Neurooncology

Adagrasib for Non-small cell lung cancer intracranial metastases

by

Adagrasib for Non-small cell lung cancer intracranial metastases

Adagrasib (Krazati) is a selective, irreversible inhibitor of the KRAS G12C mutation. Intracranial metastases (brain metastases, BM) occur in up to 40% of Non-small cell lung cancer patients, and KRAS G12C is present in ~13% of Non-small cell lung cancer intracranial metastases cases. The development of brain-penetrant KRAS G12C inhibitors like adagrasib offers a major therapeutic advance.

🔍 Evidence for Intracranial Efficacy

1. Preclinical Evidence

Christian Migliarese et al. (2025) showed that adagrasib crosses the blood-brain barrier (BBB) in orthotopic brain metastasis mouse models.

Brain exposure confirmed through pharmacokinetic assays.

In adagrasib-resistant SW1573 cells, the combination with abemaciclib (a CDK4/6 inhibitor) induced apoptosis and extended survival.

Monotherapy with adagrasib prolonged survival in adagrasib-sensitive H2122 BM models.

2. Clinical Evidence

Early-phase trials (e.g., KRYSTAL-1) reported intracranial responses:

Objective intracranial response rate (ORR): ~33–42%

Some patients with measurable brain metastases showed partial responses or stable disease.

CNS penetration confirmed by CSF concentration data in limited cohorts.

Well-tolerated at 600 mg BID, though GI side effects and QTc prolongation may occur.

📊 Key Strengths

✅ Selective targeting of KRAS G12C

✅ Oral administration

✅ BBB penetration

✅ Durable CNS activity

✅ Synergy with agents like CDK4/6 inhibitors in resistant clones

⚠️ Limitations

⚠️ Not all patients respond; resistance via bypass pathways (e.g., MET, EGFR) occurs.

⚠️ Limited efficacy in KRAS wild-type or non-G12C tumors.

⚠️ CNS toxicity, although manageable, must be monitored—particularly in combination regimens.

⚠️ Long-term CNS efficacy is still being investigated in larger, controlled trials.

🧪 Ongoing Trials

Several trials are evaluating adagrasib for NSCLC with brain metastases:

KRYSTAL-1: Phase 1/2 study evaluating adagrasib as monotherapy or in combination.

KRYSTAL-10: Combining adagrasib with checkpoint inhibitors (e.g., pembrolizumab).

Trials incorporating abemaciclib, EGFR inhibitors, and MEK inhibitors are also underway.

🧠 Conclusion

Adagrasib represents a significant step forward in treating NSCLC with brain metastases harboring KRAS G12C mutations, especially due to its oral availability, brain penetration, and target selectivity. While promising, combination strategies and biomarker-guided patient selection will be critical to maximize its CNS efficacy and overcome resistance.

Co-existing genomic alterations such as homozygous deletion of CDKN2A/B may impact the utility of adagrasib. Migliarese et al., therefore, explored the combination therapy employing adagrasib and abemaciclib, a brain-penetrant CDK4/6 inhibitor, in NSCLC BM models driven by KRAS-G12C and CDKN2A loss. In both adagrasib-resistant SW1573 cells and adagrasib-responsive H2122 cells, the combination of adagrasib and abemaciclib was slightly synergistic in inhibiting cell viability in vitro through targeting the KRAS-ERK and CDK4/6-Rb signaling pathways. Combination treatment was necessary to activate caspase 3/7-mediated apoptosis in SW1573 cells, while adagrasib alone and in combination comparably elicited apoptosis in H2122 cells. In vivo, combination treatment with adagrasib (75 mg/kg) twice daily and abemaciclib (50 mg/kg) daily was associated with body weight loss (about 10%) in mice bearing orthotopic BM derived from SW1573 or H2122 cells, requiring a 50% dose reduction of adagrasib in some animals. Notably, combination treatment, but neither monotherapy, extended animal survival in the SW1573 model. On the other hand, adagrasib monotherapy and combination were similarly effective at prolonging survival, while abemaciclib monotherapy was ineffective in the H2122 model. Pharmacokinetic studies confirmed brain-penetrant properties of both agents and revealed drug-drug interactions as abemaciclib exposures in the plasma and brains were increased by the presence of adagrasib. Immunohistochemistry demonstrated on-target pharmacodynamic effects of both agents in BM in mice. The work thus supports that the combination therapy of adagrasib and abemaciclib can offer a therapeutic strategy in NSCLC BM genomically characterized by KRAS-G12C and CDKN2A loss 1)

Migliarese et al. provide compelling preclinical evidence that co-targeting KRAS G12C and CDK4/6 pathways may overcome resistance to adagrasib in brain metastases from NSCLC with CDKN2A/B loss. The mechanistic rationale is sound, and the use of brain-penetrant drugs is a major strength. However, toxicity, modest synergy, and pharmacokinetic concerns limit immediate clinical enthusiasm.

📌 Clinical Implications The combination may be most useful in adagrasib-resistant, CDKN2A-deleted BM, but careful dose adjustment and monitoring will be essential.

Future trials must integrate immunotherapy arms and investigate biomarkers of response beyond KRAS/CDKN2A status.

There’s a need for phase I trials with adaptive dosing, especially in patients with CNS involvement.

1)

Migliarese C, Sadeh Y, Torrini C, Turna Demir F, Nayyar N, Yamazawa E, Ishikawa Y, Ijad N, Summers EJ, Elliott A, Rahbaek L, Saechao B, Hallin J, Brastianos PK, Wakimoto H. Combination therapy of adagrasib and abemaciclib in non-small cell lung cancer brain metastasis models genomically characterized by KRAS-G12C and homozygous loss of CDKN2A. Acta Neuropathol Commun. 2025 May 2;13(1):88. doi: 10.1186/s40478-025-01993-2. PMID: 40317086.

IDH-mutant glioma

by

IDH-mutant glioma

Latest PubMed-Related Articles

IDH-Mutant Glioma Classification (WHO 2021)

The classification of IDH-mutant gliomas according to the World Health Organization Classification of Tumors of the Central Nervous System 2021 is summarized in the table below:

Tumor Type IDH Status 1p/19q Status Key Features Available Grades
Astrocytoma IDH-mutant Mutant Intact ATRX loss, TP53 mutation Grade 2, 3, or 4
Oligodendroglioma IDH-mutant and 1p/19q-codeleted Mutant Codeleted TERT promoter mutation, ATRX retained Grade 2 or 3
Glioblastoma Wildtype — TERT/EGFR amplification or +7/−10 signature, or necrosis/microvascular proliferation Always Grade 4

Additional Notes

  • The term glioblastoma, IDH-mutant is no longer used. These tumors are now classified as Astrocytoma, IDH-mutant, Grade 4.
  • The presence of CDKN2A/B homozygous deletion upgrades astrocytoma, IDH-mutant to WHO Grade 4 even in the absence of necrosis or microvascular proliferation.

