The Nervous System

🧠 Central Nervous System (CNS)

🧩 1. Overview

CNS includes: Brain and spinal cord
Protected by: Skull and vertebrae (rigid compartments)
Average brain weight:
- Males: ~1400 gm
- Females: ~1250 gm
Main divisions of brain:
- Cerebrum – largest part
- Cerebellum – smaller, posterior part
No lymphatic drainage in brain

🧬 2. Types of CNS Tissues

Tissue Type	Origin	Examples
Neuroectodermal	Ectoderm	Neurons & neuroglia
Mesodermal	Mesoderm	Microglia, meninges, blood vessels

🧠 3. Neurons

Functional unit of CNS
Do not divide after birth → damage is irreversible
Parts:
- Cell body (Perikaryon) – contains nucleus, Nissl bodies
- Axon – sends signals
- Dendrites – receive signals

Special features:

Nissl substance: RNA + rough ER (basophilic)
Other structures: Neurofilaments, lipofuscin, synaptic vesicles
Neuromelanin: Found in substantia nigra neurons

Responses to Injury:

Central chromatolysis
Atrophy
Degeneration
Intraneuronal storage
Neuropil: Mesh-like area of dendrites & axons

🧫 4. Neuroglia (Supportive Cells)

Includes 3 main types:

i) Astrocytes

Star-shaped cells
Types:
- Protoplasmic (gray matter)
- Fibrous (white matter)
Functions:
- Support neurons
- Form blood-brain barrier
- In injury → gliosis (scar-like reaction)
- May form Rosenthal fibers or corpora amylacea

ii) Oligodendrocytes

Fewer, short processes
Function: Form & maintain myelin in CNS
Diseases: Seen in leukodystrophies, MS
Satellite cells (gray matter), Interfascicular cells (white matter)

iii) Ependymal Cells

Line ventricles & spinal canal
Ciliated, help circulate CSF
Involved in CSF formation and absorption

🧪 5. Microglia

Act like macrophages of CNS
Originate from mesoderm
Become rod cells or gitter cells in injury
Perform phagocytosis (neuronophagia)

🧱 6. Meninges (CNS Coverings)

i) Dura Mater

Tough, fibrous outer layer
Attached to skull (inner periosteum)
Epidural space lies between dura and bone (in spinal canal)

ii) Leptomeninges (Thin, delicate)

Pia mater: Directly on brain surface
Arachnoid mater: Above pia, under dura
Subarachnoid space:
- Between pia and arachnoid
- Contains CSF, arteries, veins
- Extends around vessels as Virchow-Robin space
Subdural space: Potential space between dura and arachnoid

🧠 Summary Table

Component	Key Features/Functions
Neurons	Signal transmission; non-dividing
Astrocytes	Support, blood-brain barrier, gliosis
Oligodendrocytes	Myelin formation in CNS
Ependymal cells	Line ventricles, influence CSF
Microglia	Phagocytes; clean up debris
Dura Mater	Tough outer covering
Pia-Arachnoid	Vascular, CSF-containing layer

🧠 Developmental Anomalies of the CNS

🌱 Causes of Developmental Malformations:

Inherited (genetic)
Acquired factors:
- Viral infections (e.g., rubella in pregnancy)
- Drugs (e.g., thalidomide)
- Radiation
- Fetal anoxia (lack of oxygen during development)

📘 1. Spinal Cord Defects (Spina Bifida)

Type	Description
Spina bifida occulta	Mildest form; vertebral defect only; skin may show dimple or hairy patch
Spina bifida cystica	Severe form with cystic swelling over the spine

Types of Spina Bifida Cystica:

Condition	Description
Meningocele	Only meninges herniate (dura + arachnoid)
Meningomyelocele	Spinal cord/nerve roots also herniate into the sac
Myelocele / Syringomyelocele	Open neural tissue plate, CSF leakage, no skin covering

💡 Associated problems:

Hydrocephalus,
Arnold-Chiari malformation,
Paraplegia,
Bladder/Bowel dysfunction

📘 2. Cranial Neural Tube Defects

Defect Type	Description
Cranial meningocele	Herniation of meninges through skull defect
Encephalocele	Herniation of brain tissue + meninges

