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1. Pathology of CNS
DR Naila Awal
Department of pathology

2. Structure of brain

3. 1) Cerebrum-
Center for high complex function- memory, learning, emotion , language.
Parts- Frontal, Parietal, Temporal & Occipital lobes.
2) Cerebellum-
Movement, balance & posture
3) Medulla oblongata-
• Controls automatic & homeostatic function such as swallowing, digestion,
breathing.
• GM- neural cell bodies
It process & stores information
• WM- nerve fiber
Carry information from 1 tract of brain to another.

4. Cells of CNS
1) Neuron
Injury- Apoptotsis (Brain tumor)
Necrosis (Red neuron- Hypoxic damage)
Neuronal loss( neurodegenerative disease)
Axonal degeneration
Inclusions (Alzheimer’s – Neurofibrillary Tangles
Parkinson’s - Lewy body)
2) Glial cell-
• Astrocyte-
• Star shaped
• Nuclei- round –oval with peripheral nucleoli,
• Cytoplasm –highly branched
• Tissue injury- Hypertrophy & hyperplasia (astrogliosis)
• Oligodendrocyte-
• Relatively large cell lymphocyte-like nuclei with perinuclear halo.

5. • Ependyma cell
• Cuboidal to columnar cells having cilia/microvilli
lining the ventricle
3) Microglial cell-
Act as a macrophage/ monocyte system in the brain
• infection/injury- Proliferate

6. Disease of CNS
• Congenital anomalies
• Perinatal brain injury
• Trauma
• Cerebrovascular disease
• Infection
• Demyelinating disease
• Degenerative disease
• Tumors

7. Congenital anomalies
• Neural tube defect
• Anencephaly-
• absence of cranial vault.
• Encephalocele-
• Herniation of brain tissue through
defective cranium.

8. • Spina bifida occulta-
• incomplete closing of the vertebra and membranes around the spinal cord.
• Meningocele –
• Meninges protude through small opening.
• Meningomyeocele-
• Herniation of spinal cord & meningeal tissue through vertebral defect

9. • Forebrain anomalies`-
Megalencephaly- Volume of brain is abnormally large.
Microcephaly- Volume of brain is small.
• Cause- Chromosomal abnormalities
Fetal alcohol syndrome
HIV infection acquired in utero.
Lissencephaly (Agyria)- ↓ number of gyri or
total absence of gyri

10. Polymicrogyria-
• ↑ number of small irregular gyri
Holoprosencephaly-
• Incomplete seperation of cerebral hemisphere
across midline. (Trisomy 13)

11. Neuronal heterotopias-
• Collection of neuron in abnormal location.
(Periventricular- usually WM)
Agenesis of corpus callosum-

12. • Posterior fossa anomalies
• Dandy Walker malformation-
• Enlarged posterior fossa.
• Absence of cerebellar vermix or
• Presence in rudimentary form in anterior portion
• Replaced by large midline cyst lined by ependyma

13. • Arnold Chiari malformation-
• Small posterior fossa
• Downward extension of vermis or displacement through foramen magnum

14. • Hydromyelia- Multisegmental expansion of central canal of spinal cord.
• Syringomyelia- Formation of fluid filled cleft like cavity in spinal cord.

15. Perinatal brain injury
• Important cause of childhood neurological disability.
• Common cause-
• Maternal disease
• Placental abnormalities
• Most Common underlying pathology-
• Hemorrhage
• Infraction

16. Trauma
• Site & consequence-
• Frontal lobe- Clinically silent
• Spinal cord- Severely disable
• Brain stem- Fatal
• Types of injury-
• Skull fracture
• Parenchymal injury
• Traumatic vascular injury

17. • Skull fracture-
• Cause- Stepping off a lader
Fall due to unconsciousness
• Parenchymal injury-
• Concussion- Altered consciousness, secondary to head injury.
• Contusion (Bruise)
• Coup & Contre-coup injury-
When the head is struck ,the impact causes
contusion at the point of the contact(coup injury)
& on the opposite side of the brain
(Contre-coup injury)

18. • Diffuse axonal injury
• During rapid acceleration of head, some parts of the brain can move separately
from other parts destroy axon necessary for brain functioning

19. • Epidural hematoma
Site- B/w skull & DM
Temporal skull fracture
↓
Injury to middle meningeal artery
↓
Extravasation of blood
↓
Seperation of DM from inner surface of skull
↓
Accumulation of blood (Haematoma)

20. • Subdural hematoma
Site-B/w DM & AM
• Venous bleeding is self limited
Sequence-
• Lysis of clot-1 wk
• Growth of fibroblast into hematoma2wks
• Development of hyalinized connective tissue1-3 months.