Although IDH-mutant glioma generally has a better prognosis than its IDH-wildtype counterparts, considerable prognostic heterogeneity persists among patients with the same IDH mutation. A study of Wang et al. has primarily focused on the different IDH statuses or grades, while the metabolic heterogeneity within IDH-mutant gliomas remains insufficiently characterized. This study aims to identify transcriptomic metabolic subtypes and associated immune microenvironment differences to better understand survival variability and potential therapeutic targets in IDH-mutant glioma.

Patients with IDH-mutant gliomas were included from four public datasets (TCGA, n = 373; CGGA325, n = 167; CGGA693, n = 333; GLASS, n = 100), supplemented by 22 cases from Beijing Tiantan Hospital as an independent cohort. Consensus clustering was used to define novel metabolic subtypes. Clinical features were assessed using chi-square tests and Kaplan-Meier analysis. Metabolic profiles were characterized through enrichment analysis and GSVA; immune infiltration was analyzed using CIBERSORTx and ESTIMATE. Tumor samples from the independent cohort underwent untargeted metabolomics for validation. LASSO regression was applied to select metabolic signatures, and the CGP2014 drug library was used for drug screening.

Three metabolic subtypes (C1-C3) with distinct prognoses (p < 0.05) were identified. C1 exhibited enhanced carbohydrate and nucleotide metabolism; C2 displayed upregulated amino acid and lipid metabolism; and C3 demonstrated elevated lipid, nucleotide, and vitamin metabolism. These patterns were validated in the independent cohort. Subtypes were also correlated with immune infiltration. A 13-gene metabolic signature was established to stratify prognostic risk and suggest subtype-specific drug sensitivities.

The study provided a novel metabolic subtype for IDH-mutant glioma and highlighted these patients’ metabolic heterogeneity and potential therapeutic strategies 1)

Wang et al. provide compelling evidence that metabolic subtyping in IDH-mutant gliomas is biologically meaningful and prognostically informative. Despite the limitations of validation scope and functional depth, the study opens promising avenues for metabolism-guided precision neuro-oncology.

IDH-Mutant Glioma Subtypes

IDH-mutant gliomas, although generally associated with better prognosis, show considerable biological and clinical heterogeneity. Recent transcriptomic and metabolic profiling has revealed distinct subtypes with prognostic and therapeutic implications.

Molecular Subtypes (Traditional WHO Classification)

Subtype IDH Status 1p/19q Status Common Features WHO Grades
Astrocytoma, IDH-mutant Mutant Intact TP53 mutation, ATRX loss Grade 2, 3, or 4
Oligodendroglioma, IDH-mutant Mutant Codeleted TERT promoter mutation, ATRX retained Grade 2 or 3

Metabolic Subtypes (Wang et al., 2025)

Subtype Dominant Metabolism Prognosis Immune Microenvironment Notes
C1 Carbohydrate & nucleotide metabolism Poor Less immune infiltration Higher proliferation signature
C2 Amino acid & lipid metabolism Intermediate Moderate immune activity May benefit from lipid metabolism-targeted drugs
C3 Lipid, nucleotide & vitamin metabolism Favorable Higher immune infiltration Most differentiated; possible immunogenic role

Summary

  • These subtypes are defined by transcriptomic and metabolic profiling, not by histopathology alone.
  • A 13-gene metabolic signature has been proposed to distinguish these subtypes and guide potential treatment.
  • Future therapy may be subtype-specific, focusing on metabolism and immune modulation.
1)

Wang P, Wang J, Fang Z, Chen Q, Zhang Y, Qiu X, Bao Z. Novel metabolic subtypes in IDH-mutant gliomas: implications for prognosis and therapy. BMC Cancer. 2025 Apr 30;25(1):815. doi: 10.1186/s12885-025-14176-y. PMID: 40307749.

Posterior Pituitary Tumor

by

Posterior Pituitary Tumor

Latest PubMed Articles

A posterior pituitary tumor (PPT) is a rare, often benign neoplasm that originates from the neurohypophysis, also known as the posterior lobe of the pituitary gland.

In 2017, the WHO established that pituicytoma, granular cell tumor (GCT) and spindle cell oncocytoma (SCO) are posterior pituitary tumors (PPT). Data suggests that these tumours probably arise from the pituicytes and may constitute a spectrum of a unique histopathological entity.

Histological Subtypes

Posterior pituitary tumors comprise three main subtypes:

Although histologically distinct, these tumors likely represent a spectrum of a single pathological entity due to shared immunohistochemical markers and origin.

Clinical Presentation

Symptoms are often nonspecific and may resemble those of non-functioning pituitary tumors. Common findings include:

Diagnosis

  • MRI: Typically shows a solid sellar or suprasellar mass, often isointense on T1 and T2, with homogeneous contrast enhancement.
  • Endocrine testing: May reveal hormonal deficiencies or elevations.
  • Histology & Immunohistochemistry:

Treatment and Prognosis

  • Surgical resection is the mainstay of treatment. Approaches include:
  • Complications:
  • Adjuvant therapy: radiotherapy may be used in cases of residual or recurrent tumor.
  • Prognosis:
    • Excellent tumor-specific survival (near 100% at 5 years)
    • Endocrine dysfunction often persists or worsens postoperatively

Retrospective cohort studies

A retrospective cohort study offers a valuable contribution to the limited literature on posterior pituitary tumors (PPTs), analyzing 19 patients treated over 23 years at a single academic center. Despite the rarity of these tumors—pituicytoma (PC), granular cell tumor (GCT), and spindle cell oncocytoma (SCO)—the authors manage to draw meaningful insights into their clinical presentation, surgical management, and long-term endocrine impact 1).

Including three distinct histological subtypes allows for a comparative analysis that reveals intriguing differences, such as the significantly higher preoperative BMI in GCT patients and the sharp postoperative increase in BMI, highlighting possible metabolic derangements associated with this tumor type. The predominance of symptoms like headache, visual impairment, and sexual dysfunction echoes the nonspecific but debilitating nature of sellar pathology.

