Management

Antihypertensive Medication After Intracerebral Hemorrhage

by

Antihypertensive Medication After Intracerebral Hemorrhage

Latest PubMed Articles

🧠 1. Acute Phase Management (First Hours to Days)

🎯 Goal: Reduce hematoma expansion and improve outcomes

Target Blood Pressure (BP):

  • SBP 150–220 mmHg → Lower to <140 mmHg is generally safe and may improve outcomes (AHA/ASA 2022)
  • SBP >220 mmHg → Consider aggressive reduction with ICU-level monitoring

IV Antihypertensives:

Drug Class Notes
Labetalol α/β-blocker Often first-line; good for rapid BP control
Nicardipine Calcium channel blocker Preferred for titratable infusion
Clevidipine Calcium channel blocker Short half-life, easily adjustable
Esmolol β1-selective blocker Useful for short-term, fast-acting control
Hydralazine Direct vasodilator Less predictable; not first-line

Avoid: Overly rapid BP drops, especially with elevated intracranial pressure (ICP)

🔁 2. Secondary Prevention (Long-Term Management)

🎯 Goal: Prevent recurrent ICH and vascular events

BP Target:

  • Long-term: SBP <130 mmHg
  • Avoid SBP <110 mmHg (risk of hypoperfusion)

Preferred Antihypertensive Classes:

Class Example Notes
ACE inhibitors Enalapril, Ramipril Good stroke prevention evidence
ARBs Losartan, Candesartan Well tolerated alternative to ACEi
Thiazide diuretics Hydrochlorothiazide Often used in combo therapy
Calcium channel blockers Amlodipine Useful as monotherapy or in combinations

Key Trials:

📌 Clinical Pearls

  • Titrate IV to oral meds with continuous monitoring
  • Consider Spontaneous Intracerebral Hemorrhage Etiology (hypertensive vs amyloid-related) for long-term goals
  • Tailor treatment to age, comorbidities, renal function, and prior drug response

TRICH Score

In a prospective cohort study with external validation study components, the authors used data from a longitudinal ICH registry (2011–2022) for score development and validated the model prospectively in three independent hospitals (2020–2022) 1)

The study aims to develop and validate a clinical score (the TRICH score) to predict the need for ≥3 antihypertensive medications three months after intracerebral hemorrhage (ICH), to guide early and individualized blood pressure management.

Clinically Relevant Tool: The TRICH score addresses a clear clinical need: stratifying patients by future antihypertensive needs post-ICH.

– Well-Defined Cohorts: The development and validation cohorts are clearly defined and separate, lending credibility to the generalizability within the studied population.

– Statistical Rigor: The use of multivariate logistic regression, β-coefficients for score construction, and AUC for model performance are standard and appropriate.

– Good Discrimination: The TRICH score achieved a c-statistic of 0.79 in the development and 0.76 in the validation cohort, indicating good predictive performance.

– Subgroup Analyses: The study explores performance in subgroups (e.g., uncontrolled hypertension vs controlled, CAA vs non-CAA), which is useful for clinical interpretation.

Limitations

– Ethnic Homogeneity: All participants were from Hong Kong hospitals, likely representing predominantly Han Chinese patients. This limits external validity, especially in multiethnic or Western populations.

– Short Follow-up: The score is tailored to predict medication needs at 3 months. It remains unclear whether it has predictive power for long-term hypertension control or cardiovascular outcomes.

– Exclusion Criteria Bias: Patients who died before 90 days or lacked follow-up were excluded. These patients might represent a higher-risk group, potentially introducing survivorship bias.

– Simplification Risks: While score simplification (e.g., dichotomizing age or BP ranges) improves usability, it may reduce nuance in individual patient profiles.

The TRICH score has the potential to assist clinicians in initiating early intensive antihypertensive therapy in appropriate post-ICH patients, especially those with a high risk of needing triple therapy. However, caution is warranted to avoid overtreatment in those with transient BP elevation due to acute stress or underlying cerebral amyloid angiopathy.

The model performed better in patients with previously uncontrolled or untreated hypertension, reinforcing its value in guiding care where hypertension is known but uncontrolled. Lack of differentiation in patients with or without CAA suggests that further refinements or adjunct markers may be needed for this subgroup.

Future Directions

– External validation in diverse populations, including Caucasian, African descent, and South Asian cohorts.

– Integration of biomarkers or imaging (e.g., MRI markers of CAA) to refine predictions.

– Evaluation of the TRICH score’s impact on clinical outcome when used in routine care.

Conclusion

This well-conducted cohort study introduces a practical clinical tool—the TRICH score—for anticipating antihypertensive requirements after ICH. Despite its promise, broader validation and studies on downstream outcomes are essential before widespread implementation.

1)

So CH, Yeung C, Ho RW, Hou QH, Sum CHF, Leung W, Wong YK, Liu KCR, Kwan HH, Fok J, Yip EK, Sheng B, Yap DY, Leung GKK, Chan KH, Lau GKK, Teo KC. Triple Antihypertensive Medication Prediction Score After Intracerebral Hemorrhage (the TRICH Score). Neurology. 2025 May 13;104(9):e213560. doi: 10.1212/WNL.0000000000213560. Epub 2025 Apr 4. PMID: 40184593.

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.

Disparities and Variability in Hospital Management of Mild Traumatic Brain Injury

by

Disparities and Variability in Hospital Management of Mild Traumatic Brain Injury

Latest Pubmed Titles

1. Socioeconomic Disparities

Insurance status significantly influences management decisions:

Uninsured patients are less likely to be admitted, even when clinical factors may justify observation.

Privately insured or Medicare/Medicaid-covered individuals often receive more resource-intensive care, including imaging, neurosurgical consults, and longer admissions.

2. Racial and Ethnic Disparities

Non-White, non-Black, non-Hispanic patients may experience:

Lower odds of discharge to home

Longer hospital stays but not necessarily associated with better outcomes

Potential underuse or delayed access to follow-up care (rehabilitation, neuropsychology)

3. Hospital-Level Variability

Wide differences exist between hospitals in:

Admission rates for mTBI

Length of stay (LOS) for admitted patients

Discharge disposition (home vs. skilled nursing facility vs. rehab)

Level 1 trauma centers tend to have longer LOS, but paradoxically, their patients are less likely to be discharged home, possibly reflecting:

More cautious or protocol-driven care

Complex patient populations

System inefficiencies or defensive medicine practices

4. Geographic Variation

Rural vs. urban hospitals may differ in resource availability:

Rural centers might discharge more patients directly from the ED due to lack of neuroimaging or neurosurgical backup.

