Glioma & Glioblastoma (GBM)
WHO Grade I–IV · Most Common Primary Malignant Brain Tumour in Adults
Gliomas are primary brain tumours arising from glial cells (astrocytes, oligodendrocytes, ependymal cells). Glioblastoma (GBM, WHO Grade IV astrocytoma) is the most aggressive, representing ~50% of all gliomas. Despite advances, median overall survival remains ~15 months with the Stupp protocol. Low-grade gliomas (Grade II) may remain stable for years before malignant transformation.
Progressive headache, new-onset seizures, focal neurological deficit, personality change, speech difficulty. Any of these warrants urgent MRI brain with contrast.
Signs & Symptoms by Location
Diagnosis
Ring-enhancing lesion with central necrosis and surrounding oedema = classic GBM. FLAIR sequences essential for low-grade glioma extent. MR Spectroscopy (choline:NAA ratio) confirms malignancy.
Initial emergency scan. Shows mass effect, midline shift, calcification. Less sensitive than MRI but widely available at BVH.
Surgical biopsy is definitive. IDH1/2 mutation (better prognosis), MGMT promoter methylation (predicts temozolomide response), 1p/19q co-deletion (oligodendroglioma). Aga Khan Lab (Karachi) offers full panel.
Eloquent cortex mapping (motor, speech, visual) for surgical planning. Diffusion Tensor Imaging tracks white matter tracts. Available at IDC Multan (GE Signa 1.5T).
Treatment Approaches
Maximal Safe Resection is the cornerstone of glioma management. Extent of resection (EOR) directly correlates with survival — supratotal resection (removing MRI-invisible infiltrated tissue) may improve outcomes in IDH-mutant gliomas.
- Standard craniotomy — performed at BVH under Zeiss operating microscope with BodyTom CT verification for resection confirmation
- Awake craniotomy — for eloquent cortex tumours (speech/motor areas); real-time cortical mapping prevents permanent deficits. Pioneered by Dr. Wasif at BVH without formal IONM
- Fluorescence-guided surgery (5-ALA) — Pink fluorescence distinguishes tumour from brain; improves EOR in GBM (recommended by AANS/CNS guidelines)
- Stereotactic biopsy — BodyTom + ARC frame at BVH for deep/eloquent lesions not amenable to open resection
- Tumour Treating Fields (TTF/Optune) — Approved adjunct for GBM; continuous electrical fields worn as cap. Limited availability in Pakistan.
Stupp Protocol (Standard of Care for GBM): Concomitant temozolomide (75mg/m²/day) during radiotherapy followed by 6 cycles of adjuvant temozolomide (150–200mg/m² days 1–5 of 28-day cycle).
- Temozolomide (TMZ) — alkylating agent; most effective in MGMT promoter-methylated tumours (55% of GBM). Standard at major cancer centres Pakistan
- Bevacizumab (Avastin) — Anti-VEGF; improves PFS but not OS in recurrent GBM. Used at SKMCH Lahore, AKUH Karachi
- PCV chemotherapy — Procarbazine, CCNU, vincristine for 1p/19q co-deleted oligodendroglioma; superior to TMZ alone (CATNON trial)
- Dexamethasone — Critical for perioperative and radiation-associated cerebral oedema. 4–16mg/day adjusted to symptoms; taper after radiation. Avoid prolonged use
- Levetiracetam (LEV) — Preferred prophylactic AED; no CYP450 interactions with chemotherapy. 500–1000mg BD standard
Radiotherapy is essential for all high-grade gliomas and for low-grade gliomas with high-risk features (age >40, subtotal resection, large tumour).
- Standard RT — 60 Gy in 30 fractions over 6 weeks (for GBM, WHO Grade IV) or 54 Gy in 30 fractions (Grade III)
- Short-course RT (40Gy/15fr) — For elderly/frail GBM patients; non-inferior per Nordic and NOA-08 trials
- Stereotactic Radiosurgery (SRS) — Boost for small residual or recurrent GBM; Gamma Knife/Cyberknife (available Lahore/Karachi)
- Proton therapy — Theoretical advantage of reduced exit dose for paediatric brain tumours; not yet available in Pakistan
For low-grade gliomas (WHO Grade II) with IDH mutation, low-risk features, and small size: active surveillance with serial MRI every 3–6 months may be appropriate, especially in young patients with incidentally discovered tumours.