One of the most striking findings is the persistence or worsening of endocrine dysfunction postoperatively, with minimal recovery over time. This aligns with other literature indicating that surgery for PPTs, though often necessary, rarely restores pituitary function and may even exacerbate deficits. This point emphasizes the need for realistic patient counseling and robust endocrinological follow-up.

Surgical management was nearly evenly split between transsphenoidal and transcranial, a decision likely driven by tumor size and anatomical considerations. Gross total resection (GTR) was achieved in 58% of cases, with a 16% recurrence rate—relatively low, but not negligible, especially considering the benign histology of these tumors. All recurrences were managed with adjuvant radiation therapy, which raises questions about its early use in subtotal resections.

The study’s strengths include its well-defined cohort, detailed subgroup analysis, and long-term follow-up. However, the small sample size and single-center design inherently limit generalizability. Moreover, the retrospective nature introduces potential bias in data collection and outcome assessment.

From a translational perspective, this work underlines a key clinical dilemma: the balance between oncological control and iatrogenic endocrine morbidity. Future prospective multicenter studies with standardized follow-up protocols could help establish evidence-based guidelines for PPTs, including early identification of patients at risk for metabolic deterioration.

This study is a sobering reminder that not all “benign” tumors are benign in consequence. While the tumor-specific survival was excellent (100% at 5 years), the lingering endocrine and metabolic sequelae merit equal attention. Clinicians managing these rare entities must prepare for a dual challenge: surgical precision and long-term systemic management.

Retrospective observational studies

A retrospective observational study was conducted at a single neurosurgical center over 10 years (2013–2023). The authors reviewed medical records and histopathological samples of patients diagnosed with primary TTF1-positive posterior pituitary tumors (PPT) 2).

Summary of Findings

Out of over a decade of surgical activity, only nine PPT cases were identified, reflecting the rarity of this tumor type, which constituted just 0.6% of all sellar/suprasellar operations at the institution.

Breakdown of tumor types:

Key clinical observations:

  • Median patient age: 53 years
  • 66.7% male
  • Frequent symptoms: panhypopituitarism, visual deficits, and headaches
  • Common MRI features: isointense T1 signal, suprasellar extension in GCT and pituicytoma

Notable radiological clue:

  • GCTs demonstrated a “star-like crack” pattern, which may aid in preoperative suspicion.

Critical Appraisal

Strengths

  • The study is one of the few focused exclusively on TTF-1 positive PPTs with confirmed histopathology, adding valuable long-term clinical and imaging data.
  • It provides rare insights into surgical outcomes, emphasizing the challenge posed by the firm and vascular nature of SCO.

Weaknesses

  • As a single-center, retrospective study, external validity is limited. Multicentric studies would be needed to confirm the imaging-histopathology correlations suggested.
  • The sample size is very small (n=9), limiting the statistical power and generalizability of the conclusions.
  • The lack of a control group or comparative data restricts interpretation of surgical or radiotherapeutic outcomes.

Clinical Relevance

  • Preoperative suspicion of SCO or GCT based on radiological features could impact surgical planning and patient counseling, given the tendency for subtotal resection and adjuvant therapy.
  • The report underscores the importance of long-term follow-up due to the limited curative potential of these tumors, even with aggressive intervention.

Conclusion

This study serves as a useful reference for neurosurgeons and endocrinologists managing rare TTF-1-positive PPTs. It highlights the diagnostic difficulty, surgical complexity, and the need for improved strategies to manage these lesions. Future studies should aim to include multicenter cohorts, genetic profiling, and standardized protocols for treatment and surveillance.

Retrospective case series

The aim of Guerrero-Pérez F et al. from the Department of Endocrinology, Department of Pathology, Department of Endocrinology, Hospital Universitari de Bellvitge, Barcelona, Department of Endocrinology, Hospital Universitari Mutua Terrassa, Barcelona, Department of Endocrinology, Hospital Universitario Príncipe de Asturias, Madrid, Department of Neurosurgery, Hospital Universitario Miguel Servet, Zaragoza, Department of Endocrinology, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Department of Endocrinology, Hospital General Universitario de Alicante, Spain is to report the clinical findings and surgical outcomes of 16 patients with PPT. They also evaluated the tissue specimens available in light of current knowledge.

PPT were 7 pituicytomas, 3 GCT and 6 SCO. Patients mean age was 55 years old and 75% were female. Basal hormonal study showed hyperprolactinemia (43.7%) and hypopituitarism (37.5%). There was no case of diabetes insipidus (DI). MRI showed sellar/suprasellar masses with mean size of 19.7mm. PPT was not suspected in any patient. Fifteen patients underwent surgery and complications were common: 20% had perioperative bleeding (one patient died because of a massive haemorrhage), 57.1% hypopituitarism, 35.7% permanent DI and 21.4% underwent a second surgery. Pathological findings shown positivity for thyroid transcription factor 1, vimentin and negativity for cytokeratin and chromogranin A in all specimens evaluated. S100 protein was positive in 88.8% of tumours. Ki67 was ≥ 3% in 66.6% and ranged from 4-7% in SCO.

PPT have similar histology, clinical features and are frequently misdiagnosed as nonfunctioning pituitary tumours. However, post-surgical complications including haemorrhage are common. A high clinical suspicion is needed to presume the diagnosis prior surgery and diminish the high morbidity of these tumours 3).

1)

Kremenevski N, Schnell O, Coras R, Buchfelder M, Hore N. Clinical, surgical, and endocrine outcome following treatment of posterior pituitary tumors: a retrospective cohort study. Pituitary. 2025 Apr 5;28(2):45. doi: 10.1007/s11102-025-01518-z. PMID: 40186832.
2)

Lamback E, da Silva Camacho AH, Castro Araujo AC, Wildemberg LE, Cabrera Filho FD, Andreiuolo F, Kasuki L, Ventura N, Chimelli L, Gadelha MR. TTF1-positive posterior pituitary tumors: a single-center experience of 10 years. Endocrine. 2025 Apr 3. doi: 10.1007/s12020-025-04214-x. Epub ahead of print. PMID: 40175820.
3)

Guerrero-Pérez F, Vidal N, Marengo AP, Pozo CD, Blanco C, Rivero-Celada D, Díez JJ, Iglesias P, Picó A, Villabona C. Posterior pituitary tumours: the spectrum of a unique entity. A clinical and histological study of a large case series. Endocrine. 2018 Oct 1. doi: 10.1007/s12020-018-1774-2. [Epub ahead of print] PubMed PMID: 30276594.