📘 3. Syringomyelia & Syringobulbia

Syringomyelia = Cavity in spinal cord
Syringobulbia = Cavity in brainstem (medulla)

🧪 Key Features:

Usually begins near central canal
Surrounded by glial tissue
May affect spinothalamic tracts → leads to:
- Loss of pain and temperature in affected areas

📘 4. Arnold-Chiari Malformation

A group of brain malformations involving brainstem and cerebellum
Caused by failure of normal brain folding (pontine flexure)

🔍 Type II Arnold-Chiari (Most common)

Often seen with:

Meningomyelocele
Hydrocephalus (50% cases)

📌 Key Features of Type II Arnold-Chiari:

Elongated medulla + part of 4th ventricle extending into the neck
S-shaped bend at medulla–spinal cord junction
Cerebellar vermis and tonsils herniate through foramen magnum
Blocks CSF flow → leads to internal hydrocephalus

🧠 Clinical Importance:

Early detection through prenatal ultrasound
Surgical correction may be required for severe cases
Neurologic symptoms depend on the type and severity

💧 Hydrocephalus

Definition: Increased volume of cerebrospinal fluid (CSF) in the skull → causes ventricular dilatation

🔁 CSF Flow Pathway

Formed: In choroid plexus of lateral, 3rd, and 4th ventricles
Flows:
1. Lateral ventricles
2. → Foramina of Munro → 3rd ventricle
3. → Aqueduct of Sylvius → 4th ventricle
4. → Foramina of Magendie & Luschka
5. → Subarachnoid space → absorbed by arachnoid villi

📘 Types of Hydrocephalus

Type	Description
Primary	Actual ↑ in CSF + raised ICP
Secondary	Compensatory CSF ↑ due to brain tissue loss (normal pressure)

📌 Primary Hydrocephalus Causes

1. Obstructive (Non-Communicating)

Block in ventricular system
CSF can’t reach subarachnoid space
Causes:
- Aqueduct stenosis
- Arnold-Chiari malformation
- Tumors (ependymoma, medulloblastoma)
- Meningitis, hemorrhage

2. Communicating Hydrocephalus

Block after CSF reaches subarachnoid space
CSF flows between ventricles, but absorption is poor
Causes:
- Overproduction: choroid plexus papilloma
- ↓ Absorption: meningitis, SAH, dural sinus thrombosis

🧬 Secondary Hydrocephalus

Occurs due to brain atrophy or infarction
No raised pressure
Called normal pressure hydrocephalus

🔍 Morphological Features

Dilated ventricles
Thin, stretched brain tissue
Fontanelles open in infants
Engorged scalp veins
May damage ependymal lining

🦠 CNS Infections – Simplified Notes

🛤️ Routes of Infection into the CNS

Bloodstream – Most common (via arteries or septic emboli)
Direct implantation – Skull fracture, surgery
Local extension – From ear (otitis media), sinus infections
Along nerves – Viruses like rabies, herpes

📘 Major CNS Infections

1️⃣ Meningitis – Inflammation of the meninges

Types:

Type	Cause	Key Features
Pachymeningitis	Dura inflammation	Rare, often due to trauma or chronic infections
Leptomeningitis	Pia-arachnoid inflammation	Very common; usually infectious

A. Acute Pyogenic (Bacterial) Meningitis

Common organisms:
- Neonates: E. coli
- Children: H. influenzae
- Young adults: Neisseria meningitidis
- Elderly: Streptococcus pneumoniae

🧪 CSF Findings:

Cloudy or purulent CSF
↑ Pressure, ↑ Neutrophils, ↑ Protein
↓ Glucose
Bacteria seen on Gram stain

B. Acute Viral (Aseptic) Meningitis

Caused by viruses: Enteroviruses, mumps, HSV, HIV, etc.