- Watch-and-wait (selected Grade II) — Randomised evidence supports observation for truly low-risk Grade II (RTOG 9802). Requires 3-monthly MRI
- Symptom management — Antiepileptic drugs for seizures; analgesia for headache; corticosteroids for acute oedema
- Palliative care — For recurrent/refractory GBM: dexamethasone titration, pain management, psychological support, family counselling
While no alternative medicine has proven anti-tumour efficacy in rigorous clinical trials, several integrative approaches may improve quality of life and tolerance of conventional treatment. Always discuss with your neurosurgeon before starting any supplement.
- Mindfulness-Based Stress Reduction (MBSR) — Reduces anxiety and improves quality of life in brain tumour patients (Level B evidence, AANS). Available via clinical psychologist
- Omega-3 fatty acids — May reduce inflammation; fish oil 2–4g/day. No proven direct anti-tumour effect. Generally safe alongside standard treatment
- Curcumin (turmeric) — In vitro anti-glioma activity; limited human clinical trial data. 1–4g/day oral curcumin generally safe. Avoid high doses with warfarin
- Cannabis/CBD — THC/CBD combinations show synergy with TMZ in preclinical models (GW Pharmaceuticals trial ongoing). CBD oil (non-psychoactive) may help with nausea and sleep
- Acupuncture — Evidence for chemotherapy-induced nausea and fatigue management. Not for tumour treatment
- Prayer and spiritual care — The spiritual dimension of healing (رُوحانی علاج) is central to patient wellbeing. Islamic healing practices (Ruqyah, Dua) complement medical care and are encouraged alongside treatment
St. John's Wort reduces dexamethasone and corticosteroid levels by 50% via CYP3A4 induction. Avoid completely during chemotherapy and steroid therapy.
References — Glioma
- Mayo Clinic Glioma — Diagnosis & Treatment. mayoclinic.org
- Barrow Glioblastoma: Current Treatment Strategies. barrowneuro.org
- Stupp 2005 Stupp R et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. NEJM 2005;352:987–996
- WHO 2021 WHO Classification of Tumours of the Central Nervous System. 5th edition, 2021
- Cleveland Clinic Brain Tumor: Glioblastoma. my.clevelandclinic.org
Meningioma
Most Common Primary Intracranial Tumour · WHO Grade I–III
Meningiomas arise from arachnoid cap cells of the meninges. They are the most common primary intracranial tumour (36% of all brain tumours). Approximately 80% are WHO Grade I (benign) with excellent prognosis after complete resection. Grade II (atypical) and Grade III (anaplastic) carry higher recurrence rates. They compress rather than invade brain tissue.
Signs & Symptoms
Treatment
Microsurgical resection is first-line for symptomatic meningiomas. The Simpson grading system (I–V) describes the extent of resection and correlates with recurrence risk.
- Simpson Grade I — Complete resection including dural attachment + involved bone. 5-year recurrence 9%. Gold standard target
- Simpson Grade II — Complete tumour removal + coagulation of dural attachment. Recurrence 19%
- Simpson Grade IV/V — Partial resection; for skull base or sinus-involved tumours. Followed by adjuvant radiosurgery
- At BVH: Craniotomy under Zeiss microscope, BodyTom CT for skull base cases, post-op MRI at 3 months
- Pre-operative embolisation — For large vascular meningiomas; reduces intraoperative bleeding by 40–60%
- Gamma Knife SRS — <3cm tumours, cavernous sinus location, or recurrent lesions. 5-year tumour control 95% for Grade I. Available at Shaukat Khanum / NICVD Karachi
- Fractionated RT — Large meningiomas or those near optic apparatus where single-fraction SRS dose is limited. 50–54 Gy in 25–28 fractions
- Proton therapy — Skull base atypical/malignant meningiomas; not yet available in Pakistan
For small (<3cm), asymptomatic, incidentally discovered meningiomas in elderly patients: active surveillance with annual MRI is recommended. Growth rate averages 0.24cm/year; approximately one-third do not grow over 5 years.
