Learning about Neurosurgery and Neurology

10/10/2025

https://www.oreilly.com/library/view/bad-data-handbook/9781449324957/

What is bad data? Some people consider it a technical phenomenon, like missing values or malformed records, but bad data includes a lot more. In this handbook, data expert Q. Ethan... - Selection from Bad Data Handbook [Book]

05/10/2025

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2832545

Practice Variation in Perioperative Dexamethasone Use and Outcomes in Brain Metastasis Resection

This comparative effectiveness study evaluates whether the cumulative dose of dexamethasone is associated with overall and progression-free survival among patients in Germany and Austria who underwent brain metastasis resection.

03/10/2025

🚗 Driving Fitness in Neuro-Oncology Patients (Germany)

Driving ability is often impaired in patients with brain tumors. Two key terms must be distinguished:

Fitness to drive: The actual ability to drive safely at a specific moment.

Eligibility to drive: A long-term legal and medical assessment of whether a person is fit to hold a driver’s license.

🔪 After Brain Tumor Surgery

Patients are considered unfit to drive for at least 3 months after any brain surgery, regardless of whether seizures occurred.

⚡ Seizures & Structural Epilepsy

A single seizure in the presence of a brain tumor qualifies as structural epilepsy under German law.

This results in a 12-month driving ban (Group 1: private car, motorcycle), starting from the last seizure.

🕒 Each new seizure resets the 12-month clock.

🚛 Commercial Drivers (Group 2: trucks, buses)

Very strict rules apply.

Five years seizure-free are required for re-licensing – in practice, often unattainable for brain tumor patients.

💊 Antiepileptic Drugs (AEDs)

Changing AED dosage (without stopping): driving may continue if no seizures occur.

Stopping AEDs: driving not permitted during tapering and for 3 months afterwards.

⚖️ Legal Aspects & Patient Responsibility

Germany does not have a legal obligation for doctors to report illnesses affecting driving.

However, patients are legally responsible for ensuring they do not endanger themselves or others.

❗ Violating this can lead to:

License revocation

Loss of insurance coverage

Criminal charges in case of an accident

✅ It is strongly advised to document the medical counselling in the patient chart and discharge letter.

🧠 Other Neurological Impairments

Besides seizures, the following can also impair driving fitness:

Visual field deficits

Hemiparesis

Cognitive impairments

Behavioral/personality changes

In such cases, an individual risk assessment is necessary, according to German medical guidelines.

🧪 Recommended (but not legally binding):

Neuropsychological testing

On-road driving assessment with a neuropsychologist

🧾 Only a formal traffic medicine report ("verkehrsmedizinisches Gutachten") is legally binding in licensing procedures.

📋 Summary Table
Situation Legally Fit to Drive?
< 3 months after brain tumor surgery ❌ No
After 1 seizure with a brain tumor ❌ 12-month ban (Group 1)
Seizure-free on medication (≥12 months) ✅ Yes, Group 1 only
Changing AEDs (no seizures) ✅ Allowed
Stopping AEDs ❌ Ban until 3 months after tapering
Commercial driving (Group 2) ❌ Generally not eligible
Cognitive/visual/motor deficits ➡️ Individual assessment needed
❓Q&A

1. Can I drive immediately after brain tumor surgery?
No. A 3-month ban applies regardless of seizures.

2. What if I only had one seizure?
If a tumor is present, it counts as epilepsy → 12-month ban.

3. Can I drive while tapering off my AEDs?
No. You must not drive while stopping medication and for 3 months after.

4. Will my doctor report me to authorities?
No. Doctors are not obligated to report you – but you must not drive if you're unfit.

5. How do I get a legally binding clearance?
Only through a formal traffic medicine assessment (Verkehrsmedizinisches Gutachten).

03/10/2025

🧪 Key Innovations in WHO 2021
✅ Transition to Arabic Grading:

The former WHO Grade I–IV has become CNS WHO Grade 1–4

This aligns brain tumor grading with that of other organ systems.

