NURO PATHO

FULL

CNS TUMOURS

1. What are the general characteristics, classification, and effects of CNS tumors?

2. How do diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma differ?

3. What are the key molecular and clinical differences between primary and secondary glioblastoma?

4. How do you recognize oligodendroglioma?

5. What are the key features of ependymoma?

6. What are the characteristic features of medulloblastoma?

7. What are the key features of meningioma?

8. : How do the three WHO grades of meningioma differ?

9. How do metastatic CNS tumors present, and which primary cancers commonly spread to the brain?

10. Can you identify CNS tumors from their molecular markers, locations, and histological hallmarks?

1. Answer:

   General characteristics

   • Brain metastases are more common than primary brain tumors.

   • CNS tumors account for approximately 20% of pediatric tumors.

   • Even low-grade tumors may infiltrate extensive brain tissue, causing neurological deficits and making complete resection difficult.

   • Tumors rarely spread outside the CNS, even when highly malignant.

   • The anatomical location affects prognosis independently of tumor type and grade.

   • Unlike many carcinomas, CNS tumors do not have recognizable premalignant or in situ lesions.

   Major categories

   • Gliomas: astrocytomas, oligodendrogliomas, and ependymomas.

   • Embryonal tumors: medulloblastoma.

   • Meningiomas.

   • Metastatic tumors.

   General effects

   • Local compression, invasion, and destruction of neural tissue.

   • Raised intracranial pressure: headache, vomiting, and papilledema.

   • CSF obstruction: hydrocephalus.

   • Herniation: subfalcine, transtentorial, or tonsillar.

   • Pituitary or hypothalamic involvement: hormonal disturbances.

   WHO grading

   • Grade I: circumscribed, often curable with surgery.

   • Grade II: infiltrative, slow-growing, may recur.

   • Grade III: malignant features, including anaplasia and increased mitoses.

   • Grade IV: highly malignant, with necrosis and microvascular proliferation.

   Exam trap: A low-grade CNS tumor can still have a poor outcome because of infiltration or its anatomical location.

2. All three arise from astrocytes, commonly in the cerebral hemispheres.

   Diffuse astrocytoma — Grade II

   • Usually occurs in adults in the fourth to sixth decades.

   • Often affects the frontal and temporal lobes.

   • Molecular changes: IDH1/IDH2, ATRX, and TP53 mutations.

   • Grossly: poorly defined, gray, infiltrative tumor without a discrete mass.

   • Microscopically: mild to moderate cellularity, fibrillary background, mild nuclear pleomorphism, few mitoses, and no necrosis.

   Anaplastic astrocytoma — Grade III

   • Represents progression from a lower-grade astrocytoma.

   • More cellular, with nuclear atypia and prominent mitotic activity.

   • Retains the IDH mutation in the lecture’s described progression.

   • No necrosis yet.

   • Reported median survival in the lecture: 5–10 years.

   Glioblastoma — Grade IV

   • The most aggressive primary malignant brain tumor in the lecture.

   • More common in older adults.

   • Rapid growth, edema, hemorrhage, and necrosis.

   • Microscopy: marked cellularity, pleomorphic cells, high mitotic activity, pseudopalisading necrosis, and microvascular proliferation.

   • GFAP is positive.

   • MRI: irregular ring-enhancing lesion.

   • Can cross the corpus callosum, producing a butterfly glioma.

   • Median survival in the lecture: approximately 15–18 months despite treatment.

   Exam trap:

   • Grade II: few mitoses, no necrosis.

   • Grade III: increased mitoses and atypia, no necrosis.

   • Grade IV: necrosis and microvascular proliferation.

3. Answer:

   Primary glioblastoma

   • Develops de novo, without a recognized lower-grade precursor.

   • Typically affects older adults.

   • The lecture lists EGFR amplification, TP53 mutation, and TERT mutation.

   Secondary glioblastoma

   • Evolves from a lower-grade astrocytoma.

   • Typically affects younger patients.

   • Associated with IDH mutation.

   Clinical presentation

   • Headache.

   • Seizures.

   • Focal neurological deficits.

   • Rapid progression due to tumor growth, edema, and tissue destruction.

   Gross appearance

   • Variegated tumor with firm white areas and soft yellow areas.

   • Necrosis, cystic degeneration, and hemorrhage may occur.

   Why does glioblastoma recur?

   Its infiltrative margins allow tumor cells to remain beyond the visible tumor, even after surgery.

