Treatment of the Craniocervical Junction – Regenerative Therapy

(Also known as the PICL procedure, which treats both the posterior and anterior ligaments and joints)

What is the Craniocervical Junction (CCJ)?

The craniocervical junction (CCJ) is the region where the base of the skull meets the upper cervical vertebrae (C0–C1–C2). This zone allows head movement, protects the brainstem, and contains important blood vessels and nerves.
However, due to trauma, poor posture, joint degeneration, autoimmune disease, or connective tissue weakness, it may become unstable, causing various symptoms.

What is the CCJ, and why can it become unstable?

The CCJ is the most mobile part of the neck. It includes the atlanto-occipital (AO) and atlantoaxial (AA) joints, which allow head flexion, extension, side bending, and rotation. The central ligaments — such as the alar, apical, and cruciform ligaments — stabilize the odontoid process (dens) of C2 to prevent it from shifting toward the spinal cord.

Instability occurs when these ligaments become lax or injured. This can happen suddenly (e.g., in a car accident, even at low speeds below 20 km/h) or gradually (e.g., from poor posture while sitting at a computer).
Risk factors: female gender, long and slender neck, low headrest during a car crash, autoimmune disease (e.g., rheumatoid arthritis), or genetic predisposition (e.g., Ehlers–Danlos syndrome).

When the ligaments are loose, the joints move excessively — a condition called microinstability. Muscles compensate by tightening, which can cause spasms, pain, nerve compression (e.g., occipital nerve), and later arthritis. Over time, this may lead to nerve inflammation or spinal canal narrowing.

How is Craniocervical Instability (CCI) diagnosed?

Diagnosis is primarily based on medical history and symptoms, as these provide the most relevant information. For example, it is important to determine whether the symptoms (neck pain, headache, dizziness, fatigue) appeared suddenly after trauma or developed gradually. Certain antibiotics may also contribute to ligament injury.
During the physical examination, neck movement, muscle tension, painful trigger points, and possible neurological signs (numbness, weakness) are evaluated.
Imaging studies such as X-ray, MRI, or CT play a secondary role since they often fail to detect instability. They are mainly used to rule out other conditions such as tumors or fractures. Their sensitivity and specificity are limited, so findings must always be interpreted together with the patient’s symptoms.
Dynamic studies (e.g., flexion–extension or rotational MRI, CT, or DMX) are becoming more common, as both physicians and patients seek a more precise diagnosis. However, experts still lack consensus on standard diagnostic criteria.
There are clear cases where CCI can be confirmed, but it cannot always be completely ruled out.
At our clinic, we collaborate closely with radiologists, and dynamic MRI evaluation is available and interpreted by experienced specialists.

We perform a cervical functional examination at our clinic in neutral, flexion, extension, and lateral flexion positions This provides diagnostic information comparable to a Digital Motion X-ray (DMX) video exam. This examination involves capturing static fluoroscopic images at neutral, mid-range, and end-range positions of the cervical spine. These specific positions typically yield sufficient data to assess cervical instability, such as C1–C2 overhang or abnormal translation, with significantly lower radiation exposure than continuous DMX. A continuous DMX exam (video, 3 minutes) delivers an estimated effective dose of 0.9–5.4 mSv, whereas acquiring 10 static fluoroscopic images (as described) results in a substantially lower dose of 0.015–0.09 mSv, approximately 1–10% of the DMX dose, due to the reduced exposure time (approximately 3 seconds total vs. 180 seconds).

Nevertheless, the diagnosis of nonsurgical CCI currently relies far more on history and physical examination than on imaging, as there is not enough data to clearly demonstrate the line between normal and abnormal.

More details on imaging

What “micro-instability” at the upper neck means

Ligament looseness around the top of the spine, especially where the skull meets the first two neck bones (the craniocervical junction, CCJ), can make the area a little too mobile without showing a clear break or a big joint slip. Standard red-flag X-ray rules—like the ADI, BAI, BDI, and Powers ratio—are good at spotting obvious instability, but they can miss subtle, soft-tissue injuries (“discoligamentous” injuries). Some injuries only show up later, not right after the event (Mayer 2013 [14]).