Papilledema Differential Diagnosis

by

Papilledema Differential Diagnosis

Latest PubMed Articles

Papilledema refers to optic disc swelling due to increased intracranial pressure (ICP). However, when optic disc edema is noted, it’s crucial to distinguish true papilledema from other causes of disc swelling.

Structured differential diagnosis

🔴 True Papilledema (due to increased ICP)

Caused by elevated pressure in the cerebrospinal fluid (CSF):

Intracranial Mass Lesions Tumors (gliomas, metastases, meningiomas)

Abscesses

Hematomas

Cerebral Edema Trauma

Hypoxic-ischemic injury

Hypertensive encephalopathy

Hydrocephalus Obstructive (e.g., aqueductal stenosis)

Communicating (e.g., post-meningitic)

Idiopathic Intracranial Hypertension (IIH) Especially in young obese females

Cerebral Venous Sinus Thrombosis May mimic IIH

Meningitis/Encephalitis Infectious or inflammatory processes causing brain swelling

⚠️ Disc Edema NOT Due to Raised ICP

Unilateral or BilateralOptic Neuritis

Multiple sclerosis

Neuromyelitis optica (NMOSD)

MOG-antibody associated disease

Ischemic Optic Neuropathy

Non-arteritic (NAION): common in elderly, associated with vascular risk

Arteritic (AAION): e.g., giant cell arteritis

Infiltrative or Neoplastic Optic Neuropathy

Lymphoma

Leukemia

Sarcoidosis

Toxic/Nutritional Optic Neuropathy

Methanol, ethambutol

Vitamin B12 deficiency

Congenital Pseudopapilledema

Optic disc drusen

Hypermetropic crowded discs

Other Mimickers

Papillophlebitis (in young patients with retinal vein congestion)

Uveitis (posterior)

Hypertensive retinopathy (Grade IV with disc edema)

🧪 Workup

Neuroimaging: MRI/MRV to rule out mass lesion, thrombosis

Lumbar Puncture: Measure opening pressure, CSF analysis (after imaging)

OCT: Assess retinal nerve fiber layer thickness

Visual fields: Enlargement of blind spot common in papilledema

Fundus autofluorescence/ultrasound: To detect optic disc drusen

Review

A comprehensive review_article by Susan P. Mollan offers a timely update on the diagnosis and management of papilledema, a condition characterized by bilateral optic disc swelling due to raised intracranial pressure. The article is particularly relevant in the context of increasing cases of idiopathic intracranial hypertension (IIH), strongly correlated with the global rise in obesity 1)

A standout strength of this review lies in its emphasis on differentiating true papilledema from pseudopapilledema, a common diagnostic pitfall. The discussion on the role of optical coherence tomography (OCT) is especially valuable. The inclusion of recent imaging biomarkers and structural OCT changes improves clinical accuracy in distinguishing optic disc edema from congenital anomalies like buried optic nerve head drusen.

The article also highlights the multidisciplinary nature of papilledema care. Effective management relies on collaboration between ophthalmologists and neurologists, with shared responsibilities in both diagnosis and treatment—especially crucial when symptoms such as visual field defects and chronic headache are present.

However, the review could have benefitted from a more in-depth exploration of emerging therapies for cerebrospinal fluid (CSF) regulation. Although newer treatment pathways are mentioned, details on pharmacologic or surgical innovations are limited. Further commentary on the role of neuroimaging advancements, particularly with high-resolution MRV (magnetic resonance venography), would have added a more complete clinical picture.

In conclusion, this article is an essential read for any clinician managing patients with suspected raised intracranial pressure. It combines updated diagnostic strategies with practical insights into team-based care, although it leaves room for more discussion on therapeutic frontiers.

Difficulties occur in the differential diagnosis of papilledema against similar changes of the optic nerve head seen during ophthalmoscopy 2)

Causes of papilledema include intracranial tumors, idiopathic intracranial hypertension (pseudotumor cerebri), subarachnoid hemorrhage, subdural hematoma and intracranial inflammation. Optic disc edema may also occur from many conditions other than papilledema, including central retinal artery or vein occlusion, congenital structural anomalies, and optic neuritis 3).

References

1)

Mollan SP. Papilledema. Continuum (Minneap Minn). 2025 Apr 1;31(2):436-462. doi: 10.1212/CON.0000000000001556. PMID: 40179403.
2)

Serova NK, Eliseeva NM. Zastoinyi disk zritel’nogo nerva kak priznak vnutricherepnoi gipertenzii [Papilledema as a sign of intracranial hypertension]. Vestn Oftalmol. 2022;138(4):87-93. Russian. doi: 10.17116/oftalma202213804187. PMID: 36004596.
3)

Whiting AS, Johnson LN. Papilledema: clinical clues and differential diagnosis. Am Fam Physician. 1992 Mar;45(3):1125-34. PMID: 1543098.

Incidental meningioma active surveillance

by

Incidental meningioma active surveillance

Active surveillance is a non-interventional management strategy where the tumor is closely monitored with regular imaging and clinical assessments instead of immediate treatment.

Indications for Active Surveillance

Asymptomatic patients

Tumor discovered incidentally

Small size (< 2–3 cm)

No mass effect or brain edema

No radiological signs of aggressiveness (e.g., brain invasion, rapid growth)

The patient has significant comorbidities or advanced age

The tumor is located in an eloquent or high-risk area for surgery

Surveillance Protocol (Typical Schedule)

Baseline MRI with contrast to characterize the tumor

Follow-up MRI at 6 months

If stable → annual imaging for 5 years

If still stable → consider imaging every 2–3 years

Lifelong monitoring is most cases, especially in younger patients

Clinical Follow-up

Regular neurological exams

Monitor for new symptoms: headache, seizures, focal deficits, cognitive changes

Reassess management if:

Tumor grows (commonly defined as >2 mm/year)

New or worsening symptoms appear

Advantages of Active Surveillance Avoids risks of surgery or radiation

Preserves the quality of life in asymptomatic individuals

Many meningiomas remain stable for years or a lifetime

When to Reconsider Treatment Radiological progression (volume increase, edema, mass effect)

Symptom development

Patient preference changes

Tumor in surgically accessible location with low expected morbidity

Cohort studies

A population-based study explores the prevalence and symptomatology of incidentally found meningiomas in a specific aging population—the 70-year-olds participating in the Gothenburg H70 Birth Cohort Study. The authors analyzed MRIs from 792 individuals and found a 1.8% prevalence of incidental meningiomas, with a notable gender skew (12 of the 14 cases were female) 1)

One of the key strengths of this work is its community-based sampling, which reduces the referral bias often present in hospital-based series. It also adds valuable information to the growing body of literature supporting a more conservative treatment approach in asymptomatic or minimally symptomatic individuals, especially in the elderly.