21. • Sequelae of brain trauma
• Post traumatic hydrocephalus
• Post traumatic dementia
• Punch drunk syndrome
• Hydrocephalus
• Diffuse axonal injury
• Post traumatic epilepsy
• Psychiatric disorder

22. Cerebrovascular Diseaese
• 3rd leading cause of death (1st heart disease, 2nd -carcinoma)
• Cerebral Infraction-
• Types-
• (Red infract)-multiple, sometimes confluent petechial haemorrhage, associated
with embolic event
• Non haemorrhagic (pale infract)- associated with thrombosis.
• Gross-
• 1st 6hrs- minimal change
• 48 hrs-pale, swollen
• corticomedullary junction –indistinct
• 2-10 days- gelatinous, friable, distinct infract border.
• 10 days-3wks- liquefaction begins.

23. • M/E-
1st 12 hrs- Red neuron (eosinophilic degeneration of neuron)
Swelling of astrocyte
48hrs- Neutrophilic infiltration
2-3wks- Macrophage predominant.
Lipid laden macrophage
Fluid filled cavity
After several months- Dense glial scar.

24. • Hypertensive Cerebrovascular disease
Most important effect of HTN-
1) lacunar infract
2)Slit haemorrhage
3) Hypertensive encephalopathy
• Lacunar infract-
Gross-
Single/ multiple cavitary infract (Infract)
M/E-
Areas of tissue loss with scattered lipid laden macrophage
& surrounding gliosis.

25. • Hypertensive encephalopathy-
• Gross-
• Edematous brain with or without transtentorial or tonsillar herniation.
• M/E-
• Petechiae & fibrinoid necrosis of arteriole in GM & WM.

26. • Intracranial haemorrhage-
• Intracerebral haemorrhage-
• Acute hemorrhage- Extravasation of blood with compression of adjacent
parenchyma.
• Old hemorrhage- Cavitary destruction of brain with rim of brownish discoloration.
• M/E-
Central core- clotted blood
Surrounded brain tissue- odematous,
anoxic neuronal & glial change.
Eventualy edema resolves, pigment & lipid laden macrophage
& reactive astrocyte is seen in the periphery of the lesion.

27. • Sub arachnoid haemorrhage-
• Most common cause- Rupture of saccular aneurysm.
• Saccular aneurysm-
• Common sites-

28. • Morphology-
• Unruptured anurysm thin walled, outpouching along the circles of Wilis
• 2-3cm in diameter
• Bright red, shiny surface & thin translucent wall.
• Wall or lumen of aneurysm- Atheromatous plaque, Calcification or thrombotic
occlution.
• The neck of aneurysm wide/ narrow.
• Ruptured usually occurs at the apex of sac.
• The sac is made up of thickened hyaline intima.

29. • Vascular malformation-
1)AV malformation
2)Cavernous malformation
3) Capillary telengiectasia
4)Venous angioma (varices)

30. Infection of CNS
• Meningitis- Infection of meninges
• Types-
• Infectious-Acute pyogenic
Chronic
Aseptic
• Chemicals- drugs

31. • Acute meningitis
• Cause-
• Neonate- E . Coli, G-B strep
• Adolesence & adult- Neisseria meningitidis
• Elder- Streptococcus pneumoniae, Liesteria monocytogens.
• Gross-
• Exudate- within leptomeniges & over the surface of the brain
• H. influenzae- basal
• Pneumococcal- over the cerebral convexities near the sagittal sinus.

32. A thick layer of suppurative
exudate covers the brain
stem & cerebellum &
thickens the leptomeninges

33. M/E- neutrophilic exudate involving the meninges at the left, with prominent
dilated vessels. There is edema and focal inflammation in the cortex to the right.

34. • Acute focal suppurative
• Cerebral abscess-
• Direct implantation of micro organism
• Local-mastoiditis,Paranasal sinusitis
• Haematogenous spread- from heart, lung,distal bone or after tooth extraction
• Predisposing factor-
• Acute bacterial endocarditis-multiple abscess
• Congenital cyanotic Heart disease -Rt to Lt shunt
• Chronic pulmonary sepsis- bronchiectasis
• Immunosuppression.

35. • Gross-
• There is a liquefactive center with
• yellow pus surrounded by a thin wall.
• M/E-
• Liquefactive necrosis
• Around the necrosis, exuberent granulation tissue with neovascularization
• Fibrous capsule
• Outside the capsule, zone of reactive gliosis with numerous gemistocytic astrocytes.