What MRI and CT can and can’t tell you

  • MRI is best for seeing ligaments themselves. It can show if a ligament is continuous or looks swollen or “bright,” which suggests irritation or edema. Sequences often used: proton density, T1 3D VIBE, and STIR (Mantripragada 2020 [13]; Ulbrich 2012 [10]).
  • Studies have found more bright signal in key CCJ ligaments (alar and transverse) in some whiplash patients than in healthy volunteers (Krakenes 2001 [2], 2006 [5]).
  • But this is not black-and-white. A prospective study reported that people with chronic neck pain (not necessarily whiplash) had more of these bright spots, and they didn’t change over a year—so the signal may not always equal a new trauma injury (Vetti 2011 [8]). It is certainly possible that chronic overuse leads to cervical instability, but in such cases, establishing a diagnosis is less straightforward.
  • CT is excellent for bone detail. It can show measurements like the lateral atlantodental interval (LADI). In trauma patients who had an asymmetric LADI on CT but no other neck injury, MRI helped only when the patient also had symptoms. In patients without symptoms, “abnormalities” often turned out to be normal variation, risking overtreatment (Endler 2021 [4])

Why single measurements can mislead

  • Plain X-rays are two-dimensional. Overlapping anatomy can fake a problem. Example: on the open-mouth view, the atlas can look “offset” just because the head is slightly rotated.
  • Population studies show that some things once labeled “pathologic” can appear in healthy people, like an asymmetric LADI or apparent odontoid–lateral mass differences driven by head tilt rather than injury (Chen 2011 [6]; Guenkel 2015 [3]).
  • Bottom line: there’s overlap between normal and abnormal. Context matters.

The “Rule of Spence” and newer evidence

  • The classic rule says: in C1 fracture (Jefferson) the combined lateral mass displacement on the open-mouth view is >7 mm, assume the transverse atlantal ligament (TAL) is torn.
  • Modern work shows TAL failure can happen at much smaller displacements. Cadaver tests found TAL failures around ~3 mm (Woods 2017 [11]). CT-flexion models showed that increases in ADI after TAL injury were more sensitive than lateral overhang (Perez-Orribo 2016 [15,16]). Relying on the old rule alone can miss real injuries (Park 2015 [7]).
  • Some accepted cutoffs (e.g., ADI, BDI) look too generous compared with CT-based norms (Rojas 2007 [9]).

Motion studies: when “how it moves” matters

  • Classic work set normal ranges for how each neck level moves on flexion–extension X-rays and showed that routine films may underestimate instability in whiplash (Panjabi & Dvorak 1988 [12]).
  • Videofluoroscopy (DMX) can track small translations and angles over time. It has shown that even small abnormal slides can be clinically relevant (Wu 2007 [1]).
  • Caveat: dynamic tests depend heavily on technique, positioning, and who measures them. Inter-observer differences are real.

Practical takeaways for patients

  • No single test proves or rules out subtle CCJ instability.
  • MRI helps see ligament condition, but bright signals are not always fresh tears.
  • CT and X-ray measurements are useful, but some “abnormal” numbers show up in healthy people.
  • Dynamic imaging (flexion–extension X-rays, dynamic CT/MRI, DMX) can reveal micro-instability, but results must be read with caution.
  • The most reliable approach is to match imaging with symptoms and exam findings, and to avoid both under- and overtreatment.

References:

  1. Shyi-Kuen Wu, Li-Chieh Kuo, Haw-Chang H. Lan, Sen-Wei Tsai, Chiung-Ling Chen, Fong-Chin Su – The quantitative measurements of the intervertebral angulation and translation during cervical flexion and extension – Eur Spine J (2007) 16:1435–1444, DOI 10.1007/s00586-007-0372-4; Received: 26 September 2006 / Revised: 26 February 2007 / Accepted: 31 March 2007 / Published online: 27 April 2007 _ Springer-Verlag 2007
  2. J. Krakenes, B. R. Kaale, G. Moen, H. Nordli, N.E. Gilhus, J. Rorvik – MRI assessment of the alar ligaments in the late stage of whiplash injury – a study of structural abnormalities and observer agreement – Neuroradiology (2002) 44: 617–624, DOI 10.1007/s00234-002-0799-6, Received: 15 October 2001 Accepted: 22 January 2002 Published online: 8 June 2002 _ Springer-Verlag 2002
  3. S. Guenkel, M. J. Scheyerer, G. Osterhoff, G. A. Wanner, H.‑P. Simmen,·C. M. L. Werner – It is the lateral head tilt, not head rotation, causing an asymmetry of the odontoid‑lateral mass interspace – Eur J Trauma Emerg Surg, DOI 10.1007/s00068-015-0602-0, Received: 16 July 2015 / Accepted: 16 November 2015 © Springer-Verlag Berlin Heidelberg 2015
  4. Christoph H. Endler, MD* • Daniel Ginzburg, MD* • Alexander Isaak, MD • Anton Faron, MD • Narine Mesropyan, MD • Daniel Kuetting, MD • Claus C. Pieper, MD • Patrick A. Kupczyk, MD • Ulrike I. Attenberger, MD • Julian A. Luetkens, MD – Diagnostic Benefit of MRI for Exclusion of Ligamentous Injury in Patients with Lateral Atlantodental Interval Asymmetry at Initial Trauma CT, Radiology 2021; 300:633–640 • https://doi.org/10.1148/radiol.2021204187
  5. Jostein Krakenes, MD, PhD,* and Bertel R. Kaale, MT† – Magnetic Resonance Imaging Assessment of Craniovertebral Ligaments and Membranes After Whiplash Trauma – SPINE Volume 31, Number 24, pp 2820 –2826, ©2006, Lippincott Williams & Wilkins, Inc.
  6. Yuchun Chen • Zerui Zhuang • Weili Qi •Haiying Yang • Zhenping Chen • Xinjia Wang • Kangmei Kong – A three-dimensional study of the atlantodental interval in a normal Chinese population using reformatted computed tomography – Surg Radiol Anat (2011) 33:801–806, DOI 10.1007/s00276-011-0817-7, Received: 9 November 2010 / Accepted: 25 April 2011 / Published online: 6 May 2011, Springer-Verlag 2011
  7. Heui-Jeon Park, MD, PhD , Dong-Gune Chang, MD, PhD, Jong-Beom Park, MD, PhD, Whoan Jeang Kim, MD, PhD , Kyung-Jin Song, MD, PhD , Woo-Kie Min, MD, PhD, Seung Chan Park, MD . Radiologic criteria to predict injury of the transverse atlantal ligament in unilateral sagittal split fractures of the C1 lateral mass – Park et al. Medicine (2019) 98:36
  8. N. Vetti, J. Kråkenes, T. Ask, K.A. Erdal, M.D.N. Torkildsen, J. Rørvik, N.E. Gilhus, A. Espeland – Follow-Up MR Imaging of the Alar and Transverse Ligaments after Whiplash Injury: A Prospective Controlled Study – AJNR Am J Neuroradiol 32:1836 – 41 / Nov 2011 / www.ajnr.org
  9. C.A. Rojas, J.C. Bertozzi, C.R. Martinez, J. Whitlow – Reassessment of the Craniocervical Junction: Normal Values on CT – AJNR Am J Neuroradiol 28:1819 –23 / Oct 2007 / www.ajnr.org
  10. Erika Jasmin Ulbrich, Sandra Eigenheer, Chris Boesch, Juerg Hodler, André Busato, Christian Schraner, Suzanne E. Anderson, Harald Bonel, Heinz Zimmermann, Matthias Sturzenegger – Alterations of the Transverse Ligament: An MRI Study Comparing Patients With Acute Whiplash and Matched Control Subjects – Musculoskeletal Imaging • Original Research
  11. Rafeek O. Woods, MD, Serkan Inceoglu, PhD , Yusuf T. Akpolat, MD, Wayne K. Cheng, MD, Brice Jabo, MD, MPH, Olumide Danisa, MD – C1 Lateral Mass Displacement and Transverse Atlantal Ligament Failure in Jefferson’s Fracture: A Biomechanical Study of the “Rule of Spence” – www.neurosurgery-online.com / Copyright C© 2017 by the Congress of Neurological Surgeons /RESEARCH—LABORATORY / NEUROSURGERY / VOLUME 0 | NUMBER 0 | 2017 |
  12. J. DVORAK, MD, D. FROEHLICH, MD, L. PENNING, MD,† H. BAUMGARTNER, MD, and M. M. PANJABI, PhD – Functional Radiographic Diagnosis of the Cervical Spine: Flexion/Extension – SPINE, VOLUME 13, NUMBER 7, 1988 / RADIOGRAPHIC DIAGNOSIS DROVAK ET AL / Accepted for publication February 22, 1988
  13. Sravanthi Mantripragada, Anbalagan Kannivelu and Wilfred CG Peh – Magnetic resonance imaging of cervical ligamentous anatomy and traumatic ligamentous injuries – Journal of Medical Imaging and Radiation Oncology (2020) Submitted 5 November 2019; accepted 6, February 2020., doi:10.1111/1754-9485.13016– © 2020 The Royal Australian and New Zealand College of Radiologists
  14. M. Mayer • J. Zenner • A. Auffarth • M. Blocher • M. Figl • H. Resch • H. Koller – Hidden discoligamentous instability in cervical spine injuries: can quantitative motion analysis improve detection? – Eur Spine J, DOI 10.1007/s00586-013-2854-x, Received: 13 May 2012 / Revised: 5 November 2012 / Accepted: 3 June 2013 _ Springer-Verlag Berlin Heidelberg 2013
  15. Luis Perez-Orribo, MD , PhD,1 Laura A. Snyder, MD ,2 Samuel Kalb, MD ,2 Ali M. Elhadi, MD ,2 Forrest Hsu, MD ,2 Anna G. U. S. Newcomb, MS ,1 Devika Malhotra, BA ,1 Neil R. Crawford, PhD,1 and Nicholas Theodore, MD 2 – Comparison of CT versus MRI measurements of transverse atlantal ligament integrity in craniovertebral junction injuries. Part 1: A clinical study – J Neurosurg Spine February 26, 2016
  16. Luis Perez-Orribo, MD , PhD,1 Samuel Kalb, MD ,2 Laura A. Snyder, MD ,2 Forrest Hsu, MD ,2 Devika Malhotra, MD ,1 Richard D. Lefevre, BS ,1 Ali M. Elhadi, MD ,2 Anna G. U. S. Newcomb, MS ,1 Nicholas Theodore, MD ,2 and Neil R. Crawford, PhD1 – Comparison of CT versus MRI measurements of transverse atlantal ligament integrity in craniovertebral junction injuries. Part 2: A new CT-based alternative for assessing transverse ligament integrity – J Neurosurg Spine February 26, 2016

