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CENTRAL NERVOUS SYSTEM

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Apr 05, 2026 PDF Available

Topic Overview

🧠 CENTRAL NERVOUS SYSTEM

🔶 PATTERNS OF INJURY IN THE NERVOUS SYSTEM

🔹 Neuronal Injury

🔸 Reversible Injury

  • Cellular swelling (hydropic change)

  • Mild mitochondrial dysfunction

  • Decreased ATP production (early stage)

  • No nuclear changes

  • Potential for recovery if insult removed

🔸 Irreversible Injury

  • Severe mitochondrial damage

  • Membrane damage → Ca²⁺ influx

  • Lysosomal rupture

  • Nuclear changes:

    • Pyknosis

    • Karyorrhexis

    • Karyolysis

🔴 Red Neuron (Acute Ischemic Neuron) — VERY HIGH-YIELD

  • Seen 12–24 hours after ischemia

  • Features:

    • Shrunken neuron

    • Intensely eosinophilic cytoplasm

    • Loss of Nissl substance

    • Pyknotic nucleus

🔶 Liquefactive Necrosis (CNS Specific)

  • Characteristic type of necrosis in brain

  • Mechanism:

    • Enzymatic digestion of dead cells

    • Softening → cystic cavity formation

  • Seen in:

    • Cerebral infarction

    • Abscess

🔶 Selective Vulnerability (VERY IMPORTANT MCQ)

  • Certain neurons are more sensitive to hypoxia

📊 Table: Selective Vulnerability

Region Cells Affected
Hippocampus CA1 pyramidal neurons
Cerebellum Purkinje cells
Cerebral cortex Layers 3 & 5 neurons
Watershed zones Border areas (ACA–MCA)

🔶 Astrocyte Response (Gliosis)

  • Most important repair mechanism in CNS

  • Astrocytes proliferate → form glial scar

  • Marker:

    • GFAP (glial fibrillary acidic protein)

🔹 Functions

  • Structural support

  • Blood-brain barrier maintenance

  • Repair after injury

🔶 Oligodendrocyte Injury

  • Responsible for myelin formation

  • Injury leads to:

    • Demyelination

  • Seen in:

    • Multiple sclerosis

    • Viral infections (PML)

🔶 Microglial Activation

  • CNS macrophages

  • Activated in:

    • Infection

    • Necrosis

🔹 Features

  • Proliferation

  • Formation of:

    • Microglial nodules

    • Neuronophagia

🔶 Axonal Injury

  • Causes:

    • Trauma

    • Ischemia

🔹 Changes

  • Axonal swelling

  • Disconnection

  • Formation of retraction balls

🔶 Regeneration vs Permanent Damage

  • CNS neurons have limited regenerative capacity

  • Healing occurs via:

    • Gliosis (not true regeneration)

📊 TABLES

📊 Table: CNS Cells vs Functions

Cell Type Function
Neurons Signal transmission
Astrocytes Support, BBB, repair
Oligodendrocytes Myelination
Microglia Phagocytosis
Ependymal cells CSF lining

📊 Table: Reversible vs Irreversible Neuronal Injury

Feature Reversible Irreversible
Cell swelling Present Severe
Mitochondria Mild damage Severe damage
Nucleus Normal Pyknosis/karyorrhexis
Outcome Recovery possible Cell death

📊 Table: Selective Vulnerability (HIGH-YIELD)

Structure Vulnerability
Hippocampus (CA1) Most sensitive
Purkinje cells Highly sensitive
Cortex layers 3,5 Moderate
Watershed areas Hypotension sensitive

🔬 SLIDES (EXAM FAVORITE)

🔬 Red Neuron

Image

Image

  • Shrunken neuron

  • Bright eosinophilic cytoplasm

  • Pyknotic nucleus

  • Loss of Nissl substance

🔬 Gliosis

Image

 

  • Increased astrocytes

  • Dense fibrillary background

  • GFAP positive

🔬 Microglial Nodules

Image

Image

  • Clusters of microglia

  • Surround damaged neurons

  • Seen in viral infections

🧠 DIAGRAMS

🧠 Neuron Injury → Gliosis Pathway

Injury
↓
Neuronal damage
↓
Microglial activation
↓
Astrocyte proliferation
↓
Glial scar formation (gliosis)

🧠 CNS Cellular Response Diagram

Injury
↓
Neurons → necrosis
↓
Microglia → phagocytosis
↓
Astrocytes → gliosis
↓
Oligodendrocytes → demyelination
↓
Outcome:

  • Repair (gliosis)

  • Permanent deficit

🟢 FINAL HIGH-YIELD SUMMARY

  • Red neuron = marker of acute ischemia

  • Liquefactive necrosis = hallmark of brain infarction

  • Gliosis = main CNS repair mechanism

  • Selective vulnerability = important exam concept

  • Microglial nodules = seen in viral infections

  • CNS has minimal regenerative capacity

 

 

🧠 CENTRAL NERVOUS SYSTEM

🔶 EDEMA, HERNIATION, HYDROCEPHALUS

🔷 CEREBRAL EDEMA

🔹 Types

🔸 Vasogenic Edema

  • Most common type

  • Due to blood-brain barrier (BBB) disruption

  • Fluid accumulates in extracellular space

  • Predominantly affects white matter

🔸 Cytotoxic Edema

  • Due to cellular injury (ATP depletion)

  • Failure of Na⁺/K⁺ pump → intracellular swelling

  • Affects neurons, astrocytes, endothelial cells

  • Involves gray + white matter

🔸 Interstitial Edema

  • Due to CSF flow obstruction

  • Seen in hydrocephalus

  • CSF leaks into periventricular white matter

🔹 Causes

  • Tumors

  • Infections (abscess, meningitis)

  • Trauma

  • Ischemia / infarction

  • Hydrocephalus

🔹 Pathogenesis

  • BBB disruption → vasogenic edema

  • Energy failure → cytotoxic edema

  • CSF obstruction → interstitial edema

  • ↑ Intracranial pressure → ↓ cerebral perfusion → secondary injury

📊 TABLE

📊 Vasogenic vs Cytotoxic Edema

Feature Vasogenic Edema Cytotoxic Edema
Mechanism BBB disruption Cellular injury
Fluid location Extracellular Intracellular
Area involved White matter Gray + white matter
Causes Tumor, inflammation Ischemia, hypoxia
Reversibility Potentially reversible Often irreversible

🔬 SLIDES (EXAM FAVORITE)

🔬 Edematous Brain (Flattened Gyri)

  • Swollen brain

  • Flattened gyri

  • Narrowed sulci

  • Increased intracranial pressure

🧠 DIAGRAM

🧠 Edema Pathogenesis Flowchart

Injury (tumor / ischemia / trauma)
↓
BBB disruption / ATP depletion
↓
Fluid accumulation
↓
Brain swelling
↓
↑ Intracranial pressure
↓
↓ Cerebral perfusion
↓
Secondary neuronal injury

🔷 HYDROCEPHALUS

🔹 Types

🔸 Non-communicating (Obstructive)

  • Block within ventricular system

  • Example: aqueductal stenosis

🔸 Communicating

  • Impaired CSF absorption

  • No obstruction in ventricles

  • Example: post-meningitis fibrosis

🔸 Normal Pressure Hydrocephalus

  • Mild ventricular enlargement

  • Classic triad:

