a few millimeters of the medial border of the ipsilateral lateral mass of C1, the stylet is removed to check for CSF return. Dural tenting is expected, and CSF return may not happen until the needle is past the midline. Venous blood is commonly encountered as the needle enters the epidural venous plexus.

After the dura is pierced, an additional 1 to 2 mm is advanced to pierce the arachnoid, and the needle stylet is removed to see if there is CSF outflow. Once CSF flow is verified, the bevel of the needle is rotated either 90°, so the bevel faces toward the patient’s feet or 180 degrees, so it faces ventrally to optimize CSF flow. Manual aspiration is not recommended. As needed, CSF is drained or collected, therapeutic drugs are injected, or myelographic dye is injected. The contrast medium is injected slowly and always under fluoroscopic guidance. The patient’s head position should be adjusted by elevating the head of the table to avoid intracranial flow. When the procedure is finished, the stylet is reinserted, and the needle is withdrawn, and pressure is applied on the puncture site. Semi-sitting or sitting position is stressed while the patient is in bed to drop the contrast agent into the lower thecal sac and reduce post puncture headache.[26][27]

Only a nonionic contrast agent should be used for myelography because ionic contrast agents have significant neurotoxicity. The recommended doses for myelography via C1–C2 puncture are 7–12.5 mL for iohexol 180 mg I/mL, 6 to 12.5 mL for iohexol 240 mg I/mL, and 4 to 10 mL for iohexol 300 mg I/mL.

Complications

Suboccipital puncture and lateral cervical puncture can lead to minor and major complications as these are interventional procedures and require a great deal of expertise. Following are some common complications of these procedures:

Suboccipital Puncture

  • Infection
  • Hemorrhage
  • Post-puncture headache
  • Collection of CSF
  • Neurological injury
  • PICA laceration[28]
  • Oropharyngeal pain due to stimulation of fibers of C1 or superior cervical ganglion to C1[29]

Lateral Cervical Puncture

  • Puncture of the spinal cord producing Lhermitte sign[30][31]
  • Infection
  • Subarachnoid hemorrhage
  • Vertebral artery puncture
  • PICA puncture (rare)
  • Pain at the puncture site
  • Neurological injury
  • Anxiety
  • Headaches
  • Neck spasms
  • CSF leak
  • Nausea

Clinical Significance

Both techniques, the suboccipital puncture, and the cervical C1-C2 puncture should be well known.

On some occasions, one procedure can be used as an alternative to the other.

These procedures, although rarely performed, offer an alternative to obtaining CSF when a lumbar puncture is contraindicated.

The overall rate of adverse reactions with a cervical puncture (4.9%) is slightly higher than that of a lumbar puncture approach (3.4%).[17]

Cervical myelograms performed via lateral C1–C2 puncture produces major complications in less than 0.05%, most commonly associated with cervical spine hyperextension during positioning.[32]

All C1-2 punctures should be monitored with lateral fluoroscopy for accurate needle positioning and prevention of contrast medium injection into the spinal cord.

The frequency of headache after C1–C2 puncture is lower than that after lumbar puncture, and, in most cases, last less than 24 hours. It occurs in approximately 10% to 25% of patients.

Enhancing Healthcare Team Outcomes

Suboccipital puncture and lateral C1-C2 cervical puncture are procedures that can be associated with many serious complications; one of them is vertebral artery damage. Thus it is imperative to evaluate the indications and perform a thorough anatomical assessment of the patient before the procedure. A collaborative approach is an ideal way to limit the complications of this procedure. Before the procedure, the patient should have the following done:

  • Evaluated by the pulmonary and cardiologist to optimize lung and heart function
  • Discuss with the neuroradiologist the pertinent anatomy to prevent complications
  • Be assisted by the nurse for education about the procedure and intraprocedural assistance
  • Seen by the anesthesiologist if sedation is necessary
  • Be consulted by the pharmacist for post-op headache management, antiemetics, and the use of blood thinners if needed

An interprofessional team that provides an integrated approach to pre and postprocedure care can help achieve the best possible outcomes. Collaboration shared decision making, and communication is a crucial element for a good result.


