Neuropathology

Fighting the Fracture Cascade: Early and Repeated Balloon Kyphoplasty as a Bridge Until the Effects of Osteoporosis Treatment Become Apparent in a Super-Aged Patient

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In a case report by Tanaka et al., published in Cureus in May 2025, and authored by clinicians from the Departments of Neurosurgery at the International University of Health and Welfare Narita Hospital (Narita), Shiroishi Kyoritsu Hospital (Shiroishi), Shojima Neurosurgery (Saga), Imari Arita Kyoritsu Hospital (Arita), and the Department of Neurology at Shiroishi Kyoritsu Hospital, the authors describe the management of an 87-year-old patient with a cascade of adjacent osteoporotic vertebral fractures. The purpose of the report is to highlight the role of early and repeated balloon kyphoplasty (BKP) as an effective bridging strategy to preserve mobility, spinal alignment, and independence in super-aged patients, until the delayed therapeutic effects of pharmacologic osteoporosis treatments, such as teriparatide, become evident 1)

1. Overinterpretation of a Single Case

The fundamental flaw of this report is its excessive generalization from a single anecdotal case. No matter how long the follow-up, one patient’s trajectory cannot justify broad clinical recommendations, especially regarding a high-cost and procedure-intensive strategy like repeated BKP.

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Pituitary apoplexy: surgical or conservative? A meta-analytical insight.

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In a Systematic Review and Meta-Analysis, Xia et al., from the First College of Clinical Medical Science, Three Gorges University & Yichang Central People’s Hospital, Yichang, Hubei, China, published in Frontiers in Surgery. The authors compared recovery outcomes of neurosurgical vs. conservative treatment in patients with pituitary apoplexy, aiming to provide evidence-based guidance for clinical decision-making.

Recovery from ophthalmoplegia improved wih surgery 3).

The authors claim to provide evidence-based guidance for choosing between surgical and conservative treatment in pituitary apoplexy through a meta-analysis of 33 years of literature.

They conclude that surgery significantly improves ocular muscle paralysis but yields no benefit over conservative management for visual acuity, visual field, or endocrine outcomes.

💣 Critical Issues

1. Methodological Superficiality

Despite claiming a rigorous meta-analysis, the study relies on a fixed-effects model—a questionable choice given the expected heterogeneity across decades of heterogeneous, mostly retrospective, observational studies. This choice artificially narrows confidence intervals and potentially overstates precision. No rationale is given for not using a random-effects model, which is standard in clinical meta-analyses dealing with variable populations and treatment protocols.

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Systematic Review of the predictive value of negative brain or low probability brain MRIs in patients with CSF venous fistulas

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The article titled “Systematic Review of the Predictive Value of Negative Brain or Low Probability Brain MRIs in Patients with CSF Venous Fistulas” (American journal of neuroradiology) is a systematic review analyzing data from nine studies (898 patients) to assess how reliably negative brain MRI or low-probability MRI scores (Bern, Mayo) can rule out cerebrospinal fluid (CSF) venous fistulas, a surgically treatable cause of spontaneous intracranial hypotension (SIH) 1).

The authors found that although negative brain MRI has a high negative predictive value (89%), CVFs were still identified in a notable number of patients—especially when using the Mayo score (NPV only 65%).

The authors conclude that negative imaging does not exclude CVF, and invasive spinal imaging (e.g., DSM, dynamic CT myelography) should be considered in cases with strong clinical suspicion. This is especially relevant for neurosurgeons, as surgical ligation of CVFs may be necessary.

All authors are affiliated with Cedars-Sinai Medical Center (Los Angeles), with Dr. Wouter I. Schievink, a neurosurgeon, being a leading expert in the field of CSF leaks.

This so-called systematic review by Tay et al. (AJNR, June 2025) ambitiously sets out to clarify the diagnostic value of negative brain MRI in detecting cerebrospinal fluid venous fistulas (CVFs), yet ends up as a textbook example of how quantitative gloss can’t save a weak clinical premise.