    • Gait disturbance

    • Urinary incontinence

    • Dementia

🔹 Causes

  • Congenital malformations

  • Tumors

  • Infections (meningitis)

  • Hemorrhage

  • Aqueductal stenosis

🔹 Pathophysiology

  • CSF accumulation → ventricular dilation

  • Compression of brain parenchyma

  • Periventricular ischemia

  • In infants → head enlargement

  • In adults → increased intracranial pressure

📊 TABLE

📊 Types of Hydrocephalus

Type Mechanism Example
Non-communicating Obstruction of CSF flow Aqueductal stenosis
Communicating Impaired absorption Meningitis
Normal pressure Chronic CSF imbalance Elderly patients

🔬 SLIDES (EXAM FAVORITE)

🔬 Ventricular Dilation

Image

Image

  • Enlarged ventricles

  • Thinning of brain parenchyma

  • Periventricular changes

🧠 DIAGRAM

🧠 CSF Circulation Pathway

Choroid plexus
↓
Lateral ventricles
↓
Foramen of Monro
↓
Third ventricle
↓
Aqueduct of Sylvius
↓
Fourth ventricle
↓
Foramina of Luschka & Magendie
↓
Subarachnoid space
↓
Arachnoid villi
↓
Venous sinuses

🟢 FINAL HIGH-YIELD SUMMARY

  • Vasogenic edema = BBB breakdown

  • Cytotoxic edema = cell injury (ATP failure)

  • Interstitial edema = CSF leakage

  • Flattened gyri = hallmark of cerebral edema

  • Hydrocephalus = ventricular dilation

  • Normal pressure hydrocephalus triad = gait + incontinence + dementia

  • CSF flow pathway = very important for exams

 

🔷 HERNIATION

🔹 Types

🔸 Subfalcine (Cingulate) Herniation

  • Cingulate gyrus displaced under falx cerebri

  • Can compress anterior cerebral artery (ACA)

  • Leads to:

    • Contralateral lower limb weakness

🔸 Transtentorial (Uncal) Herniation

  • Medial temporal lobe (uncus) herniates through tentorial notch

🔹 Effects

  • Compression of CN III (oculomotor nerve) → ipsilateral dilated pupil

  • Compression of posterior cerebral artery (PCA) → occipital infarction

  • Compression of brainstem → altered consciousness

🔸 Tonsillar Herniation

  • Cerebellar tonsils herniate through foramen magnum

🔹 Effects

  • Compression of medulla

  • Leads to:

    • Respiratory arrest

    • Cardiovascular instability

    • Sudden death

🔹 Clinical Effects (General)

  • Increased intracranial pressure

  • Headache, vomiting

  • Altered consciousness

  • Pupillary changes

  • Focal neurological deficits

  • Brainstem compression → life-threatening

📊 TABLE

📊 Types of Herniation vs Features

Type Structure Involved Structure Compressed Clinical Feature
Subfalcine Cingulate gyrus ACA Leg weakness
Transtentorial (Uncal) Medial temporal lobe CN III, PCA Dilated pupil, vision loss
Tonsillar Cerebellar tonsils Medulla Respiratory arrest

🔬 SLIDES (EXAM FAVORITE)

🔬 Brain Compression Findings

Image

Image

  • Midline shift

  • Compression of ventricles

  • Flattened gyri

  • Displacement of brain structures

🧠 DIAGRAM

🧠 Brain Herniation Diagram

Mass lesion (tumor / hemorrhage / edema)
↓
Increased intracranial pressure
↓
Displacement of brain tissue
↓

Types:

  • Subfalcine → cingulate under falx

  • Transtentorial → uncus through tentorium

  • Tonsillar → cerebellum through foramen magnum

↓
Compression of vessels / nerves / brainstem
↓
Ischemia + neurological deficits
↓
Death (if untreated)

🟢 FINAL HIGH-YIELD SUMMARY

  • Herniation = displacement of brain due to increased ICP

  • Subfalcine → ACA compression → leg weakness

  • Uncal → CN III palsy → dilated pupil

  • Tonsillar → medullary compression → death

  • Midline shift = important radiological finding

  • Brainstem compression = most dangerous outcome

 

🔶 CEREBROVASCULAR DISEASES

🔷 HYPOXIA, ISCHEMIA, INFARCTION

🔹 Global Ischemia

  • Due to systemic hypotension or hypoxia

  • Causes:

    • Cardiac arrest

    • Shock

    • Severe blood loss

🔹 Effects

  • Diffuse brain injury

  • Most severe damage in selectively vulnerable neurons

  • Severe cases → watershed infarcts

🔹 Focal Ischemia

  • Due to localized interruption of blood flow

  • Causes:

    • Thrombosis

    • Embolism

🔹 Effects

  • Localized infarction in vascular territory

  • Example:

    • Middle cerebral artery infarct

🔹 Infarction Types

🔸 Pale (Non-hemorrhagic) Infarct

  • Due to arterial occlusion

  • Common in:

    • Heart

    • Kidney

    • Brain (early stage)

🔸 Hemorrhagic Infarct

  • Due to:

    • Venous occlusion

    • Reperfusion injury

  • Blood leaks into necrotic tissue

🔶 Liquefactive Necrosis

  • Characteristic necrosis in CNS infarction

  • Enzymatic digestion → tissue becomes soft

  • Leads to:

    • Cystic cavity formation

🔶 Selective Vulnerability (HIGH-YIELD)

  • Certain neurons are more sensitive to hypoxia

🔹 Most Vulnerable

  • Hippocampus (CA1)

  • Purkinje cells (cerebellum)

  • Cortical neurons (layers 3 & 5)

🔶 Watershed Infarcts (VERY IMPORTANT)

  • Occur in border zones between arterial territories

  • Common region:

    • ACA–MCA junction

🔹 Causes

  • Severe hypotension

🔹 Features

  • Bilateral cortical injury

  • Often wedge-shaped lesions

📊 TABLES

📊 Global vs Focal Ischemia

Feature Global Ischemia Focal Ischemia
Cause Hypotension / hypoxia Thrombosis / embolism
Distribution Diffuse Localized
Neuronal damage Selective vulnerability Territory-specific infarct
Example Cardiac arrest MCA infarct

📊 Vulnerable Neurons

Region Cells
Hippocampus CA1 neurons
Cerebellum Purkinje cells
Cortex Layers 3 & 5
Watershed zones Border areas

🔬 SLIDES (EXAM FAVORITE)

🔬 Red Neurons

Image

 

  • Shrunken neurons

  • Bright eosinophilic cytoplasm

  • Pyknotic nucleus

🔬 Liquefactive Necrosis

  • Soft, cystic areas

  • Macrophage infiltration

  • Loss of normal architecture

🧠 DIAGRAM

🧠 Ischemia → Infarction Pathway

Vascular occlusion (thrombus / embolus)
↓
Reduced blood flow
↓
Hypoxia
↓
ATP depletion
↓
Ion pump failure (Na⁺/K⁺)
↓
Cellular swelling (cytotoxic edema)
↓
Calcium influx
↓
Enzyme activation
↓
Cell death
↓
Liquefactive necrosis
↓
Cyst formation

