1. BASIC PATHOLOGICAL ASPECTS OF NERVOUS SYSTEM PATHOLOGY
Esti D. S. Soetrisno B.
Rino Pattiata
Departement Anatomic Pathology Faculty of Medicine
University of Indonesia

2. BASIC PATHOLOGICAL MANIFESTATION OF SOME DISTURBANCES
DYS – NEURO EMBRYOGENESIS
ABORTION / INTRA-UTERINE FETAL DEATH (IUFD)
ABNORMALITIES : TERATOGENIC, MONSTER, CONGENITAL ANOMALY
AGENESIS : There is no processus (anlage) of all or partial part of NS
 No formation of NS  IUFD
APLASIA : There is only NS Streak Formation
 abortion
HYPOPLASIA : Failure to growth of all or partial part of NS
 Hypotrophy (Micro Insize)  Hypofunction / Fatal
e.g Microensephaly, Arnold – Chiary Syndrome

3. Hyperplasia : Overgrowth parts of NS
e.g Macroensephaly, Hydrocephallus, Function?
Hypertrophy: True Hypertrophy / Pseudo Hypertrophy
Defect On Enclosing of the Neural Tube
There is “Cele” Formation, or Spina Bifida Formation (Occulta/Aperta)
e.g Meningocele, Encephalo -/ Myelo – Meningcocele, Syringo -Encephalo –/ Myelo – Meningcocele (Syringo Myelia)

6. DYS – HISTOGENESIS :
incorrect migration and/or naturation – differentation
ECTOPIC :
mature tissue found in abnormal places
HETEROPIC :
intermingled of some mature tissues in abnormal places
HAMARTOMA :
abnormal composition of mature tissues at its normal places
NEOPLASMA (GEN MUTATION) :
benign and malignant

7. Abnormalities of anatomy / location of NS
DYS – NEUROANATOMY
Abnormalities of anatomy / location of NS
- Dyslocation
- Reverse of Several Centre
DYS - NEUROCHEMISTRY
- NEUROPHYSIOLOGY
INHIBIT : Slow Conduction – Slow Movement / Analysis / etc
EXCITE : Rapid / Hyperactivity (ies)
DYS – REGULATION / CONTROL : UNCONTROL MOVEMENT – PATHOLOGICAL REFLEXES
DYSFUNCTIONAL
IMPULS CONDUCT

8. CNS CELLS NEURON GLIAL CELL CHOROID PLEXUS CELL ASTROCYTE
OLIGODENDROGLIA
EPENDYMA
MICROGLIA
CHOROID PLEXUS CELL

9. OLIGO DENDROGLIA
NEURON
ASTROCYTE

10. Neuron Effector cells of Nervous System
Neuron loss with progressive aginh
Neuron of CNS cannot effectively regenerate axons over long distance → limit ability of CNS to respond to different type of injury
Infarct transects internal capsule creates permanent motor deficiti
Neuron in CNS don’t remyelinate → demyelinating disease causes permanent functional deficit (multipel sclerosis)

11. PIGMENTED NEURON
( SUBSTANTIA NIGRA )
neuromelanin

12. ATROPHIC NEURON hyperchromatic Loss of neurons
* global/regional reduction (atrophic)
* single neuron

13. ATROPHIC
CEREBRAL CORTEX

14. CHROMATOLYSIS
Injured neuron swell → cytoplasm swell → chromatolysis: response to injury
Reversible/death
CYTOPLASM FLUID ACCUMULATION
MARGINATION
NUCLEUS
NISSL SUBSTANCE

15. CENTRAL CHROMATOLYSIS
ANTERETROGADE DEGENERATION

16. Astrocyte
Support neurons
Promote repair

17. ASTROCYTE

18. GLIOSIS Reaction to injury Proliferation of astrocyte
Evolves in hours to day and persists to an extent that is usually commensurate with the severity of injury
Reactive astrocyte : gemistocytic astrocyte: exentric plump nuclei, eosinophilic cytoplam
Glial scar: composed of reactive astrocytes and their processes.