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Temporal trends and risk factors associated with stroke mortality among cancer patients

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In a retrospective cohort study published in the Journal of Clinical Neuroscience, Ahmed et al. with Cleveland Clinic Cerebrovascular Center, West Virginia University participation 1) analyzed data from over 5.9 million patients diagnosed with a first primary cancer, based on the SEER database (2000–2020). The study aimed to quantify the risk of stroke-related death (SD) in cancer patients and to identify temporal trends and associated clinical and demographic risk factors. Stroke-related mortality (SD) among cancer patients has significantly declined over the past two decades across all cancer types and both sexes. However, older age, non-white race, male sex, and specific cancer types—notably nervous system, respiratory, and head and neck cancers—are associated with a higher risk of stroke death. Conversely, patients receiving chemotherapy or radiotherapy had a lower risk of SD compared to those who received no treatment.

⚠️ Fatal Methodological Flaws

No Clinical Stroke Classification

The authors report on “stroke mortality” without differentiating ischemic vs. hemorrhagic strokes, nor providing stroke etiology or timing relative to cancer diagnosis or cancer treatment—rendering any mechanistic or preventative inference purely speculative.

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Intraoperative ICG-VA with FLOW800 and multimodal fusion neuro-navigation for the resection of arteriovenous malformation with reduced blood loss

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In a retrospective cohort study, Yang et al. from The First Affiliated Hospital of Soochow University (Suzhou, Jiangsu) and Beijing Tiantan Hospital, Capital Medical University (Beijing, China), published in World Neurosurgery, evaluated the safety and effectiveness of combining intraoperative indocyanine green video angiography (ICG-VA) with FLOW800 and multimodal fusion neuronavigation in the microsurgical resection of brain arteriovenous malformations (AVMs).

The combined use of ICG-VA, FLOW800, and multimodal neuro-navigation was associated with:

Reduced intraoperative blood loss

Improved functional outcomes

Lower rates of postoperative complications and reoperation

→ Enhancing both the safety and efficacy of AVM microsurgery.

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A flashy mix of fluorescence imaging, hemodynamic mapping, and navigation overlays is presented as a major leap forward in AVM surgery. Ninety patients, split into two groups. Outcomes like hemoglobin drop and mRS are tracked. Sounds solid. Until you actually read it.

⚠️ Fatal Methodological Flaws Retrospective Bias Parade: No randomization. No matching. No controls for AVM grade, eloquence, or preoperative hemorrhage. The groups may as well be different species.

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High activity of human cytomegalovirus in patients with Sjögren’s disease

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In a cross-sectional observational study using immunohistochemistry and serology to assess human cytomegalovirus (HCMV) activity in salivary gland tissue and serum samples, Pantalone et al. (Karolinska Institutet, Stockholm; Turku University, Finland) — published in Clinical Immunology — investigated the presence and potential role of HCMV in patients with Sjögren’s disease (SD).

Their findings showed:

  • SD patients had significantly higher expression of HCMV proteins in salivary gland tissue:
    1. HCMV-IE: 88.9%
    2. HCMV-LA: 69.2%
    3. HCMV-pp65: 45.8%
  • HCMV-specific IgM was more frequent in SD patients than in controls (32.1% vs. 13.4%, p = 0.04)
  • HCMV-IgG titers were significantly elevated in the SD group (p < 0.0001)

These results suggest a possible role of active or latent HCMV infection in the pathogenesis of Sjögren’s disease, although a causal relationship has not been established.

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🧠 Takeaway Message for Neurosurgeons

While Sjögren’s disease is primarily a rheumatologic condition, this study provides important implications for neurosurgeons:

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Engineering of CD63 Enables Selective Extracellular Vesicle Cargo Loading and Enhanced Payload Delivery.

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In a preclinical experimental study, Obuchi et al. (2025)—with contributions from the Department of Neurosurgery at Leiden University Medical Center—engineered extracellular vesicles for selective cargo loading and enhanced functional delivery, using a modified CD63 scaffold and VSV-G fusion, with in vivo validation in mouse brain models. 1)

🚫 1. Rebranding Complexity as Innovation The authors tout a modular EV engineering system using CD63, mCherry, FLAG-tags, nanobody fusions, and VSV-G. But this is not scientific ingenuity—it’s molecular bricolage. Each component is repurposed from older literature and glued together without real conceptual novelty. The result? A bloated acronym soup with more moving parts than scientific value.

