N-hexyl Cyanoacrylate [Neurosurgery Wiki]

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===== N-hexyl Cyanoacrylate =====

**N-hexyl [[cyanoacrylate]]** (NHCA) is a fast-polymerizing liquid embolic agent used in endovascular procedures to occlude blood vessels in the treatment of vascular malformations, such as arteriovenous malformations (AVMs) and dural arteriovenous fistulas (dAVFs).

==== 🔬 Chemical Description ====
> ''NHCA is a long-chain alkyl derivative of cyanoacrylate, composed of monomers that rapidly polymerize upon contact with ionic fluids (e.g., blood or saline), forming a solid cast within the vessel.''

NHCA is part of the **cyanoacrylate family** of adhesives, differing from shorter-chain compounds (e.g., n-butyl cyanoacrylate, NBCA) by its:
  * **Slower polymerization speed**
  * **Greater flexibility and control during injection**
  * **Improved radiopacity when mixed with Lipiodol**

===== NHCA vs NBCA: Comparative Summary =====

**Cyanoacrylates** are fast-polymerizing liquid embolic agents used in endovascular procedures. The two most used types in neurointervention are:
  * **NBCA** = N-butyl cyanoacrylate  
  * **NHCA** = N-hexyl cyanoacrylate

==== 🧪 Chemical Structure ====
  * **NBCA**: Shorter alkyl chain (4 carbon atoms)  
  * **NHCA**: Longer alkyl chain (6 carbon atoms)

→ Longer chains polymerize **more slowly**, allowing greater control.

==== ⏱️ Polymerization Speed ====
  * **NBCA**: Very fast polymerization → hard to control
  * **NHCA**: Slower polymerization → more time to reach the nidus

→ NHCA is more **forgiving** during injection.

==== 🧬 Handling Characteristics ====
  * **NBCA**: Higher risk of **catheter entrapment**, requires rapid and decisive injection
  * **NHCA**: Easier manipulation, more predictable penetration, especially when diluted 1:4 with Lipiodol

==== 🎯 Target Penetration ====
  * **NBCA**: Often used for **proximal feeder** embolization or high-flow AVMs
  * **NHCA**: Better suited for **deep intranidal** penetration due to slower flow and better control

==== 🧯 Risk of Non-target Embolization ====
  * **NBCA**: Higher risk due to abrupt polymerization
  * **NHCA**: Lower risk with proper dilution and technique

==== 💰 Cost and Availability ====
  * **NBCA**: Widely available, inexpensive
  * **NHCA**: Slightly higher cost, less widely available

==== 💉 Common Dilution Agent ====
  * Both are typically diluted with **Lipiodol** to modulate polymerization and increase radiopacity

==== 🧠 Clinical Use Cases ====
^ Use Case ^ NBCA ^ NHCA ^
| High-flow AVMs | ✅ | ⚠️ |
| Deep nidus penetration | ⚠️ | ✅ |
| Preoperative devascularization | ✅ | ✅ |
| Risky anatomy with tortuous feeders | ⚠️ | ✅ |

==== ⚠️ Limitations ====
  * Both are **permanent**, **non-resorbable**, and carry risk of embolizing healthy tissue
  * Require experienced operators
  * Neither offers the **plug-and-push** properties of agents like Onyx or PHIL

==== 📎 References ====
  * Murias Quintana E, et al. *Use of NHCA...* Cureus. 2025;17(5):e84290.
  * Chapot R, et al. *Neurointerventional embolic agents: a technical and practical overview.*



==== 💉 Clinical Application ====
NHCA is used as a **liquid embolic agent** in:
  * Intranidal AVM embolization
  * Preoperative devascularization
  * Arterial feeder occlusion
  * Treatment of superficial vascular malformations
  * Selected dAVFs

==== 🧪 Formulation and Delivery ====
  * Commonly diluted with **Lipiodol** (usually 1:3 to 1:4 ratio) to modulate viscosity and radiopacity.
  * Requires **coaxial microcatheter systems** and precise control to avoid non-target embolization.
  * Compatible with **DMSO-free catheters**, unlike Onyx or PHIL.