🧪 CSF Findings:

Clear/slightly turbid CSF
↑ Pressure
↑ Lymphocytes
Normal or mild ↑ Protein
Normal Glucose
Sterile culture (no bacteria)

C. Chronic Meningitis

Tuberculous: Common in children & adults
Cryptococcal: Common in immunocompromised (e.g., AIDS)

🧪 CSF Findings:

Clear/turbid CSF with fibrin web
↑ Pressure
↑ Lymphocytes + macrophages
↑ Protein
↓ Glucose
TB: Acid-fast bacilli (ZN stain)
Cryptococcus: India ink or mucicarmine stain

2️⃣ Encephalitis – Infection of brain tissue (parenchyma)

A. Bacterial Encephalitis

Rare alone, often follows meningitis
Brain abscess: From ear infections, sinusitis, endocarditis
Tuberculoma: Mass of granulomas with caseation
Neurosyphilis: Seen in late syphilis
- Tabes dorsalis: Loss of coordination, Argyll-Robertson pupil
- General paralysis of insane: Psychiatric + motor symptoms

B. Viral Encephalitis

Common viruses: HSV, polio, rabies, HIV, measles (SSPE)

🧠 General features:

Perivascular lymphocytes
Microglial nodules + neuronophagia
Inclusion bodies (e.g., Negri bodies in rabies)

3️⃣ Special Viral Infections

A. HIV Encephalopathy (AIDS Dementia Complex)

Caused by immune activation (not direct viral infection of neurons)
Features: Dementia, gliosis, giant cells, vacuoles in white matter

B. Progressive Multifocal Leukoencephalopathy (PML)

Caused by JC virus
Seen in AIDS patients
Demyelination in multiple areas
Affects oligodendrocytes

C. Spongiform Encephalopathy (CJD)

Caused by prions (no DNA/RNA)
Rapid dementia + myoclonus
Brain shows spongy vacuoles, no inflammation
Fatal within months

4️⃣ Fungal and Protozoal Encephalitis

Type	Pathogen	Common in
Fungal	Candida, Aspergillus, Cryptococcus	Immunosuppressed (e.g. AIDS)
Protozoal	Toxoplasma, Amoeba, Malaria	AIDS, poor sanitation, endemic areas

🧠 Summary Table: CSF in Meningitis

Feature	Normal	Bacterial	Viral	Tuberculous
Appearance	Clear	Cloudy/purulent	Clear/sl. turbid	Clear/fibrin web
Pressure (mm H₂O)	60–150	↑ (>180)	↑ (>250)	↑ (>300)
Cells (/μL)	0–4	↑ Neutrophils	↑ Lymphocytes	↑ Lymphocytes
Protein (mg/dL)	15–45	↑↑	Normal/sl. ↑	↑
Glucose (mg/dL)	50–80	↓	Normal	↓
Bacteriology	Sterile	Bacteria present	Sterile	TB/Cryptococcus

🧠 Cerebrovascular Diseases

✅ Definition

Cerebrovascular diseases involve blood vessels of the brain, leading to either ischemia (lack of blood supply) or hemorrhage (bleeding).

📌 Main Brain Effects

A. Ischemic Brain Damage
B. Intracranial Hemorrhage

🩸 A. ISCHEMIC BRAIN DAMAGE

🧬 Causes:

Thrombosis (clot in blood vessel)
Embolism (moving clot from heart/lung)
Atherosclerosis
Arteritis
Low oxygen (hypoxia/anoxia)
External compression
Trauma

🔥 Types of Ischemia:

Type	Description
Global hypoxic-ischemic encephalopathy	General reduction in brain blood flow (e.g., cardiac arrest)
Cerebral infarction	Local blockage of blood flow → area of brain dies

🧪 Mechanisms of Brain Oxygen Loss (Anoxia):

Anoxic anoxia – low oxygen in air
Anaemic anoxia – low hemoglobin
Histotoxic anoxia – cell poisons (e.g., cyanide)
Ischemic (stagnant) anoxia – blocked blood flow

🧠 Patterns of Ischemic Damage:

Pattern	Description
Selective neuronal damage	Neurons die first (most sensitive to oxygen loss)
Laminar necrosis	Patchy death in cortical layers
Watershed infarcts	Occur in border zones between major arteries (e.g., ACA-MCA)

🔬 Microscopic Changes Over Time:

Time After Ischemia	Changes
0–12 hrs	No visible change
12–24 hrs	Red neurons (damaged cells)
2–7 days	Tissue softening, neuron loss, gliosis
Weeks–Months	Liquefaction, cyst formation

💢 Cerebral Infarction

🩸 Common Causes:

Arterial occlusion – thrombus or embolus (from heart)
Venous occlusion – rare, often due to cancer
External compression – e.g., brain herniation

🧠 Types of Infarcts:

Anaemic infarct: Pale, soft, swollen → leads to cyst
Haemorrhagic infarct: Red, often due to embolus breaking apart or venous blockage

🔬 Microscopic Stages:

Neuronal necrosis, neutrophils, myelin breakdown
Macrophages clean dead tissue
Astrocytosis & glial scar formation
Chronic cystic infarct (fluid-filled cavity)

🧠 Small infarcts due to hypertension = lacunar infarcts

💥 B. INTRACRANIAL HAEMORRHAGE

🔹 Types:

Type	Cause
Intracerebral hemorrhage	Usually due to hypertension
Subarachnoid hemorrhage	Usually from ruptured aneurysm

❗ Other Causes of Hemorrhage:

Arteriovenous malformations
Bleeding disorders (e.g., leukemia)
Brain tumors with bleeding

🧠 Key Term: Stroke

Sudden onset of focal neurological deficit
May cause: weakness (hemiplegia), coma, paralysis

🧠 TIA = transient ischemic attack (temporary loss of blood flow)

🔴 1. Intracerebral Hemorrhage (ICH)

Definition:
Spontaneous bleeding into brain tissue, most often due to hypertension.

Key Facts:

Common in middle-aged hypertensives.
Caused by rupture of tiny aneurysms in small arteries.
Common sites: Basal ganglia, pons, cerebellum.
Sudden onset: Headache, loss of consciousness, neurological signs.
40% mortality in 3–4 days (often due to bleeding into ventricles).

Gross Features:

Dark clot in brain parenchyma.
May compress ventricles.
After healing → apoplectic cyst (fluid-filled cavity with gliosis & haemosiderin).

🧠 2. Subarachnoid Hemorrhage (SAH)

Definition:
Bleeding into subarachnoid space, most commonly due to ruptured berry aneurysm.

Berry Aneurysm:

Round bulges at artery bifurcations (e.g., Circle of Willis).
Not congenital but develop due to weak arterial walls.
Associated with polycystic kidney disease & coarctation of aorta.

Common Sites:

Anterior communicating artery
Posterior communicating artery
Middle cerebral artery
Internal carotid bifurcation

Clinical Features:

Sudden severe headache, loss of consciousness
Blood in CSF
Risk of rebleeding

Complications:

Vasospasm → infarction
Intracerebral hematoma

🚑 3. Trauma to CNS

A. Epidural Hematoma

Arterial blood collects between dura & skull (usually due to skull fracture)
From middle meningeal artery rupture
Rapid expansion → emergency!

B. Subdural Hematoma

Venous blood between dura & arachnoid
Can be acute (trauma) or chronic (brain atrophy)
Chronic type has a membrane and liquid blood

C. Parenchymal Brain Injury

Type	Features
Concussion	Transient loss of consciousness; full recovery
Diffuse Axonal Injury	Widespread axonal shearing → coma/vegetative state
Contusion/Laceration	Blunt trauma to brain → necrosis, bleeding, haemosiderin (golden color)
Traumatic ICH	Multiple bleeds due to torn brain vessels
Brain Swelling	Local or diffuse after trauma

⚡ 4. Demyelinating Diseases

Definition:
Diseases where the myelin sheath is damaged (not the neuron itself), mostly due to immune or viral causes.