Urban or academic centers may admit more patients for observation and follow-up care coordination.

5. Clinical Protocols and Decision Tools

Variability is also driven by a lack of standardization:

Some centers use evidence-based decision rules (e.g., Canadian CT Head Rule), while others rely on individual clinician judgment.

Institutional differences in admission criteria for elderly patients, those on anticoagulants, or those with minor CT findings.

🧩 Implications for Practice and Policy

Disparities in mTBI care may lead to:

Under-treatment of vulnerable populations

Over-utilization in low-risk cases due to defensive medicine

Inefficient use of hospital resources

There’s a growing need for:

Nationally standardized care pathways

Cultural competence training

Policy reform targeting access and equity

Quality benchmarking across institutions

Scoping reviews

A scoping review, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, was used to explore three electronic databases- PubMed, Medline, and CINAHL. Searches identified peer-reviewed empirical literature addressing aspects of the Social determinants of health and HDs related to TBI. A total of 123 records were identified and reduced to 27 studies based on the inclusion criteria. Results revealed that race/ethnicity was the most commonly reported Social determinant of health impacting TBI, followed by an individual’s insurance status. Health disparities were noted to occur across the continuum of TBI, including TBI risk, acute hospitalization, rehabilitation, and recovery. The most frequently reported HD was that Whites are more likely to be discharged to inpatient rehabilitation compared to racial/ethnic minorities. Health disparities associated with TBI are most commonly associated with the race/ethnicity SDoH, though insurance status and socioeconomic status commonly influence health inequities as well. The additional need for evidence related to the impact of other, lesser-researched SDoH is discussed, as well as clinical implications that can be used to target intervention for at-risk groups using an individual’s known Social determinants of health 1)

Retrospective observational cohort studies

A total of 122,406 patients with mTBI were included.

Vattipally et al. performed hierarchical logistic regression to investigate associations of patient-level variables with inpatient admission. Among hospitalized patients, a hierarchical linear regression was constructed for associations with LOS, including hospitals as a random effects term. Based on random effects coefficients, hospitals were classified as high-LOS outliers or non-outliers.

Main measures: Univariable comparisons on facility characteristics were performed. Patients were propensity score matched across hospital outlier status, and a multivariable logistic regression for associations with discharge to home was performed.

Results: The median age was 63 years (interquartile range [IQR], 42-77 years), and 111 306 (91%) patients experienced inpatient admission. Uninsured status was associated with lower odds of inpatient admission (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.65-0.76; P < .001). After excluding very low-volume hospitals, 80,258 admitted patients were treated across 469 hospitals, and 98 were designated as high-LOS outliers. These were more likely to be Level 1 trauma centers (76% vs. 26%; P < .001). After matching, patients treated at high-LOS outlier hospitals were less likely to experience home discharge (OR, 0.89; 95% CI, 0.85-0.93; P < .001). This effect was amplified for patients identifying as non-White, non-Black, non-Hispanic other races (P = .003).

Inpatient admission after mTBI varies by insurance status, with uninsured patients less likely to be admitted. There is significant interhospital variation in LOS, with Level 1 trauma centers more likely to be high-LOS outliers. Despite their longer LOS, patients treated at outlier hospitals experienced lower odds of home discharge 2).

This study provides valuable evidence on disparities and variability in the hospital management of patients with mild traumatic brain injury (mTBI) in the United States. Using a large national dataset and robust statistical methods, the authors demonstrate that factors such as insurance status, hospital type, and patient race/ethnicity significantly influence decisions around hospital admission, length of stay (LOS), and likelihood of discharge to home.

However, the retrospective design and reliance on administrative data limit causal interpretation and prevent adjustment for key clinical variables. The classification of hospitals as LOS outliers should also be interpreted with caution, as longer stays may reflect more comprehensive care or greater patient complexity, rather than inefficiency.

Overall, the study highlights the urgent need for healthcare policies aimed at reducing inequities and standardizing care criteria for mTBI, while still respecting patient-level nuances and hospital contexts. Future research should integrate more detailed clinical data and explore targeted interventions to improve both equity and efficiency in mTBI care.

A secondary analysis of ED visits in the National Hospital Ambulatory Medical Care Survey for the years 1998 through 2000 was performed. Cases of mTBI were identified using ICD-9 codes 800.0, 800.5, 850.9, 801.5, 803.0, 803.5, 804.0, 804.5, 850.0, 850.1, 850.5, 850.9, 854.0, and 959.01. ED care variables related to imaging, procedures, treatments, and disposition were analyzed along racial, ethnic, and gender categories. The relationship between race, ethnicity, and selected ED care variables was analyzed using multivariate logistic regression with control for associated injuries, geographic region, and insurance type.

The incidence of mTBI was highest among men (590/100,000), Native Americans/Alaska Natives (1026.2/100,000), and non-Hispanics (391.1/100,000). After controlling for important confounders, Hispanics were more likely than non-Hispanics to receive a nasogastric tube (OR, 6.36; 95% CI = 1.2 to 33.6); nonwhites were more likely to receive ED care by a resident (OR, 3.09; 95% CI = 1.9 to 5.0) and less likely to be sent back to the referring physician after ED discharge (OR, 0.47; 95% CI = 0.3 to 0.9). Men and women received equivalent ED care.

There are significant racial and ethnic but not gender disparities, in ED care for mTBI. The causes of these disparities and the relationship between these disparities and post-mTBI outcome need to be examined 3).

1)

Johnson LW, Diaz I. Exploring the Social Determinants of Health and Health Disparities in Traumatic Brain Injury: A Scoping Review. Brain Sci. 2023 Apr 23;13(5):707. doi: 10.3390/brainsci13050707. PMID: 37239178; PMCID: PMC10216442.
2)

Vattipally VN, Jiang K, Weber-Levine C, Kramer P, Davidar AD, Hersh AM, Winkle M, Byrne JP, Azad TD, Theodore N. Patient and Hospital Factors Associated With Hospital Course for Patients With Mild Traumatic Brain Injury. J Head Trauma Rehabil. 2025 Apr 1. doi: 10.1097/HTR.0000000000001056. Epub ahead of print. PMID: 40167490.
3)

Bazarian JJ, Pope C, McClung J, Cheng YT, Flesher W. Ethnic and racial disparities in emergency department care for mild traumatic brain injury. Acad Emerg Med. 2003 Nov;10(11):1209-17. doi: 10.1111/j.1553-2712.2003.tb00605.x. PMID: 14597497.