Details

Updated:

8/23/2023 12:39:13 PM

References


[1]

Săceleanu MV, Marinescu AA, Mohan AG, Popescu M, Ciurea AV. Remember the Romanian pioneers: Alexandru Obregia (1860-1937) - first in vivo suboccipital puncture. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie. 2019:60(1):333-336     [PubMed PMID: 31263864]


[2]

DE Souza TFS. Pioneers in the cisterna magna puncture. Arquivos de neuro-psiquiatria. 2020 Mar:78(3):176-178     [PubMed PMID: 32215456]


[3]

Loebe FM. [History and significance of suboccipital puncture]. Psychiatrie, Neurologie, und medizinische Psychologie. 1988 Oct:40(10):617-20     [PubMed PMID: 3070592]


[4]

Semmler A, Smulders Y, Struys E, Smith D, Moskau S, Blom H, Linnebank M. Methionine metabolism in an animal model of sepsis. Clinical chemistry and laboratory medicine. 2008:46(10):1398-402. doi: 10.1515/CCLM.2008.277. Epub     [PubMed PMID: 18844494]

Level 3 (low-level) evidence

[5]

Hinderer C, Bell P, Vite CH, Louboutin JP, Grant R, Bote E, Yu H, Pukenas B, Hurst R, Wilson JM. Widespread gene transfer in the central nervous system of cynomolgus macaques following delivery of AAV9 into the cisterna magna. Molecular therapy. Methods & clinical development. 2014:1():14051. doi: 10.1038/mtm.2014.51. Epub 2014 Dec 10     [PubMed PMID: 26052519]


[6]

Kozler P, Sobek O, Pokorny J. Biochemical manifestations of the nervous tissue degradation after the blood-brain barrier opening or water intoxication in rats. Neuro endocrinology letters. 2016:37(2):114-20     [PubMed PMID: 27179573]

Level 3 (low-level) evidence

[7]

Kozler P, Sobek O, Pokorný J. Signs of myelin impairment in cerebrospinal fluid after osmotic opening of the blood-brain barrier in rats. Physiological research. 2015:64(Suppl 5):S603-8     [PubMed PMID: 26674284]


[8]

Katz N, Goode T, Hinderer C, Hordeaux J, Wilson JM. Standardized Method for Intra-Cisterna Magna Delivery Under Fluoroscopic Guidance in Nonhuman Primates. Human gene therapy methods. 2018 Oct:29(5):212-219. doi: 10.1089/hgtb.2018.041. Epub 2018 Aug 14     [PubMed PMID: 30032644]


[9]

Hordeaux J, Hinderer C, Goode T, Buza EL, Bell P, Calcedo R, Richman LK, Wilson JM. Toxicology Study of Intra-Cisterna Magna Adeno-Associated Virus 9 Expressing Iduronate-2-Sulfatase in Rhesus Macaques. Molecular therapy. Methods & clinical development. 2018 Sep 21:10():68-78. doi: 10.1016/j.omtm.2018.06.004. Epub 2018 Jul 14     [PubMed PMID: 30073178]


[10]

MULLAN S, HARPER PV, HEKMATPANAH J, TORRES H, DOBBIN G. PERCUTANEOUS INTERRUPTION OF SPINAL-PAIN TRACTS BY MEANS OF A STRONTIUM90 NEEDLE. Journal of neurosurgery. 1963 Nov:20():931-9     [PubMed PMID: 14186094]


[11]

MULLAN S, HARPER PV, TANI E, VAILATI G, LATHROP KA. A NUCLEAR NEEDLE FOR USE IN NEUROSURGERY. Journal of neurosurgery. 1963 Nov:20():940-7     [PubMed PMID: 14186095]


[12]

Rosomoff HL, Brown CJ, Sheptak P. Percutaneous radiofrequency cervical cordotomy: technique. Journal of neurosurgery. 1965 Dec:23(6):639-44     [PubMed PMID: 5217032]


[13]

Skalpe IO, Amundsen P. Thoracic and cervical myelography with metrizamide. Clinical experiences with a water-soluble, non-ionic contrast medium. Radiology. 1975 Jul:116(1):101-6     [PubMed PMID: 1138257]


[14]

Rice JF, Bathia AL. Lateral C1-2 puncture for myelography: posterior approach. Radiology. 1979 Sep:132(3):760-2     [PubMed PMID: 472270]


[15]

Zivin JA. Lateral cervical puncture: an alternative to lumbar puncture. Neurology. 1978 Jun:28(6):616-8     [PubMed PMID: 565895]


[16]

Graser C, Kohlmeyer K, Papke M. [Myelography with metrizamide (author's transl)]. Deutsche medizinische Wochenschrift (1946). 1979 Apr 6:104(14):511-4     [PubMed PMID: 436614]


[17]