What symptoms can CCJ instability cause?

Symptoms vary and may mimic other disorders such as fibromyalgia or vestibular (balance) problems. Common complaints include:

  • Headache at the back of the head radiating to the forehead, eyes, or ears (cervicogenic headache, often one-sided, sharp, or throbbing)
  • Neck pain, stiffness, muscle tension (especially in neck and shoulder muscles), shoulder pain
  • Dizziness, tinnitus (ringing in the ears), blurred vision, “brain fog” (difficulty concentrating, forgetfulness)
  • Fatigue and fibromyalgia-like pain throughout the body
  • Other symptoms: palpitations, digestive issues, hot flashes, nausea (possibly due to vagus nerve involvement)
  • In more severe cases: difficulty holding the head upright, transient weakness or numbness affecting the entire body; rarely, eye movement disturbance or tongue deviation

Ligamentous laxity in the neck often causes microinstability, which over time leads to muscle spasm, headaches, and nerve entrapment.

How does regenerative treatment work?

The goal of regenerative (restorative) medicine is to activate the body’s natural healing processes.
The treatment uses biologic materials such as platelet-rich plasma (PRP) or bone marrow concentrate (BMC), which promote:

  • new collagen formation
  • strengthening of ligaments and joint capsules
  • improved blood circulation and oxygen supply
  • restoration of neck balance and proprioception (sense of position)

The goal is to restore ligament stability in the neck, thereby reducing pain and improving head–neck coordination.

What are the treatment options for CCI?

Low grade instability (WAD 0) typically responds well to physical therapy.

Severe CCI  (WAD 3-4) typically requires neurosurgical intervention to prevent permanent disability and nerve damage.

Cases in between (WAD grade 1-3) patients typically have difficulty finding diagnosis and treatment. These patients may be treated with regenerative medicine, although there is no consensus in the medical literature.

How does regenerative treatment work?

The goal of regenerative (restorative) medicine is to activate the body’s natural healing processes.
The treatment uses biologic materials such as platelet-rich plasma (PRP)  or bone marrow concentrate LINK TO https://fajdalomklinika.hu/en/treatments/stem-cell-treatment/)which promote:

  • new collagen formation
  • strengthening of ligaments and joint capsules
  • improved blood circulation and oxygen supply
  • restoration of neck balance and proprioception (sense of position)

The goal is to restore ligament stability in the neck, thereby reducing pain and improving head–neck coordination.