✅ Distinction Between Tumor Types:

CNS tumors are now clearly separated into:

Diffuse gliomas, adult type

Diffuse gliomas, pediatric type

Other glial, glioneuronal, and neuronal tumors

✅ New Entities Introduced:

Examples:

Diffuse hemispheric glioma, H3 G34-mutant

High-grade astrocytoma with piloid features

MN1-altered astroblastoma

Desmoplastic myxoid tumor of the pineal region

🧬 Molecular Markers: Diagnostic & Prognostic Role

Certain molecular changes are now required for diagnosis, e.g.:

Tumor Entity Required Molecular Marker(s)
Astrocytoma, IDH-mutant IDH1/2 mutation, ATRX loss, +/- CDKN2A/B deletion
Oligodendroglioma, IDH-mutant IDH1/2 mutation and 1p/19q codeletion
Glioblastoma, IDH-wildtype TERT promoter mutation, EGFR amp, +7/–10 signature (even without necrosis)
Ependymoma, PFA H3 K27me3 loss, EZHIP overexpression
Diffuse midline glioma H3K27M mutation or EZHIP overexpression
🧬 DNA Methylation Profiling

Now considered essential for many diagnoses

Used in:

High-grade astrocytoma with piloid features

Atypical teratoid rhabdoid tumors

Ependymoma subtypes

Medulloblastoma subgrouping (WNT, SHH, non-WNT/non-SHH)

Tool: molecularneuropathology.org
for classifier use

🧠 Tumor Grading Examples:
Tumor Type CNS WHO Grades
Astrocytoma, IDH-mutant 2, 3, 4
Oligodendroglioma, IDH-mutant 2, 3
Glioblastoma, IDH-wildtype 4 (by definition)
Ependymoma (posterior fossa) 2 or 3
Meningioma 1, 2, 3

Note: CDKN2A/B homozygous deletion upgrades IDH-mutant astrocytomas to Grade 4, even without necrosis or vascular proliferation.

🧪 NOS vs. NEC

NOS (Not Otherwise Specified): Incomplete molecular workup

NEC (Not Elsewhere Classified): Complete workup, but no match to known entities

🧩 Quiz Questions (Based on the 2021 WHO Classification)
Question 1:

What molecular alterations are necessary to diagnose an oligodendroglioma?

Answer:
IDH1 or IDH2 mutation and combined whole-arm 1p/19q codeletion.

Question 2:

How can a diffuse glioma without histological necrosis still be classified as glioblastoma, IDH-wildtype?

Answer:
If it shows TERT promoter mutation, EGFR amplification, or +7/–10 chromosomal pattern, it is classified as glioblastoma, IDH-wildtype (CNS WHO Grade 4), even without classic histological features.

Question 3:

Which molecular marker is most characteristic for a high-grade astrocytoma with piloid features?

Answer:
KIAA1549::BRAF fusion, CDKN2A/B homozygous deletion, and ATRX loss. Diagnosis often confirmed by methylation profiling.

Question 4:

What distinguishes the two main molecular subgroups of posterior fossa ependymomas?

Answer:

Group A (PFA): Loss of H3K27me3, EZHIP overexpression

Group B (PFB): Retains H3K27me3, lacks EZHIP overexpression

Question 5:

Why is DNA methylation profiling considered indispensable in the 2021 WHO classification?

Answer:
It allows histology-independent diagnosis, especially in complex or rare tumors, and provides reproducible classification across centers. It's also critical for confirming new or ambiguous entities.

01/10/2025

🧰 Step-by-Step Measurement Technique to identify the Stefanion

✅ 1. Identify the midline

Palpate and mark the glabella (between the eyebrows) and nasion.

Trace the sagittal midline posteriorly using a pen.

✅ 2. Mark the coronal suture

From the nasion, measure:

~12 cm posteriorly along the midline → this approximates the coronal suture.

Mark this line across the skull (perpendicular to sagittal midline).

✅ 3. Locate the superior temporal line

Palpate the temporalis muscle ridge (the superior temporal line) above the ear.

