{
  "abstract": "Amyotrophic lateral sclerosis (ALS) is characterized by prion-like propagation of misfolded TAR DNA-binding protein 43 (TDP-43) and superoxide dismutase 1 (SOD1) across motor neuron pools. Because any circulating pharmacological agent must cross the blood-brain and blood-spinal cord barriers (BBB and BSCB), this review proposes active craniospinal tensioning (ACT) as a mechanical, non-pharmacological route to disease modification that acts on cerebrospinal fluid (CSF) and venous pressure dynamics rather than requiring penetration of these barriers. ACT is proposed to engage a single Monro-Kellie/Queckenstedt pressure continuity through two concurrent mechanisms: suboccipital venous occlusion-rebound, hypothesized to transiently raise and release craniospinal CSF pressure via venous compression and thereby accelerate venous-side glymphatic efflux; and dural pull-recoil, hypothesized to generate a reciprocal CSF pressure gradient via spinal elongation, agitating perivascular CSF directly while inducing a coupled venous pressure gradient. Because both mechanisms act concurrently on a shared venous-side target, the combined maneuver is proposed to be more potent than either delivered alone, as in prior work on pelvis-stabilized axial spinal traction (PSAST), which lacks the occlusion-rebound component. A secondary, hypothesis-generating micro-biochemical axis, cerebral venous preconditioning (CVPC), proposes that the same occlusion-rebound cycle produces capillary/venule wall strain sufficient to activate heat shock factor 1 (HSF-1) across the neurovascular unit, independent of oxygen tension, with a possible but uncharacterized contribution from hypoxia-inducible factor 1-alpha (HIF-1α). The two routes are non-exclusive, with the macro-fluidic axis alone proposed as sufficient. This framework is entirely theoretical, requires preclinical and clinical validation, and is intended as a template for related proteinopathy-driven neurodegenerative diseases, including Parkinson's disease, Huntington's disease, spinocerebellar ataxia, and fatal familial insomnia, addressed in forthcoming work.",
  "abstract_shown": true,
  "affiliations": [
    "Chiropractic, Private Chiropractic Practice, Vancouver, CAN."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Huan-Wei Chen",
      "orcid": "0009-0008-4777-9273"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ewtsx6g27rmea.bib",
  "cited_by": 1,
  "doi": "10.7759/cureus.117043",
  "fulltext_url": "https://europepmc.org/articles/PMC13716142",
  "id": "ewtsx6g27rmea",
  "issns": [
    "2168-8184"
  ],
  "landing_url": "https://europepmc.org/article/MED/42953823",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Medical Physics"
    ],
    [
      "heading",
      "Neurology"
    ],
    [
      "heading",
      "Preventive Medicine"
    ],
    [
      "openalex",
      "2728|Amyotrophic Lateral Sclerosis Research"
    ]
  ],
  "openalex": "W7214605191",
  "pdf_url": "https://europepmc.org/articles/PMC13716142?pdf=render",
  "pmcid": "PMC13716142",
  "pmid": "42953823",
  "published": "2026-09-28",
  "publisher": "Cureus Inc.",
  "ris": "https://research.draconitic.com/paper/ewtsx6g27rmea.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42953823",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42953823"
    },
    {
      "first_seen": "2026-11-01T12:23:12Z",
      "native_id": "PMC13716142",
      "source": "pmc",
      "url": "https://doi.org/10.7759/cureus.117043"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "heading:Neurology",
      "subfield": "neurology"
    },
    {
      "field": "physics",
      "origin": "heading:Medical Physics",
      "subfield": "biological-medical"
    }
  ],
  "title": "Bypassing the Blood-Central Nervous System (CNS) Barrier: A Dual-Axis Framework for Amyotrophic Lateral Sclerosis (ALS) Utilizing Glymphatic-Lymphatic Clearance and In Situ Chaperone Synthesis.",
  "title_text": "Bypassing the Blood-Central Nervous System (CNS) Barrier: A Dual-Axis Framework for Amyotrophic Lateral Sclerosis (ALS) Utilizing Glymphatic-Lymphatic Clearance and In Situ Chaperone Synthesis.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:23:12Z",
  "url": "https://research.draconitic.com/paper/ewtsx6g27rmea",
  "venue": "Cureus",
  "versions": []
}