🟢 FINAL HIGH-YIELD SUMMARY

  • Global ischemia = diffuse brain injury

  • Focal ischemia = territorial infarct

  • Liquefactive necrosis = hallmark of CNS infarction

  • Red neurons = early ischemic change

  • Selective vulnerability = important exam concept

  • Watershed infarcts = hypotension-related injury

  • MCA territory = most commonly affected

 

🔷 INTRACRANIAL HEMORRHAGE

🔹 Epidural Hematoma

  • Bleeding between skull and dura mater
  • Cause:
    • Trauma → middle meningeal artery rupture
  • Classically associated with:
    • Temporal bone fracture

🔹 Features

  • Lucid interval (temporary recovery after injury)
  • Rapid neurological deterioration

🔹 Subdural Hematoma

  • Bleeding between dura and arachnoid mater
  • Cause:
    • Bridging vein rupture
  • Common in:
    • Elderly (brain atrophy)
    • Infants

🔹 Features

  • Slow progression
  • Chronic hematoma possible

🔹 Subarachnoid Hemorrhage (SAH)

  • Bleeding into subarachnoid space

🔹 Causes

  • Berry aneurysm rupture (Circle of Willis)
  • Trauma

🔹 Features

  • Sudden severe headache:
    • “Worst headache of life”
  • Neck stiffness
  • Photophobia

🔹 Intraparenchymal Hemorrhage

  • Bleeding within brain parenchyma

🔹 Causes

  • Hypertension (most common)
  • Charcot–Bouchard microaneurysms
  • Amyloid angiopathy

🔹 Common Sites

  • Basal ganglia
  • Thalamus
  • Pons

📊 TABLE

📊 Epidural vs Subdural vs Subarachnoid Hemorrhage

Feature Epidural Subdural Subarachnoid
Location Skull–dura Dura–arachnoid Subarachnoid space
Vessel Middle meningeal artery Bridging veins Berry aneurysm
Onset Rapid Slow Sudden
Classic feature Lucid interval Gradual decline Thunderclap headache
CT finding Biconvex (lens-shaped) Crescent-shaped Diffuse blood in CSF

🔬 SLIDES (EXAM FAVORITE)

🔬 Hemorrhage Sections

 

https://media.licdn.com/dms/image/v2/D5622AQHzjTou2yrbUQ/feedshare-shrink_800/B56Zus5HZSIUAg-/0/1768132215242?e=2147483647&t=eFcJj5Wclu0QIN0N-GsoRI2h9T6D4OKjDMZKH460Dgg&v=beta

 

https://www.researchgate.net/publication/356282118/figure/fig2/AS%3A1124662457188375%401645151833815/Histology-of-the-hematoma-wall-and-cerebral-tissue-a-H-E-stain-shows-scattered-petechial.png

  • Accumulation of blood
  • Compression of adjacent brain tissue
  • Disruption of normal architecture

🧠 DIAGRAM

🧠 Hemorrhage Location Diagram

Trauma / vascular rupture
↓

Locations:

  • Epidural → skull–dura (arterial)
  • Subdural → dura–arachnoid (venous)
  • Subarachnoid → CSF space
  • Intraparenchymal → brain tissue

↓
Mass effect
↓
↑ Intracranial pressure
↓
Brain compression
↓
Neurological deficits

🔷 OTHER VASCULAR DISEASES

🔹 Hypertensive Encephalopathy

  • Due to severe uncontrolled hypertension
  • Leads to:
    • Cerebral edema
    • Vascular damage

🔹 Features

  • Headache
  • Confusion
  • Seizures

🔹 Lacunar Infarcts

  • Small infarcts in deep brain structures

🔹 Common Sites

  • Basal ganglia
  • Thalamus
  • Internal capsule

🔹 Cause

  • Chronic hypertension → small vessel disease

🔹 Vascular Malformations

  • Congenital abnormalities of vessels

🔹 Types

  • Arteriovenous malformation (AVM)
  • Cavernous malformation

📊 TABLE

📊 Small Vessel vs Large Vessel Disease

Feature Small Vessel Disease Large Vessel Disease
Vessel size Small penetrating arteries Major cerebral arteries
Cause Hypertension Atherosclerosis
Lesions Lacunar infarcts Territorial infarcts
Common site Basal ganglia Cortex

🔬 SLIDES (EXAM FAVORITE)

🔬 Lipohyalinosis

 

https://www.ahajournals.org/cms/10.1161/HYPERTENSIONAHA.123.19943/asset/28078169-bce9-477f-976e-98b9a3f36a30/assets/graphic/hypertensionaha.123.19943.fig02.jpg

 

https://www.researchgate.net/profile/Lea-Grinberg/publication/306289121/figure/fig1/AS%3A396807592005632%401471617710592/Example-of-small-vessel-disease-A-Subcortical-white-matter-exhibiting-hyaline.png

  • Thickened vessel wall
  • Hyaline deposition
  • Luminal narrowing

🧠 DIAGRAM

🧠 Hypertension → Vessel Damage Pathway

Chronic hypertension
↓
Endothelial damage
↓
Hyaline deposition (lipohyalinosis)
↓
Vessel wall thickening
↓
Luminal narrowing
↓
Reduced blood flow
↓
Lacunar infarction / hemorrhage

🟢 FINAL HIGH-YIELD SUMMARY

  • Epidural hematoma = middle meningeal artery + lucid interval
  • Subdural hematoma = bridging vein rupture + slow onset
  • Subarachnoid hemorrhage = berry aneurysm + sudden headache
  • Intraparenchymal hemorrhage = hypertension-related
  • Lacunar infarcts = small vessel disease (basal ganglia)
  • Lipohyalinosis = hallmark of hypertensive vascular damage
  • CT patterns = highly important for exams

 

 

🔶 CNS TRAUMA

🔷 TRAUMATIC PARENCHYMAL INJURIES

🔹 Concussion

  • Mild traumatic brain injury
  • Transient loss of neurological function
  • No structural brain damage

🔹 Features

  • Loss of consciousness (brief)
  • Confusion
  • Amnesia

🔹 Contusion

  • Bruising of brain tissue due to trauma
  • Occurs at:
    • Site of impact (coup)
    • Opposite side (contrecoup)

🔹 Common Sites

  • Frontal lobes
  • Temporal lobes

🔹 Features

  • Hemorrhage
  • Edema
  • Tissue necrosis

🔹 Diffuse Axonal Injury (DAI)

  • Severe brain injury due to shearing forces
  • Caused by:
    • Rapid acceleration–deceleration (e.g., road traffic accidents)

🔹 Pathology

  • Axonal stretching and tearing
  • Disruption of neuronal connections

🔹 Common Sites

  • Corpus callosum
  • Brainstem
  • Gray-white matter junction

🔹 Clinical Features

  • Immediate loss of consciousness
  • Persistent coma

📊 TABLE

📊 Concussion vs Contusion vs Diffuse Axonal Injury

Feature Concussion Contusion Diffuse Axonal Injury
Severity Mild Moderate Severe
Structural damage Absent Present Diffuse axonal damage
Mechanism Functional disturbance Direct impact Shearing forces
Loss of consciousness Brief Variable Immediate, prolonged
Outcome Reversible May progress Often poor prognosis

🔬 SLIDES (EXAM FAVORITE)