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

Peginterferon alfa-2a for cystic craniopharyngioma treatment

by

Peginterferon alfa-2a for cystic craniopharyngioma treatment

J.Sales-Llopis

Neurosurgery Department, General University Hospital Alicante, Spain

Craniopharyngiomas, especially their cystic forms, pose unique management challenges due to their proximity to critical neurovascular structures. Intracystic therapies offer a minimally invasive alternative to repeated surgical interventions. Over the past decade, interferon-alfa-2a/2b emerged as a viable intracystic treatment due to its anti-proliferative and immune-modulating properties, coupled with low toxicity. However, discontinuation of commercial availability prompted the search for alternatives.

Hedrich et al. describes a retrospective case series, including five patients with intracystic peginterferon alfa-2a for cystic craniopharyngioma treatment according to an innovative care protocol. After initial CP cyst aspiration, peginterferon alfa-2a was injected once per week via an Ommaya reservoir for 6 weeks followed by response assessment with MRI.

Patients’ age ranged from 4 to 54 years (four patients <12 years, one adult patient). Intracystic therapy with peginterferon alfa-2a was tolerated well by all five individuals without any major toxicities and resulted in cyst shrinkage in all of the five patients. The importance of a permeability study prior to commencing intracystic therapy became apparent in one patient who suffered from cyst leakage.

Intracystic treatment with peginterferon alfa-2a was found to be a tolerable and efficacious treatment modality in patients with cystic craniopharyngioma. This experience warrants further research with a larger number of patients with measurement of long-term efficacy and safety outcomes 1).

The authors propose peginterferon alfa-2a, a pegylated form with extended half-life and established safety profile in other indications, as a substitute, presenting a retrospective case series evaluating its feasibility and safety.

Study Design and Methodology

– Design: Retrospective case series

– Sample: 5 patients (age 4–54; 4 children, 1 adult)

– Protocol: After initial cyst aspiration, peginterferon alfa-2a was administered weekly for 6 weeks via an Ommaya reservoir.

– Follow-up: MRI for response assessment

– Pre-treatment: Permeability study was highlighted as essential following one adverse case of leakage.

🔎 Strengths:

– Innovative use of peginterferon alfa-2a to fill a therapeutic gap.

– Uniform protocol across cases.

– Clear documentation of safety and early efficacy.

– Broad age range increases generalizability.

⚠️ Limitations:

– Very small sample size (n=5) limits statistical validity.

– Retrospective nature introduces potential bias and lacks standardized outcome metrics.

– Short-term follow-up; no data on recurrence, endocrine impact, or long-term survival.

– No comparator group (e.g., standard interferon alfa-2a or surgery-only) limits interpretation of relative efficacy.

Results

– Safety: No major toxicities reported in any patient.

– Efficacy: Cyst shrinkage achieved in all five patients.

– Complication: One patient experienced leakage, underscoring the need for a permeability test.

The data supports the hypothesis that peginterferon alfa-2a is a safe and potentially effective intracystic agent in this context.

Discussion and Clinical Relevance

This study provides preliminary real-world evidence that peginterferon alfa-2a can serve as an effective intracystic treatment option for cystic craniopharyngiomas, particularly important in the wake of discontinued access to interferon alfa-2a. The lack of significant toxicity is encouraging, especially in pediatric patients.

However, due to the small number of cases and lack of long-term outcome data, the findings should be interpreted as hypothesis-generating rather than practice-changing. Further research in prospective, multi-institutional trials with larger cohorts is warranted.

Conclusion Hedrich et al. offer a promising alternative approach for managing cystic craniopharyngiomas using peginterferon alfa-2a. The treatment appears feasible, safe, and effective in the short term. Yet, the study’s limitations — particularly its size and retrospective design — mean that broader validation is essential before widespread clinical adoption.

Comparative Analysis of Intracystic Treatments

Peginterferon alfa-2a vs Bleomycin vs Radioisotopes

Feature/Agent Peginterferon alfa-2a Bleomycin Radioisotopes (e.g., P-32, Y-90)
Mechanism of Action Immunomodulatory and antiproliferative Cytotoxic antibiotic causing DNA strand breaks Beta radiation causing localized cyst wall necrosis
Dosing Protocol Weekly x6 via Ommaya Multiple instillations (e.g., 4–6 doses over weeks) Single or repeated instillation; dosimetry-based
Age Use Pediatric and adult Caution in young children due to neurotoxicity Generally avoided in children <5–6 years old
Safety Profile Excellent short-term tolerability in small series Risk of chemical meningitis, neurotoxicity Risk of CSF leak, radiation necrosis, hypothalamic damage
Key Risks Cyst leakage (1 case in 5); minimal toxicity Seizures, necrosis if drug leaks to parenchyma Radiation exposure to critical adjacent structures
Regulatory Access Off-label, emerging use Widely available Often restricted, requires radiopharmacy services
Onset of Response Gradual shrinkage over weeks Moderate to rapid Rapid but with potential delayed adverse effects
Imaging Follow-up MRI after 6 weeks MRI at regular intervals Imaging + dosimetry (CT/SPECT) required
Long-Term Data Limited (new approach, case series only) Moderate, decades of use Available, esp. from Europe, but often in outdated protocols
Procedure Requirements Ommaya reservoir; permeability test recommended Ommaya reservoir or catheter Ommaya + radiation safety protocols

Summary Recommendations

Agent Advantages Disadvantages
Peginterferon alfa-2a Favorable safety, non-cytotoxic, off-label alternative to IFN-α2a Limited experience, unclear long-term outcomes
Bleomycin Effective and accessible; longer track record Neurotoxicity risk if leakage occurs; more systemic side effects
Radioisotopes Potent and often effective with fewer instillations Technically demanding; radiation risks; contraindicated in very young children

When to Consider Each Treatment?

* Peginterferon alfa-2a → Ideal for younger children or when minimal toxicity is essential. Requires close monitoring and permeability testing. * Bleomycin → Suitable where experience exists with its use. Effective but requires caution regarding leakage and systemic toxicity. * Radioisotopes → Best reserved for specialized centers with radiation safety protocols and older pediatric or adult patients with refractory cysts.

.

🧠 Flowchart Logic

Is the patient under 5 years old?

→ Yes → ❌ Avoid radioisotopes

→ No → ✅ Radioisotopes may be considered

Is radiation facility & radiopharmacy available?

→ Yes → Consider radioisotopes

→ No → Proceed to next

Is cyst accessible with Ommaya and permeability confirmed?

→ No → ❌ Intracystic therapy not recommended

→ Yes → Proceed to next

Is neurotoxicity a major concern (e.g., very young child, hypothalamic proximity)?

→ Yes → ✅ Prefer Peginterferon alfa-2a

→ No → Proceed to next

Institutional experience with bleomycin?