Yousem DM, Gujar SK. Are C1-2 punctures for routine cervical myelography below the standard of care? AJNR. American journal of neuroradiology. 2009 Aug:30(7):1360-3. doi: 10.3174/ajnr.A1594. Epub 2009 Apr 15     [PubMed PMID: 19369600]


[18]

Gong D, Yu H, Yuan X. A new method of subarachnoid puncture for clinical diagnosis and treatment: lateral atlanto-occipital space puncture. Journal of neurosurgery. 2018 Jul:129(1):146-152. doi: 10.3171/2017.1.JNS161089. Epub 2017 Jul 28     [PubMed PMID: 28753111]


[19]

Cox TC, Stevens JM, Kendall BE. Vascular anatomy in the suboccipital region and lateral cervical puncture. The British journal of radiology. 1981 Jul:54(643):572-5     [PubMed PMID: 7260511]


[20]

Brinjikji W, Cloft H, Kallmes DF. Anatomy of the posterior inferior cerebellar artery: relevance for C1-C2 puncture procedures. Clinical anatomy (New York, N.Y.). 2009 Apr:22(3):319-23. doi: 10.1002/ca.20785. Epub     [PubMed PMID: 19280655]


[21]

Gonsette RE. Cervical myelography with a new resorbable contrast medium: Amipaque. Acta neurologica Belgica. 1976:76(5-6):283-5     [PubMed PMID: 1007892]


[22]

Gonsette RE. Cervical myelography with metrizamide by suboccipital puncture. Acta radiologica. Supplementum. 1977:355():121-6     [PubMed PMID: 299660]


[23]

Emde H, Huber G, Piepgras U. [Cisternography with 111Indium-DTPA (author's transl)]. Der Radiologe. 1977 Nov:17(11):471-7     [PubMed PMID: 579455]


[24]

Petkov S, Kitov D, Mironov A. [Retrograde positive ventriculography by sub-occipital catheterization of the ventricular system (author's transl)]. Acta neurochirurgica. 1978:41(4):327-33     [PubMed PMID: 308295]


[25]

Pachmann S, Bruning R, Schaffer M, Dühmke E. Suboccipital lateral injection of intrathecal chemotherapy in a patient with mantle cell lymphoma. Onkologie. 2004 Feb:27(1):68-71     [PubMed PMID: 15007252]


[26]

Orrison WW, Eldevik OP, Sackett JF. Lateral C1-2 puncture for cervical myelography. Part III: Historical, anatomic, and technical considerations. Radiology. 1983 Feb:146(2):401-8     [PubMed PMID: 6687370]


[27]

Daniels SP, Schweitzer AD, Baidya R, Krol G, Schneider R, Lis E, Chazen JL. The Lateral C1-C2 Puncture: Indications, Technique, and Potential Complications. AJR. American journal of roentgenology. 2019 Feb:212(2):431-442. doi: 10.2214/AJR.18.19584. Epub 2018 Dec 4     [PubMed PMID: 30512994]


[28]

Portela LA, Souza V, Pahl FH, Cardoso AC, Vellutini Ede A, Mutarelli EG, Machado Ldos R, Livramento JA. Laceration of the posterior inferior cerebellar artery by suboccipital puncture of the cisterna magna: case report. Arquivos de neuro-psiquiatria. 2004 Sep:62(3B):882-4     [PubMed PMID: 15476089]

Level 3 (low-level) evidence

[29]

Rossitti SL, Araújo JF, Zuiani AR, Balbo RJ. [Pharyngeal pain during lateral suboccipital puncture]. Arquivos de neuro-psiquiatria. 1989 Jun:47(2):182-6     [PubMed PMID: 2597009]


[30]

Rossitti SL, Balbo RJ. [Lhermitte's sign during lateral cervical puncture: survey of possible accidents in the lateral C1-C2 puncture and report of 2 cases of spinal cord penetration]. Arquivos de neuro-psiquiatria. 1990 Sep:48(3):341-7     [PubMed PMID: 2264789]

Level 3 (low-level) evidence

[31]

Johansen JG,Orrison WW,Amundsen P, Lateral ral C1-2 puncture for cervical myelography. Part I: Report of a complication. Radiology. 1983 Feb;     [PubMed PMID: 6687368]


[32]

Robertson HJ, Smith RD. Cervical myelography: survey of modes of practice and major complications. Radiology. 1990 Jan:174(1):79-83     [PubMed PMID: 2294575]

Level 3 (low-level) evidence