⚠️ What’s pitched as a breakthrough is closer to a tech demo in search of a clinical rationale.

❌ 2. Absence of Disease-Relevant Application Despite name-dropping CRISPR, Cre, and Cas9, no disease context is addressed. No glioma model. No neurodegenerative target. No proof that the cargo accomplishes anything biologically meaningful in the recipient tissue. The mouse brain “validation” is just a fluorescent readout, not a therapeutic outcome.

The cargo arrives, but so what? This is payload delivery without a payload purpose.

🧪 3. Methodological Blind Spots No quantification of EV heterogeneity or functional subpopulations.

No rigorous comparison with alternative delivery systems (e.g., AAVs, lipid nanoparticles).

No evidence of endosomal escape for actual cytoplasmic/nuclear action.

No dose-response curves, toxicity profiling, or repeatability metrics.

This is a biotech prototype, not a therapy-in-the-making.

🔥 4. VSV-G: The Short-Term High, Long-Term Problem The use of VSV-G, a viral fusogen with broad tropism and high immunogenicity, is particularly careless. While it boosts in vitro uptake and helps “sell” delivery efficiency, it introduces a critical translational liability: poor specificity, potential immune activation, and unsuitability for clinical use.

❝Putting VSV-G on EVs is like installing a rocket engine on a paper boat—it moves faster, but it’s doomed to burn out or sink.❞

🧱 5. Structural Inefficiency and Complexity The system requires:

Engineering CD63 with dual tags

Fusing cargo to a nanobody

FLAG-based purification

VSV-G pseudotyping

TEV protease cleavage

This is logistically unscalable for clinical or industrial production and riddled with points of failure. The more components you bolt on, the more it resembles a lab curiosity, not a deliverable platform.

📉 6. Journal Inflation and Institutional Complacency The publication in J Extracell Vesicles is not a mark of impact, but rather a reflection of how EV journals have drifted into translational cosplay, applauding synthetic elegance over clinical relevance. The heavyweight affiliations (MGH, Harvard, etc.) likely ensured acceptance despite the absence of therapeutic depth or mechanistic rigor.

🧠 Conclusion: A study more interested in showing what’s technically possible than what’s biologically meaningful. It trades therapeutic relevance for engineering flair, while ignoring the hard questions of targeting, safety, scalability, and necessity.

This is not a step toward Evidence-based medicine—it’s a flashy side road to nowhere.

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Obuchi W, Zargani-Piccardi A, Leandro K, Rufino-Ramos D, Di Lanni E, Frederick DM, Maalouf K, Nieland L, Xiao T, Repiton P, Vaine CA, Kleinstiver BP, Bragg DC, Lee H, Miller MA, Breakefield XO, Breyne K. Engineering of CD63 Enables Selective Extracellular Vesicle Cargo Loading and Enhanced Payload Delivery. J Extracell Vesicles. 2025 Jun;14(6):e70094. doi: 10.1002/jev2.70094. PMID: 40527733.

Epithelioid angiosarcoma of the cervical spine: A case report.

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Nan et al. 1) describe a rare case of epithelioid angiosarcoma (EA) involving the cervical spine, presenting with pathological fracture and kyphotic deformity, and document the surgical and adjuvant management as well as the clinical outcome in the World Journal of Clinical Cases.

1. Predictable Yet Pointless

The authors claim novelty by describing a rare anatomical presentation of EA. However, this degenerates into a predictable narrative with no new pathophysiological insights, no hypothesis generated, and no clinical paradigm challenged. It is the kind of “rare case” that proliferates in low-barrier journals precisely *because* it demands no intellectual risk.

2. Zero Diagnostic Value

The authors bypass the opportunity to deepen our understanding of the radiological-morphological signature of EA in the spine. No comparative imaging, no differential diagnostic flowchart, no histopathological discussion beyond standard CD31/CD34 immunostaining. If this case had been published in 1995, it would be equally uninformative.