→ Yes → Consider bleomycin

→ No → Consider peginterferon alfa-2a

1)

Hedrich C, Patel P, Haider L, Taylor T, Lau E, Hook R, Dorfer C, Roessler K, Stepien N, Lippolis MA, Schned H, Koeller C, Mayr L, Azizi AA, Peyrl A, Lopez BR, Lassaletta A, Bennett J, Gojo J, Bartels U. Feasibility, tolerability, and first experience of intracystic treatment with peginterferon alfa-2a in patients with cystic craniopharyngioma. Front Oncol. 2024 Jul 10;14:1401761. doi: 10.3389/fonc.2024.1401761. PMID: 39050573; PMCID: PMC11266088.

Racial disparities in hydrocephalus treatment

by

Racial disparities in hydrocephalus treatment

Several studies of administrative data have noted higher mortality rates for Black/African American children with shunted hydrocephalus. A longitudinal study of children with hydrocephalus secondary to myelomeningocele showed lower lifetime rates of shunt revision in minority children compared to White children, indicating a possible disparity in hydrocephalus treatment. The goal of this study is to identify racial and ethnic disparities in mortality or shunt revision rates by using the Hydrocephalus Clinical Research Network (HCRN) hydrocephalus registry sample.

The HCRN registry was queried for patients with shunted hydrocephalus for whom data on all lifetime hydrocephalus procedures were available. Patients with a primary shunt placement before 2023 were included, with follow-up extending through March 19, 2024. A Cox proportional hazards model was created to determine the effect of race and ethnicity on mortality while controlling for age at initial shunt placement, sex, hydrocephalus etiology, gestational age at birth, and the presence of complex chronic conditions. Similarly, a proportional means model was used to evaluate the association with the lifetime number of shunt revision surgeries. The author hypothesized that when controlling for other variables, minority children would have higher mortality and fewer shunt revision surgeries than White children.

A total of 5656 children were included in the analysis of mortality. There were 579 deaths. Race and ethnicity were independently associated with mortality, with Black (HR 1.32, 95% CI 1.05-1.65), other non-White (HR 1.39, 95% CI 1.03-1.86), and Hispanic (HR 1.50, 95% CI 1.22-1.84) children having a higher mortality rate than White children. In the analysis of 4081 children with shunts, Hispanic ethnicity was also independently associated with fewer total shunt revisions (HR 0.84, 95% CI 0.72-0.98).

In children with hydrocephalus, when controlling for other factors, there is a higher mortality rate among Hispanic, Black, and other non-White children, and fewer shunt revisions among Hispanic children. These findings highlight important potential disparities in hydrocephalus treatment 1).

Patient race (i.e., White; Native Hawaiian, or other Pacific Islander) was found to be associated with iNPH development. Meanwhile, after excluding those with cerebrovascular disease, cardiovascular risk factors were not found associated with iNPH. Lastly, iNPH cases were more inclined to have a history of alcohol use disorder and prior psychiatric disorder. Overall, this data reveals that a racial disparity exists amongst iNPH, as well as highlights the role of various cardiovascular and psychiatric risk factors, which can potentially provide direction in etiology elucidation 2).

Among preterm infants with intraventricular hemorrhage and resultant PHH, black infants and those insured by Medicaid have significantly increased mortality but these 2 effects are independent. Further studies are needed to fully understand the factors affecting these racial and socioeconomic disparities 3).

Findings in a study, that utilized US population-level data, suggest the presence of racial and socioeconomic status outcome disparities following pediatric CSF shunting procedures 4).

A retrospective chart review was performed on all pediatric patients who underwent ventriculoperitoneal shunting from 1990-2010 at the Department of Neurological Surgery, University of Rochester Medical Center, 601 Elmwood Ave., Box 670, Rochester, NY, 14642, USA. Race and insurance type were recorded and assessed against specific outcome measures to statistically compare complication rates.

A complete record was found for 373 patients who received 849 shunting procedures at the institution. No differences were found between racial groups and insurance type for overall shunt survival, total revision number, or average time to failure. However, nonwhite patients spent an average of 3 days longer in the hospital at initial shunting (p = 0.04), and those with public insurance stayed for 5 days longer (p = 0.002). Patients with public insurance were more likely to present with shunt failure from outside hospitals (p = 0.005) and be born prematurely (p < 0.001). Private patients were more likely to have a neoplasm present at the time of initial shunt placement (p = 0.003).

While the overall revision rate was not affected by race or insurance status, there were significant delays in discharge for patients with public insurance. Moreover, potential disparities in outpatient access to primary physicians and specialists may be affecting care 5)

The literature examining racial and ethnic disparities in pediatric hydrocephalus reveals consistent evidence that minority populations, particularly Black, Hispanic, and other non-White children, experience worse outcomes compared to their White counterparts. The primary study by Rocque et al. (2025) using the Hydrocephalus Clinical Research Network (HCRN) registry strengthens the case for systemic inequities in healthcare delivery and outcomes.

1. Strengths of the Primary Study (Rocque et al., 2025)

Large, prospective dataset: With 5,656 children included in the mortality analysis and 4,081 in the shunt revision cohort, the study offers robust statistical power. Rigorous methodology: The use of Cox proportional hazards models and control for confounding variables (e.g., age at initial shunt, gestational age, chronic conditions) increases the reliability of the observed associations. Novel findings: The association of higher mortality in minority children and fewer revisions in Hispanic children, despite controlling for clinical variables, points to care process disparities rather than purely biological explanations.

2. Limitations and Interpretative Cautions

Causality remains unclear: The study is observational. While associations are strong, they do not establish causality. The lower revision rate among Hispanic children could either reflect undertreatment, barriers to access, or better surgical outcomes — though the higher mortality suggests the former. Socioeconomic data not directly integrated: While race and ethnicity are analyzed, insurance status, income level, and neighborhood-level SES indicators are not included. This limits insight into the complex interplay between race and class. Data source limitations: The HCRN centers may not be fully representative of all geographic or institutional contexts, potentially introducing bias. Synthesis with Supporting Literature The findings of Rocque et al. are echoed across several studies:

Jin et al. (2016) and Attenello et al. (2015) highlight that racial and economic disparities are independent predictors of increased mortality in hydrocephalus and related pathologies (e.g., PHH). Medicaid coverage — a proxy for low SES — independently correlates with worse outcomes, reinforcing the notion that both race and poverty are crucial risk factors.

Walker et al. (2014) found no differences in shunt survival or revision numbers, but nonwhite and publicly insured children had longer hospital stays and were more likely to present with complications from outside facilities, suggesting disparities in pre- and post-hospital care access, rather than in acute management.