This bony ridge curves up and forward from the zygomatic arch toward the forehead.

✅ 4. Find the Stefanion

Intersection of:

Coronal suture line (from step 2),

Superior temporal line (from step 3)

This point is the Stefanion.

Usually:

~2.5–3.5 cm lateral from midline

~1–2 cm above the lateral edge of the forehead/hairline

✅ 5. Double-check with imaging (optional)

If you have preoperative 3D CT or MRI, you can correlate external landmarks (nasion, external auditory canal, etc.) to map the Stefanion precisely.

📏 Example of measurement (approximate in adults)
Landmark Distance from Reference
From nasion (midline) ~12 cm posterior (coronal suture)
From midline sagittal suture ~2.5–3.5 cm lateral
From zygomatic arch (vertical) ~4–5 cm superior
🧠 Why identify Stefanion?

Frontal burr hole site (e.g. for bifrontal craniotomy)

Symmetric planning of craniotomies

Anatomic orientation in low-tech settings (when neuronavigation is unavailable)

⚠️ Tip for surgery

In many neurosurgical setups, the burr hole is placed slightly posterior to the Stefanion for:

Minimal muscle dissection

Better frontal sinus avoidance

Safe access to frontal dura

01/10/2025

https://www.youtube.com/watch?v=j6Xd95RbIas
Good webinar to check this topic.

Enjoy the videos and music you love, upload original content, and share it all with friends, family, and the world on YouTube.

01/10/2025

🧬 Molecular Tumor Boards (MTB) and Growth Modulation Index (GMI) in Neuro-Oncology
🔍 Why Molecular Tumor Boards?

Neuro-oncology faces unique challenges:

Over 120 tumor entities in the CNS (according to WHO CNS5 classification)

Limited therapeutic options for many entities

Few clinical studies for rare or late-stage tumors

High molecular heterogeneity within and across tumors

With next-generation sequencing (NGS), methylation profiling, and RNA-based diagnostics becoming increasingly available, the key challenge is interpreting complex molecular data to inform treatment decisions.

That’s where Molecular Tumor Boards (MTBs) step in.

🧠 What is a Molecular Tumor Board?

An MTB is a multidisciplinary platform that brings together:

Neuro-oncologists & oncologists

Neurosurgeons

Pathologists & molecular biologists

Radiologists

Genetic counselors

Bioinformaticians

Their goal is to evaluate molecular profiling data (e.g., IDH mutation, TERT promoter, EGFR, FGFR3, CDKN2A/B loss, etc.) in the clinical context to derive biomarker-driven therapy recommendations — often off-label.

📊 Levels of Evidence in MTB Therapy Recommendations

Two common classification systems are used:

1. In-House 4-Level Scheme

Level 1a: Efficacy shown in the same tumor entity (e.g., FGFR inhibitor in FGFR-altered glioma)

Level 1b: Efficacy shown in a different entity (e.g., EGFR-inhibitor in colon CA with EGFR mutation)

Level 2: Data from preclinical models or retrospective cohorts

Level 3: Case reports or mechanistic rationale only

2. ESMO ESCAT Scale

ESCAT I (A–C): Evidence strong enough for clinical routine

ESCAT II (A–B): Investigational, should ideally be studied in trials

ESCAT III–V: Hypothetical or combination targets

ESCAT X: No actionable target

📐 What is the Growth Modulation Index (GMI)?

In precision oncology, standard randomized trials are often not feasible for rare alterations. Hence, GMI is a pragmatic tool.

✅ Definition:

GMI = PFS2 / TTP1

PFS2: Progression-Free Survival under second-line treatment

TTP1: Time to Progression on prior (first-line) treatment

If GMI > 1.3, this suggests a clinically meaningful benefit from the second-line treatment compared to the first.