36. Chronic meningoencephalitis
• Cause-
• M .TB
• Treponema pallidum
• Borrelia

37. • Chronic bacterial meningoencephalitis
• Tuberculosis
• Gross-
• Sub aracnoid space fibrinoid exudate .
• Discrete white granules scattered over leptomeninges.
• Tuberculoma- well circumscribed intraparenchymal mass.
• M/E-
• Central core of casseous necrosis surrounded by
• tuberculous granulomatous reaction.
• Long standing case-
• Fibrous adhesive arachnoiditis.
In Mycobacterium avium intracellulare complex-
Confluent sheets of macrophage filled with
organism with little /no granuloma.

38. • Neurosyphilis
• Tertiary stage of neurosyphilis
• Occurs in 10% of patient with untreated patient.
• Pattern-
1) Meningovascular neurosyphilis-
• Chronic meningitis with numerous plasma cell
• Associated with oblitereted endarteritis
2) Paretic neurosyphilis-
• Inflammation
• Parenchymal damage--
• Loss of neuron
• Proliferation of microglia (rod cell)
• Gliosis
• Iron deposition

39. 3) Tabes dorsalis-
• Loss of both axons & myelin in dorsal root
• Atrophy of dorsal column of spinal cord.

40. • Viral meningoencephalitis
• M/E-
• Perivascular lymphocyte cuffing
• Multiple foci of necrosis in GM & WM
• Neuronphagia- single cell neuronal necrosis with phagocytosis of debris
• Microglial nodules
• Severe cases- necrotizing vasculitis with focal haemorrhage.

41. Herpes infection
• Gross-
• Extensive destruction of inferior frontal & anterior temporal lobe.
• M/E-
• Necrotizing inflammation
• Perivascular inflammatory infiltrate
• Cowdry type-1 intranuclear inclusion viral inclusion in neuron & glial cell.

42. CMV infection
• Occurs-
• Fetus
• Immunosuppressed individual
• Common- AIDS patient
• M/E-
Prominent cytomegalic cell with
intranuclear & intracytoplasmic inclusion.

43. Rabies infection
• Gross- Intense edema
• Vascular congestion
• M/E-
• Widespread neuronal degeneration most severe in brain stem
• Inflammation
• Negri body (Pathognomic)

44. HIV infection
• M/E-
• Microglial nodule- near the small blood vessels
• Multinucleated giant cell

45. Progressive multifocal encephalopathy
• Cause- JC polyoma Virus
• Gross- Irregular poorly defined areas of demyelination
• M/E-
• Center- Scattered lipid laden macrophage
• At the edge of the lesion- enlarge oligodendrocytic nuclei with glassy
amorphilic viral inclusion.
• Within the lesion- bizzare giant astrocyte with irregular hyperchromatic nuclei
mixed with reactive astrocyte.

46. Sub acute Sclerosing Panencephalitis
• Cause- Measles virus
• M/E-
• Widespread gliosis & myelin degeneration
• Viral inclusion within nuclei of oligodendrocyte & neuron
• Inflammation of WM & GM & neurofibrillary tangles.

47. Fungal Meningoencephalitis
• Causative organism-
• Candida
• Mucor- most common with Diabetic ketoacidosis.
• Aspergillus
• Cryptococcus ( frequency in AIDS patient)
• Endemic area-
• Histoplasma
• Coccidioides
• Blastomyces

48. • Fungal infection- 3 main pattern-
• Chronic meningitis
• Vasculitis- frequently seen in mucormycoses & Aspergillous
• Parenchymal invasion- commonly seen in Candida
• Cryptococcus

49. • Candida – Multiple microabscess with/ without granuloma
formation.

50. • Cryptococcus-
• Gross- Multiple small cyst in basal ganglia
• M/E-
• Soap bubbles – Gelatinous material within subarachnoid space & small cyst in
parenchyma.

51. Others infection
• Protozoal infection-
• Malaria
• Toxoplasmosis
• Amoebiasis
• Trypanosomiasis
• Rickettsial infection-
• Typus
• Rocky mounted spotted fever
• Metazoal disease-
• Cysticercosis
• Echinococcosis

52. Toxoplasmosis
• Gross-
• Cerebral abscess
• M/E-
• Central necrosis surrounded by acute & chronic inflammatory cell
• Periphery of necrotic foci- Free tachyzoites & encysted bradyzoite.
• Organism seen by –
• H & E or Giemsa stain
• Immunocytochemical stain