   Exam clue: An older patient with a rapidly progressive neurological deficit and an irregular ring-enhancing cerebral lesion suggests glioblastoma.

4. Answer:

   Origin and location

   • Derived from oligodendrocytes.

   • Usually occurs in adults aged 40–50 years.

   • Commonly affects the cerebral hemispheres, especially the frontal and temporal lobes.

   • Often slow-growing and may present with seizures or headache.

   Molecular markers

   • IDH mutation.

   • Combined 1p/19q chromosomal codeletion.

   • TERT mutation is also listed in the lecture.

   Gross appearance

   • Relatively well-circumscribed, soft, gelatinous tumor.

   • May show cysts, focal hemorrhage, and calcification.

   Microscopic hallmarks

   • Fried-egg appearance: round nuclei surrounded by clear perinuclear halos.

   • Chicken-wire capillaries: delicate branching vessels.

   • Microcalcifications are common.

   Prognosis

   • Best prognosis among the diffuse glial tumors described in the lecture.

   • Grade II median survival: approximately 10–20 years.

   • Grade III median survival: approximately 5–10 years.

   Exam trap: Fried-egg cells plus chicken-wire vessels and IDH mutation with 1p/19q codeletion strongly indicate oligodendroglioma.

5. Answer:

   Origin

   - Arises from ependymal cells lining the ventricles and the central canal of the spinal cord.

   Typical locations

   • Children: fourth ventricle, particularly in the posterior fossa.

   • Adults: spinal cord; the lecture notes an association with NF2.

   Molecular changes listed

   • ZFTA fusion.

   • YAP1 fusion.

   • MYCN amplification.

   Clinical presentation

   • Fourth-ventricle obstruction can cause hydrocephalus, vomiting, and raised intracranial pressure.

   • Posterior fossa tumors may cause ataxia.

   • Spinal tumors may cause back pain and sensory changes.

   Microscopic hallmarks

   • Perivascular pseudorosettes: tumor cells arranged around blood vessels with a fibrillary zone between the cells and the vessel.

   • Ependymal rosettes: tumor cells arranged around a true central lumen.

   Prognosis: Depends on the anatomical site and molecular subtype; the lecture describes it as generally poor.

   Exam trap: A child with obstructive hydrocephalus and a fourth-ventricle tumor, or a tumor showing perivascular pseudorosettes, suggests ependymoma

6. Answer:

   Definition and location

   • Highly malignant embryonal tumor.

   • Usually occurs in children.

   • Arises in the cerebellum, classically the cerebellar vermis.

   • The lecture states that it accounts for approximately 20% of pediatric brain tumors.

   Clinical presentation

   • Rapid growth.

   • Obstructive hydrocephalus.

   • Increased intracranial pressure, including headache and vomiting.

   • CSF dissemination can produce spinal drop metastases.

   Morphology

   • Grossly: gray, friable cerebellar mass that may fill the fourth ventricle.

   • Microscopically: densely packed small round blue cells with high mitotic activity.

   • Homer-Wright rosettes: tumor cells arranged around a central fibrillary core.

   Molecular subtypes

   • WNT-activated: associated with β-catenin pathway alterations; best prognosis, with approximately 90% five-year survival in the lecture.

   • SHH-activated: occurs in infants and adults; intermediate prognosis in the lecture.

   Treatment and prognosis

   • Treatment may include surgical excision, chemotherapy, and radiotherapy.

   • The lecture reports that overall five-year survival may reach 75% with treatment.

   Exam trap: Child + cerebellar vermis tumor + small round blue cells + Homer-Wright rosettes = medulloblastoma.

7. Answer:

   Origin and epidemiology

   • Arises from meningothelial cells of the arachnoid.

   • Usually attached to the dura.

   • Accounts for approximately 20% of intracranial tumors in the lecture.

   • More common in middle-aged women.

   • May occur along dural sinuses, cerebral convexities, parasagittal regions, or the spinal cord.

   • NF2 tumor-suppressor gene loss on chromosome 22 is a key association.

   • May enlarge during pregnancy; progesterone receptors are relevant.

   Clinical features

   • Symptoms arise mainly from compression rather than invasion.

   • May cause headache, seizures, or focal neurological deficits.

   • Most are separable from the underlying brain.

   • Contrast MRI may show a dural tail sign.

   • Multiple meningiomas may be associated with NF2 or previous radiation.