📚 Case Example: The FFCD 0307 Trial

A phase III randomized trial in 416 patients with metastatic gastric cancer, testing:

Arm A: ECX → FOLFIRI

Arm B: FOLFIRI → ECX

🔹 GMI assessable in 42% of patients
🔹 Median GMI was 0.53 overall, indicating less benefit from second-line
🔹 GMI > 1.3 was observed in only 15%
🔹 These patients had longer OS (14.9 vs. 11.5 months)
🔹 PFS2 correlated with OS better than GMI

This trial demonstrated how GMI can reveal therapeutic benefit not obvious from overall survival or response rate comparisons.

📉 Limitations of GMI

Biased by selection: Only patients surviving long enough for 2nd-line

Low GMI in aggressive tumors: Like glioblastoma

Requires precise and uniform timing of scans

Tumor growth assumption: Assumes constant kinetics between treatments

📌 Practical Takeaways for Neuro-Oncology

MTBs are essential for interpreting molecular data beyond histology

Biomarker-guided treatments should follow structured frameworks (e.g., ESCAT)

GMI is useful, especially for rare targets, but has clear limits

Early integration of MTB (not only at exhaustion of standard therapies) can improve decision-making

❓Questions to Consider
1. What is the definition of GMI?

Answer:
GMI is the ratio of PFS2 (progression-free survival under second-line therapy) to TTP1 (time to progression on first-line therapy).

2. When is a GMI considered clinically meaningful?

Answer:
A GMI > 1.3 suggests a potential benefit of the new treatment. This threshold was proposed in early precision oncology trials and is still used as a rough guide.

3. Why is PFS2 often more reliable than GMI?

Answer:
PFS2 directly measures the time a treatment controls disease, whereas GMI is a relative measure, subject to timing biases and inter-patient variability. In the FFCD 0307 trial, PFS2 correlated more strongly with overall survival than GMI.

4. What are actionable targets commonly discussed in neuro-oncology MTBs?

Answer:

IDH1/2 mutations → IDH inhibitors (e.g., ivosidenib, vorasidenib)

TERT promoter mutations → experimental/poor prognosis marker

FGFR fusions/mutations → FGFR inhibitors

BRAF V600E mutations → BRAF/MEK inhibitors

CDK4/6 amplifications → CDK inhibitors

NTRK fusions → TRK inhibitors (e.g., larotrectinib)

5. What limits the clinical implementation of MTB recommendations?

Answer:

Off-label drug use requires insurance approval

Tissue heterogeneity and subclonality affect target validity

Timing: The MTB process can take 6–10 weeks

Lack of trials for some targets/indications

24/09/2025

Theory post: The Radiobiological Theory Behind EQD2 and its clinical implications

24/09/2025

🧠 Case of the Week | High-Grade Astrocytoma with Piloid Features (HGAP)

Patient: 50-year-old male developed new-onset horizontal diplopia shortly after recovering from a mild infection. Initial symptoms were subtle and attributed to fatigue, but when they persisted, an MRI was performed about 4 weeks later.

Imaging:
MRI showed a ring-enhancing lesion in the right thalamo-mesencephalic region, with surrounding edema but no spinal axis involvement. The lesion was deep-seated and caused progressive hydrocephalus, prompting VP shunt placement.
First biopsy attempt was non-diagnostic. A second, FET-PET-guided biopsy was performed for improved targeting.

Histology & Molecular Findings:
Moderate cellularity, increased mitotic activity, no necrosis, no microvascular proliferation
IDH-wildtype (no R132H mutation)
No H3 K27M mutation, retained ATRX expression
DNA methylation profiling (EPIC): classified as High-Grade Astrocytoma with Piloid Features (HGAP)
CDKN2A/B homozygous deletion, MGMT promoter methylated

Additional findings:
FGFR3 mutation (p.S380N) – likely pathogenic
PTPN11 mutation (p.D61V) – possibly oncogenic

Management:
Following interdisciplinary tumor board discussion, the patient was started on Stupp-like treatment:
Radiation up to 60 Gy + concurrent Temozolomide (75 mg/m²)
Followed by adjuvant TMZ in 5/28 schedule
The treatment was well tolerated. He returned to work part-time and is also followed by psycho-oncology.

