Pathology of nervous system

1. Veterinary
Pathology of
Nervous System

5. Malformations of the Central Nervous
System
Ø Variety is greater than in other tissues
Ø Teratogens are manifested in nervous system
with disproportionately high frequency
l Morphological
• Gross
• Microscopic
l Functional – inherited biochemical defects
l Neither morphological nor biochemical basis –
idiopathic epilepsy
Ø Embryonal development

6. Malformations of Nervous System
ØMicroencephaly – cerebrum –
Akbane virus, bovine viral diarrhea,
border disease virus in lambs
(Pestivirus)
ØCortical Dysplasia
lNeuronal heterophia
lMicrogyria – small convolutions

7. Synophthalmos (cyclopia)
Inherited prolonged
Gestation - calf
Nervous system
l Cyclopia – single large median eye
l Cebocephaly – less severe

8. Dysraphic States – combined defects
Ø Anencephaly
Ø Encephalocele due to
Crania bifida
Ø Meningocele-
Ø Myelocele-Spinal cord
protrusion
Ø Segmental Aplasia and
hypoplasia of spinal cord

9. Hydrocephalus
l Congenital
l Acquired
• Vitamin A deficiency
• Cerebral atrophy in old dogs
• Inflammatory in most of the cases
• Neoplasms
• Parasitic cysts
• Protozoan parasites (Toxoplasmosis)

10. Hydranencephaly
Ø Absence of cerebral hemispheres – Necrosis –
viruses
l Akabane disease
l blue tongue
l Rift valley fever
l pestiviruses
l Cystic cavitation of brain evolving from a destructive
process in prenatal life
l White matter of cerebral hemispheres
l Single or multiple cysts

11. Viral Infections as causes of
Developmental Defects
Ø Akabane virus (teratogen)
l arthrogryposis (vertebral canal)
l hydranencephaly
Ø Blue tongue virus
l Necrotizing encephalopathy
l Retinopathy
Ø Rift valley fever
l Hydranencephaly and porencehaly
Ø Bovine viral diarrhoea
l Cerebellar hypoplasia, hydranencephaly
Ø Border disease
l Affected lambs show gross tremors
Ø Feline Parvovirus

12. Circulatory lesions
ØHyperemia
ØHemorrhage
lEpidural
lSubdural
ØEdema
lAcquired hydrocephalus
lMeningitis
lTrauma, inflammation

13. Trauma
Ø Concussion – transient loss of
consciousness and reflex activity
Ø Contusion – architecture of tissue remains
- hemorrhage
Ø Laceration – disruption of architecture
Ø Fracture of skull
Ø Injuries of spinal cord
Ø Stenosis of spinal canal

14. Degeneration and Necrosis
Ø Senile---aging
Ø Anoxia
l Cerebral embolism, thrombosis, arteriosclerosis,
or hemorrhage
l Sodium chloride poisoning cause anoxia,
l Cyanide thiocyanide (Sorghums, linseed
concentrates)(goitrogenic),
l CO (carboxyhemoglobin)
l Nitrates methemoglobin
l Fluoroacetate –inhibit enzymes
l Hypoglycemia (ketosis, pregnancy toxemia,
insuline therapy) energy deficient
l Thiamine – Bracken fern, horsetail, fish, sulfates
– phosphorylated thiamine is the coenzyme and
participates in all carboxylations and other
reactions

15. Encephalopathy and
Encephalomalacia; Myelomalcia
Ø Poliomalacia
Ø Leukomalcia- PVL
Ø Wallerian Degeneration
Clinical manifestation of diseases of the
nervous system
• Twitching of face, ears and eye lids,
grinding of teeth, salivation
• Paralysis
• Opisthotonus, torticolus, nystagamus
• Convulsions/seizures– a dozen types of
epilepsy…..

16. Perivascular cuffing
Accumulation of inflammatory /neoplastic
cells in Virchow –Robin spaces around
blood vessels seen in viral disease .1-16
cells thick layer.