Ghaffari-Rafi et al. (2020), while focused on iNPH, support that race (and potentially psychiatric comorbidities) may play a role in disease development and care patterns. Though not directly comparable to pediatric hydrocephalus, these data emphasize broader racialization of neurological care.

Key Themes and Implications

A. Structural and Institutional Bias These disparities may arise from implicit bias, differential access to care, differences in follow-up protocols, or parental engagement shaped by historical mistrust in healthcare institutions. Fewer shunt revisions in Hispanic children, despite higher mortality, may suggest under-recognition or under-treatment of shunt failures.

B. Socioeconomic Determinants

Insurance status, hospital of origin, and perinatal history (e.g., prematurity) are proxies for healthcare fragmentation and unequal resources. The intersection of race and poverty likely amplifies risks.

C. Need for Systems-Level Interventions

Enhance equity in post-operative follow-up and early complication detection. Implement community-based interventions and education programs to support families from underserved populations. Broaden inclusion of socioeconomic variables in large-scale registries like HCRN to better understand root causes.

Conclusions

The consistent signal across studies — that racial and socioeconomic disparities affect outcomes in pediatric hydrocephalus — underscores an urgent need for targeted policy, educational, and clinical interventions. The findings from the HCRN dataset should galvanize the neurosurgical community to address not only technical outcomes but also systemic inequities in pediatric neurosurgical care.

1)

Rocque BG, Jensen H, Reeder RW, Rozzelle CJ, Kulkarni AV, Pollack IF, McDowell MM, Naftel RP, Jackson EM, Whitehead WE, Pindrik JA, Isaacs AM, Strahle JM, McDonald PJ, Tamber MS, Hankinson TC, Browd SR, Hauptman JS, Krieger MD, Chu J, Riva-Cambrin J, Limbrick DD, Holubkov R, Kestle JRW, Wellons JC. Racial disparities in hydrocephalus mortality and shunt revision: a study from the Hydrocephalus Clinical Research Network. J Neurosurg Pediatr. 2025 Mar 21:1-9. doi: 10.3171/2024.12.PEDS24371. Epub ahead of print. PMID: 40117669.
2)

Ghaffari-Rafi A, Gorenflo R, Hu H, Viereck J, Liow K. Role of psychiatric, cardiovascular, socioeconomic, and demographic risk factors on idiopathic normal pressure hydrocephalus: A retrospective case-control study. Clin Neurol Neurosurg. 2020 Jun;193:105836. doi: 10.1016/j.clineuro.2020.105836. Epub 2020 Apr 28. PMID: 32371292.
3)

Jin DL, Christian EA, Attenello F, Melamed E, Cen S, Krieger MD, McComb JG, Mack WJ. Cross-Sectional Analysis on Racial and Economic Disparities Affecting Mortality in Preterm Infants with Posthemorrhagic Hydrocephalus. World Neurosurg. 2016 Apr;88:399-410. doi: 10.1016/j.wneu.2015.12.046. Epub 2015 Dec 28. PMID: 26732967.
4)

Attenello FJ, Ng A, Wen T, Cen SY, Sanossian N, Amar AP, Zada G, Krieger MD, McComb JG, Mack WJ. Racial and socioeconomic disparities in outcomes following pediatric cerebrospinal fluid shunt procedures. J Neurosurg Pediatr. 2015 Jun;15(6):560-6. doi: 10.3171/2014.11.PEDS14451. Epub 2015 Mar 20. PMID: 25791773.
5)

Walker CT, Stone JJ, Jain M, Jacobson M, Phillips V, Silberstein HJ. The effects of socioeconomic status and race on pediatric neurosurgical shunting. Childs Nerv Syst. 2014 Jan;30(1):117-22. doi: 10.1007/s00381-013-2206-5. Epub 2013 Jun 30. PMID: 23811830.

Salovum for severe traumatic brain injury

by

Salovum for severe traumatic brain injury

J.Sales-Llopis

Neurosurgery Department, General University Hospital Alicante, Spain

Antisecretory Factor and Salovum® in Severe Traumatic Brain Injury: A New Frontier in Neurocritical Care

Severe traumatic brain injury (TBI) remains a leading cause of disability and mortality worldwide despite continuous advancements in neuroimaging, neurocritical care, and surgical techniques. Elevated intracranial pressure (ICP) is a major contributor to secondary brain injury, often determining patient prognosis. Current treatments, including hyperosmolar therapy, decompressive craniectomy, and sedation, provide variable efficacy with significant risks.

A promising new approach involves the use of antisecretory factor (AF), a naturally occurring protein with anti-inflammatory and fluid-regulating properties, commercially available as Salovum®. Recent studies suggest that AF may play a crucial role in reducing ICP and improving clinical outcomes in severe TBI.

Clinical Evidence Supporting Antisecretory Factor in Severe TBI

The AFISTBI and SASAT Trials

Two exploratory randomized, placebo-controlled clinical trials are currently evaluating the role of AF in severe TBI. The AFISTBI trial (ClinicalTrials.gov NCT04117672) is a single-center phase 2 study conducted at Skane University Hospital, Sweden. This trial examines the impact of Salovum® supplementation for five days in adults with severe TBI (GCS < 9) requiring ICP monitoring and microdialysis catheter insertion. The primary endpoint is ICP reduction, while secondary endpoints include inflammatory mediator levels in plasma and cerebrospinal fluid.

Similarly, the SASAT trial (ClinicalTrials.gov NCT03339505) is a phase 2, double-blind, randomized trial conducted at Tygerberg University Hospital, South Africa. It evaluates 30-day mortality, treatment intensity level (TIL), and ICP control in 100 patients randomized to receive either Salovum® or placebo.

Pilot Studies and Case Series

Several preliminary studies have demonstrated the potential of AF in reducing ICP. A pilot study by Gatzinsky et al. investigated four patients with severe TBI and refractory intracranial hypertension treated with Salovum®. The study found that when administered rectally, AF significantly reduced ICP without adverse events, offering a novel delivery route for neurocritical care patients with impaired gastric emptying.

Additionally, a case series by Cederberg et al. evaluated five patients with severe TBI who received Salovum® via nasogastric tube for five days. Three patients exhibited successful ICP control without the need for barbiturates, while four had favorable long-term outcomes. Importantly, no toxicity or adverse effects were observed, underscoring the safety of AF therapy in this population.

Mechanism of Action and Potential Therapeutic Implications

AF exerts its effects by modulating fluid balance and inflammatory responses in the brain. Preclinical models suggest that AF can suppress excessive cerebrospinal fluid production, reduce blood-brain barrier permeability, and attenuate neuroinflammation, all critical mechanisms in controlling ICP and secondary brain injury.