   Morphology

   • Grossly: firm, well-circumscribed, dural-based mass compressing brain tissue.

   • Microscopically:

     • Whorled clusters of meningothelial cells.

     • Psammoma bodies: concentric calcified spherules.

   WHO grades

   • Grade I: benign; complete excision is often curative.

   • Grade II: atypical, with features such as increased mitoses and brain invasion.

   • Grade III: anaplastic, with marked atypia and high mitotic activity.

   Exam trap: Dural tail + whorled cells + psammoma bodies = meningioma.

8. Answer:

   Grade I — Benign

   • Most common.

   • Includes meningothelial, fibroblastic, transitional, psammomatous, and secretory subtypes.

   • Meningothelial: syncytial-like lobules with indistinct cell membranes.

   • Fibroblastic: elongated cells with abundant collagen.

   • Transitional: features of both meningothelial and fibroblastic types.

   • Psammomatous: numerous psammoma bodies.

   • Secretory: gland-like spaces containing PAS-positive eosinophilic material.

   • Complete excision is usually curative.

   Grade II — Atypical

   • Increased mitotic activity.

   • May show brain invasion, prominent nucleoli, and necrosis.

   • Greater recurrence risk than Grade I.

   Grade III — Anaplastic

   • Frank anaplasia.

   • High mitotic activity.

   • May resemble high-grade carcinoma or sarcoma.

   • Highest recurrence and malignant potential of the three grades.

   Key principle: Recurrence risk correlates with tumor grade. Recurrent or atypical lesions may require radiotherapy.

   Exam trap: Meningioma is usually benign, but not all meningiomas are benign; Grade II and III lesions have more aggressive behavior.

9. Answer:

   Key facts

   • Metastatic tumors are the most common intracranial tumors in adults.

   • They originate outside the CNS.

   • Common primary sites include:

     • Lung.

     • Breast.

     • Melanoma.

     • Kidney.

     • Gastrointestinal tract.

   Typical pattern

   • Often multiple lesions.

   • Frequently located at the gray–white matter junction.

   Clinical effects

   • Depend on the number, size, and location of lesions.

   • May produce headache, seizures, focal neurological deficits, edema, or raised intracranial pressure.

   How to distinguish them from primary brain tumors

   • Multiple lesions at the gray–white junction, particularly in a patient with known systemic cancer, strongly suggest metastases.

   • Primary CNS tumors arise from cells or tissues within the CNS, such as glial or meningeal cells.

   Exam trap: In an adult with a history of lung or breast cancer and multiple brain lesions, consider metastatic disease first.

10. Answer:

    Tumor	Key marker or association	Classic hallmark
    Diffuse astrocytoma	IDH1/2; ATRX and TP53	Infiltrative tumor, fibrillary background
    Anaplastic astrocytoma	Often retains IDH mutation	Atypia and increased mitoses, without necrosis
    Glioblastoma	EGFR-related changes; molecular profile varies	Pseudopalisading necrosis and microvascular proliferation
    Oligodendroglioma	IDH mutation + 1p/19q codeletion	Fried-egg cells and chicken-wire capillaries
    Ependymoma	ZFTA/YAP1 fusions; subtype-dependent	Perivascular pseudorosettes and ependymal rosettes
    Medulloblastoma	WNT or SHH subtype	Small round blue cells and Homer-Wright rosettes
    Meningioma	NF2 association	Whorls and psammoma bodies
    Metastatic tumor	Depends on systemic primary	Often multiple lesions at the gray–white junction

    Quick location associations

    • Cerebral hemispheres: diffuse astrocytoma, glioblastoma, oligodendroglioma.

    • Fourth ventricle in children: ependymoma.

    • Cerebellar vermis in children: medulloblastoma.

    • Dura: meningioma.

    • Gray–white junction, often multiple lesions: metastases.

    🔥 Absolute exam traps

    • Pseudopalisading necrosis + microvascular proliferation: Glioblastoma.

    • Fried-egg cells + chicken-wire vessels: Oligodendroglioma.

    • Perivascular pseudorosettes: Ependymoma.

    • Homer-Wright rosettes: Medulloblastoma.

    • Psammoma bodies + dural tail: Meningioma.

    • Butterfly lesion crossing the corpus callosum: Glioblastoma.

    • Child + cerebellar vermis + hydrocephalus: Medulloblastoma.

    • Adult + multiple brain lesions at the gray–white junction: Metastases.