The study challenges the reflexive assumption that nonspecific symptoms like headache or dizziness are attributable to small, incidentally found meningiomas. This is crucial, as overattribution can lead to unnecessary neurosurgical interventions, with accompanying risks and psychological burden.

On the flip side, the small absolute number of identified meningiomas (n=14) limits the statistical power to detect nuanced associations between clinical variables and tumor presence. Furthermore, the authors did not perform longitudinal follow-up to assess tumor growth or symptom progression, which could be relevant in determining the true clinical impact of these incidental findings.

In summary, this study provides solid evidence that supports watchful waiting in many cases of incidental meningioma, particularly in elderly women. It underscores the need for clinical restraint and careful consideration before attributing symptoms or deciding on intervention.

Retrospective Comparative Cohort Study with Propensity Score Matching

Hallak et al. employ a retrospective study design with propensity score matching to balance confounding factors between patients undergoing stereotactic radiosurgery (SRS) and those under active surveillance 2)

Key findings include:

  • Superior radiological control in the SRS group (97.37%) compared to observation (71.93%), with a statistically significant advantage (p < 0.01).
  • Neurological safety appears slightly compromised in SRS (1.39% new deficits), while no new deficits occurred under surveillance.
  • The need for surgical resection was low in both arms, slightly higher in the observation group (3.5% vs 0.9%), though not statistically significant (p = 0.063).
  • A trend toward lower mortality in the SRS group (9.65% vs 18.42%) was noted, yet without reaching statistical significance (p = 0.06). Notably, no deaths in the observation group were directly attributed to meningioma progression.

From a clinical decision making perspective, the study underscores the value of personalized management. While SRS offers more robust tumor control, the marginal increase in risk of neurological complication, coupled with a non-significant impact on survival or surgical rescue, suggests watchful waiting remains a valid approach—especially in patients with limited life expectancy or comorbidities.

Future prospective trials with functional outcomes, quality-of-life metrics, and cost-effectiveness analyses are needed to refine treatment algorithms. Nevertheless, this article adds weight to current trends toward de-escalation in certain low-risk neurosurgical cases.

1)

de Dios E, Näslund O, Choudhry M, Berglund M, Skoglund T, Sarovic D, Rydén L, Kern S, Skoog I, Thurin E. Prevalence and symptoms of incidental meningiomas: a population-based study. Acta Neurochir (Wien). 2025 Apr 3;167(1):98. doi: 10.1007/s00701-025-06506-7. PMID: 40178655.
2)

Hallak H, Mantziaris G, Pikis S, Islim AI, Peker S, Samanci Y, Nabeel AM, Reda WA, Tawadros SR, El-Shehaby AMN, Abdelkarim K, Emad RM, Mathieu D, Lee CC, Liscak R, Alvarez RM, Kondziolka D, Tripathi M, Speckter H, Bowden GN, Benveniste RJ, Lunsford LD, Jenkinson MD, Sheehan J. A retrospective comparison of active surveillance to stereotactic radiosurgery for the management of elderly patients with an incidental meningioma. Acta Neurochir (Wien). 2025 Feb 6;167(1):37. doi: 10.1007/s00701-025-06452-4. PMID: 39912992; PMCID: PMC11802698.

Fourth ventricle tumor surgery complications

by

Fourth ventricle tumor surgery complications

Fourth ventricle tumor surgery is delicate and carries specific risks due to the complex anatomy of the region. The fourth ventricle lies in the posterior fossa of the brain, nestled between the brainstem and cerebellum. Because of this, complications can involve vital neurological structures.

🔴 Neurological Complications

Cranial Nerve Deficits

Especially CN VI (abducens), CN VII (facial), and CN VIII (vestibulocochlear).

May cause diplopia, facial weakness, or hearing loss.

Cerebellar Dysfunction

Ataxia, dysmetria, intention tremor.

Can be transient or permanent.

Brainstem Injury

Risk of respiratory or cardiovascular instability.

It can lead to coma or death in extreme cases.

Mutism / Cerebellar Cognitive Affective Syndrome

Especially in pediatric patients after resection of medulloblastomas or ependymomas.

Characterized by mutism, emotional lability, and executive dysfunction.

💧 CSF-related Complications

Hydrocephalus (pre- or post-operative)

Due to obstruction of CSF pathways (aqueduct or outlets of the fourth ventricle).

May require an external ventricular drain (EVD) or VP shunt.

CSF Leak / Pseudomeningocele

From poor dural closure or pressure buildup.

Risk of infection or wound healing issues.

Meningitis / Ventriculitis

Especially if there’s a CSF leak or prolonged drain use.

💉 Vascular Complications

Hemorrhage

Intraoperative bleeding from a tumor or surrounding vessels.

Postoperative hematoma causing brainstem compression.

Ischemia

Injury to perforating arteries (e.g., branches of the posterior inferior cerebellar artery – PICA).

It can cause infarcts in the brainstem or cerebellum.

🛌 Systemic and General Complications

Infection

Seizures (rare for the posterior fossa)

Respiratory compromise (especially in children or after brainstem manipulation)

Wound complications

🧠 Tumor-specific factors

Ependymomas: Adherence to the floor of the 4th ventricle increases brainstem injury risk.

Medulloblastomas: prone to CSF spread, so thorough surgical and oncologic planning is key.

Choroid plexus tumors: highly vascular, bleeding risk.

Cohort studies

In a large multicenter cohort study Persson et al. investigate postoperative word-finding abilities in children undergoing posterior fossa tumor surgery (PFTs), with data from 184 children across Europe. The authors address a critical yet understudied postoperative complication—word-finding difficulty, which goes beyond classic cerebellar mutism syndrome (CMS) and focuses on more subtle higher-order language impairments 1)

The study’s key strength lies in its pre- and postoperative comparisons using a speeded picture-naming test, providing quantitative insights into word retrieval speeds. Interestingly, the results reveal no significant change between pre- and postoperative performance on average. This means that while some children improved, others declined, underscoring the heterogeneous outcomes in PFT surgeries.

A striking finding is that 95% of children performed more than two standard deviations slower than age norms after surgery, despite no aggregate decline. This discrepancy suggests that even without a gross drop in individual scores, the cohort as a whole demonstrates clinically significant delays, potentially overlooked in standard assessments.