==== ✅ Advantages ====
  * Deep intranidal penetration possible
  * Fast solidification on contact with blood
  * No need for DMSO-compatible devices
  * Lower cost compared to Onyx

==== ⚠️ Limitations and Risks ====
  * Risk of catheter entrapment if not withdrawn promptly
  * Permanent and non-resorbable
  * Potential for **non-target embolization**
  * Rapid polymerization can be difficult to control in tortuous anatomy
  * No long-term outcome data for some formulations (e.g., NHCA vs. NBCA)

==== 🧠 Related Agents ====
  * NBCA (n-butyl cyanoacrylate)  
  * Onyx (ethylene-vinyl alcohol copolymer)  
  * PHIL (precipitating hydrophobic injectable liquid)  
  * Squid (EVOH-based)

===== Case series =====

In a retrospective single-center [[case series]] (n=22 patients, 24 procedures) with no [[control group]] or [[comparison]], Murias Quintana et al. from the Hospital Universitario Central de Asturias, [[Oviedo]],  Hospital Clínic de [[Barcelona]], Hospital Universitario Marqués de Valdecilla, [[Santander]], Alfried Krupp Krankenhaus, [[Essen]], Hospital Universitario de [[Salamanca]]
((Murias Quintana E, Rodríguez Castro J, Puig J, Gil García A, Chapot R, Maestro V, Llibre JC, Gutiérrez Morales JC, García Arias F, Vega P. Use of [[N-hexyl Cyanoacrylate]] [[Monomer]]s for the [[Treatment]] of Intra- and Extracranial [[Arteriovenous Malformation]]s: A Single-Center Experience. Cureus. 2025 May 17;17(5):e84290. doi: 10.7759/cureus.84290. PMID: 40525034; PMCID: PMC12169607.))
aim to describe outcomes after the use of N-hexyl cyanoacrylate (NHCA, "Magic Glue") for AVM embolization.  
Despite its stated aim of evaluating "strengths and limitations," the article offers a one-sided, promotional narrative that lacks critical analysis.

===== 🧱 Structural and Conceptual Weaknesses =====

=== 1. Journal-Level Issues: "Cureus Syndrome" ===
The journal *[[Cureus]]* is increasingly known for:
  * Minimal [[peer review]]
  * Inflated author lists
  * A tendency to prioritize upload speed over [[scientific rigor]]

This paper reinforces that [[reputation]], providing more of a procedural diary than a peer-reviewed study. It embodies [[editorial complacency]] and [[academic dilution]].

=== 2. Lowest Tier of Evidence ===
A retrospective case series offers no comparative insight. There is:
  * No [[randomization]]
  * No [[control group]]
  * No[[ prospective]] [[outcome]] [[measure]]s

This is not [[hypothesis]]-[[test]]ing [[research]] — it’s purely [[observational]], anecdotal reporting.

===== 📉 Methodological Limitations =====

=== 3. "Success" Is Redefined to Mean Nothing ===
The paper defines ''[[technical success]]'' as “the outcome achieved based on objective.” This is circular reasoning and renders the concept of success meaningless.

=== 4. Data Dump of Technical Details ===
Injection times and catheter models are listed with obsessive detail:
  * HeadWay Duo 167 cm in 70.8%
  * Magic 1.2F in the rest
  * Injection times: 27 seconds to 9 minutes 38 seconds

Yet none of these details translate to improved patient care or clinical insight.

=== 5. Zero Complications ≠ Safety ===
No [[adverse event]]s in 24 procedures cannot be extrapolated as “[[safe]].” This [[cohort]] is underpowered to detect rare but serious complications — a classic false sense of [[security]].

===== 🤹 Interpretation Bias and Overreach =====

=== 6. 12.5% Success = "Effective"? ===
Only '''3 out of 24 cases (12.5%)''' achieved complete occlusion with a single NHCA injection. The authors still call it "effective." This is an example of:
  * ::unjustified enthusiasm::
  * ::intellectual dishonesty::

=== 7. Promotional Tone ===
Frequent use of the term "Magic Glue" and positive adjectives for NHCA give this paper the tone of a product brochure, not a neutral scientific analysis.

===== 🧠 What's Missing? =====
Key omissions include:
  * No clinical or imaging follow-up data
  * No outcome measures beyond technical success
  * No comparison with other embolic agents (Onyx, PHIL, Squid)
  * No cost-benefit analysis
  * No discussion of failure cases or limitations in complex AVMs

===== 🧾 Conclusion =====
This paper does not meet the standards of a rigorous scientific study. It provides:
  * No high-quality evidence
  * No clinically useful guidance
  * No long-term data

It reinforces the perception of *Cureus* as a platform for uploading technically correct but scientifically irrelevant work. A procedural note disguised as research, this article is a missed opportunity to meaningfully contribute to the field of neurointerventional radiology.

**Final [[Verdict]]:**  
This is not a "[[study]]" — it is a [[technical anecdote]] polished with promotional language and framed in a journal that too often rewards upload volume over scientific substance.



==== 📎 References ====