1. Dr. Mohammed Alorjani, MD EBP
Pathology of
Nervous System (I) -1
2016
Dr. Mohammed Alorjani, MD EBP

2. Characteristic cellular features in the CNS
OUTLINE:
Characteristic cellular features in the CNS
General patterns of CNS cell pathology following
various types of injury
Consequences of ↑ CNS pressure
Patterns of CNS vascular disease including trauma & perinatal CNS injuries
Patterns of CNS infection 2

3. Significant features in CNS Pathology

4. Extremely susceptible to increased I.C.P.
Highly susceptible to ischemia & hypoxia
Site of lesion may be more important than its nature
Selective vulnerability of defined structures to disease processes
Selective function of neurons in different sites  Same process but different symptoms
No regeneration  gliosis not fibrosis

5. Component cells of CNS Neurons Glial cells & fibers: Meninges:
Astrocyte
Oligodendrocyte
Ependymal cells
Microglia
Meninges:
Meningothelial cells
Connective tissue & BV

6. Reactions of components to injury
Neurons:
A- Acute injury:
I- Necrosis:
12-24 hrs Irreversible ischemia/hypoxia:
RED NEURONS
with injured axons → axonal swelling →
SPHEROIDS
II- Apoptosis in development, aging…..

8. Red Neurons in ischemic injury

9. B - Chronic or subacute injury:
Degenerative diseases
Neuronal loss & replacement by gliosis in progressive diseases, usually selective
Neuronal processes may be thickened & tortuous (Dystrophic Neurites)
e.g. Parkinson’s Disease, Alzheimer’s
disease …….. etc.

10. C -Axonal injury lead to:
Cell body swelling & Central Chromatolysis
D- Inclusions:
Nuclear or cytoplasmic e.g. viral infections
E - Accumulations e.g.
lipofuscin, complex lipids & abnormal proteins e.g. Tay Sach Disease …

12. Chromatolysis

13. Viral nuclear inclusions

14. Rabies, cytoplasmic inclusions

15. Lipid Accumulation

16. Astrocytes:
Respond by ↑number & size
Commonest reactive change is Gliosis
May lead to Fibrillary astrocytes
Gemistocytes –
Swollen reactive astrocytes with acidophilic cytoplasm (↑GFAP)
Rosenthal fibers –
Aggregates of thick eosinophilic astrocytic fibers, in old gliosis or some low grade glial tumors

17. GFAP immunostain showing reactive astrocytes

18. Arrows pointing at Gemistocytes

19. Gemistocytes
Rosenthal fibers

20. Oligodendrocytes: Ependymal cells: - Deranged in demyelinating disease
- Synthesis & maintenance of myelin
- Deranged in demyelinating disease
- Inclusions in specific viral infections
Ependymal cells:
- Ependymal Granulations ??
- Inclusions characteristic of CMV

21. Scavengers of the brain:
Microglia:
Scavengers of the brain:
Macrophages in infarction: (Gitter cells)
Elongated cells in syphilis: (Rod cells)
Aggregates of microglia around injured
cells: (Microglial nodules)
Aggregate around dead neurons:
(Neuronophagia)

22. Neuronophagia

23. Microglia showing neuronophagia

25. Increased Intracranial Pressure

26. Definition:  in CSF pressure > 15 mm. Hg
Manifestations:
Papilledema & visual disturbances
Nausea & vomiting
Headache
Neck stiffness
Mental status changes
Others

27. Pathophysiology: Brain 70% , CSF 15% , Blood 15%
Intracranial compartments are balanced
Expansion in any component is first
compensated by  in the rest
i.e.  CSF,  blood ,  ventricular size
If P.  15-20mm.Hg , compensation fails
Displacements & Herniations
Usually to opposite side of lesion 
contralateral ± ipsilateral symptoms

28. TYPES OF HERNIATIONS:

29. Types of herniation

30. 1- Subfalcine herniation
Herniation of Cingulate gyrus under falx cerebri into the subfalcine space
Pressure on Anterior
Cerebral Artery 
Cerebral infarction