Clinical Questions (→ Answers below in the thread):

What is a High-Grade Astrocytoma with Piloid Features (HGAP)? How is it classified in the 2021 WHO CNS 5th edition?

How do you manage deep-seated midline tumors when the first biopsy is non-diagnostic?

What is the significance of FET-PET in planning glioma biopsy or surgery?

Do CDKN2A/B deletion and MGMT promoter methylation influence treatment decisions in HGAP?

Would you treat this tumor like a glioblastoma (WHO CNS grade 4)? Why or why not?

Answers below....
What is a High-Grade Astrocytoma with Piloid Features (HGAP)? How is it classified in the WHO 2021?

Answer:
HGAP is a new, molecularly defined CNS tumor entity included in the 2021 WHO classification (5th edition). It shares histological overlap with pilocytic astrocytoma but behaves biologically more aggressively, resembling high-grade gliomas. It is IDH-wildtype and lacks classic GBM histology (e.g., necrosis, microvascular proliferation).
Diagnosis is based primarily on DNA methylation profiling.

2. How do you manage deep-seated midline tumors when the first biopsy is non-diagnostic?

Answer:
Repeat biopsy should be guided by functional imaging (e.g., FET-PET or FDG-PET) to identify metabolically active tumor regions.
🔍 FET-PET improves target selection and avoids sampling necrotic or reactive areas.
⚠️ Invasive resection is often not feasible in deep-seated structures (e.g., thalamus), so diagnostic yield from biopsy is crucial.

3. What is the significance of FET-PET in planning glioma biopsy or surgery?

Answer:
FET-PET (Fluoroethyltyrosine-PET) provides information on amino acid transport and metabolic tumor activity.
✔️ Useful for:

Target planning in non-enhancing gliomas

Distinguishing tumor progression vs. pseudoprogression

Identifying high-yield biopsy sites in heterogenous lesions
It outperforms contrast MRI in certain gliomas, especially low-grade or midline tumors.

4. Do CDKN2A/B deletion and MGMT promoter methylation influence treatment decisions in HGAP?

Answer:

CDKN2A/B homozygous deletion is associated with worse prognosis, as in glioblastoma.

MGMT promoter methylation predicts better response to Temozolomide and is used to justify Stupp-like protocols even in IDH-wildtype tumors.
→ In this case, aggressive therapy was warranted, especially with both high-risk (CDKN2A/B del) and treatment-responsive (MGMT+) markers.

5. Would you treat this tumor like a glioblastoma (WHO grade 4)? Why or why not?

Answer:
Yes — while HGAP is not a "glioblastoma" per se, it behaves aggressively and carries a poor prognosis (5-year OS ~50% per Reinhardt et al., 2018).
🧪 No standard trial exists for HGAP yet, so Stupp protocol (RT + TMZ) is considered reasonable and commonly used by analogy to IDH-wildtype high-grade gliomas.
🧬 Personalized trials (e.g., for FGFR or PTPN11 mutations) may emerge in the future, but currently: treat as high-grade astrocytoma.

22/09/2025

Clinical Case Discussion | IDH-mutant Grade 2 Oligodendroglioma – What Would You Consider?

A 52-year-old female patient was diagnosed with a WHO CNS grade 2 oligodendroglioma (IDH1-mutant, 1p/19q-codeleted) following gross-total resection of a non-enhancing right frontal mass. The MGMT promoter was methylated.

Postoperatively, no adjuvant therapy was given, in line with EANO guidelines for low-grade gliomas with favorable molecular features and complete resection.
Follow-up imaging at 14 months revealed T2/FLAIR progression (no contrast enhancement, no mass effect). The patient remained asymptomatic (KPS 90%, no seizures). The lesion slowly increased on volumetric imaging.

Current situation:
No contrast enhancement
No prior radio- or chemotherapy
Molecularly favorable glioma
Radiological progression (non-enhancing)

Clinical Questions – and evidence-based answers:

1️⃣Would you initiate Vorasidenib now or continue active surveillance?