🔬 Axonal Retraction Balls

https://www.mdpi.com/ijms/ijms-18-02600/article_deploy/html/images/ijms-18-02600-g002.png

https://www.researchgate.net/publication/321507984/figure/fig2/AS%3A11431281386832630%401745085604377/A-Scattered-axonal-retraction-balls-stained-with-Congo-Red-arrows-scale-bar-250.tif

  • Swollen axonal ends
  • Disconnected axons
  • Marker of diffuse axonal injury

🧠 DIAGRAM

🧠 Diffuse Axonal Injury Mechanism

Rapid acceleration–deceleration
↓
Shearing forces
↓
Axonal stretching
↓
Axonal rupture
↓
Disconnection of neurons
↓
Diffuse brain dysfunction
↓
Coma

🔷 TRAUMATIC VASCULAR INJURY

🔹 Hemorrhage Types

  • Epidural hemorrhage
  • Subdural hemorrhage
  • Subarachnoid hemorrhage
  • Intraparenchymal hemorrhage

🔹 Secondary Ischemia

  • Trauma → increased intracranial pressure
  • ↓ Cerebral blood flow
  • Leads to:
    • Hypoxia
    • Neuronal injury
    • Infarction

🟢 FINAL HIGH-YIELD SUMMARY

  • Concussion = transient functional disturbance
  • Contusion = structural brain injury (coup–contrecoup)
  • DAI = shearing injury → immediate coma
  • Axonal retraction balls = hallmark of DAI
  • Corpus callosum + brainstem = commonly affected
  • Secondary ischemia = major cause of worsening injury

 

 

🔶 CONGENITAL MALFORMATIONS & PERINATAL INJURY

🔷 MALFORMATIONS

🔹 Neural Tube Defects

  • Due to failure of neural tube closure (day 22–28 of gestation)
  • Strong association with folate deficiency

🔹 Types

  • Anencephaly → absence of brain and skull
  • Spina bifida:
    • Occulta
    • Meningocele
    • Myelomeningocele

🔹 Chiari Malformation

  • Structural defect involving cerebellum and brainstem

🔹 Types

  • Type I:
    • Cerebellar tonsillar herniation
    • Often asymptomatic
  • Type II (Arnold–Chiari):
    • Associated with myelomeningocele
    • Brainstem involvement

🔹 Dandy–Walker Malformation

  • Congenital malformation of posterior fossa

🔹 Features

  • Enlarged posterior fossa
  • Cystic dilation of 4th ventricle
  • Agenesis of cerebellar vermis

🔹 Agenesis of Corpus Callosum

  • Failure of development of corpus callosum

🔹 Features

  • Cognitive impairment
  • Seizures
  • May be asymptomatic

📊 TABLE

📊 CNS Malformations Comparison

Condition Defect Key Features
Neural tube defects Failure of tube closure Anencephaly, spina bifida
Chiari malformation Cerebellar herniation Brainstem compression
Dandy-Walker Posterior fossa defect Cystic dilation
Agenesis of corpus callosum Absent commissural fibers Cognitive deficits

🔬 SLIDES (EXAM FAVORITE)

🔬 Neural Tube Defects

 

https://upload.wikimedia.org/wikipedia/commons/7/7e/Spina-bifida.jpg

 

https://assets.medlink.com/content/article-media/anendl32.jpg

  • Open neural tube
  • Exposed neural tissue
  • Structural deformity

🧠 DIAGRAM

🧠 Neural Tube Development

Neural plate formation
↓
Neural fold elevation
↓
Neural tube closure (day 22–28)
↓
Brain and spinal cord formation

Failure of closure
↓
Neural tube defects

🔷 PERINATAL BRAIN INJURY

🔹 Hypoxic Ischemic Encephalopathy (HIE)

  • Due to perinatal asphyxia

🔹 Causes

  • Placental insufficiency
  • Birth complications

🔹 Features

  • Diffuse brain injury
  • Selective neuronal necrosis

🔹 Germinal Matrix Hemorrhage

  • Occurs in premature infants

🔹 Pathogenesis

  • Fragile vessels in germinal matrix
  • Bleeding into ventricles

🔹 Periventricular Leukomalacia (PVL)

  • White matter injury around ventricles

🔹 Causes

  • Ischemia in premature infants

🔹 Features

  • Necrosis of white matter
  • Leads to cerebral palsy

📊 TABLE

📊 Term vs Preterm Brain Injury

Feature Term Infants Preterm Infants
Type of injury Cortical injury Periventricular injury
Common lesion Hypoxic injury PVL
Hemorrhage Less common Germinal matrix hemorrhage
Outcome Cognitive deficits Motor deficits

🔬 SLIDES (EXAM FAVORITE)

🔬 Periventricular Leukomalacia

 

https://static.cambridge.org/binary/version/id/urn%3Acambridge.org%3Aid%3Abinary-alt%3A20210806115051-47125-mediumThumb-15979fig34_13.jpg?pub-status=live

 

https://media.springernature.com/m685/springer-static/image/art%3A10.1203%2F00006450-200111000-00003/MediaObjects/41390_2001_Article_BFpr2001219_Fig1_HTML.jpg

  • Necrosis of periventricular white matter
  • Cystic lesions
  • Loss of normal structure

🧠 DIAGRAM

🧠 Hypoxia → Neonatal Brain Injury Pathway

Perinatal hypoxia
↓
Reduced cerebral blood flow
↓
ATP depletion
↓
Cellular injury
↓

Outcomes:

  • Hypoxic ischemic encephalopathy
  • Germinal matrix hemorrhage
  • Periventricular leukomalacia

🟢 FINAL HIGH-YIELD SUMMARY

  • Neural tube defects = failure of closure (day 22–28)
  • Folate deficiency = major risk factor
  • Chiari II = associated with myelomeningocele
  • Dandy-Walker = cystic dilation of 4th ventricle
  • PVL = most important lesion in premature infants
  • Germinal matrix hemorrhage = fragile vessels
  • HIE = global hypoxic injury in neonates

 

 

🔶 INFECTIONS OF NERVOUS SYSTEM

🔷 EPIDURAL & SUBDURAL INFECTIONS

🔹 Abscess Formation

  • Localized collection of pus between skull and meninges
  • Types:
    • Epidural abscess
    • Subdural abscess

🔹 Pathogenesis

  • Spread from:
    • Skull infection (osteomyelitis)
    • Sinusitis
    • Otitis media

🔹 Spread

  • Direct extension from adjacent infection
  • Hematogenous spread (rare)
  • Rapid spread in subdural space due to lack of barriers

🔷 MENINGITIS

🔹 Acute Bacterial Meningitis

🔹 Common Organisms

  • Neonates:
    • E. coli
    • Group B Streptococcus
  • Adults:
    • Streptococcus pneumoniae
    • Neisseria meningitidis

🔹 Pathology

  • Neutrophilic exudate in subarachnoid space
  • Thick purulent material

🔹 Viral (Aseptic) Meningitis

🔹 Causes

  • Enteroviruses (most common)
  • HSV

🔹 Pathology

  • Lymphocytic infiltrate
  • Mild inflammation

🔹 Chronic Meningitis

🔹 Causes

  • Tuberculosis
  • Fungal infections (Cryptococcus)

🔹 Features

  • Granulomatous inflammation
  • Basal meningitis (TB)

📊 TABLE

📊 Bacterial vs Viral vs TB Meningitis

Feature Bacterial Viral TB/Fungal
Onset Acute Subacute Chronic
Cells Neutrophils Lymphocytes Lymphocytes
CSF protein High Mild ↑ High
CSF glucose Low Normal Low
Severity Severe Mild Moderate