    • IDH mutation + 1p/19q codeletion: Oligodendroglioma.

    Necrosis and microvascular proliferation: Key features of WHO Grade IV diffuse glioma in the lecture.

• General CNS Tumor Rule: Metastases are more common than primary brain tumors, CNS tumors account for roughly 20% of childhood cancers, and they almost never spread outside the central nervous system.

• 📈 WHO Grading System: Grade I tumors are benign and curable, Grade II are infiltrative and slow-growing, Grade III display malignant features and mitoses, and Grade IV are highly malignant with necrosis and microvascular proliferation.

• 🦋 Glioblastoma (Grade IV): The most common and aggressive primary malignant brain tumor characterized by pseudopalisading necrosis, microvascular proliferation, GFAP positivity, ring-enhancing lesions on MRI, and the classic "butterfly glioma" pattern crossing the corpus callosum.

• 🍳 Oligodendroglioma: Defined microscopically by "fried-egg" cells (round nuclei with a clear perinuclear halo), a "chicken-wire" capillary pattern, microcalcifications, and signature 1p/19q codeletion with IDH mutation.

• 🌹 Ependymoma: Frequently located in the 4th ventricle in children (causing hydrocephalus) or the spinal cord in adults (associated with NF2), histologically highlighted by perivascular pseudorosettes.

• 🌀 Medulloblastoma: A highly malignant pediatric cerebellar tumor forming sheets of small round blue cells with Homer-Wright rosettes, known for CSF dissemination ("drop metastases") and a WNT-activated subtype carrying a 90% 5-year survival rate.

• 🐚 Meningiomas: Benign dural-attached tumors originating from arachnoid cap cells, prevalent in middle-aged women, linked to NF2 gene loss (22q) and progesterone receptors, featuring microscopic whorled cell clusters, Psammoma bodies, and a dural "tail sign" on MRI.

• 🎯 Metastatic Brain Tumors: The most common intracranial tumors in adults, typically originating from the lung, breast, melanoma, kidney, or GI tract, and characteristically localized at the gray-white junction.

STEOKE

1. What is a stroke, and what are its three main pathogenic mechanisms?

2. . What is the difference between functional hypoxia and cerebral ischaemia?

3. What is global cerebral ischaemia, and what determines its clinical outcome?

4. What are the morphological changes in global cerebral ischaemia?

5. What is focal cerebral ischaemia, and what are the common causes of embolic infarction?

6. How do thrombotic and embolic cerebral infarctions differ? What are lacunar infarcts?

7. What are the two types of cerebral infarcts, and how do they differ morphologically?

8. What are the microscopic changes following a cerebral infarction, and what is the final outcome?

9. What are the major causes and types of intracranial haemorrhage

10. What are the important vascular abnormalities and complications associated with stroke?

SACCULAR ANURESUM ANT OMMUNICATING ARTERY

Let's turn this whole topic into a Brain Blood Vessel Drama 🎭🧠.

🎈 Part 1: Berry Aneurysm

Imagine a brain artery develops a tiny balloon.

🎈 This balloon is called a saccular (berry) aneurysm.

The balloon wall is thin and weak.

One day, pressure inside rises...

💥 POP!

The aneurysm usually ruptures at its apex (the tip of the balloon).

Blood spills into the space around the brain.

➡ Subarachnoid Hemorrhage (SAH)

Associations

Think of two patients who have weak connective tissues:

🫘 Polycystic kidney disease

🤸 Ehlers-Danlos syndrome

They're more likely to form berry aneurysms.

---

⚡ Part 2: Subarachnoid Hemorrhage

A patient is sitting normally.

Suddenly:

🤯

"THIS IS THE WORST HEADACHE OF MY LIFE!"

This is the famous:

Thunderclap headache

Maximal intensity within seconds.

---

What would lumbar puncture show?

The CSF becomes:

🩸 Bloody

or later

🟡 Yellow (xanthochromia)

Think:

Blood sits in CSF → hemoglobin breaks down → yellow color.

---

The Sneaky Villain: Vasospasm

A few days later (3-10 days), the patient seems stable.

Then the nearby arteries become angry and start squeezing.

🫨 Arteries go into spasm.

Less blood reaches the brain.

➡ Secondary ischemic infarction.

Mnemonic: "First bleed doesn't always kill. The vasospasm may come back for revenge."

---

Hydrocephalus

Blood can clog CSF pathways.

🚰 Like a blocked drain.