17. Perivascular cuffing

18. Intracellular inclusion bodies
May be viral or non viral ,intracytoplasmic or
intranuclear.
A) Viral inclusions .examples .Negri bodies
in rabies ,intracytoplasmic. Herpes and
adenovirus produce intranuclear inclusion
bodies and Distemper virus produce both
types .

19. Interacellular inclusion bodies
B) Non viral inclusion bodies . e.g . Lafora
bodies in old dogs

20. Storage diseases
These are characterized by accumulation of
materials resistant to or exceeding the
capacity for intracellular digestion
,disposal or transport .e.g lysosomal
storages diseases ,Sphingolipids
,gangliosides ,glycoproteins
,mucopolysaccharides.
Appear as empty vacuoles .Tremors
,epilepsy ,blindness

21. Malacia & Malacic diseases
Malacia means softening /necrosis
Encephlomalacia …..softening of brain
Myelomalacia ………softening of spinal cord
Varies with spp ,age ,location ,volume of
tissue &cause
Fast in fetus & immature tissue
Also fast in grey matter than white matter

22. Focal symmetrical
Poliomylomalacia
Bilateral symmetrical lesions in sheep
Cause not known
Lesions not recognized grossly except
chronic cases
Microscopically softening is observed in
ventral horns with liquefaction
&mineralized accumulation
No cerebral signs

23. Polioencephalomalacia in
Ruminants(PEM)
Characterized by softening restricted to
cerebrocortical grey matter
Also called cerebrocortical necrosis or
laminar cortical necrosis
No occular lesions
Brain lesions can not be recognized grossly
Animal show muscular tremors ,blindness
,twiching of face ,ear , grinding of teeth

24. Polioencephalomalacia in Sheep

25. Lesions
Vary with severity and duration
Young animal die more rapidly than old ones
Fresh cortex shows laminar pale areas-0.1-
1mm wide in grey area
Microscopically …necrosis of neurons.
Neurons converted into eosinophilic
globules
Leptomings are thickened
Edema & demyelination

26. Causes
Water deprivation
Deficiency of Thiamine (vit B1)
Disturbance in metabolism of Thiamine
Sulpher compounds(Sulphate ,Sulphite )

27. Thiamine deficiency
Dietary requirements of carnivores
Synthesized through by microbial
fermentation in rumen and large intestine
in equines
caused by Thiamine splitting enzymes or
alkaline pH, Sulpher compounds
Anorexia , drooling , ataxia , convulsions
Vascular dilation, hemorrhages &necrosis of
periventricular grey matter

29. Salt (NaCl) poisoning
May be direct or indirect
Direct salt poisoning :problem of salinity of
drinking water
Observed in thirsty cattle
Also observed when salt supplements given
after prolonged restriction
Clinical sign :vomiting ,polyurea, diarrhea
,knuckling of fetlock & blindness

31. Salt poisoning
Indirect salt poisoning :
Neurological disease
Animal become deaf ,blind with increase
intraocular pressure
Lesions restricted to brain
Abundance of eosinophils in the meninges &
Virchow –Robin spaces
Pathognomonic lesion : cortical laminar
changes &cerebral eosinophilia

32. Mycotoxic
leukoencephlomalacia
Ø Neurological syndrome occur in horses
Ø Fumanisin B1 produce by Fusarium
verticelloide and F.proliferatum
Ø Affected animal shows drowsiness
,impaired vision , pharyngeal paralysis
,staggering
Ø Moldy fodders contain toxins of Fusarium

33. Ø Necrosis of white matter of cerebral
hemisphere
Ø Affected area are soft pulpy ,depressions
with small hemorrhages
Ø May be diffused edematous swelling of
adjacent white matter
Ø Lesion may be bilateral but unsymmetrical

34. Ø Microscopically :irreugal soft areas in
white matter
Ø Irregular cavities surround blood
vessels
Ø eosinophils infiltration
Ø Lipofuscin in macrophages

35. Lead poisoning
Ø Common and fatal in horses ,dog ,cats
Ø Acute in cattle ,chronic in horse
Ø Source of poisoning :In cattle ,licking of
paint and metallic lead stored in batteries
Ø Permanent inhalation of fumes and
contaminated pasture