🔬 SLIDES (EXAM FAVORITE)

🔬 Neutrophilic Exudate (Bacterial Meningitis)

https://webpath.med.utah.edu/jpeg5/CNS190.jpg

https://media.springernature.com/m685/springer-static/image/art%3A10.1038%2Fmodpathol.2013.30/MediaObjects/41379_2013_Article_BFmodpathol201330_Fig1_HTML.jpg

  • Dense neutrophilic infiltrate
  • Purulent exudate
  • Thickened meninges

🔬 Lymphocytic Infiltrate (Viral Meningitis)

https://www.researchgate.net/publication/327521752/figure/fig3/AS%3A963520606769160%401606732622371/Histopathology-in-listerial-meningitis-mice-model-Mild-meningeal-infiltration-a-score.png

https://www.researchgate.net/publication/337971276/figure/fig2/AS%3A836952748208128%401576556493016/An-example-of-cerebrospinal-fluid-histology-in-viral-meningitis-where-you-would-see.png

  • Lymphocyte predominance
  • Mild inflammation
  • No pus formation

🧠 DIAGRAM

🧠 Meningitis Pathogenesis

Pathogen entry (blood / direct spread)
↓
Crosses blood-brain barrier
↓
Multiplication in CSF
↓
Inflammatory response
↓
Cytokine release
↓
Leukocyte infiltration
↓
Meningeal inflammation
↓
↑ Intracranial pressure
↓
Neurological symptoms

🔷 PARENCHYMAL INFECTIONS

🔹 Brain Abscess

  • Localized infection in brain parenchyma

🔹 Causes

  • Bacterial infection
  • Spread from:
    • Sinusitis
    • Otitis
    • Endocarditis

🔹 Features

  • Central necrosis
  • Surrounding edema
  • Capsule formation

🔹 Viral Encephalitis

🔸 HSV Encephalitis (VERY HIGH-YIELD)

  • Most common cause of fatal sporadic encephalitis
  • Affects:
    • Temporal lobes

🔹 Features

  • Hemorrhagic necrosis
  • Edema
  • Altered consciousness

🔹 Toxoplasmosis

  • Seen in immunocompromised patients
  • Causes:
    • Multiple brain lesions

📊 TABLE

📊 Brain Abscess vs Encephalitis

Feature Brain Abscess Encephalitis
Cause Bacterial Viral
Lesion Localized Diffuse
Pus Present Absent
Necrosis Central Diffuse
Edema Marked Moderate

🔬 SLIDES (EXAM FAVORITE)

🔬 Microabscess

https://www.researchgate.net/profile/Jorgen-Agerholm/publication/258213054/figure/fig1/AS%3A195380781293569%401423593816450/Focal-brain-microabscess-The-abscess-consists-of-a-necrotic-centre-surrounded-by-a-rim.png

https://www.researchgate.net/publication/344056482/figure/fig4/AS%3A955085941129216%401604721641838/Fig-7-Section-in-Pons-of-sheep-brain-showing-micro-abscess-and-liquifactive-necrosis.jpg

  • Small collections of neutrophils
  • Necrotic center

🔬 Viral Inclusion Bodies

https://www.pathologyoutlines.com/imgau/cnshsvencephalitisbrq.jpg

https://upload.wikimedia.org/wikipedia/commons/6/6f/Histopathology_of_Negri_bodies_in_rabies_encephalitis.png

  • Intranuclear inclusions
  • Seen in viral infections (HSV)

🧠 DIAGRAM

🧠 Brain Abscess Formation

Infection (hematogenous / direct spread)
↓
Local inflammation
↓
Cerebritis (early stage)
↓
Necrosis
↓
Capsule formation
↓
Mature abscess

🟢 FINAL HIGH-YIELD SUMMARY

  • Bacterial meningitis = neutrophilic exudate
  • Viral meningitis = lymphocytic infiltrate
  • TB meningitis = chronic granulomatous inflammation
  • HSV encephalitis = temporal lobe + hemorrhagic necrosis
  • Brain abscess = localized pus formation
  • Toxoplasmosis = multiple lesions in immunocompromised
  • Meningitis → increased ICP → neurological symptoms

 

🔷 CONGENITAL INFECTIONS (TORCH)

🔹 Subcontents

🔸 Cytomegalovirus (CMV)

  • Most common congenital viral infection
  • Affects:
    • Periventricular region

🔹 Features

  • Periventricular calcification
  • Microcephaly
  • Hearing loss

🔸 Toxoplasmosis

  • Caused by Toxoplasma gondii
  • Transmission:
    • Transplacental

🔹 Features

  • Diffuse intracranial calcification
  • Hydrocephalus
  • Chorioretinitis

🔸 Rubella

  • Congenital viral infection

🔹 Features

  • Sensorineural deafness
  • Cardiac defects
  • Cataracts

📊 TABLE

📊 TORCH Infections Comparison

Infection Key Feature Brain Finding
CMV Most common Periventricular calcification
Toxoplasmosis Severe infection Diffuse calcification
Rubella Congenital triad Mild CNS involvement

🔷 PRION DISEASES

🔹 Creutzfeldt–Jakob Disease (CJD)

  • Rapidly progressive neurodegenerative disease
  • Caused by abnormal prion protein

🔹 Features

  • Rapid dementia
  • Myoclonus
  • Fatal outcome

🔹 Pathogenesis

  • Normal prion protein (PrPc) converts into abnormal form (PrPsc)
  • Abnormal protein:
    • Misfolded
    • Protease resistant
  • Leads to:
    • Accumulation in brain
    • Neuronal damage

📊 TABLE

📊 Types of Prion Diseases

Type Example
Sporadic CJD
Familial Genetic mutation
Acquired Iatrogenic / variant CJD

🔬 SLIDES (EXAM FAVORITE)

🔬 Spongiform Change

https://www.researchgate.net/profile/Lorenzo-Gonzalez-4/publication/5342800/figure/fig1/AS%3A216433943420928%401428613281347/Spongiform-change-in-the-obex-of-the-brain-from-a-clinically-affected-BSE-challenged.png

https://upload.medbullets.com/topic/113087/images/liberski3_1color.jpg

  • Vacuolation of neuropil
  • Sponge-like appearance
  • Neuronal loss
  • No inflammation

🧠 DIAGRAM

🧠 Prion Protein Conversion

Normal PrPc
↓
Misfolding
↓
Conversion to PrPsc
↓
Aggregation
↓
Neuronal damage
↓
Spongiform change
↓
Neurodegeneration

🟢 FINAL HIGH-YIELD SUMMARY

  • CMV = periventricular calcification
  • Toxoplasmosis = diffuse calcification
  • Rubella = congenital triad
  • Prion diseases = protein misfolding disorders
  • PrPsc = abnormal infectious protein
  • Spongiform change = hallmark of prion disease
  • No inflammation in prion diseases

 

 

🔶 DEMYELINATING DISEASES

🔷 MULTIPLE SCLEROSIS

🔹 Autoimmune Pathogenesis

  • Chronic immune-mediated demyelinating disease of CNS
  • Involves:
    • CD4+ T cells
    • B cells (antibodies)
    • Macrophages