31. 2- Transtentorial hernation
Uncinate herniation of medial temporal lobe through free margin of tentorium
Pressure on PCA  Occipital
infarction
3rd.& 6th. Cranial Nerves.  ipsilateral dilated pupil &
impaired eye movement
Cerebral peduncle compression on opposite side  ipsilateral hemiparesis

32. 3- Tonsillar herniation
Herniation of cerebellar tonsil and medulla through foramen magnum
BRAIN STEM !!!
Pressure on respiratory & cardiac centers

33. Cardiorespiratory failure & death DURET Hemorrhages:
Result :
Brain stem compression & hemorrhage
Acute obstruction CSF
Cardiorespiratory failure & death
DURET Hemorrhages:
* Midline and paramedian brain stem
hemorrhage secondary to brain herniation
due to increased ICP above the tentorium
from any cause.
* Cause ? Laceration of penetrating veins
and arteries supplying upper brain stem

34. Duret hemorrhage

35. Causes of Increased ICP
1- Cerebral Edema
i - Vasogenic due topermeability with dysfunction of blood brain barrier
Extracellular
More in white matter
Localized or Generalized
Infarcts, contusions, tumors, abcesses…
ii- Cytotoxic due to neuronal & glial injury
Intracellular
More in grey matter
More in toxic & metabolic causes

36. Flattened gyri often signify edema. Why
Flattened gyri often signify edema. Why? Ans: compression against the calvarium
Dry flat gyri 36

37. Sulci narrowed, blurred markings
Normal white matter
Edematous white matter

38. 2- Infarction & Hemorrhage
3- Infections - Abscesses & meningitis
4- Tumors - Primary & Secondary
5- Trauma - especially in diffuse brain damage
6- Hydrocephalus

39. CSF Flow Made in the ventricles Flows down aqueduct into 4th ventricle
Out into subarachnoid space
Up to arachnoid granulations
Back into the blood
Obstructions in movement will lead to
hydrocephalus
CSF Flow

40. CSF FLOW

41. HYDROCEPHALUS Amount of CSF is balanced between its
generation & resorption.
Otherwise, hydrocephalus develops.
Excess CSF in ventricular system with
enlarged ventricles, caused by
I-  resorption in inflammation &
obstruction
ii- Overproduction of CSF, e.g. in some
tumors

42. Hydrocephalus maybe acute  rapid ICP
Chronic with compensation, mainly in children  Large head, thin skull

43. Fontanelle closure is the key factor whether hydrocephalus will result in any cranial enlargement
Fontanelle closure is the factor whether hydrocephalus will result in cranial enlargement 43

44. Hydrocephalus. Magnetic resonance image of a child with communicating hydrocephalus, involving all ventricles.

45. Hydrocephalus. Dilated lateral ventricles seen in a coronal section through the midthalamus.

46. Types of Hydrocephalus:
1- Noncommunicating:
Due to obstruction of CSF flow within the
ventricles.
Localized to site of obstruction.

47. Due to a malformation or
acquired obstruction at foramina –
Post-inflammatory
Tumors
Gliosis around aqueduct of Sylvius
Intraventricular hemorrhage…etc

49. 2- Communicating:
Impaired resorption.
Generalized to all ventricles.
- Post meningitis
- Post subarachnoid hemorrhage
3- Normal pressure (ex vacuo)
- Brain infarcts & Degenerative diseases
- Compensatory  CSF & Dilatation of
ventricles.

50. Congenital Malformations
May involve brain or spinal cord, causes ???
May be associated with mental retardation,
or hydrocephalus …etc
Include:
Neural Tube defects e.g. Spina Bifida occulta, meningomyelocele, encephalocele, anencephaly…
Forebrain defects
Post. fossa defects e.g. Arnold Chiari Syndrome.
Spinal cord defects.

51. Arrow points at meningomyelocele

52. ANENCEPHALY

53. Thank you