3. Therapeutic Confusion Disguised as Aggressiveness

Two major spine surgeries (posterior decompression + anterior corpectomy) followed by immediate radiotherapy in a moribund patient demonstrate therapeutic overreach without oncological strategy. There is no discussion on multidisciplinary planning, palliative thresholds, or whether delaying surgery or avoiding the second procedure might have prevented ARDS. The reader is left with the impression of a surgical reflex, not an evidence-based decision.

4. No Discussion of Differential Diagnosis or Biomarkers

In a tumor type notorious for being misdiagnosed as metastasis, chordoma, or sarcoma NOS, the absence of a differential diagnostic framework or advanced markers (ERG, FLI1, HHV-8, etc.) is alarming. Histological laziness cloaked in “rare disease” rhetoric.

5. Outcome Reporting: Conveniently Truncated

The patient dies 3 weeks after surgery, yet the discussion fails to draw any causal or cautionary link between the interventions and the fatal ARDS. No autopsy data, no postmortem imaging, no pulmonary workup. This omission sterilizes the clinical narrative, reducing it to anecdote.

6. Ethically Murky

The case implicitly raises an ethical dilemma—should maximal surgery be performed in aggressive, terminal tumors without demonstrated systemic control? Yet the authors shy away from even mentioning this, let alone framing it for academic discussion.

7. Journal Choice Reflects the Paper’s Weakness

Published in a journal known for minimal peer review stringency, the article offers no citations of recent molecular or targeted therapy advances, no engagement with broader oncological guidelines, and no rationale for the treatment decisions beyond procedural listing.

Definitions (for Teaching Purposes)

  • Histological laziness: Failing to provide in-depth pathology discussion beyond CD31/CD34 and H&E staining in vascular tumors.
  • Surgical reflex: The tendency to operate based on mechanical findings (compression, fracture) without integrating prognosis or systemic disease behavior.
  • Ethical sterilization: Avoiding uncomfortable questions about futility, risk-benefit tradeoffs, and overtreatment in end-stage patients.
  • Postmortem evasion: Reporting a perioperative death without diagnostic closure (autopsy, imaging, or medical reflection).

Conclusion

This case report is an example of procedural reporting devoid of scientific merit, clinical reflection, or ethical introspection. It contributes nothing to the understanding of EA, its diagnosis, biology, or management—beyond reiterating its rarity. In its current form, it is neither hypothesis-generating nor practice-changing, and serves as a cautionary tale on how not to write a case report.

Suggested Revisions

  • Include comparative radiology with metastatic disease and primary bone tumors.
  • Provide autopsy findings or detailed explanation of respiratory decline.
  • Discuss therapeutic alternatives (e.g., single-stage surgery, biopsy + RT, palliative care).
  • Frame the case within an oncological decision-making algorithm.
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Nan YH, Chiu CD, Chen WL, Chen LC, Chen CC, Cho DY, Guo JH. Epithelioid angiosarcoma of the cervical spine: A case report. World J Clin Cases. 2025 Jun 16;13(17):101593. doi: 10.12998/wjcc.v13.i17.101593. PMID: 40524767; PMCID: PMC11866273.

Protective Effect of Resveratrol Against Intracranial Aneurysm Rupture in Mice

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In vivo animal studies

Type of study:: In vivo animal study (murine intracranial aneurysm model) First author:: Dang et al. Author affiliations::

  • Hamamatsu University School of Medicine, Hamamatsu
  1. Dept. of Neurosurgery
  2. Dept. of Anesthesia and ICU
  3. Dept. of Medical Education
  4. Dept. of Pharmacology
  • Asahikawa University School of Medicine, Asahikawa
  1. Dept. of Anesthesia and ICU
  • Hamamatsu Medical Center, Hamamatsu
  1. Dept. of Neurosurgery

Journal:: Journal of Neuroscience Research Purpose:: To evaluate whether dietary resveratrol prevents formation or rupture of intracranial aneurysms via anti‑inflammatory mechanisms. Conclusions::

  • No significant reduction in aneurysm formation incidence
  • Marked reduction in rupture rate (88 % → 40 %, p=0.026)
  • Modulation of inflammatory markers: ↑Sirt1, ↓Nfkb1, ↓Tnf

Citation:: 1)

Critical Review

1. Model limitations The elastase + DOCA‑salt murine model poorly reflects human aneurysm pathophysiology, lacking hemodynamic fidelity. No histological validation of aneurysm similarity or wall integrity is presented.