The ability of AF to reduce ICP through non-invasive means could have profound implications for the management of TBI. In resource-limited settings where advanced neurosurgical interventions may not be readily available, Salovum® presents a cost-effective adjunct to standard neurocritical care.

Challenges and Future Directions

While preliminary data are promising, larger, multicenter randomized controlled trials (RCTs) are needed to validate these findings. Understanding the optimal dosing, administration route, and long-term effects of AF therapy remains crucial. Additionally, integrating AF into current TBI treatment protocols will require further evaluation of its interactions with existing therapies.

Conclusion

Antisecretory factor, as delivered via Salovum®, represents an exciting new frontier in TBI management. With ongoing trials exploring its efficacy, AF has the potential to become a groundbreaking adjunctive therapy for reducing ICP and improving outcomes in severe TBI patients. If confirmed in larger studies, the use of Salovum® could redefine the standard of care in neurocritical care settings, providing a safer and more accessible treatment alternative for ICP control.

Despite recent advances in neuroimaging and neurocritical care, severe traumatic brain injury (TBI) is still a major cause of severe disability and mortality, with increasing incidence worldwide. Antisecretory factor (AF), commercially available as Salovum®, has been shown to lower intracranial pressure (ICP) in experimental models of, e.g., TBI and herpes encephalitis. A study by Réen et al. aims to assess the effect of antisecretory factors in adult patients with severe TBI on ICP and inflammatory mediators in extracellular fluid and plasma.

In a single-center, randomized, placebo-controlled clinical phase 2 trial, investigating the clinical superiority of Salovum® given as a food supplement for 5 days to adults with severe TBI (Glasgow Coma Scale (GCS) < 9), admitted to the neurocritical intensive care unit (NICU) at Skane university hospital. All patients with GCS < 9 and clinical indication for insertion of ICP-monitor and microdialysis catheter will be screened for inclusion and assigned to either the treatment group (n = 10) or placebo group (n = 10). In both groups, the primary outcome will be ICP (mean values and change from baseline during intervention), registered from high-frequency data monitoring for 5 days. During trial treatment, secondary outcomes will be inflammatory mediators in plasma and intracerebral microdialysis perfusate days 1, 3, and 5.

Trial registration: ClinicalTrials.gov NCT04117672. Registered on September 17, 2017. Protocol version 6 from October 24, 2023 1).

A study aims to assess the effect as measured by 30-day mortality, treatment intensity level (TIL), and intracranial pressure (ICP).

This single-center, double-blind, randomized, placebo-controlled clinical phase 2 trial, investigating the clinical superiority of Salovum® given as a food supplement to adults with severe TBI (GCS < 9), presenting to the trauma unit at Tygerberg University Hospital, Cape Town, South Africa, that are planned for invasive ICP monitoring and neurointensive care, will be screened for eligibility, and assigned to either treatment group (n = 50) or placebo group (n = 50). In both groups, the primary outcome will be 30-day mortality, recorded via hospital charts, follow-up phone calls, and the population registry. Secondary outcomes will be treatment intensity level (TIL), scored from hospital charts, and ICP registered from hospital data monitoring.

Trial registration: ClinicalTrials.gov NCT03339505 . Registered on September 17, 2017. Protocol version 3.0 from November 13, 2020 2)

Four patients with severe TBI (Glasgow Coma Scale < 9) that required neurointensive care with ICP monitoring due to signs of refractory intracranial hypertension were investigated. One hundred milliliters of Salovum®, a commercially available egg yolk powder with high contents of AF peptides, was administrated either via nasogastric (patients 1 and 2) or rectal tube (patients 2, 3, and 4) every 8 h for 2 to 3 days as a supplement to the conventional neurointensive care. ICP was registered continuously. Plasma levels of AF were measured by enzyme-linked immunosorbent assay (ELISA) to confirm that Salovum® was absorbed appropriately into the bloodstream.

Results: In the first two patients, we observed that when delivered by the nasogastric route, there was an accumulation of the Salovum® solution in the stomach with difficulties to control ICP due to impaired gastric emptying. Therefore, we tested to administer Salovum® rectally. In the third and fourth patients, who both showed radiological signs of extensive brain edema, ICP could be controlled during the course of rectal administration of Salovum®. The ICP reduction was statistically significant and was accompanied by an increase in blood levels of AF. No adverse events that could be attributed to AF treatment or the rectal approach for Salovum® administration were observed.

Conclusions: The outcomes suggest that AF can act as a suppressor of high ICP induced by traumatic brain edema. Use of AF may offer a new therapeutic option for targeting cerebral edema in clinical practice 3).

A case series of five adult patients with severe TBI, treated with Salovum. The objective of the intervention was to evaluate safety and, if possible, its effect on intracranial pressure and outcome. Patients received 1 g Salovum per kilo of body weight divided into six doses per 24 h. Each dose was administered through the nasogastric tube. Patients were scheduled for 5 days of treatment with Salovum. Intracranial pressure was controlled in all patients. In three of five patients, intracranial pressure could be controlled with Salovum and deep sedation (no barbiturates), except during periods of gastroparesis. Five of five patients had a favorable short-term outcome, and four of five patients had a favorable long-term outcome. No toxicity was observed. We conclude that at least three of the five treated patients experienced an effect of Salovum with signs of reduction of intracranial pressure and signs of clinical benefit. To validate the potential of antisecretory factors in TBI, a prospective, randomized, double-blind, placebo-controlled trial with Salovum has been initiated. The primary outcome for the trial is 30-day mortality; secondary outcomes are treatment intensity level, intracranial pressure, and number of days at the neurointensive care unit 4).

References

1)

Réen L, Cederberg D, Marklund N, Visse E, Siesjö P. Antisecretory factor in severe traumatic brain injury (AFISTBI): protocol for an exploratory randomized placebo-controlled trial. Trials. 2025 Feb 7;26(1):43. doi: 10.1186/s13063-025-08760-7. PMID: 39920739.
2)

Cederberg D, Harrington BM, Vlok AJ, Siesjö P. Effect of antisecretory factor, given as a food supplement to adult patients with severe traumatic brain injury (SASAT): protocol for an exploratory randomized double blind placebo-controlled trial. Trials. 2022 Apr 23;23(1):340. doi: 10.1186/s13063-022-06275-z. PMID: 35461285; PMCID: PMC9034076.
3)

Gatzinsky K, Johansson E, Jennische E, Oshalim M, Lange S. Elevated intracranial pressure after head trauma can be suppressed by antisecretory factor-a pilot study. Acta Neurochir (Wien). 2020 Jul;162(7):1629-1637. doi: 10.1007/s00701-020-04407-5. Epub 2020 May 22. PMID: 32445122; PMCID: PMC7295841.
4)

Cederberg D, Hansson HA, Visse E, Siesjö P. Antisecretory Factor May Reduce ICP in Severe TBI-A Case Series. Front Neurol. 2020 Mar 6;11:95. doi: 10.3389/fneur.2020.00095. PMID: 32210902; PMCID: PMC7067821.