CSF accumulates:

➡ Hydrocephalus

Can be:

• Communicating

• Noncommunicating

---

🎈 Quick Memory Chain

Berry aneurysm ⬇ Ruptures ⬇ Subarachnoid hemorrhage ⬇ Thunderclap headache ⬇ Bloody/xanthochromic CSF ⬇ Vasospasm (3-10 days) ⬇ Infarction or hydrocephalus

---

🔌 Part 3: AVM (Arteriovenous Malformation)

Normally:

Artery → Capillary → Vein

Nice and orderly.

---

In an AVM:

Artery ⟹ Vein

No capillary bed.

It's like connecting a fire hydrant directly to a garden hose. 🚒➡🪴

The high-pressure arterial blood enters veins.

The veins can't handle it.

⚠ Bleeding risk increases.

---

Typical Patient

Young person (10-30 years old) comes with:

⚡ Seizures

or

🩸 Intracranial hemorrhage

---

If AVM is Huge

The heart works overtime pumping blood through this shortcut.

❤💨

Can lead to:

High-output heart failure

---

Story Memory

🚒 Artery skips capillaries and dumps blood straight into a vein.

Vein says:

"I'm not built for this pressure!"

Result:

⚡ Seizures 🩸 Bleeding

---

🩸 Part 4: Hypertensive Cerebrovascular Disease

Imagine chronic hypertension constantly punches small brain vessels.

👊👊👊👊

Over years the vessel wall becomes weak.

This causes:

1. Massive Intracerebral Hemorrhage

Weak vessel ruptures.

💥

Large bleed into brain tissue.

---

2. Lacunar Infarcts

Tiny vessel becomes occluded.

🕳 Small "lakes" (lacunes) form.

Think:

Hypertension → small vessel disease → lacunar infarcts

---

3. Slit Hemorrhages

Tiny linear hemorrhages from damaged vessels.

---

4. Hypertensive Encephalopathy

Blood pressure shoots up dramatically.

The brain swells.

Patient develops:

🤕 Headache

😵 Confusion

🤮 Vomiting

⚡ Seizures

---

🌋 Part 5: Vasculitis

Imagine the immune system attacks blood vessels.

🔥 Vessel wall inflammation

The vessel narrows.

Less blood reaches brain tissue.

➡ Infarction

---

Primary Angiitis of CNS

The inflammation is confined mainly to CNS vessels.

Patients may develop:

🧠 Diffuse encephalopathy

😕 Cognitive dysfunction

Confusion and thinking problems.

---

One Exam Story 🎈 Berry aneurysm

Weak balloon on artery.

💥 Rupture

Causes SAH.

🤯 SAH

Thunderclap headache + bloody/xanthochromic CSF.

🫨 Later

Vasospasm causes infarction.

🚰 Blood blocks CSF

Hydrocephalus.

🚒 AVM

Artery directly connected to vein → seizures and bleeding.

👊 Hypertension

Damages small vessels → hemorrhage and lacunar infarcts.

🔥 Vasculitis

Inflamed vessels → cerebral infarction.

---

Ultra-high-yield mnemonic

🎈 Berry bursts → SAH
🤯 SAH screams ("worst headache ever")
🫨 Spasm strikes later (3-10 days)
🚒 AVM = artery meets vein
👊 HTN hits small vessels
🔥 Vasculitis inflames vessels

This is essentially the entire vascular pathology chapter condensed into one memory story. 🧠✨

1. A stroke is an acute neurological event caused by a disturbance in cerebral blood flow.

   The three main mechanisms are:

   1. Thrombotic occlusion: A blood clot forms within a cerebral vessel.

   2. Embolic occlusion: Material travels from elsewhere and blocks a cerebral vessel.

   3. Vascular rupture: A blood vessel ruptures, causing haemorrhage.

   The two major categories are:

   • Ischaemic stroke: Due to impaired blood supply and oxygenation.

   • Haemorrhagic stroke: Due to rupture of cerebral vessels.

2. - Functional hypoxia: Oxygen delivery or utilisation is impaired, but cerebral blood flow remains intact.

   Causes:

   • High altitude (low oxygen partial pressure).

   • Severe anaemia.

   • Carbon monoxide poisoning.

   • Cyanide poisoning.

   - Ischaemia: Reduced or interrupted blood flow to brain tissue.

   Causes:

   • Hypotension.

   • Vascular obstruction.

   • A combination of both.

   Ischaemia can be transient or permanent and may lead to infarction.