- Annual MRI for 3–5 years; if stable, extend to 2-yearly
- Treat if growth >2mm/year, symptoms develop, or patient preference
- Anti-oedema: dexamethasone 4–8mg/day for acute worsening while awaiting surgery
- Mifepristone (RU-486) — Progesterone receptor antagonist; limited evidence, not standard of care
- Hydroxyurea — Used for recurrent unresectable Grade I; disease stabilisation rather than regression
- AED prophylaxis — Only if seizure history; levetiracetam preferred. Not routine post-operative prophylaxis per AANS guidelines
References — Meningioma
- Mayo Clinic Meningioma. mayoclinic.org
- Barrow Meningioma Treatment at Barrow. barrowneuro.org
- Simpson 1957 Simpson D. The recurrence of intracranial meningiomas. J Neurol Neurosurg Psychiatry 1957;20:22–39
Pituitary Adenoma
Benign Pituitary Gland Tumour · Functioning & Non-Functioning Subtypes
Pituitary adenomas arise from the anterior pituitary gland and represent ~10–15% of all intracranial tumours. Classified as microadenomas (<10mm) or macroadenomas (≥10mm). Functioning adenomas secrete excess hormones (prolactin, GH, ACTH, TSH); non-functioning adenomas cause symptoms through mass effect on surrounding structures.
Signs & Symptoms
Treatment
Endoscopic endonasal trans-sphenoidal surgery (EETS) is the gold standard for most pituitary adenomas except prolactinomas. No external incision; approach through nostril. Fully operational at BVH with dedicated endoscope and pituitary set.
- Excellent visual field recovery post-surgery (up to 90% improvement)
- Hormonal remission: ~75% for microadenoma Cushing's, ~50% for macroadenoma
- Complications: CSF leak (3–5%), diabetes insipidus (transient 20%), hypopituitarism
- Pituitary apoplexy: emergency EETS within 24–72h for visual deterioration
- Cabergoline/Bromocriptine — First-line for prolactinomas (>90% efficacy); significantly shrinks macro-prolactinomas. Surgery reserved for drug-resistant or intolerant cases
- Somatostatin analogues (Octreotide, Lanreotide) — For acromegaly; normalise GH/IGF-1 in ~50–60%. Monthly injections
- Pegvisomant — GH receptor antagonist for acromegaly refractory to somatostatin analogues
- Ketoconazole/Metyrapone/Pasireotide — Medical management of Cushing's disease awaiting surgery or recurrence
- Hormone replacement — Thyroxine, hydrocortisone, testosterone/oestrogen for hypopituitarism
- Gamma Knife SRS — For residual/recurrent adenoma post-surgery; target margin >3mm from optic chiasm
- Hormonal control in functioning adenomas: 40–70% over 5–10 years (slower than surgery)
- Risk of late hypopituitarism in 20–30% of radiosurgery-treated adenomas
References — Pituitary
- MGH Pituitary Tumor Program. massgeneral.org
- Cleveland Clinic Pituitary Adenoma. my.clevelandclinic.org
Traumatic Brain Injury (TBI)
Mild, Moderate & Severe TBI · GCS Classification · NICU Management
TBI results from external mechanical force causing temporary or permanent neurological dysfunction. Classified by GCS: Mild (13–15), Moderate (9–12), Severe (≤8). RTA (Road Traffic Accidents) is the leading cause in Pakistan. Bifrontal contusions, temporal contusions, and diffuse axonal injury (DAI) are the most common patterns in high-speed impact.
GCS <13, pupil asymmetry, deteriorating consciousness, focal deficit, post-traumatic seizure, significant mechanism → immediate CT head. Do NOT delay for history-taking.