✅ Answer:
Yes, Vorasidenib can be considered. According to the INDIGO trial (Mellinghoff et al., 2024), Vorasidenib significantly prolonged progression-free survival (PFS) and delayed the need for further intervention in patients with non-enhancing, IDH-mutant low-grade gliomas, including oligodendrogliomas.
🕒 PFS: 27.7 months (Vorasidenib) vs. 11.1 months (placebo).
This case matches the trial inclusion criteria: non-enhancing lesion, no prior RT/CT, measurable progression.

2️⃣ Would you wait for contrast enhancement before starting treatment?

❌ Not necessarily.
Enhancement indicates blood-brain barrier breakdown and may suggest malignant transformation. In INDIGO, only non-enhancing gliomas were included, and early treatment was associated with better outcomes.
🔁 Waiting for enhancement may miss the therapeutic window where targeted therapy is most effective.

3️⃣ Would you consider re-resection?

🔄 Depends.
Re-resection may be an option if the lesion is accessible and progression is localized. However, in non-enhancing tumors with subtle progression, systemic therapy like Vorasidenib might be less invasive and equally effective in delaying further progression or symptoms.

4️⃣ Is Vorasidenib approved and available?

🌍 Status:

FDA approved (August 2024) for IDH-mutant diffuse gliomas.

EMA approval pending but expected.

Access may vary by country – check local regulatory/clinical trial availability.

5️⃣ What is the role of radiation/PCV/Temozolomide in this setting?

🚫 Not first-line here.
In IDH-mutant, 1p/19q-codeleted oligodendrogliomas, radiotherapy + PCV is indicated after subtotal resection or in case of enhancement/progression.
💊 For non-enhancing, molecularly favorable, slowly progressing tumors, Vorasidenib offers a low-toxicity, delay-first-intervention strategy.

20/09/2025

Clinical Case: Hemorrhagic Glioblastoma in an Elderly Patient

A 75-year-old woman was referred after her first bilateral seizure with transient postictal delirium and Todd’s paresis. MRI showed a right parieto-temporal, heterogeneously contrast-enhancing mass with intratumoral hemorrhage (GE T2*) and perilesional edema (FLAIR), causing compression of CSF spaces and the atrium of the lateral ventricle (see uploaded image).

First intervention: 5-ALA-guided gross total resection
Histopathology: Glioblastoma, IDH-wildtype (CNS WHO grade 4)
MGMT promoter: Unmethylated

Due to pre-frailty and age, hypofractionated radiotherapy only was performed.

At 11 months: Local recurrence with new left upper quadrantanopia → re-resection (5-ALA) → adjuvant Temozolomide (5/28)

After 2.5 months: Seizure cluster → trauma with frontal SDH → multifocal progression (not resectable) → Lomustine initiated after discussion.

❓ Targeted Questions for Discussion:

Would you have offered combined chemoradiotherapy upfront?

What are your criteria for re-resection in elderly GBM patients?

Do you routinely use 5-ALA in recurrent surgery?

How do you balance QoL vs aggressive treatment in pre-frail patients?

What is your go-to second-line treatment after TMZ in elderly patients?

✅ Answers:

No. Given the patient’s age, pre-frailty, and unmethylated MGMT, upfront monotherapy with short-course radiotherapy was appropriate and supported by data (e.g. Nordic trial, NOA-08).

Re-resection is considered when there’s localized recurrence, good performance status, and expected symptom relief or prolonged control. In this case: new deficit, unifocal lesion → justified.

Yes. 5-ALA is useful even in recurrence to guide maximal safe resection, especially when contrast enhancement is ambiguous.

Balance is key: cognition, independence, tumor burden, and patient preference matter. In this case, radiotherapy was de-intensified, and chemotherapy individualized.

Lomustine (CCNU) is standard second-line. Its effect is modest, especially in MGMT-unmethylated cases, but acceptable toxicity makes it viable when re-irradiation isn’t.