A. Multiple Sclerosis (MS)

Most common demyelinating disease

Age: 20–40 years
Cause: Unknown (likely autoimmune)
Affects: Optic nerve, spinal cord, brain
Course: Relapsing and remitting
First sign often: Optic neuritis

Pathology:

Plaques (demyelinated areas in white matter)
Active plaque: inflammation, macrophages, demyelination
Old plaque: no inflammation, gliosis, axonal loss

B. Perivenous Encephalomyelitis

Includes two post-infectious allergic conditions:

Disease	Key Features
Acute Disseminated Encephalomyelitis	After viral illness or vaccine; good prognosis
Acute Necrotizing Hemorrhagic Encephalitis	Severe form; rapid deterioration; may be fatal

Both involve inflammation around veins
Caused by immune reaction against myelin

Other CNS Disorders

1. Degenerative Diseases of the CNS

Definition: Progressive, irreversible loss of neurons, often with unknown causes. Many are genetic.
Key Features:
- Symmetric and selective neuron loss
- Progressive over years
- Commonly genetic or sporadic

Important Types:

Disease	Key Features	Pathology
Alzheimer's Disease	Commonest dementia in elderly	Neuritic plaques, neurofibrillary tangles, amyloid in vessels
Parkinsonism	Tremors, rigidity, postural imbalance	Depigmentation of substantia nigra, Lewy bodies in neurons

2. Metabolic Diseases of the CNS

A. Hereditary Types:
1. Neuronal Storage Diseases: e.g. Tay-Sachs, Gaucher's
2. Leucodystrophies: Myelin formation defects (e.g. Krabbe’s)
3. Other Errors: e.g. Wilson’s disease, galactosaemia
B. Acquired Types:
- Due to problems in other organs (liver, kidney, pancreas)
- Includes:
  - Anoxic encephalopathy
  - Hepatic and uraemic encephalopathy
  - Electrolyte and endocrine-related encephalopathies

3. Nutritional Diseases of the CNS

Deficiency	CNS Effect
Thiamine (B1)	Wernicke’s encephalopathy, Korsakoff’s psychosis
Vitamin B12	Subacute combined degeneration of spinal cord
Folic acid	Spinal cord degeneration
Niacin	Pellagra
Vitamin E	Spinocerebellar syndrome
Chronic Alcoholism	Cerebellar degeneration

4. Tumors of the CNS

Primary Tumors: Arise in brain/spinal cord
Secondary Tumors: Metastasis from other organs
Common Tumors:
- Gliomas (50–60%) – Most common
- Meningiomas (25%)
- Schwannomas (10%)

WHO Classification of CNS Tumors:

Gliomas: Astrocytoma, Oligodendroglioma, Ependymoma, Choroid plexus papilloma
Neuronal Tumors: Neuroblastoma, Ganglioneuroma
Poorly Differentiated Tumors: Medulloblastoma
Others: Meningioma, Schwannoma, Primary CNS lymphoma, Metastatic tumors

4a. Astrocytomas (Gliomas) – WHO Grading

Grade	Type	Key Features
I	Juvenile pilocytic astrocytoma	Children; slow-growing; cystic
II	Fibrillary astrocytoma	Common; well-differentiated
III	Anaplastic astrocytoma	More cellular; mitoses present
IV	Glioblastoma multiforme	Most aggressive; necrosis, vascular proliferation

4b. Other CNS Tumors

Oligodendroglioma: Uniform round cells with halos; slow-growing; calcification common
Ependymoma: Arises in ventricles/spinal cord; forms rosettes/pseudorosettes
Choroid Plexus Papilloma: Benign; forms papillary masses in ventricles
Medulloblastoma: Common in children; aggressive; cerebellar tumor

1. Other Primary Intraparenchymal Tumors

A. Haemangioblastoma

Origin: Unknown, may be part of von Hippel-Lindau syndrome.
Age group: Young adults, more common in males.
Associated with: Polycythemia (increased RBCs) in some cases.
Microscopy:
- Many thin-walled blood vessels.
- Lipid-rich (foamy) stromal cells.

B. Primary CNS Lymphoma

Common in: AIDS and immunocompromised patients.
Location: Around ventricles (periventricular).
Microscopy:
- Grows around blood vessels (angiocentric pattern).
- Composed of large B-cells with frequent mitoses.