The study identifies fourth ventricle tumor as a specific risk factor (B = -4.09, p < 0.05), linking it to possible damage of the dentato-thalamo-cortical pathway. This aligns with previous neuroanatomical models implicating cerebellar-thalamo-cortical circuits in language function, not just motor planning.

From a clinical perspective, these findings call for routine postoperative language screening—even in patients who do not develop mutism—to detect subtle deficits that may affect communication and academic performance. Furthermore, early intervention strategies may be needed, particularly for children with tumours in higher-risk locations.

This study contributes valuable evidence supporting the existence of subtle yet functionally important postoperative language impairments in children with PFTs. It urges the neurooncology and neuropsychology communities to broaden the scope of postoperative assessments to include not only mutism but also word-finding and higher cognitive-linguistic functions.

1)

Persson K, Grønbæk J, Tiberg I, Fyrberg Å, Castor C, Andreozzi B, Frič R, Hauser P, Kiudeliene R, Mallucci C, Mathiasen R, Nyman P, Pizer B, Sehested A, Boeg Thomsen D; CMS study group. Postoperative word-finding difficulties in children with posterior fossa tumours: a crosslinguistic European cohort study. Childs Nerv Syst. 2025 Mar 12;41(1):128. doi: 10.1007/s00381-025-06787-4. PMID: 40075014; PMCID: PMC11903548.

Meningioma grade

by

Meningioma grade

World Health Organization grade 1 meningioma.

World Health Organization grade 2 meningioma.

World Health Organization grade 3 meningioma.

The current system of grading has been shown to be unsatisfactory due to its poor reproducibility as well as the considerable variability within grades. With the increasing availability of genomic and epigenomic profiling, several markers have been suggested to correlate with the location, histological subtype, and clinical behavior of meningiomas. These developments have enabled the development of targeted therapy, as well as individualized use of currently available adjuvant methods. These include copy number alterations (CNAs), specific genetic abnormalities (germline and sporadic), and genome-wide methylation profiles 1).

Cohort Studies

Chromosome 1p Loss and 1q Gain for Grading of Meningioma

Type of study: Cohort Study Citation: JAMA Oncol. 2025 Apr 3. doi: 10.1001/jamaoncol.2025.0329. Online ahead of print.

Authors: Alexander P. Landry et al. PMID: 40178835

Critical Review

This multicenter cohort study spanning institutions in Canada, the US, and Germany offers a compelling contribution to the evolving field of molecular neuropathology and meningioma grading. It critically addresses the limitations of the 2021 WHO CNS classification, which incorporated rare markers like homozygous deletion of CDKN2A an B and TERT promoter mutations, by proposing more broadly applicable cytogenetic criteria based on copy number alterations 2).

Key findings include:

  • Loss of chromosome 1p in WHO grade 1 meningiomas correlates with significantly reduced progression-free survival (PFS), approximating outcomes of WHO grade 2 tumors.
  • Combined 1p loss and 1q gain predicted outcomes similar to WHO grade 3, regardless of histopathological grade.
  • These alterations show strong prognostic power, suggesting their inclusion could refine and personalize the current WHO CNS grading system.

The study’s strength lies in its large sample size (n = 1964), long follow-up, and integration of genomic and clinical data. Its statistical approach—mainly Cox regression analysis—was well-suited to evaluate prognostic factors across grades. The authors convincingly demonstrate that current grading overlooks key genomic drivers of progression and recurrence.

Clinical implications:

Incorporating 1p loss as a criterion for WHO grade 2 and 1q gain for WHO grade 3 would allow for a more accurate risk stratification and better patient management. This aligns with the current momentum in neuro-oncology to move beyond histology and adopt integrated molecular grading—already in place for entities like glioma.

Limitations:

  • Although multicenter, some variability in pathology protocols and treatment across sites could have introduced bias.
  • Radiation exposure was not uniformly reported, which could affect PFS independently of genetic markers.
  • The study does not explore the cost or feasibility of widespread cytogenetic screening, which is critical for real-world application.

Conclusion:

This paper is a significant step toward a more nuanced and genomically-informed meningioma classification system. The proposed inclusion of chromosome 1p loss and 1q gain into future WHO grading guidelines deserves serious consideration by the neuro-oncologic community and classification committees.

Back to meningioma section

1)

Goyal-Honavar A, Jayachandran R, Chacko G. Meningiomas – transition from traditional histological grading to molecular profiling in WHO CNS5: A Review. Indian J Pathol Microbiol. 2022 May;65(Supplement):S83-S93. doi: 10.4103/ijpm.ijpm_1085_21. PMID: 35562138.
2)

Landry AP, Wang JZ, Patil V, Liu J, Gui C, Ellenbogen Y, Ajisebutu A, Yefet L, Wei Q, Singh O, Sosa J, Mansouri S, Cohen-Gadol AA, Tabatabai G, Tatagiba M, Behling F, Barnholtz-Sloan JS, Sloan AE, Chotai S, Chambless LB, Mansouri A, Makarenko S, Yip S, Ehret F, Capper D, Tsang DS, Moliterno J, Gunel M, Wesseling P, Sahm F, Aldape K, Gao A, Zadeh G, Nassiri F. Chromosome 1p Loss and 1q Gain for Grading of Meningioma. JAMA Oncol. 2025 Apr 3. doi: 10.1001/jamaoncol.2025.0329. Epub ahead of print. PMID: 40178835.

Mayo Clinic Vestibular Schwannoma Quality of Life Index 

by

“Improving access to vestibular schwannoma quality of life research through multilanguage translations of the Mayo Clinic Vestibular Schwannoma Quality of Life Index” (*Carlson et al., J Neurosurg. 2025;142(Suppl):S2. doi:10.3171/2024.11.JNS242317*)

This article reports on the translation of the Mayo Clinic Vestibular Schwannoma Quality of Life Index into six widely spoken languages: Simplified Chinese, Spanish, Japanese, Arabic, French, and Norwegian. It is presented as a digital supplement to the *Journal of Neurosurgery* and is positioned as a response to a key limitation in vestibular schwannoma research: the lack of validated, multilingual tools to assess the quality of life (QOL) in a culturally diverse patient population.

The VSQOL Index, developed originally in English, is a domain-specific tool covering eight core categories that reflect the multidimensional burden of VS, ranging from hearing loss to psychosocial and cognitive impacts. The article emphasizes accessibility, global equity in research, and the potential for cross-cultural validation.

2. Strengths

– Timely and Inclusive Effort: In a field increasingly aware of the importance of patient-reported outcomes (PROs), the expansion of the VSQOL Index to multiple languages addresses a real and urgent need. The effort reflects a commitment to diversity, equity, and inclusion (DEI) in neurosurgical research.