🔹 Mechanism

  • Trigger (environmental/genetic)
    ↓
    Activation of autoreactive T cells
    ↓
    Cross blood-brain barrier
    ↓
    Recognition of myelin antigens
    ↓
    Cytokine release
    ↓
    Inflammation
    ↓
    Demyelination
    ↓
    Axonal damage

🔹 Plaques

  • Characteristic lesion of MS
  • Well-demarcated areas of:
    • Demyelination
    • Gliosis

🔹 Common Sites

  • Periventricular white matter
  • Optic nerves
  • Brainstem
  • Spinal cord

🔹 Clinical Features

  • Relapsing-remitting course
  • Visual disturbances:
    • Optic neuritis
  • Motor weakness
  • Sensory symptoms
  • Ataxia
  • Internuclear ophthalmoplegia

📊 TABLE

📊 Features of Multiple Sclerosis

Feature Description
Pathogenesis Autoimmune demyelination
Lesion Plaques
Location Periventricular white matter
Course Relapsing-remitting
CSF finding Oligoclonal bands
Key symptom Optic neuritis

🔬 SLIDES (EXAM FAVORITE)

🔬 Demyelinated Plaques

 

https://www.pathologyoutlines.com/imgau/cnsmultiplesclerosisBRQMultz01.jpg

 

https://www.researchgate.net/profile/Emily-Leibovitch/publication/303816446/figure/fig6/AS%3A416365036617731%401476280568501/Histological-features-of-MS-lesions-with-phase-rim-Chronic-demyelination-colocalizes.png

  • Loss of myelin
  • Relative preservation of axons (early)
  • Inflammatory infiltrate
  • Reactive gliosis

🧠 DIAGRAM

🧠 Autoimmune Demyelination Pathway

Trigger (genetic + environmental)
↓
T-cell activation
↓
Entry into CNS
↓
Myelin antigen recognition
↓
Cytokine release
↓
Inflammation
↓
Demyelination
↓
Plaque formation
↓
Neurological deficit

🔷 OTHER ACQUIRED DEMYELINATING DISEASES

🔹 Acute Disseminated Encephalomyelitis (ADEM)

  • Acute inflammatory demyelinating disease
  • Often follows:
    • Viral infection
    • Vaccination

🔹 Features

  • Rapid onset
  • Diffuse demyelination
  • Monophasic course

🔹 Progressive Multifocal Leukoencephalopathy (PML)

  • Caused by JC virus infection
  • Occurs in:
    • Immunocompromised patients (HIV, transplant)

🔹 Pathology

  • Viral infection of oligodendrocytes
  • Multifocal demyelination

🔹 Features

  • Progressive neurological deficits
  • No significant inflammation

🟢 FINAL HIGH-YIELD SUMMARY

  • MS = autoimmune demyelinating disease
  • Plaques = hallmark lesion
  • Optic neuritis = common presentation
  • Oligoclonal bands = diagnostic clue
  • ADEM = post-infectious, monophasic
  • PML = JC virus infection in immunocompromised
  • Demyelination = central feature of all these diseases

 

 

🔷 LEUKODYSTROPHIES

🔹 Metachromatic Leukodystrophy

  • Caused by arylsulfatase A deficiency
  • Leads to accumulation of sulfatides

🔹 Pathology

  • Progressive demyelination of CNS and peripheral nerves

🔹 Features

  • Motor dysfunction
  • Peripheral neuropathy
  • Cognitive decline

🔹 Krabbe Disease

  • Caused by galactocerebrosidase deficiency
  • Leads to accumulation of psychosine (toxic to oligodendrocytes)

🔹 Pathology

  • Severe demyelination
  • Presence of globoid cells

🔹 Features

  • Developmental delay
  • Optic atrophy
  • Peripheral neuropathy

📊 TABLE

📊 Leukodystrophies Classification

Disease Enzyme Defect Accumulated Substance Key Feature
Metachromatic leukodystrophy Arylsulfatase A Sulfatides Peripheral neuropathy
Krabbe disease Galactocerebrosidase Psychosine Globoid cells

🔶 METABOLIC & TOXIC DISORDERS

🔷 NUTRITIONAL DISEASES

🔹 Wernicke Encephalopathy

  • Due to vitamin B1 (thiamine) deficiency
  • Common in:
    • Chronic alcoholism

🔹 Triad

  • Confusion
  • Ophthalmoplegia
  • Ataxia

🔹 Pathology

  • Lesions in:
    • Mammillary bodies
    • Periventricular regions

🔹 Vitamin B12 Deficiency

  • Leads to:
    • Subacute combined degeneration

🔹 Pathology

  • Demyelination of:
    • Posterior columns
    • Lateral corticospinal tracts

🔹 Features

  • Paresthesia
  • Ataxia
  • Weakness

📊 TABLE

📊 Nutritional CNS Disorders

Disorder Deficiency Key Features
Wernicke encephalopathy Vitamin B1 Confusion, ophthalmoplegia, ataxia
B12 deficiency Vitamin B12 Posterior column degeneration

🔷 METABOLIC DISORDERS

🔹 Hepatic Encephalopathy

  • Due to liver failure → ammonia accumulation

🔹 Pathology

  • Alzheimer type II astrocytes

🔹 Features

  • Altered mental status
  • Asterixis
  • Coma (severe cases)

🔹 Uremia

  • Due to renal failure

🔹 Features

  • Encephalopathy
  • Cognitive dysfunction
  • Seizures

🔹 Central Pontine Myelinolysis

  • Caused by rapid correction of hyponatremia

🔹 Pathology

  • Demyelination of pons

🔹 Features

  • Quadriplegia
  • Dysphagia
  • Locked-in syndrome (severe)

🟢 FINAL HIGH-YIELD SUMMARY

  • Leukodystrophies = inherited demyelinating disorders
  • Metachromatic leukodystrophy = sulfatide accumulation
  • Krabbe disease = psychosine toxicity + globoid cells
  • Wernicke encephalopathy = B1 deficiency triad
  • B12 deficiency = posterior column demyelination
  • Hepatic encephalopathy = ammonia toxicity + astrocyte changes
  • Central pontine myelinolysis = rapid Na correction → pontine demyelination

 

🔷 TOXIC DISORDERS

🔹 Alcohol

  • Chronic alcohol use → direct neurotoxicity + nutritional deficiency

🔹 Effects

  • Cerebral atrophy
  • Wernicke encephalopathy (B1 deficiency)
  • Korsakoff syndrome:
    • Memory loss
    • Confabulation

🔹 Heavy Metals

🔸 Lead

  • Interferes with neurotransmission
  • Causes:
    • Cognitive impairment
    • Encephalopathy (children)

🔸 Mercury

  • Causes:
    • Sensory neuropathy
    • Cerebellar dysfunction

🧠 DIAGRAM

🧠 Ammonia Toxicity Pathway

Liver failure
↓
Ammonia accumulation
↓
Crosses blood-brain barrier
↓
Astrocyte uptake
↓
Glutamine formation
↓
Osmotic swelling of astrocytes
↓
Cerebral edema
↓
Neuronal dysfunction

🔶 NEURODEGENERATIVE DISEASES

🔷 ALZHEIMER DISEASE

🔹 Pathogenesis

🔸 Amyloid β Deposition

  • Derived from amyloid precursor protein (APP)
  • Forms:
    • Extracellular plaques