36. Clinical sign
Ø Paralysis ,convulsions , abdominal pain ,
pharyngeal paralysis
Ø No specific lesions in lead poisoning and
diagnosis based on chemical analysis
Ø mild edema in brain
Ø Laminar cortical necrosis
Ø segmented degeneration of axon

37. Neurodegenrative diseases
Ø Toxic substance affect synoptic functions
Ø Example are tetanus ,strychnine poisoning
Ø In tetanus inhibitory neurotransmitter
glycine is blocked by presynaptic blockade
of its release

38. Organo Mercural poisoning
Both organic and inorganic mercural salts
can cause toxicity.
Usually caused by organic salts as ethyl
mercural phosphate used for fungal
control in seeds.
Blindness, incoardination,convulsion,coma.
Gross lesion..swollen kidneys pale and wet
cerebral swellings.

39. Microscopic appearance
Ø Acute tubular necrosis(proteinuria)
Ø Degeneration of purkinji cells
Ø Damage to granular cells of cerebellum
Ø In cattle------purkinji cells are lost at tip of
folia

40. Arsenic poisoning
Ø By ingestion or percutaneous absorption
from fluids like insecticides and herbicides
Ø Acute or chronic
Ø Diarrhoea,depression,convulsions,
tremors and incoordination
Ø Hepatocellular necrosis and edema in
kidneys

41. Neonatal copper deficiency
(swayback,enzootic ataxia)
Ø Congenital condition-------- swayback
Ø Delayed form-------enzootic ataxia
Ø Component of enzyme cytochrome
oxidase, superoxide dismutase and
protein ceruloplasmin
Ø In lambs ,goat kids and piglets
Ø Absolute primary or conditional secondary
Ø Effect on CNS------In utero and during
early neonatal life

42. lesions
Ø Bilateral gelatinous softening and
cavitations
Ø In kids------high incidence of cerebellar
degeneration and peripheral motor axon
degeneration
Ø Hypomyelination and demyelination
Ø Neuronal and axonal degeneration

43. Necrosis of Neurones
Ø Nissl substance (Tigeroid substance)
disappears
Ø Eosinophilia instead of basophilia
Ø Vacuolization
Ø Necrosis of neuroglia

44. Ischemic Lesions
Ø Type and size of obstruction
Ø The degree and duration of ischemia
Ø The injury may vary from a temporary functional
disturbance to infarction and necrosis
Ø Neurones and oligodendrocytes are the most
sensitive
Ø Astrocytes are moderately sensitive
Ø Microlia and blood vessels are quite resistant
Ø Gray matter more sensitive than white matter

45. ØChemicals and Plant
poisons
lLead – cattle, sheep, horses
– paints, batteries, pipes –Fatal
in 12-24 hrs– chronically
ingested have cumulative
effect (bones)
•Boiled linseed oil,
gasolene, lead arsinate
spray
•Protoplasmic poison
Alcohol - acetylaldehyde

46. ØMycotoxins –
Mycotoxic
Leukoencephalomalcia
of horses
lFusarium moniliforme
(corn)
lMania rather than
neurologic deficit
lNecrosis of white matter
of cerebral hemisperes
lHepatic involvement

47. Neurodegenerative Diseases
synaptic function
Ø Botulism
Ø Strychnine
Ø Tetanus
Ø Hereditary conditions
Extensor spasm and hyperesthesia
The activity of inhibitory neurotransmitter
glycine is blocked

48. Central neuropathies and
axonopathies
Ø Compressive optic neuropathy – vitamin A
deficiency
Ø Organomercurial poisoning
l Ethyl mercury phosphate
l Mercury p-toluene sulphonamide
l Fish - on shores
l Lesions like lead poisoning

49. Central and peripheral
neuropathies and axonalpathies
ØOrganophosphates
lInactivate esterases
lDegeneration of distal part of
axones
ØArsenic
lHyperesthesia, ataxia, blindness,
edema of white matter, extenssive
Wallerian degeneration
ØCopper deficiency
lCytochrome oxidase, and
superoxide dimutase, protein
ceruloplasmin – Wallerian
degeneration spinal cord, neuronal
degeneration
Damage to phospholipids
Oxidative phosphorylation
Swayback or
enzootic ataxia