– Breadth of Domains: The eight domains covered are comprehensive and clinically relevant, reflecting an understanding of VS as a condition that affects patients beyond physical symptoms.

– Noncommercial Open Access: Making the tool freely available for noncommercial use significantly boosts its adoption potential in both research and clinical settings.

– Forward-Looking Implementation Strategy: By inviting further translations and offering a methodology for doing so, the authors promote scalability and community collaboration.

3. Limitations and Areas for Improvement

– Lack of Validation Data for Translations: A critical omission is the absence of psychometric validation data for the translated versions. Translation alone does not ensure cultural equivalence or measurement validity. Were back-translations performed? Were cognitive interviews or pilot tests conducted in native-speaking populations?

– No Discussion on Linguistic/Cultural Adaptation Challenges: Certain concepts (e.g., “regret” or “impact on employment”) may not translate directly or may have different cultural connotations, particularly in non-Western contexts. This nuance is missing.

– Digital Supplement Format: The article feels more like a resource announcement than a full scientific paper. There’s no detailed methodology on how the translations were produced, reviewed, or tested. A table comparing the original and translated items or discussing challenges in specific languages would have enriched the value.

– Unclear How This Affects Clinical Decision-Making: Although QOL is important, the article could have outlined practical examples of how this tool has been or could be used to guide treatment planning, shared decision-making, or monitoring outcomes in real-world clinics.

4. Future Directions

– Cross-Cultural Validation Studies: Essential next steps include conducting validation study in diverse populations to confirm that the VSQOL Index is both reliable and sensitive across languages and cultures.

– Integration into Registries and Trials: The authors could propose integrating the VSQOL Index into prospective multicenter studies or national registries, which would increase the visibility and utility of the tool.

– Digital Implementation: The use of a mobile app or integration with electronic health records (EHRs) for real-time patient input could enhance its impact and usability in clinical workflows.

Conclusion

Carlson et al. make a significant and commendable contribution to the field of vestibular schwannoma research by expanding the reach of a multidimensional QOL assessment tool through multilingual translation. However, to truly fulfill its potential, the translated versions must undergo rigorous psychometric validation, and future work should aim to embed the Index in clinical and research settings more explicitly. As it stands, this is a valuable first step—but just the beginning—in making QOL data accessible and actionable in a globalized neurosurgical landscape.

Monocarboxylate transporter

by

Monocarboxylate transporter

Monocarboxylate transporters (MCTs) are a family of membrane proteins that mediate the transport of monocarboxylates such as lactate, pyruvate, and ketone bodies across the plasma membrane, often coupled with H⁺ ions. These transporters are essential for maintaining intracellular and extracellular pH homeostasis and supporting metabolic adaptation, particularly under hypoxic and glycolytic conditions common in malignant tumors.

🔍 MCTs in Glioma Pathobiology

🧬 Key Isoforms: MCT1 (SLC16A1): High affinity for lactate, expressed in both oxidative and glycolytic cells.

MCT4 (SLC16A3): Low affinity but high capacity, induced by hypoxia-inducible factor 1 (HIF-1α) and upregulated in highly glycolytic, hypoxic tumors.

MCT2 (SLC16A7): Highest affinity for lactate, recently recognized for its nuanced regulation in astrocytes and glioma cells in response to pH, hypoxia, glucose, and lactate, as shown by Caruso et al. 1).

🧪 Molecular Functions in GBM: Glioblastoma (GBM), the most aggressive primary brain tumor, exhibits a hallmark aerobic glycolytic phenotype (Warburg effect), leading to excessive lactate production. MCT1 and MCT4 mediate lactate efflux to prevent “self-poisoning,” facilitating:

Tumor cell survival under metabolic stress

Invasion of surrounding tissue

Immune evasion via acidic microenvironment

🏥 Relevance in Neurosurgical Practice 1. Tumor Aggressiveness & Surgical Planning High MCT1/4 expression correlates with aggressive tumor biology in GBM 2)

Their presence may mark invasive margins or hypoxic cores, which are difficult to resect and more likely to recur. Future intraoperative imaging (e.g., hyperpolarized MRI or pH-sensitive probes) may enable visualization of metabolically active MCT-rich zones to optimize resection margins.

2. Pathological Diagnosis and Immunohistochemistry MCT1/4 immunoreactivity can aid in distinguishing IDH-wildtype GBM from lower-grade gliomas when molecular data is incomplete. Pathologists and neurosurgeons may use MCT staining to infer tumor grade, prognosis, and potential therapeutic vulnerability.

3. Adjunctive Therapies Post-Resection Targeting MCTs offers a metabolism-based adjuvant approach.

Syrosingopine, a dual MCT1/4 inhibitor with CNS penetration, demonstrates apoptotic and anti-invasive effects in glioma cell lines and is a candidate for clinical repurposing.

Combined therapies (e.g., with metformin) may synergize to exhaust tumor metabolic plasticity.

4. Neurosurgical Research and Innovation MCTs are a valuable focus in translational neuro-oncology:

Biopsy targeting, tumor banking, and delivery of MCT inhibitors (e.g., via convection-enhanced delivery) are emerging research avenues.

Understanding the pH-lactate-hypoxia interplay via MCT regulation (as described by Caruso et al.) may lead to new molecular imaging markers or pH-responsive delivery systems.

⚠️ Current Limitations

No MCT-targeting therapy is yet approved for clinical neurosurgical use.

Expression heterogeneity within tumors and across patients complicates therapeutic targeting.

Isoform-specific inhibitors with safe CNS profiles are needed.

Non-invasive radiological detection of MCT activity is still under development.

🧩 Clinical Takeaway for Neurosurgeons

Monocarboxylate transporters—particularly MCT1 and MCT4—are more than molecular curiosities; they are critical markers and mediators of glioma aggressiveness. Their expression informs diagnosis, surgical planning, and offers a metabolic Achilles’ heel that could be exploited through adjuvant therapy. As glioma therapy moves toward precision medicine, MCTs represent a bridge between metabolic biology and neurosurgical practice.

References

1)

Caruso JP et al. pH, Lactate, and Hypoxia: Reciprocity in Regulating High-Affinity Monocarboxylate Transporter Expression in Glioblastoma. Neoplasia. 2017;19(2):121-134. doi: 10.1016/j.neo.2016.12.011.
2)

Behera MM et al. The Monocarboxylate Transporters MCT1 and MCT4 Are Highly Expressed in Glioblastoma and Crucially Implicated in the Pathobiology. Neuropathology. 2025 Mar 27. doi: 10.1111/neup.70006. PMID: 40145253.