🔸 Tau Pathology

  • Hyperphosphorylated tau protein
  • Forms:
    • Neurofibrillary tangles

🔸 Genetics

  • APP gene mutation (chromosome 21)
  • Presenilin 1, Presenilin 2 mutations
  • ApoE4 allele:
    • Increases risk

🔹 Morphology

  • Diffuse cortical atrophy
  • Widened sulci
  • Enlarged ventricles

🔹 Microscopic Features

  • Amyloid plaques
  • Neurofibrillary tangles
  • Neuronal loss

📊 TABLE

📊 Alzheimer Disease vs Normal Aging

Feature Alzheimer Disease Normal Aging
Memory Severe impairment Mild decline
Brain size Marked atrophy Minimal change
Plaques Present Minimal
Tangles Prominent Rare
Progression Progressive Stable

🔬 SLIDES (EXAM FAVORITE)

🔬 Amyloid Plaques

https://upload.wikimedia.org/wikipedia/commons/8/82/Cerebral_amyloid_angiopathy_-2a-_amyloid_beta_-_high_mag.jpg

https://www.researchgate.net/publication/332410140/figure/fig3/AS%3A747642443296770%401555263257926/Brain-histology-after-Congo-Red-staining-Staining-the-Congo-Red-was-done-to-confirm-the.ppm

  • Extracellular deposits
  • β-amyloid protein
  • Surrounded by dystrophic neurites

🔬 Neurofibrillary Tangles

  • Intracellular aggregates
  • Hyperphosphorylated tau
  • Flame-shaped structures

🧠 DIAGRAM

🧠 Amyloid Cascade Hypothesis

APP
↓
Abnormal cleavage
↓
β-amyloid accumulation
↓
Plaque formation
↓
Tau phosphorylation
↓
Neurofibrillary tangles
↓
Neuronal dysfunction
↓
Neuronal death
↓
Dementia

🟢 FINAL HIGH-YIELD SUMMARY

  • Alcohol = neurotoxicity + B1 deficiency
  • Heavy metals = neuronal damage (lead, mercury)
  • Ammonia toxicity = astrocyte swelling → cerebral edema
  • Alzheimer = most common dementia
  • Amyloid plaques = extracellular
  • Neurofibrillary tangles = intracellular
  • ApoE4 = major genetic risk factor
  • Cortical atrophy = key gross feature

 

🔷 FRONTOTEMPORAL LOBAR DEGENERATION (FTLD)

🔹 Subcontents

🔸 Pathology

  • Degeneration of frontal and temporal lobes
  • Associated protein abnormalities:
    • Tau protein (FTLD-tau)
    • TDP-43 protein (FTLD-TDP)

🔹 Features

  • Early behavioral changes
  • Personality alteration
  • Disinhibition
  • Language disturbances (aphasia)

🔹 Morphology

  • Focal cortical atrophy:
    • Frontal lobe
    • Temporal lobe

🔷 PARKINSON DISEASE

🔹 Subcontents

🔸 Substantia Nigra Degeneration

  • Loss of dopaminergic neurons in substantia nigra (pars compacta)
  • Leads to:
    • Reduced dopamine levels

🔸 Dopamine Depletion

  • Imbalance in basal ganglia circuits
  • Results in:
    • Movement disorders

🔸 Lewy Bodies

  • Intracytoplasmic inclusions
  • Composed of:
    • α-synuclein

🔹 Clinical Features

  • Resting tremor
  • Rigidity
  • Bradykinesia
  • Postural instability

📊 TABLE

📊 Parkinson Disease vs Other Movement Disorders

Feature Parkinson Disease Huntington Disease
Movement Hypokinetic Hyperkinetic
Neurotransmitter Dopamine ↓ GABA ↓
Main site Substantia nigra Caudate nucleus
Tremor Present Absent
Onset Late Earlier

🔬 SLIDES (EXAM FAVORITE)

🔬 Lewy Bodies

https://upload.wikimedia.org/wikipedia/commons/thumb/a/ab/Lewy_bodies_%28alpha_synuclein_inclusions%29.svg/1280px-Lewy_bodies_%28alpha_synuclein_inclusions%29.svg.png

https://upload.medbullets.com/topic/113048/images/dementia_s9_lewy_body.jpg

  • Eosinophilic cytoplasmic inclusions
  • Contain α-synuclein
  • Seen in neurons of substantia nigra

🧠 DIAGRAM

🧠 Basal Ganglia Pathway

Substantia nigra degeneration
↓
Dopamine ↓
↓
↓ Stimulation of direct pathway
↑ Activity of indirect pathway
↓
Increased inhibitory output from basal ganglia
↓
Reduced thalamic stimulation
↓
Reduced motor cortex activity
↓
Bradykinesia and rigidity

🟢 FINAL HIGH-YIELD SUMMARY

  • FTLD = frontal + temporal lobe degeneration
  • Tau and TDP-43 = key proteins
  • Parkinson = substantia nigra degeneration
  • Dopamine ↓ = core mechanism
  • Lewy bodies = α-synuclein inclusions
  • Basal ganglia imbalance = movement disorder
  • Parkinson = hypokinetic disorder

 

 

🔷 HUNTINGTON DISEASE

🔹 Subcontents

🔸 CAG Repeat Expansion

  • Autosomal dominant disorder
  • Mutation in HTT gene (chromosome 4)
  • CAG trinucleotide repeat expansion
  • Shows anticipation (earlier onset in successive generations)

🔸 Caudate Nucleus Atrophy

  • Marked degeneration of:
    • Caudate nucleus
    • Putamen (to lesser extent)
  • Leads to:
    • Enlarged lateral ventricles

🔸 Neurotransmitter Changes

  • GABA ↓ (inhibitory neurotransmitter)
  • Also ↓ acetylcholine

🔹 Clinical Features

  • Chorea (involuntary movements)
  • Behavioral changes
  • Dementia

📊 TABLE

📊 Trinucleotide Repeat Disorders

Disease Repeat Gene Feature
Huntington disease CAG HTT Chorea
Fragile X CGG FMR1 Intellectual disability
Myotonic dystrophy CTG DMPK Muscle weakness

🔷 SPINOCEREBELLAR ATAXIAS

🔹 Subcontents

  • Group of genetic neurodegenerative disorders
  • Characterized by:
    • Progressive cerebellar degeneration

🔹 Features

  • Ataxia
  • Coordination defects
  • Gait disturbances

🔷 AMYOTROPHIC LATERAL SCLEROSIS (ALS)

🔹 Subcontents

🔸 Motor Neuron Degeneration

  • Degeneration of:
    • Upper motor neurons
    • Lower motor neurons

🔹 Features

  • Muscle weakness
  • Atrophy
  • Fasciculations
  • No sensory loss

🔶 CNS TUMORS

🔷 GLIOMAS

🔹 Astrocytoma

  • Tumor of astrocytes
  • Range from:
    • Low grade → high grade

🔹 Glioblastoma

  • Most aggressive primary brain tumor

🔹 Types

  • Primary glioblastoma
    • De novo
    • EGFR mutation
  • Secondary glioblastoma
    • Progression from lower-grade astrocytoma
    • p53 mutation

🔹 Oligodendroglioma

  • Tumor of oligodendrocytes

🔹 Features

  • 1p/19q co-deletion (diagnostic and prognostic)

