PICL for Craniocervical Instability: Promise, Plausibility, and the Evidence Gap
PICL for Craniocervical Instability:
Promise, Plausibility, and the Evidence Gap
Yoon Hang Kim, MD, MPH
Board-Certified in Preventive Medicine | Integrative & Functional Medicine Physician
October 9, 2026
About Dr. Kim
Yoon Hang Kim, MD, MPH, is board-certified in Preventive Medicine with more than 20 years of clinical experience. A University of Arizona/Andrew Weil Center for Integrative Medicine fellowship-trained physician, he holds certifications in preventive medicine, medical acupuncture, and integrative and functional medicine. Dr. Kim specializes in low dose naltrexone (LDN), autoimmune conditions, chronic pain, integrative oncology, fibromyalgia, chronic fatigue syndrome, mast cell activation syndrome (MCAS), and mold toxicity.
He is the author of eight books — including MCAS: Epidemic in Plain Sight and LDN Primer — and more than 25 peer-reviewed articles. He is the founder of the LDN Support Group.
Professional: www.yoonhangkim.com | Clinical: www.directintegrativecare.com
Introduction
For clients with craniocervical instability (CCI) who are not ready for fusion surgery — or who want to avoid it entirely — the therapeutic landscape has been frustratingly sparse. Most clinicians are left choosing between watchful waiting, aggressive surgical stabilization, or escalating cycles of physical therapy and pain management that rarely address the underlying mechanical problem. That gap is exactly where Percutaneous Implantation of Craniocervical Junction Ligaments (PICL) has entered the conversation.
Developed at the Centeno-Schultz Clinic in Broomfield, Colorado, PICL is an image-guided orthobiologic procedure that delivers autologous bone marrow concentrate directly into the damaged stabilizing ligaments of the skull–C1–C2 junction. The biological premise is compelling: rather than fusing the joint or simply managing downstream symptoms, PICL attempts to repair the source of instability. If it works, it represents exactly the kind of tissue-preserving, motion-sparing intervention that integrative and functional medicine clinicians have long hoped would emerge for CCI.
But "compelling premise" and "clinical evidence" are different things — and for PICL, that distinction matters enormously. This article examines what PICL actually is, what the current evidence does and does not show, who the appropriate candidate population might be, and what questions must be answered before this procedure can move from investigational to practice-ready.
What Is PICL — And What Makes It Different
PICL stands for Percutaneous Implantation of the Craniocervical Junction Ligaments. The developer also uses the name ePICL. The procedure targets the alar, accessory, and transverse ligaments — deep stabilizing structures that govern the relationship between the skull base, C1, and C2. These are not structures any routine injection reaches.
The procedural sequence matters clinically. First, approximately 30–60 mL of bone marrow is aspirated from the posterior superior iliac crest and processed into concentrated marrow. Second, platelet-rich plasma and platelet lysate are prepared from the same aspirate and combined with the nucleated-cell layer. Third, under total intravenous anesthesia, a needle is advanced through the posterior oropharynx — not through the neck — with endoscopic visualization and fluoroscopic guidance directing the injectate into the target ligament region. Finally, C0–C3 ligaments and facet joints receive additional orthobiologic treatment in the same session.
Two points deserve emphasis. First, this is genuinely different from posterior cervical prolotherapy or PRP injections — both anatomically and technically. The transoral approach accesses structures that cannot be safely reached from the outside. Second, the terminology "stem cell treatment" requires precision. The injectate is bone marrow concentrate — a heterogeneous preparation containing progenitor cells, platelets, growth factors, and cytokines. It is not a purified, standardized stem-cell drug product. That distinction has direct implications for how we interpret the evidence, because composition varies between individuals and processing runs.
Biological Plausibility — Strong Enough to Investigate, Not Enough to Validate
The rationale behind PICL is built on legitimate orthobiologic science. Bone marrow concentrate contains mesenchymal stromal cells, progenitor populations, and a rich array of signaling molecules that collectively may support tissue repair, modulate local inflammation, and influence fibroblast activity in ligamentous structures. Studies of bone marrow concentrate in anterior cruciate ligament injuries have shown promising early results — including a 2025 randomized trial that reported superior functional outcomes compared to exercise therapy alone at two-year follow-up.
But applying ACL evidence to the craniocervical junction requires crossing several untested bridges. The alar and transverse ligaments function under very different mechanical conditions than the ACL. Incomplete ligament regeneration in the knee is painful; at the CCJ, it may allow brainstem compression. The transoral approach introduces infection risk that knee injections do not carry. And many CCJ instability clients have underlying connective-tissue disorders, not isolated traumatic ligament injuries.
The proposed therapeutic chain — orthobiologic injection → local tissue repair → improved ligament mechanics → reduced pathological motion → clinical improvement — is plausible at each step. But plausibility is not demonstration. Each link requires independent evidence. Demonstrating that a client feels better does not confirm that their ligaments regenerated, and demonstrating a change in MRI appearance does not establish that tensile strength improved enough to matter mechanically.