Arginine Vasopressin Deficiency Diagnosis

by

🧪 Arginine Vasopressin Deficiency Diagnosis

(*formerly known as Central Diabetes Insipidus*)

🧠 Background

Deficiency results in:

Common causes:

🔍 Initial Assessment

Test Finding in AVP Deficiency
Serum sodium Often elevated
Plasma osmolality >295 mOsm/kg
Urine osmolality <300 mOsm/kg
Urine specific gravity <1.005 g/mL

💧 Water Deprivation Test (optional if diagnosis unclear)

see Water Deprivation Test

– Progressive fluid restriction – Measure: body weight, plasma osmolality, urine osmolality – Administer desmopressin (DDAVP) when appropriate

Finding AVP-D (Central) Nephrogenic DI Primary Polydipsia
Baseline urine osm Low Low Low-normal
Response to DDAVP ↑ >50% No change Slight ↑

🧠 Imaging

* Pituitary MRI to rule out structural causes * Look for loss of posterior pituitary bright spot

🏥 Postoperative Bedside Screening

Red flags (first 72h post-surgery):

  • Urine output >250 mL/h for 2–3 h
  • Urine SG <1.005 g/mL
  • Rising serum sodium >145 mmol/L

Patient self-monitoring strategy:

  • Use urine dipsticks (e.g., Combur-10)
  • Cut-off ≥1.015 g/mL reliably excludes hypotonic urine

→ Reduces need for nurse-led testing by ~50% 1).

It advances the concept of patient-participatory diagnostics and offers a replicable approach to screen for AVP-D. With thoughtful implementation, it has the potential to optimize workflows and empower patients, though accuracy limitations and clinical oversight remain essential.

👤 Patient Self-Monitoring Strategy for AVP Deficiency

Self-monitoring of urine specific gravity (SG) offers a non-invasive, accessible method for early identification of Arginine vasopressin deficiency (AVP-D) — particularly useful in the early postoperative period after pituitary surgery.

🎯 Objective

To enable patients to detect hypotonic urine (SG < 1.005 g/mL), a hallmark of AVP-D, using simple tools and clear thresholds, reducing reliance on continuous nurse monitoring.

🧪 Tools Required

Tool Description
Urine dipsticks e.g., Combur-10 test strips
SG reference chart Provided to patient (color guide or numeric)
Fluid intake/output diary Optional but useful
Basic education Brief verbal or written instructions

📌 Step-by-Step Monitoring Protocol

1. Frequency: Every 2–4 hours during the first 72h post-op (or as indicated) 2. Record:

  1. Urine SG using dipstick
  2. Time of measurement
  3. Urine volume (if known)

3. Interpretation:

  1. If SG < 1.005 → Alert nurse or clinician
  2. If SG ≥ 1.015 → No action needed

4. Look for associated symptoms:

  1. Excessive thirst (polydipsia)
  2. Frequent urination (polyuria)
  3. Light-colored or clear urine
  4. Dizziness or fatigue

A threshold of 1.015 g/mL is considered safe to rule out hypotonic urine and avoid missing AVP-D, based on current evidence.

✅ Advantages

  • Reduces nurse-led SG testing by ~50% 2)
  • Promotes early detection of AVP-D
  • Encourages patient engagement and education
  • Minimizes unnecessary interventions

⚠️ Considerations

  • Patients must be briefly trained on dipstick use and interpretation
  • Not suitable for:
    1. Patients with cognitive impairment
    2. Pediatric patients (without caregiver)
    3. Severe visual deficits
  • Always confirm low SG findings with clinical review and serum sodium

Combine self-monitoring of SG with daily weight and serum sodium trends for robust early detection of AVP-D in neurosurgical patients.

✅ Summary Table

Step Goal
Clinical evaluation Identify symptoms: polyuria, polydipsia
Serum/urine osmolality Confirm dilute urine & hyperosmolar plasma
Water deprivation test Differentiate AVP-D from other causes
Pituitary MRI Identify structural abnormalities
Urine SG monitoring post-op Early detection & workload reduction

When feasible, train patients to monitor urine SG using dipsticks. Use a safety threshold (SG ≥ 1.015) to minimize false negatives.

🔬 Imaging & Laboratory Markers of Diabetes Insipidus (DI)

🧠 T1-weighted MRI: Hyperintensity and ADH

Antidiuretic hormone (ADH) appears as a hyperintensity (HI) on T1-weighted magnetic resonance imaging in:

Key findings:

  • Disappearance of HI in the posterior lobe is a marker of ADH deficiency, often observed in DI.
  • Appearance of HI in the stalk suggests disturbances in ADH transport.

3)

💉 Serum Sodium: Perioperative Laboratory Markers

* An increase in serum sodium ≥2.5 mmol/L is a positive marker of postoperative diabetes insipidus with:

  • 80% specificity

* A serum sodium ≥145 mmol/L postoperatively indicates DI with:

  • 98% specificity

These thresholds help identify patients at risk and guide early treatment decisions after endoscopic transsphenoidal surgery (ETSS).

4)

Early changes in T1 hyperintensity and postoperative serum sodium can serve as non-invasive predictors of DI and support clinical decision-making.

References

1)

Nollen JM, Brunsveld-Reinders AH, Biermasz NR, Verstegen MJT, Leijtens E, Peul WC, Steyerberg EW, van Furth WR. Patient Participation in Urine Specific Gravity Screening for Arginine Vasopressin Deficiency in an Inpatient Neurosurgical Clinic. Clin Endocrinol (Oxf). 2025 Mar 27. doi: 10.1111/cen.15241. Epub ahead of print. PMID: 40145244.
2)

Nollen JM et al., *Clin Endocrinol (Oxf)*, 2025
3)

Hayashi Y, Kita D, Watanabe T, Fukui I, Sasagawa Y, Oishi M, Tachibana O, Ueda F, Nakada M. Prediction of postoperative diabetes insipidus using morphological hyperintensity patterns in the pituitary stalk on magnetic resonance imaging after transsphenoidal surgery for sellar tumors. *Pituitary*. 2016 Dec;19(6):552-559. PMID: 27586498
4)

Schreckinger M, Walker B, Knepper J, Hornyak M, Hong D, Kim JM, Folbe A, Guthikonda M, Mittal S, Szerlip NJ. Post-operative diabetes insipidus after endoscopic transsphenoidal surgery. *Pituitary*. 2013 Dec;16(4):445-51. PMID: 23242859