3. Global cerebral ischaemia occurs when there is a generalized reduction in cerebral perfusion.-Imagine the brain is a huge city.

   Normally, the city receives a constant supply of:

   • ❤ Blood

   • 🌬 Oxygen

   • 🍬 Glucose

   One day, a major disaster happens.

   The pumps stop working because of:

   • Cardiac arrest

   • Severe shock

   • Very low blood pressure

   • Severely reduced oxygen-carrying capacity

   Now the entire city gets less blood.

   This is global cerebral ischemia.

   Causes: Cardiac arrest, shock, severe systemic hypotension, and reduced oxygen-carrying capacity.

   Clinical outcomes depend on the severity and duration:

   • Mild ischaemia → temporary confusion → complete recovery.

   • Severe ischaemia → widespread neuronal death → severe neurological impairment or death.

   • Complete loss of all brain and brainstem functions, including respiratory drive, may meet criteria for brain death.

   Prolonged ventilation after irreversible injury may result in a swollen, softened and liquefied brain, called respirator brain.uppose the ventilator keeps the body alive for a long time after irreversible brain injury.

   Blood still circulates, but the brain itself is destroyed.

   Over time:

   🫠 Brain tissue becomes:

   • Swollen

   • Soft

   • Liquefied

   This appearance is called:

   Respirator brain

4. Gross appearance:

   • Swollen brain.

   • Wide, flattened gyri.

   • Narrowed sulci.

   • Poor distinction between grey and white matter on cut section.

   Microscopic changes according to time:

   Stage	Time	Main changes
   Early	12–24 hours	Red neurons, Cytoplasm becomes bright red (eosinophilic)neutrophil infiltration
   Subacute	24 hours–2 weeks	Macrophages, liquefactive necrosis, vascular proliferation, reactive gliosis
   Repair	After 2 weeks	Removal of necrotic tissue, cavitation and gliosis

   Red neurons show cytoplasmic eosinophilia and nuclear changes, including pyknosis(he nucleus shrinks and becomes very dark.)(Then the nucleus breaks into fragments.) and karyorrhexis. After the neuron dies, the brain calls its cleanup crew.

   Remember:

   • In the body, fibroblasts make scar tissue.

   • In the brain, astrocytes make the "scar."

   These astrocytes rush to the damaged area and say:

   "The neurons are gone. Let's clean up and fill the space."

   The astrocytes multiply and form a dense network called:

   Gliosis = Scarring of the CNS Easy Memory Trick

   If you hear:

   "Glio-"

   Think:

   Glial cells (especially astrocytes).

   If you hear:

   "-osis"

   Think:

   Increase/reaction.

   So:

   Gliosis = Proliferation of glial cells after CNS injury.

5. Focal cerebral ischaemia occurs when a cerebral artery is blocked by a thrombus or embolus, causing ischaemia and eventually infarction in the territory supplied by that vessel.

   Embolic infarctions are more common than thrombotic infarctions.

   Sources of emboli include:

   • Cardiac mural thrombi.

   • Atheromatous plaques in the carotid arteries or aortic arch.

   • Venous thromboemboli crossing through a patent foramen ovale.

   • Fat emboli, usually following bone trauma.

   Important exam point: The middle cerebral artery (MCA) is most frequently affected by embolic infarction.

   Emboli commonly lodge at vessel branches or areas of stenosis

6. infarcts?

   • Embolic occlusion: A travelling embolus blocks a cerebral artery. Embolic infarctions are more common.

   • Thrombotic occlusion: A thrombus forms locally, usually over an atherosclerotic plaque.

   Common sites of cerebral thrombosis:

   • Carotid bifurcation.

   • Origin of the middle cerebral artery.

   • Basilar artery.

   Lacunar infarcts: Small infarcts, usually only a few millimetres in diameter, caused by occlusion of small penetrating arteries.

7. morphologically?

   Feature	Ischaemic (pale) infarct	Haemorrhagic (red) infarct
   Appearance	Pale, soft and swollen	Red and soft
   Cause	Acute thrombotic or embolic occlusion	Blood extravasation into infarcted tissue
   Microscopy	Ischaemic neuronal injury and tissue necrosis	Blood extravasation and hemosiderin-laden macrophages

   An ischaemic infarct can become haemorrhagic following reperfusion, through collateral circulation or dissolution of an embolus.

   Evolution of an ischaemic infarct:

   • First 6 hours: Gross appearance may be unchanged.