Management
- Craniotomy for mass lesion — EDH >30ml, SDH >10mm or >5mm midline shift, temporal contusion >20ml with mass effect → immediate craniotomy
- Decompressive craniectomy — For malignant ICP not responsive to maximal medical management; bifrontal or unilateral
- ICP monitor insertion — For GCS ≤8 with abnormal CT; external ventricular drain (EVD) doubles as treatment and monitoring
- Manual craniotomy (BVH) — Hudson brace + Gigli saw technique used while Medisrex drill awaits restoration. Time-to-decompression target maintained within 60 minutes
- CRASH Trial: Corticosteroids (methylprednisolone/dexamethasone) CONTRAINDICATED in TBI — increases 14-day mortality significantly (NEJM 2004)
- ICP management — Head elevation 30°, avoid neck flexion. Mannitol 0.5–1g/kg IV bolus (serum osm <320). Hypertonic saline 3% (3ml/kg) for refractory ICP
- Sedation/analgesia — Propofol or midazolam infusion; fentanyl analgesia. Reduces ICP, facilitates ventilation
- Hyperventilation — Temporary measure (PaCO2 30–35); avoid prolonged use (cerebral ischaemia risk)
- Barbiturate coma — Refractory ICP unresponsive to all measures; pentobarbital/thiopental. Continuous EEG monitoring required
- Temperature management — Normothermia 36–37°C. Targeted temperature management (hypothermia) not proven to improve outcomes in adults (POLAR trial)
- Seizure prophylaxis — Levetiracetam 500mg BD × 7 days. Phenytoin no longer preferred (cognitive side effects)
- DVT prophylaxis — Sequential compression devices immediately; LMWH after 48h if haemorrhage stable
- Nutrition — Enteral feeding within 24–48h; gastroparesis common → nasojejunal tube if needed
- Mild TBI (concussion): observation, analgesia (avoid NSAIDs early), cognitive rest 24–48h, graded return to activity
- Moderate TBI: 24h observation minimum; CT if any deterioration; neuropsychological follow-up
- Cervical spine clearance: mandatory in all high-mechanism TBI; CT cervical spine required if neurological symptoms
- Multidisciplinary rehabilitation team: physiotherapy, speech therapy, occupational therapy, neuropsychology
- Cognitive rehabilitation for executive dysfunction, memory, attention
- Post-traumatic epilepsy: levetiracetam or valproate; seizure-free period required before driving
- Amantadine 100mg BD — Evidence for promoting consciousness recovery in disorders of consciousness (Giacino et al, NEJM 2012)
- Family education: post-TBI behavioural changes, fatigue, emotional lability are common and treatable
References — TBI
- Barrow Traumatic Brain Injury Resource Center. barrowneuro.org
- CRASH 2004 Roberts I et al. Effect of intravenous corticosteroids on death within 14 days in TBI. Lancet 2004;364:1321–28
- BTF 2016 Brain Trauma Foundation. Guidelines for the Management of Severe TBI. 4th edition, 2016
Hydrocephalus
Communicating & Obstructive · VP Shunt · Endoscopic Third Ventriculostomy
Hydrocephalus is the abnormal accumulation of cerebrospinal fluid (CSF) in the ventricular system, causing progressive ventricular enlargement and raised intracranial pressure. Classified as obstructive (non-communicating — blockage within ventricular system) or communicating (impaired CSF reabsorption at arachnoid granulations). It is one of the most common neurosurgical conditions managed at BVH.
Signs & Symptoms
VP (ventriculo-peritoneal) shunt is the most performed neurosurgical procedure worldwide and the mainstay of hydrocephalus management at BVH.
- Components: Ventricular catheter → Valve → Peritoneal catheter. Programmable valves (Medtronic Strata, Codman Hakim) allow non-invasive adjustment
- Shunt complications: Infection (5–10%, S. epidermidis), obstruction (15–40% at 2 years), over-drainage (subdural hygroma/haematoma), slit ventricle syndrome
- Shunt infection management: Removal + external CSF drainage + IV antibiotics (vancomycin + ceftriaxone) × 10–14 days → new shunt
- VP vs VA shunt: Ventriculo-atrial shunt for peritoneal contraindication; higher risk of septicaemia, shunt nephritis
ETV (Endoscopic Third Ventriculostomy) — creates a new pathway for CSF to bypass obstruction at aqueduct/foramina. Preferred for obstructive hydrocephalus in children >6 months. Avoids shunt hardware entirely.