A laboratory study examining eight bone marrow concentrate samples also found substantial variability in mesenchymal stromal-cell concentration, cytokine profiles, and protein content — underscoring that "bone marrow concentrate" is not a reproducible biological dose in the way a pharmaceutical drug would be.
What the Clinical Evidence Actually Shows
This is where the honest answer requires some discipline, because the available evidence is easy to misread in both directions.
What exists: A sham-controlled randomized trial has been registered (NCT03517761) and publicly described — a genuinely important design feature. The protocol compares two active procedures with two sham procedures in 80 participants. The sham group undergoes marrow aspiration to maintain blinding, receives a small posterior oropharyngeal puncture under anesthesia, and gets simulated posterior upper cervical injections. The registered primary endpoint is the Headache Impact Test, with secondary endpoints including the Neck Disability Index, pain scores, quality of life, and imaging. Outcomes are assessed three months after the second procedure.
What is significant about the design: Using a sham comparator in an interventional trial for CCI is not trivial. Invasive procedures generate substantial expectation effects, and symptom improvement alone — without a sham control — cannot distinguish true biological benefit from placebo response. The developer deserves credit for committing to this design.
What the evidence does not yet include: As of this writing, a completed, peer-reviewed PICL randomized trial results publication could not be verified in the available literature. Developer case reports, testimonials, and a trial protocol announcement represent important early signals — but they are not clinical evidence of efficacy in the same sense as a published controlled trial.
The population selection issue matters enormously: The publicly described trial specified traumatic CCI — a specific event occurring less than 10 years prior — and excluded hypermobile Ehlers-Danlos syndrome (hEDS). This is clinically significant. A substantial proportion of clients presenting with CCI in integrative and functional medicine settings have hEDS-associated hypermobility rather than isolated traumatic ligament injury. Even if the PICL trial shows favorable results in its enrolled population, those results should not automatically be generalized to hEDS clients.
What a cited "success rate" actually requires: Any percentage quoted for PICL outcomes should be evaluated against the underlying dataset: selection criteria, total number treated, loss to follow-up, number of repeat procedures required, the definition of "success," whether objective imaging outcomes improved alongside symptoms, and — critically — what adverse events occurred. Without those denominators, a percentage is marketing, not evidence.
Safety: This Is Not Your Routine Neck Injection
The phrase "minimally invasive" appears in PICL descriptions, and while the incision is certainly small, the risk profile is not. The developer's own research materials disclose potentially serious complications: infection including life-threatening meningitis (the transoral route traverses a contaminated field), nerve injury, spinal cord injury or bleeding causing temporary or permanent paralysis, and worsening of the underlying symptoms or condition.
The shared airway under general anesthesia adds procedural complexity that does not exist with cervical injections performed under conscious sedation. The proximity to the brainstem, spinal cord, and major vessels means that the margin for technical error is narrow.
None of this means PICL cannot be performed safely — the clinic has evidently performed it in a number of individuals without publicizing catastrophic outcomes. But the clinician referring a client, and the client considering it, must approach this with accurate risk framing rather than the vocabulary of an outpatient procedure.
On regulatory status: The FDA has stated that regenerative medicine therapies have not been approved for orthopedic conditions, including neck pain. This does not independently determine whether a specific autologous marrow procedure is legal or illegal in a given clinical context, and that question requires direct clarification from the treating clinic and applicable legal guidance. What it does mean is that the regulatory framework is not equivalent to FDA approval or established efficacy demonstration. Clients should ask explicitly about this distinction before proceeding.
Diagnostic Uncertainty: The Problem Before the Procedure
Before any discussion of PICL's merits, the diagnosis itself must be solid — and in clinical practice, CCI diagnosis is frequently less solid than it appears.
A 2022 systematic review of CCI in Ehlers-Danlos syndrome (Lohkamp, Marathe, and Fehlings) found that available evidence ranged from levels III to V, that consensus diagnostic criteria were lacking, and that the most commonly used radiographic parameters — the clivo-axial angle, Harris measurement, Grabb-Mapstone-Oakes measurement, and C1–C2 angular displacement — each measure different anatomical phenomena. They should not be used interchangeably or treated as equivalent surrogates for the same underlying problem.
Three concepts must remain distinct in clinical practice: hypermobility (increased range of motion, which may be constitutional and asymptomatic), radiographic instability (abnormal alignment or motion on imaging studies), and symptomatic instability (a radiographic abnormality that plausibly explains the client's clinical syndrome, with concordant symptoms and signs). The third category is the meaningful one — and it is also the most difficult to establish.