Also read: https://fajdalomklinika.hu/kezelesek/prp-regeneralo-injekcios-kezeles/

When is CCJ regenerative treatment recommended?

  • Craniocervical instability
  • Cervicogenic headache (neck-related headache)
  • Whiplash-associated disorders (WAD grades 1–3)
  • Chronic neck pain not responding to other treatments (in some cases, lower cervical treatment alone may suffice)

What happens during the procedure?

The intervention is minimally invasive and performed under image guidance (X-ray and ultrasound).
The specialist precisely targets the unstable region (e.g., AO or AA joints, ligament complex) and injects small amounts of PRP or BMC.

  • AO/AA joints and posterior ligaments: performed under sedation, patient lies prone with the neck flexed; needle placement is confirmed by fluoroscopy and contrast (DSA) to ensure no vascular uptake before injecting PRP/BMC.
  • MAA LC (median atlantoaxial ligament complex): performed under general anesthesia, patient lies supine with the mouth open, airway protected with a specialized device.
  • Lower cervical joints: treated similarly with small injection volumes.

After the procedure, mild soreness, stiffness, or swelling may occur for a few days — these are normal healing responses.

How many treatments are needed?

The number of sessions varies individually, but 2–4 treatments are typically sufficient.
Each session is spaced 4–6 weeks apart to allow tissue regeneration.

What results can be expected?

Pain and instability usually decrease gradually.
Most patients report significant improvement after 2–3 sessions, along with better daily function.
In the long term, the treatment leads to improved cervical stability and reduction of headaches and related symptoms.

What does science say about this treatment?

Regenerative medicine is an area of growing international interest, with a rapidly expanding body of scientific evidence.
Multiple high-level (“Level 1”) clinical studies have confirmed that treatments such as bone marrow concentrate (BMC), platelet-rich plasma (PRP), and prolotherapy are effective for joint disorders, especially knee osteoarthritis.
Similarly, PRP and prolotherapy are well-established for tendinopathies such as tennis elbow.
Level 1 studies also support the use of BMC and PRP for lumbar disc and facet joint pain. Although fewer studies focus on the cervical spine, case series already suggest that orthobiologic (regenerative) therapies hold promise in this area as well.
The C0–C1–C2 transoral approach is not yet described in the medical literature, and is therefore considered an experimental procedure. However, at our clinic, Dr. Stogicza has performed this intervention since 2010, with extensive experience despite the lack of published studies.

Possible side effects

Common, mild reactions:

  • Local tenderness, swelling, or muscle pain
  • Mild sore throat lasting less than 24 hours

Rare complications:

  • Infection, bleeding, or nerve irritation
  • Temporary dizziness or muscle spasm
  • Low-grade fever resolving within 24 hours
  • Severe complications (e.g., paralysis, stroke, death, epileptic seizure, permanent neurologic deficit) have not occurred but based on the anatomy and location of the procedure in theory they cannot be excluded. However, their exact frequency cannot yet be determined because of the scarcity of the medical literature (this would require statistical analysis of data from multiple physicians, thousands of patients from multiple practices).

The procedure must be performed only by a specialist with advanced experience. Safe practice requires precise fluoroscopic needle guidance, correct interpretation of contrast patterns, and high-quality anesthesia care. General anesthesia is a must for the transoral approach for clear access to the throat, while airway is protected in an immobile patient, allowing for precision needle placement to all targets.

How should the patient prepare?

  • A session with a manual therapist experienced in cervical spine treatment is performed at our clinic before the procedure.
  • Anti-inflammatory medications (e.g., ibuprofen, diclofenac) and steroids should be avoided for 2 weeks before treatment.
  • Smoking reduces the effectiveness of therapy — quitting is strongly advised.
  • Patients should not drive on the day of the procedure and should arrive with an escort.
  • Do not eat for 6 hours before the procedure; clear fluids may be consumed up to 2 hours before.

Aftercare and lifestyle

Following regenerative treatment, it is recommended to:

  • Begin physiotherapy and cervical stabilization exercises 6 weeks after the procedure (not earlier) under medical supervision.
  • Follow a protein-rich diet and take vitamin C (500 mg/day).
  • Use warm or cold compresses as needed; mild pain medication (e.g., paracetamol or tramadol) may be taken if necessary.