19. GLIOSIS

20. GEMISTOCYTE

21. OLIGODENDROGLIA Neuroectodermal origin
Myelin-producing cells during late gestational period and early neonatal

22. EPENDYMA
Modulate fluid transfer between the cerebrospinal fluid and CNS
During gestation some viral target the ependymal cell → aqueductus stenosis → congenital hydrocephalus

23. CANALIS CENTRALIS
EPENDYM

24. MICROGLIA Phagocytic macrophage-derived cells
Reactions: changes in areas of injury
2 pattern : focal and diffuse microgliosis
Microglial nodule: responses to viral or other infection.
Rod cells: prominent elongated nucleus
Gitter cells: response to necrosis: it will become phagocytic, accumulate lipid and other material

25. MICROGLIA (PHAGOCYTE)

26. ACTIVATED MICROGLIA
MYELINOLYSIS

27. INTRA NUCLEAR INCLUSION
( CYTOMEGALO VIRUS )

28. NEGRI BODY INTRACYTOPLASM (RED)
(RABIES ENCEPHALITIS)

29. VASCULAR
DILATATION
(HYPEREMIA)
PMN
NEUTROPHIL
NEURONOPHAGIA

30. HYDROCHEPALUS
TYPE :
COMMUNICANS : obstruction occurs outside ventricle system
NON-COMMUNICANS
EXVACUO (COMPENSATED)

31. HYDROCEPHALUS Primary hydrocephalus Secondary hydrocephalus
Accompanied by increased intracranial pressure
Due to:
Obstruction
Congenital
acquired
Impaired CSF absorption
Excess CSF production
Secondary hydrocephalus
Compensatory to loss of cerebral tissue

32. SITES OF OBSTRUCTION OF CSF PATHWAY
Subarachnoid space
Arachnoid granulationes
Plexus choroid
Lateral ventricle
3rd ventricle
Cerebral aqueduct
4th ventricle
Exit foramina

33. OBSTRUCTED AQUADUCT SYLVIOUS
( BRAIN TUMOR)

34. OBSTRUCTIVE HYDROCEPHALUS
( NEOPLASM )

35. OBSTRUCTIVE HYDROCEPHALUS
( INFECTION )

36. OBSTRUCTIVE HYDROCEPHALUS
( GLIAL TISSUE POST VIRAL INFECTION)

37. TRAUMA
Penetrating wounds produce hemorrhage and blast effects. Velocity contributes a blast effect to a projectile
High-velocity : it disrupts tissues by its own mass and also centrifugal blast that enlarges the diameter → immediate death
Low-velocity
Seizures are threat in healed penetrating wounds, 6-12 mo after : collagenous tissue is displaced in the brain

38. HIGH VELOCITY BULLET WOUND

39. LOW VELOCITY BULLET WOUND

40. HEMORRHAGIC TRACT
(PENETRATING WOUND)

41. Subdural hematoma
Significant cause of death from falls, assaults, vehicular acidents, sporting mishaps
Frontal/occipital area is struck by blunt object → cerebral hemispher displaced in an anteroposterior direction → hit against inner aspect
Soft cerebral tissue becomes compact then recoil → shearing effect
Usually stop after mL

43. Subdural hematoma Tissue response
Formation of granulation tissue → outer membrane
Fibroblast from outer membrane moved into the hematoma → inner membrane : 2 weeks
Evolution:
Reabsorbe leave a small amount of telltale hemosiderophage
Remain static, with potential for calcification
Enlarge : 6 months

44. CHRONIC SUBDURAL HEMATOMA
(INNER NEOMEMBRANE)

45. EPIDURAL HEMATOMA
Middle meningeal artery branches splay across temporal-parietal area
Hemorrhage into epidural space, separating dura from calvaria
4-8 hours: asymptomatic
30-50 mL: intracranial pressure increased → exceed venous pressure → circulatory stagnation and cerebral ischemia → global cerebral hypoxia