🔹 Ependymoma

  • Tumor of ependymal cells

🔹 Features

  • Common in children
  • Located in:
    • 4th ventricle

📊 TABLE

📊 Glioma Classification

Tumor Cell Type Key Feature
Astrocytoma Astrocytes Variable grade
Glioblastoma Astrocytes Highly aggressive
Oligodendroglioma Oligodendrocytes 1p/19q deletion
Ependymoma Ependymal cells Ventricular tumor

🔬 SLIDES (EXAM FAVORITE)

🔬 Pseudopalisading Necrosis (Glioblastoma)

https://www.researchgate.net/publication/6686476/figure/fig6/AS%3A280578478886921%401443906530867/Pseudopalisading-necrosis-in-a-glioblastoma-characterized-by-a-garlandlike-arrange.png

https://www.researchgate.net/publication/376226683/figure/fig1/AS%3A11431281376601858%401744670015422/Necrotic-areas-and-pseudopalisades-the-distinctive-histopathological-features-of-GBM.tif

  • Tumor cells arranged around necrotic areas
  • Highly characteristic of glioblastoma

🔬 Chicken-Wire Vessels (Oligodendroglioma)

  • Delicate branching capillaries
  • “Fried egg” cells
  • Characteristic vascular pattern

🧠 DIAGRAM

🧠 Tumor Progression Pathway

Normal glial cell
↓
Genetic mutations
↓
Cell cycle dysregulation
↓
Uncontrolled proliferation
↓
Low-grade tumor
↓
Accumulation of mutations
↓
High-grade tumor (glioblastoma)
↓
Invasion and necrosis

🟢 FINAL HIGH-YIELD SUMMARY

  • Huntington = CAG repeat + caudate atrophy + GABA ↓
  • Spinocerebellar ataxia = cerebellar degeneration
  • ALS = motor neuron disease (no sensory loss)
  • Glioblastoma = most aggressive tumor
  • EGFR (primary) and p53 (secondary) pathways
  • Oligodendroglioma = 1p/19q deletion
  • Ependymoma = 4th ventricle tumor in children
  • Pseudopalisading necrosis = hallmark of glioblastoma

 

🔷 NEURONAL TUMORS

🔹 Ganglioglioma

  • Tumor composed of:
    • Neoplastic ganglion cells + glial cells

🔹 Features

  • Usually low-grade tumor
  • Common in:
    • Temporal lobe

🔹 Clinical

  • Often presents with:
    • Seizures (young patients)

🔷 EMBRYONAL TUMORS

🔹 Medulloblastoma

  • Highly malignant embryonal tumor
  • Common in:
    • Children

🔹 Location

  • Cerebellum (midline vermis)

🔹 Features

  • Rapid growth
  • Tendency to spread via CSF (drop metastasis)

🔬 SLIDES (EXAM FAVORITE)

🔬 Small Round Blue Cells

 

https://www.pathologyoutlines.com/imgau/CNStumorSHHdewitt06.jpg

 

https://prod-images-static.radiopaedia.org/images/626167/a1457465cd2fe3b54867ad85cc3e16_gallery.jpg

  • Densely packed cells
  • Hyperchromatic nuclei
  • High nuclear-to-cytoplasmic ratio

🔬 Homer–Wright Rosettes

 

https://d1j63owfs0b5j3.cloudfront.net/term/images/rosettes-and-pseudorosettes-3236.png

 

https://www.ouhsc.edu/pathologyJTY/NeuroTest/Images/NQ-032.gif

  • Tumor cells arranged around central fibrillary space
  • No true lumen
  • Characteristic of medulloblastoma

🔷 OTHER PARENCHYMAL TUMORS

🔹 Examples

  • Pineal tumors
  • Choroid plexus tumors

🔷 MENINGIOMAS

🔹 Subcontents

  • Tumor arising from arachnoid cap cells
  • Usually benign

🔹 Key Features

  • Dural attachment
  • Associated with:
    • Estrogen receptors (more common in females)

🔹 Morphology

  • Whorled pattern of cells
  • Presence of:
    • Psammoma bodies (calcified structures)

🔬 SLIDES (EXAM FAVORITE)

🔬 Psammoma Bodies

 

https://d1j63owfs0b5j3.cloudfront.net/term/images/meningioma-histopathology-3230.png

 

https://www.webpathology.com/_next/image?q=75&url=https%3A%2F%2Fd3cyex60hhnlth.cloudfront.net%2Ffit-in%2F650x650%2Ffilters%3Aformat%28webp%29%2Fcase%2Fdetail_images%2Fc175_detail.jpg&w=1920

  • Concentric calcifications
  • Seen in meningioma

🔷 METASTATIC TUMORS

🔹 Subcontents

  • Most common brain tumors overall

🔹 Spread

  • Hematogenous route

🔹 Common Site

  • Gray-white matter junction

🔹 Common Primary Tumors

  • Lung
  • Breast
  • Melanoma

🧠 DIAGRAM

🧠 Metastasis Pathway

Primary tumor
↓
Local invasion
↓
Intravasation
↓
Circulation
↓
Extravasation (brain)
↓
Tumor deposition at gray-white junction
↓
Metastatic tumor formation

🔷 FAMILIAL TUMOR SYNDROMES

🔹 Neurofibromatosis Type 1 (NF1)

  • Mutation in NF1 gene
  • Loss of neurofibromin

🔹 Features

  • Neurofibromas
  • Café-au-lait spots
  • Optic glioma

🔹 Neurofibromatosis Type 2 (NF2)

  • Mutation in NF2 gene
  • Loss of merlin protein

🔹 Features

  • Bilateral vestibular schwannomas
  • Meningiomas

🔹 Tuberous Sclerosis

  • Mutation in TSC1/TSC2 genes

🔹 Features

  • Cortical tubers
  • Subependymal giant cell astrocytoma
  • Skin lesions

📊 TABLE

📊 Tumor Syndromes

Syndrome Gene Key Tumors
NF1 NF1 Neurofibroma, glioma
NF2 NF2 Schwannoma, meningioma
Tuberous sclerosis TSC1/TSC2 Astrocytoma

🧠 DIAGRAMS (VERY HIGH-YIELD)

🧠 NF1 Pathway

NF1 mutation
↓
Loss of neurofibromin
↓
RAS pathway activation
↓
Increased cell proliferation
↓
Tumor formation

🧠 NF2 Pathway

NF2 mutation
↓
Loss of merlin
↓
Loss of growth suppression
↓
Schwann cell proliferation
↓
Schwannoma formation
↓
Bilateral vestibular tumors

🧠 Tumor Genetics Pathway

Genetic mutation
↓
Oncogene activation
↓
Tumor suppressor loss
↓
Cell cycle dysregulation
↓
Uncontrolled proliferation
↓
Tumor growth

🟢 FINAL HIGH-YIELD SUMMARY

  • Ganglioglioma = mixed neuronal + glial tumor
  • Medulloblastoma = cerebellar tumor in children + CSF spread
  • Homer-Wright rosettes = key histological feature
  • Meningioma = dural-based tumor with psammoma bodies
  • Metastasis = most common brain tumors (gray-white junction)
  • NF1 = neurofibromin loss
  • NF2 = merlin loss + bilateral schwannomas
  • Tuberous sclerosis = cortical tubers + astrocytoma

 

 

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