Spondylodiscitis management

by

Spondylodiscitis management

J.Sales-Llopis

Neurosurgery Department, General University Hospital Alicante, Spain

Latest PubMED Articles

Spondylodiscitis, requires a multidisciplinary approach for effective management. The goal is to eradicate the infection, prevent or treat complications (e.g., deformity, neurological deficits), and restore spinal stability and function.

see Spondylodiscitis treatment

Key Components of Management

1. Diagnosis

Accurate and early diagnosis is critical for effective treatment.

  • Clinical Presentation:
    • Symptoms: Back pain (most common), fever, localized tenderness, and occasionally neurological deficits.
    • Risk factors: Immunosuppression, recent surgery, infections, or intravenous drug use.
  • Laboratory Investigations:
    • Elevated inflammatory markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and leukocytosis.
    • Blood cultures: Identify causative organisms (positive in ~50-70% of cases).
  • Imaging:
    • MRI (gold standard): High sensitivity and specificity, detects soft tissue and bone involvement.
    • CT-guided biopsy: Essential for microbiological diagnosis when blood cultures are negative.

2. Medical Management

  • Antibiotics:
    • Empiric therapy: Cover gram-positive (e.g., *Staphylococcus aureus*), gram-negative, and anaerobic organisms.
    • Targeted therapy: Adjusted based on blood or biopsy cultures.
    • Duration: 6–12 weeks (longer for complicated cases or immunocompromised patients).
  • Supportive Measures:
    • Pain management with NSAIDs or opioids.
    • Immobilization: Bracing may reduce pain and prevent deformity in acute phases.

3. Surgical Management

Surgery is indicated in specific scenarios:

  • Indications:
    • Neurological deficits (e.g., weakness, bowel/bladder dysfunction).
    • Spinal instability or deformity (e.g., kyphosis >20°).
    • Abscess formation (e.g., epidural or paravertebral abscesses).
    • Failure of medical therapy (e.g., persistent infection despite antibiotics).
  • Techniques:
    • Minimally invasive surgery (MIS): Drainage of abscesses, debridement, stabilization.
    • Open surgery: Extensive debridement and reconstruction for severe instability or deformity.

4. Rehabilitation and Follow-Up

  • Physical Therapy: Promotes recovery of function and prevents deconditioning.
  • Regular Monitoring:
    • Clinical symptoms and inflammatory markers to assess response.
    • Follow-up imaging (MRI or CT) in unresolved cases or when complications are suspected.

Complications to Monitor

  • Neurological deficits.
  • Chronic pain or deformity.
  • Spinal instability.
  • Paraspinal abscess or septicemia.
  • Relapse of infection.

Recent Advances and Recommendations

  • Minimally Invasive Surgery (MIS):
    • Preferred when feasible, due to lower morbidity and faster recovery.
  • Imaging Advances:
    • MRI techniques can differentiate between infection and malignancy more effectively.
  • Consensus Guidelines (e.g., EANS recommendations):
    • Provide structured thresholds for surgical indications and antibiotic durations.

Challenges in Management

  • Delayed diagnosis due to non-specific symptoms.
  • Rising antimicrobial resistance.
  • Balancing the risks of surgery in medically fragile patients.

Conclusion

Spondylodiscitis management requires individualized care based on patient presentation, infection severity, and comorbidities. The integration of targeted antibiotics, timely surgical intervention when indicated, and structured follow-up ensures optimal outcomes. Ongoing research is essential to refine treatment protocols and improve patient care.

Delphi consensus studies

The de novo non-specific spinal infection managements (spondylodiscitis – SD) remains inconsistent due to varying clinical practices and a lack of high-level evidence, particularly regarding the indications for surgery.

Research question: This study aimed to develop consensus recommendations for spondylodiscitis diagnosis and spondylodiscitis management, addressing diagnostic modalities, surgical indications, and spondylodiscitis treatment strategies.

A Delphi consensus study was conducted with 26 experts from the European Association of Neurosurgical Societies (EANS). Sixtytwo statements were developed on diagnostic workup, management decisions, surgical techniques, non-surgical treatment, and follow-up and submitted to the panel of experts.

Consensus was reached on 38 of 62 statements. MRI was confirmed as the gold standard for diagnosis. Regarding surgical indications, the panel agreed that any new neurological deficit, even subtle, warrants surgical consideration. Motor deficits with a motor score (MRC) below 4 and bladder or bowel dysfunction were unanimously considered clear indications for surgery. For spinal deformity and instability, thresholds such as kyphosis >20°, scoliosis >10°, and vertebral body collapse >50% were established to guide surgical decision-making. Minimally invasive surgery (MIS) was endorsed whenever feasible, and a 12 week antibiotic treatment regimen was favored in cases of complicated infections.

This EANS consensus provides updated recommendations for spondylodiscitis management, incorporating recent evidence on improved outcomes with surgical therapy. While these guidelines offer a more structured approach to clinical decision-making, further research is required to optimize surgical timing and validate the long-term impact of these treatment strategies 1).

This study successfully tackles a clinically significant challenge by providing structured recommendations for the diagnosis and management of de novo non-specific spinal infections. While the use of the Delphi method lends credibility, the reliance on expert opinion, incomplete consensus, and limited global representation are notable limitations. Nonetheless, it serves as an important step towards standardizing care for spinal infections and highlights the urgent need for further research to validate and refine these recommendations.