- ETV success rate: age-dependent. ETV-SS score predicts success probability
- Most effective for: aqueductal stenosis, posterior fossa tumour-related hydrocephalus, tectal glioma, previous shunt failure
- Risk of basilar artery injury (<0.5%) is main serious concern
- Fully operational neuroendoscope system at BVH allows ETV under direct visualisation
- Acetazolamide — Carbonic anhydrase inhibitor reducing CSF production; 25mg/kg/day in infants. Temporary bridge to surgery only; high side-effect profile
- Furosemide — Combined with acetazolamide; limited long-term evidence
- Dexamethasone — For tumour-related hydrocephalus; reduces oedema rapidly. Not for long-term CSF control
- Serial LP (lumbar punctures) — For post-haemorrhagic hydrocephalus in premature neonates: temporary measure to remove blood-stained CSF, reduce need for permanent shunt
- Tumour-related hydrocephalus (pineal, tectal glioma, posterior fossa): ETV or temporary EVD → definitive tumour surgery
- Post-meningitis hydrocephalus: VP shunt; delay 2–4 weeks after CSF sterilisation
- Post-haemorrhagic (IVH): serial LP → Omaya reservoir → VP shunt if persistent
- Aqueductal stenosis in adults: ETV preferred over shunt (lower lifetime hardware risk)
References — Hydrocephalus
- Cleveland Clinic Hydrocephalus. my.clevelandclinic.org
- Barrow Pediatric Hydrocephalus. barrowneuro.org
Brain Abscess
Focal Pyogenic Brain Infection · Aspiration vs. Excision · Antibiotic Protocols
A brain abscess is a focal, encapsulated collection of pus within brain parenchyma resulting from haematogenous spread, direct contiguous extension (sinusitis, mastoiditis, otitis media), or trauma/post-operative infection. Common organisms: Streptococci (haematogenous), mixed anaerobes (otogenic), Staphylococcus aureus (post-operative/trauma), Toxoplasma in immunocompromised.
- Stereotactic aspiration — Preferred for deep/eloquent, multiple, or <2.5cm abscesses. CT/BodyTom + ARC frame guided at BVH. Send pus for C&S, AFB, fungal stains
- Craniotomy + excision — For well-encapsulated, superficial, multiloculated, or gas-forming abscesses. Also if aspiration fails
- Repeat aspiration — If abscess re-expands after initial drainage; may need 2–3 aspirations
- Source control — Concurrent treatment of otitis media (mastoidectomy), sinusitis (FESS), dental focus is essential to prevent recurrence
Empirical antibiotic therapy while awaiting cultures. Duration: 6–8 weeks IV then oral consolidation.
| Source | Likely Organisms | Recommended Regimen |
|---|---|---|
| Haematogenous / Unknown | Streptococcus, anaerobes | Ceftriaxone 2g BD + Metronidazole 500mg TID |
| Post-traumatic / Post-op | Staphylococcus aureus, Gram-negatives | Vancomycin + Ceftazidime or Meropenem |
| Otogenic / Sinogenic | Mixed anaerobes, Streptococcus | Ceftriaxone + Metronidazole ± Vancomycin |
| Immunocompromised (HIV) | Toxoplasma, Cryptococcus, TB | Pyrimethamine + Sulfadiazine (Toxo) or HAART + empirical |
Dexamethasone 4–8mg QID with antibiotics — reduces cerebral oedema. Use only if significant mass effect; may reduce antibiotic penetration if prolonged.
Small (<1.5cm) abscesses in the early cerebritis stage, without significant mass effect, in immunocompetent patients with identified source can be managed non-operatively with close monitoring.
- Serial MRI with contrast every 2 weeks to confirm resolution
- Any neurological deterioration → immediate surgical intervention
- Anti-oedema: dexamethasone 4mg TID; taper as abscess resolves
- AED: levetiracetam 500mg BD for seizure prophylaxis during treatment
References — Brain Abscess
- Mayo Clinic Brain Abscess. mayoclinic.org
- Harvard Brain Abscess overview. Harvard Medical School Publishing