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Histological Classifier of Radiosensitivity to Spine Stereotactic Body Radiation Therapy

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In a Retrospective Cohort Study Jackson et al. 1) from the Memorial Sloan Kettering Cancer Center, New York, concluded that 30 Gy in 3 fractions is the preferred SBRT regimen for spinal metastases, even in radiosensitive tumors, because it offers better local control than 27 Gy with a similar risk of vertebral fracture requiring treatment.

Additionally:

Tumor histology strongly influences radiosensitivity — prostate and breast (Class A) respond best; GI and liver tumors (Class C) have higher failure rates.

For high-grade epidural compression (ESCC 2–3) in Class B–C tumors, separation surgery + SBRT may improve outcomes over SBRT alone.

* The study assigns biological significance to histology classes (A–C) without molecular stratification or genomic profiling — a gross simplification that ignores intratumoral heterogeneity and microenvironmental factors. * Retrospective design with non-randomized treatment allocation allows substantial selection bias (e.g., healthier patients might be more likely to receive 30 Gy). * No formal validation cohort — the classifier is proposed based on internal data, without prospective or external validation.

🔍 Conceptual Ambiguity

* “Histological classifier of radiosensitivity” suggests a predictive tool, yet the study lacks any predictive modeling or decision support framework. The term is more rhetorical than scientific. * The study mixes observational epidemiology with causal language, implying therapeutic superiority without proper adjustment for confounders.

🔄 Chronological Bias

* Treatment practices evolved over the 9-year window. Earlier patients may have been treated with less advanced planning, different immobilization, or different imaging standards — contaminating outcome comparisons.

🧮 Operator Bias and Unmeasured Variables

* No adjustment for institutional learning curve, planning margins, spinal cord tolerance constraints, or radiologist/radiation oncologist variability. * The impact of systemic therapy (e.g., concurrent immunotherapy, targeted therapy) is not accounted for — a major omission in modern oncologic outcomes.

📉 Misleading VCF Analysis

* Vertebral Compression Fracture rates are reported, but the distinction between radiologic and clinically significant fractures is vague. Moreover, attributing cause solely to dose without biomechanical modeling is speculative. * The apparent increase in overall VCF with 30 Gy, though dismissed as statistically irrelevant, raises safety concerns insufficiently explored.

🚨 Weak Surgical Analysis

* The “benefit” of separation surgery in Epidural Spinal Cord Compression (ESCC) 2–3 lesions is statistically non-significant (p = 0.051) and based on a small subgroup (n=261) — yet it is discussed as if near-clinical truth.

🧠 Final Verdict

This study sells the illusion of a refined, histology-based SBRT dosing paradigm, but offers little more than retrospective rebranding of known practice patterns. It overpromises biological insight while underdelivering methodological rigor.

Until prospectively validated, the so-called “histological classifier” remains an observational artifact, not a clinical decision tool.

📚 Recommendation

* Treat this study as exploratory, not directive. * Avoid reshaping clinical protocols solely based on its conclusions. * Demand prospective validation with molecular data and standardized planning before adopting these thresholds.

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Jackson CB, Boe LA, Zhang L, Apte A, Jackson A, Ruppert LM, Haseltine J, Mueller BA, Schmitt AM, Vaynrub M, Newman WC, Lis E, Barzilai O, Bilsky MH, Yamada Y, Higginson DS. Histological Classifier of Radiosensitivity to Spine Stereotactic Body Radiation Therapy. Int J Radiat Oncol Biol Phys. 2025 Jun 12:S0360-3016(25)00597-8. doi: 10.1016/j.ijrobp.2025.05.078. Epub ahead of print. PMID: 40516631.