Systematic review and meta-analysis

Thavarajasingam et al. aimed to compare the mortality, relapse rate, and length of hospital stay of conservative versus early surgical treatment of pyogenic spondylodiscitis. All major databases were searched for original studies, which were evaluated using a qualitative synthesis, meta-analyses, influence, and regression analyses. The meta-analysis, with an overall pooled sample size of 10,954 patients from 21 studies, found that the pooled mortality among the early surgery patient subgroup was 8% versus 13% for patients treated conservatively. The mean proportion of relapse/failure among the early surgery subgroup was 15% versus 21% for the conservative treatment subgroup. Further, it concluded that early surgical treatment, when compared to conservative management, is associated with a 40% and 39% risk reduction in relapse/failure rate and mortality rate, respectively, and a 7.75 days per patient reduction in length of hospital stay (p < 0.01). The meta-analysis demonstrated that early surgical intervention consistently significantly outperforms conservative management in relapse/failure and mortality rates, and length of stay, in patients with pyogenic spondylodiscitis 2)

Thavarajasingam et al.’s systematic review and meta-analysis provide compelling evidence that early surgical intervention significantly outperforms conservative management in pyogenic spondylodiscitis, with reductions in mortality, relapse rates, and hospital stays. However, limitations such as heterogeneity, reliance on observational data, and a lack of long-term outcome evaluation temper the strength of its conclusions. Future studies should address these gaps to enhance the robustness and applicability of the findings across diverse patient populations and healthcare environments.

Systematic review

A population-based study from Denmark showed that the incidence of spondylodiscitis rose from 2.2 to 5.8 per 100 000 persons per year over the period 1995-2008; the age-standardized incidence in Germany has been estimated at 30 per 250 000 per year on the basis of data from the Federal Statistical Office (2015). The early diagnosis and treatment of this condition are essential to give the patient the best chance of a good outcome, but these are often delayed because it tends to present with nonspecific manifestations, and fever is often absent.

Herren et al published an article based on a systematic search of Medline and the Cochrane Library for the period January 2009 to March 2017. Of the 788 articles identified, 30 publications were considered.

The goals of treatment for spondylodiscitis are to eliminate infection, restore functionality of the spine, and relieve pain. Magnetic resonance imaging (MRI) remains the gold standard for the radiological demonstration of this condition, with 92% sensitivity and 96% specificity. It also enables visualization of the spatial extent of the infection and of abscess formation (if present). The most common bacterial cause of spondylodiscitis in Europe is Staphylococcus aureus, but tuberculous spondylodiscitis is the most common type worldwide. Antibiotic therapy is a pillar of treatment for spondylodiscitis and should be a part of the treatment in all cases. Neurologic deficits, sepsis, an intraspinal empyema, the failure of conservative treatment, and spinal instability are all indications for surgical treatment.

The quality of life of patients who have been appropriately treated for spondylodiscitis has been found to be highly satisfactory in general, although back pain often persists. The risk of recurrence increases in the presence of accompanying illnesses such as diabetes mellitus, renal failure, or undrained epidural abscesses 3)

Literature review with clinical recommendations

Five influential studies on PS that have the potential to shape current practice in spinal infections were selected and reviewed. Each study was chosen for its contribution to a critical phase in PS management: diagnosis, imaging, surgical vs conservative treatment, and antibiotic duration. Recommendations were graded as strong or conditional following the GRADE methodology.

Five studies were highlighted. Article 1: Pluemer et al introduced the Spinal Infection Treatment Evaluation (SITE) Score, a novel scoring tool for standardizing treatment decision-making. Conditional recommendation to incorporate the SITE Score or SISS Score for improved treatment outcomes. Article 2: Maamari et al conducted a meta-analysis comparing imaging modalities, with conditional recommendation to consider 18F-FDG PET/CT to diagnosis PS as an adjunct to MRI which remains the gold standard. Article 3: Thavarajasingam et al demonstrated the potential survival benefit of early surgery in specific PS cases, leading to a strong recommendation for early intervention in appropriate patients. Article 4: Neuhoff et al compared conservative and surgical treatments in well-resourced settings, concluding a strong recommendation for early surgery in appropriate patients. Article 5: Bernard et al evaluated antibiotic treatment duration, with a conditional recommendation for a 6-week course in confirmed cases, based on comparable efficacy to a 12-week regimen.

Management of PS remains complex and varied. This perspective provides spine surgeons with evidence-based recommendations to enhance standardization and effectiveness in clinical practice 4).

The study represents a valuable effort to synthesize impactful research on PS management and translate it into actionable recommendations. However, its narrow scope, reliance on conditional recommendations, and limited discussion of implementation challenges restrict its immediate applicability in diverse settings. Future efforts should expand the evidence base, address variability in resources, and validate the proposed guidelines to enhance their utility in standardizing and improving care for pyogenic spondylodiscitis.

1)

Kramer A, Thavarajasingam SG, Neuhoff J, Davies B, Barbagallo G, Debono B, Depreitere B, Eicker SO, Gabrovsky N, Gandia-Gonzalez ML, Ivanov M, Kaiser R, Kaprovoy S, Konovalov N, Lafuente J, Maciejczak A, Meyer B, Pereira P, Petrova Y, Peul WC, Reizinho C, Ryang YM, Sampron N, Schär R, Tessitore E, Thomé C, Timothy J, Vleggeert-Lankamp C, Demetriades AK, Shiban E, Ringel F. Diagnosis and management of de novo non-specific spinal infections: European Association of Neurosurgical Societies (EANS) Spine Section Delphi consensus recommendations. Brain Spine. 2024 Dec 31;5:104178. doi: 10.1016/j.bas.2024.104178. PMID: 39866360; PMCID: PMC11763570.
2)

Thavarajasingam SG, Vemulapalli KV, Vishnu K S, Ponniah HS, Vogel AS, Vardanyan R, Neuhoff J, Kramer A, Shiban E, Ringel F, Demetriades AK, Davies BM. Conservative versus early surgical treatment in the management of pyogenic spondylodiscitis: a systematic review and meta-analysis. Sci Rep. 2023 Sep 20;13(1):15647. doi: 10.1038/s41598-023-41381-1. PMID: 37730826; PMCID: PMC10511402.
3)

Herren C, Jung N, Pishnamaz M, Breuninger M, Siewe J, Sobottke R. Spondylodiscitis: Diagnosis and Treatment Options. Dtsch Arztebl Int. 2017 Dec 25;114(51-52):875-882. doi: 10.3238/arztebl.2017.0875. PMID: 29321098; PMCID: PMC5769318.
4)

Bigdon SF, Vialle E, Dandurand C, Scherer J, Camino-Willhuber G, Joaquim AF, Chhabra HS, El-Sharkawi M, Bransford R, Fisher CG, Schnake KJ, Schroeder GD; AO KF Trauma and Infection Members. Streamlining the Journey of Research Into Clinical Practice: Making Your Patients and Practice Flourish Evaluation and Treatment of Pyogenic Spondylodiscitis of the Spine: AO Spine Knowledge Forum Trauma and Infection. Global Spine J. 2025 Jan 24:21925682251316814. doi: 10.1177/21925682251316814. Epub ahead of print. PMID: 39852953; PMCID: PMC11760070.