   • By 48 hours: Pale, soft and swollen.

   • Days 2–10: Gelatinous and friable; boundaries become clearer.

   • Days 10–3 weeks: Tissue liquefies, leaving a fluid-filled cavity.

8. The sequence is:

   1. After approximately 12 hours: Red neurons and oedema appear; endothelial and glial cells swell, and myelinated fibres begin to disintegrate.

   2. First several days: Neutrophils infiltrate the injured area.

   3. Following 2–3 weeks: Macrophages replace neutrophils and remove necrotic tissue.

   4. Repair: Astrocytes enlarge and proliferate around the lesion, producing reactive gliosis.

   5. Final stage: A fluid-filled cystic cavity forms, surrounded by a glial scar.

   This is due to liquefactive necrosis, the characteristic type of necrosis in brain infarction.

9. Intracranial haemorrhage may result from:

   • Hypertension and vascular wall injury.

   • Structural vascular abnormalities, such as aneurysms and AVMs.

   • Tumours.

   Important types:

   • Primary intraparenchymal haemorrhage: Spontaneous rupture of a small cerebral vessel, most commonly associated with hypertension.

   • Subarachnoid haemorrhage (SAH): Most commonly caused by rupture of a saccular (berry) aneurysm.

   • Subdural and epidural haemorrhage: Usually associated with trauma.

   Cerebral amyloid angiopathy (CAA):

   • Amyloid deposits in the walls of small and medium meningeal and cortical vessels.

   • Weakens vessel walls.

   • Causes recurrent lobar haemorrhages and small cortical microhaemorrhages, particularly in older adults.

10. A. Saccular (berry) aneurysm

    • Thin-walled arterial outpouching.

    • Rupture usually occurs at the apex.

    • Causes subarachnoid haemorrhage.

    • Associated with autosomal dominant polycystic kidney disease and Ehlers-Danlos syndrome.

    B. Subarachnoid haemorrhage

    • Sudden, excruciating thunderclap headache, often described as the worst headache ever.

    • CSF may be bloody or yellow (xanthochromic).

    • Vasospasm can occur 3–10 days after haemorrhage, potentially causing ischaemic infarction.

    • Can cause communicating or noncommunicating hydrocephalus.

    • Mortality from the first bleed is approximately 25–50%.

    C. Arteriovenous malformation (AVM)

    • Abnormal connection between arteries and veins.

    • Most common type of cerebral vascular malformation.

    • Often presents between 10 and 30 years with seizures or intracranial haemorrhage.

    • Can cause high-output heart failure when large.

    • Particularly dangerous because of bleeding risk.

    D. Hypertensive cerebrovascular disease
    Hypertension causes hyaline arteriolar sclerosis and weakens small penetrating vessels.

    Possible outcomes:

    • Massive intracerebral haemorrhage.

    • Lacunar infarcts.

    • Small slit haemorrhages.

    • Acute hypertensive encephalopathy, particularly with sudden sustained diastolic BP above 130 mmHg.

    E. Vasculitis
    Inflammation damages cerebral vessels and can cause infarction. Primary angiitis of the CNS can present with diffuse encephalopathy and cognitive dysfunction.

    Clinical case: Understanding stroke

    A 68-year-old man with hypertension and diabetes suddenly develops right-sided weakness and difficulty speaking. CT shows no intracranial haemorrhage.

    1. What is the most likely diagnosis?

    Acute ischaemic stroke.

    2. Is this ischaemic or haemorrhagic?

    Ischaemic, because CT shows no intracranial haemorrhage.

    3. Which cerebral hemisphere is likely affected?

    The left cerebral hemisphere, because it controls the right side of the body and is usually dominant for language.

    4. What is the most likely mechanism?

    Focal cerebral arterial occlusion, likely affecting the left middle cerebral artery (MCA) territory.

    The occlusion could be thrombotic or embolic. His hypertension and diabetes are risk factors for atherosclerosis, but the exact mechanism cannot be confirmed from the case alone.

    5. What type of necrosis occurs?

    Liquefactive necrosis, which is characteristic of brain infarction.

    Remember for exams

    • No haemorrhage on CT + sudden neurological deficit → suspect ischaemic stroke.

    • Right-sided weakness + difficulty speaking → suspect left hemisphere involvement.

    • MCA → commonly affected in embolic infarction.

    • Brain infarction → liquefactive necrosis.

     

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