C. Germ Cell Tumors

Rare, seen in children.
Sites: Suprasellar region and pineal area.
Examples: Germinoma, teratoma, embryonal carcinoma.

2. Tumors of Meninges

A. Meningioma

Origin: Arachnoid cap cells.
Sites: Cerebral convexities, falx cerebri, olfactory groove, spinal cord.
Common in: Adults (esp. females).
Usually benign, but can rarely become malignant.

Microscopy Types:

Meningothelial: Round cells with syncytial (merged) appearance.
Fibrous: Spindle cells in bundles.
Transitional: Whorled pattern + psammoma bodies (calcified).
Angioblastic: Vascular pattern; high recurrence.
Anaplastic: Malignant with brain invasion.

3. Metastatic Tumors

Accounts for ~25% of brain tumors.
Common primary cancers: Lung, breast, melanoma, kidney, GI tract, choriocarcinoma.
Gross appearance: Multiple, well-defined masses at grey-white junction.
Histology: Mimics the original tumor, surrounded by brain edema.

🧠 Peripheral Nervous System (PNS)

🔹 Normal Structure

PNS includes: Cranial & spinal nerves, autonomic nerves, and ganglia.
Function: Conducts sensory & motor signals to/from CNS.
Structure of nerve:
- Epineurium: Outer covering.
- Perineurium: Surrounds fascicles (bundles).
- Endoneurium: Surrounds individual nerve fibers.
Types of fibers:
- Myelinated: Thick fibers with Schwann cell-produced myelin.
- Non-myelinated: Thin, unmyelinated, still surrounded by Schwann cells.

🔹 Pathologic Reactions to Injury

Wallerian degeneration:
- Follows nerve cut/injury.
- Distal part of axon dies, regeneration via Schwann cell support.
Axonal degeneration:
- Starts at nerve endings, progresses backward.
- Poor regeneration.
Segmental demyelination:
- Myelin loss between nodes of Ranvier, axon stays intact.
- Can be repaired (remyelination).
Traumatic neuroma:
- Abnormal nerve regeneration due to scar/fibrosis after injury.

🔹 Peripheral Neuropathy

General term for nerve damage; may affect one or multiple nerves.

Types:

Polyneuropathy:
- Symmetrical; affects both feet/hands.
- Causes: Diabetes, vitamin B1/B12 deficiency, toxins (e.g. vincristine), autoimmune (e.g. Guillain-Barré).
Mononeuropathy multiplex:
- Multiple non-continuous nerves affected.
- Often seen in vasculitis.
Mononeuropathy:
- Single nerve affected (e.g. carpal tunnel).
- Causes: Compression, trauma.

🔹 Nerve Sheath Tumors

1. Schwannoma (Neurilemmoma):

Benign, from Schwann cells.
Locations: CN VIII (vestibular), spinal nerves.
Histology:
- Antoni A areas: Dense, cellular.
- Antoni B areas: Loose, myxoid.
- Verocay bodies: Palisading nuclei.
S-100 positive, no nerve invasion.

2. Neurofibroma:

Solitary or multiple (if with von Recklinghausen’s disease).
Associated with NF1 (chromosome 17).
Histology: Spindle cells, mucoid matrix, wavy nuclei.
Can turn malignant (neurogenic sarcoma).

🔹 Malignant Peripheral Nerve Sheath Tumour (MPNST)

Poorly differentiated tumor.
Arises in NF1 patients or post-radiation.
Histology: Spindle cell sarcoma, frequent mitosis, necrosis.
Aggressive, may spread to lungs and other sites.

🔸 Schwannoma vs Neurofibroma – Key Differences

Feature	Schwannoma	Neurofibroma
Capsule	Present	Absent
Location	CN VIII, spinal	Skin, visceral nerves
Cell origin	Schwann cells only	Schwann + fibroblasts
Verocay bodies	Present	Absent
S-100	Strongly positive	Variable
Malignant potential	Rare	More likely in NF1