For PICL specifically, this matters in two ways. First, if the underlying diagnosis is wrong, no amount of ligament treatment will produce durable improvement. Second, the procedure's studied population had a specific traumatic ligament injury pattern — not a generalized connective-tissue disorder — and that distinction shapes whether a given individual is even a biologically appropriate candidate.
How to Think About This Clinically
For integrative and functional medicine clinicians seeing clients with CCI or suspected CCI, PICL raises legitimate questions that deserve thoughtful answers rather than reflexive enthusiasm or reflexive dismissal.
Before considering PICL, four questions should be answered:
1. Is CCI objectively established with concordant clinical findings? Imaging findings without matching symptoms, signs, and functional impairment are not sufficient justification for a procedure at this risk level.
2. Does the client's presentation resemble the studied population? The described PICL trial enrolled individuals with traumatic onset, documented lateral overhang on digital motion X-ray or elevated Grabb-Oakes on flexion MRI, and failed conservative care — and it excluded hEDS.
3. Is there a component of neural compromise that requires surgical evaluation first? For clients with evidence of brainstem compression, myelopathy, or clinically significant cranial nerve dysfunction, an independent spine or neurosurgical assessment is a reasonable prerequisite before an investigational procedure.
4. What will the client be told about the evidence base? Clients deserve an honest conversation that distinguishes a promising investigational procedure from a proven one. The word "investigational" should appear in that conversation, not buried in the fine print.
None of this is an argument against PICL. It is an argument for informed decision-making at the standard a complex investigational procedure deserves.
Conclusion: Where the Science Stands — And What We Need Next
PICL is a biologically motivated, technically ambitious procedure that addresses a real unmet need. Clients with symptomatic upper cervical ligament injury who are not surgical candidates, who want to preserve motion, or who need an intermediate option between conservative management and fusion deserve better options than the field currently offers. PICL is trying to be one of those options — and that goal is worth supporting.
But the scientific foundation has not yet caught up with the clinical ambition. The field currently rests on a procedural rationale, a publicly described sham-controlled trial (whose results have not yet been verified in peer-reviewed publication as of this writing), developer case reports, and indirect orthobiologic evidence from different anatomical targets. That foundation is enough to justify rigorous investigation. It is not yet enough to justify clinical adoption outside of well-documented, fully informed investigational use.
The decisive next steps are: publication of the randomized trial results with full transparency about adverse events, non-responders, and repeat procedures; independent replication at centers without financial ties to the procedure; population stratification that separates traumatic ligament injury from hEDS-associated instability (particularly given that a 2026 Neurosurgical Review publication now provides a 347-client surgical screening dataset for CCI in connective tissue disorders — a substantially larger evidence base than anything published for PICL); standardization of the injectate; and long-term follow-up data that establishes whether any benefit is durable or requires ongoing repeat treatments.
As clinicians who take both biological innovation and evidence integrity seriously, we should neither dismiss PICL as fringe nor embrace it as proven. We should watch it carefully, ask the right questions, and advocate for the rigorous published evidence that clients considering it — and the field navigating CCI broadly — genuinely deserve.
Important: This article is a critical narrative review for educational purposes only. It does not constitute medical advice, a clinical recommendation for or against PICL, or legal guidance on the regulatory status of any specific procedure. Clinicians should evaluate individual clients with the full clinical picture and refer to current literature for evolving evidence. This content is not intended to replace a professional medical consultation.
Key Sources
Lohkamp LN, Marathe N, Fehlings MG. Craniocervical instability in Ehlers-Danlos syndrome. Global Spine Journal. 2022.
Henderson FC, et al. Craniocervical instability in patients with Ehlers-Danlos syndromes: outcomes analysis following occipito-cervical fusion. Neurosurgical Review. 2024;47:27.
Non-surgical treatment of anterior cruciate ligament tears with bone marrow concentrate and platelet products. BMC Musculoskelet Disord. 2025. doi:10.1186/s12891-025-09153-2
Centeno-Schultz Clinic. ePICL Procedure: Percutaneous Implantation of the CCJ Ligaments (clinic treatment webpage, accessed October 2026).
U.S. Food and Drug Administration. Important Patient and Consumer Information About Regenerative Medicine Therapies (accessed October 2026).
Regenexx LLC. Use of Bone Marrow Concentrate for Treatment of Alar, Accessory, and Transverse Ligament Injuries. ClinicalTrials.gov identifier: NCT03517761.
Surgical screening protocol for craniocervical instability secondary to Ehlers-Danlos syndrome and other connective tissue disorders: analysis of a 347 patient case series. Neurosurgical Review. 2026. doi:10.1007/s10143-026-04195-z
In health,
Yoon Hang Kim, MD, MPH
Yoon Hang Kim, MD, MPH, is the author of MCAS: Epidemic in Plain Sight and LDN Primer, both available on Amazon, and the founder of the LDN Support Group.
Professional: www.yoonhangkim.com | Clinical: www.directintegrativecare.com