46. EPIDURAL HEMATOMA Cushing reflex : protective response
HR slow to increase ventricular filling
Myocardial contraction is forceful
Systolic pressure increased
Compensatory mechanism exhausted : temporal lobe displaced downward → transtentorial herniation
Herniation compress uncus/hyppocampus against midbrain and other structures : 3rd cranial nerve
Pupil fixed and dilated

48. EPIDURAL HEMATOMA
(FRONTO PARIETAL)

49. HERNIATION Cingulate gyrus under falx cerebri
Hippocampal uncus and parahippocampal gyrus over tentorium cerebeli
Cerebelar tonsilar through foramen magnum
Any defect in the dura and skull
SITES OF HERNIATION

50. TRANSTENTORIAL
HERNIATION
(MIDBRAIN DISPLACED)

51. GLIOBLASTOMA
MULTIFORME
HEMORRHAGE
HERNIATION

54. DEGENERATIVE DISORDERS
Head, generalized cerebral atrophy – CTscan

55. DEGENERATIVE DISORDERS
Brain, cerebral cortex, Alzheimer disease, silver stain

56. DEGENERATIVE DISORDERS
Brain, cerebral cortex, neuritic plaque stained for tau protein and beta-amyloid

57. DEGENERATIVE DISORDERS
Brain, substantia nigra, Lewy bodies

58. ALZHEIMER

59. Alzheimer Amyloid β protein Neurofibrillary tangles Genetic factors
Derived from APP
Normal degradation of APP: proteolytic middle domain
Alzheimer : proteolytic in either end
Neurofibrillary tangles
Paired of helical filaments consisted of abnormal form of MAP: tau
Phosphorylation of tau results in a protein not associated with microtubules → deprives cells of its microtubules effect
Impairing axonal transport & compromising neuronal function
Genetic factors
Apolipoprotein E

60. DEGENERATIVE DISORDERS
Spinal cord, amyotrophic lateral sclerosis (A) and normal (B)

61. DEGENERATIVE DISORDERS
Brain, Creutzfeldt-Jakob disease

62. Prion disease (spongiform encephalopathies)
Transmissible neurodegenerative disease
Infectious agents is prion
Human prion gene (PRNP) express cell-surface glycoprotein bound to plasmalemma by glycolipid anchor
PrPc and PrPsc not differ in sequence except 3 dimensional conformation an patterns of glycosylation

64. Prion disease Kuru Creutzfeldt-Jacob disease (CJD) Fore people
Trembling
Canibalism
Spongiform cerebral and cerebelum
Creutzfeldt-Jacob disease (CJD)
Symptoms begin insidiously
6 months exhibits severe dementia
1 year : death

65. Prion disease
Sporadic
Inherited
Iatrogenic
New variant CJD

66. Sporadic 75% 1: 1.000.000 Polymorphisme codon 129 Classical features
Dementia
Myoclonus
Periodic spike-wave complexes

67. Genetic 15% Gertsmann-Straussler-Scheiner syndrome(GSS)
Spinocerebelar ataxia with demntia
Fatal familial insomnia
Profound disturbance of sleep-wake cycles
Sings of pyramidal and cerebellar dysfunctions
Mutation codon 178 PRNP gene

68. Iatrogenic Hormone injection Tissue grafts Medical devices
Human growth hormone (55 cases)
Human pituitary gondotropin (5 cases)
Tissue grafts
Duramater (11 cases)
Cornea (1 case)
Pericardium (1 case)
Medical devices
Depth electrode (2 cases)
Surgical instruments (not definitely proven)

69. New variant CJD
Identified following surveillance following BSE epidemic in UK
Mean age 26 years (compared to sporadic 65)
Dysesthesia, none EEG of sporadic CJD
Spngioform in basal ganglia and thalamus
Extensive PrP plaques in cerebrum and cerebelum
More PrP than sporadic CJD
BSE is likely the source of vCJD

72. Thank You