50. Peripheral axonopathies
Ø Mononeuropathies – focal compression
Ø Mononeuropath multicomplex
Ø Polyneuropathy (bilaterally symetrical)
l Equine laryngeal hemiplegia (roaring) – degeneration
of nerve left side – idiopathic
l Canine laryngeal neuropathy – old dogs
l Equine supra scapular neuropathy (sweeny)
l Equine stringhalt (extreme exaggerated flexion of the
hind limbs – Plant poisoning!
l Endocrine neuropathies (Diabetes mellitis)
l Feline Hyperliproteinemia – def. of lipoprotein lipase
activity

51. Myelinopathies
Ø Hypomyelination / Dysmyelination
Ø Leukodystrophic and Myelinolytic
Diseases
l Primary demyelination – around intact axon -
hereditary
l Leukodystrophy – hereditary –
l Myelinolysis – initial disruption of myelin
structure by extensive decompaction by
lamellae as a prelude to its break down and
removal
Ø Spongiform myelinopathies

52. Inflammation
Ø Encephalitis
Ø Myelitis
Ø Meningitis
l Leptomeningitis - pia arachnoid
l Pachymeningitis – dura arachnoid
l Choroiditis

55. Ø Epidural abscesses
l Hematogenous
l Trauma
Ø Subdural abscesses
l Paranasal sinuses
l Extension from epidural abscesses
Ø Leptomeningitis (pia-archnoid)
l Purulent – hematogenous or spread from surrounding
structures
l Sero-cellular associated with viruses
l Hemorrhagic – septicemic anthrax
l Fibrinous in malignant catarrhal fever
l Granulomatous in tuberculosis and cryptococcosis

56. Septicemic lesions, septic
embolism, and cerebral abscesses
Ø The common type of injury is inflicted on the venules of
those of cerebral white matter and to lesser extent
cerebellar white matter
Ø Sludging of blood vessels with leukocytes and
erythrocytes, degeneration of and necrosis of endothelial
cells, diapedesis
Ø Septic embolism arises from active endocarditis (G+)
septicemia due to G- organisms
Ø Abscesses from ear or sinuses

57. Hemophilus infection
ØHemophilus somnus infection
in feed lot cattle
ØHemophilus agni and
Histophilus ovis in sheep
thrombotic meningio-
encephalitis followed by
seticemia vasculitis
Hemorrhages in Brain

58. Viral infections
Ø Viruses differ in their affinity for various cells of
the nervous system
Ø Spread through olfactory and other nerves of
through blood (herpes, pseudo rabies, and
rabies)
Ø Accumulation of inflammatory cells in the
adventitia of blood vessels and perivascular
spaces (Virchow –Ribin space)
Ø Gliosis (microglaial cell degeneration)
Ø Neuronal changes (some diseases)
Ø Inclusion bodies

59. Rabies, Lyssa
ØNon suppurative
encephalomyelitides, with
ganglioneuritis, and parotid
adenitis
ØInoculation of virus in the
wounds
ØVirus first replicates in
myocytes
ØThe virus travels along
the peripheral nerves
ØCytoplasmic inclusions in
Purkinje cells, cerebellum
of cow

60. ØDumb and furious
rabies
ØLesions more
pronounced from pons
to hypothalamus
Perivascular cuffing of
lymphocytes and gliosis

61. Diseases caused by mosquito-
borne viruses
Ø 1)west Nile virus encephalitis
Ø 2)japanese encephalitis
Ø 3)alphaviruses-Equine encephalitis
Ø 4)eastern Equine encephalitis
Ø 5)western Equine encephalitis
Ø 6)Venezeulian Equine encephalitis

62. Equine encephalitis
Ø lesions

63. Protozoal Infections
Ø Babesia, Theileria, Trypanosoma, and
Toxoplasma

64. Parasitic infections
Ø Coenurus cerebralis
Ø Lavae of Angiostrogylus cantonesis in
dogs

65. Bovine spongiform encephalitis
Prion disease
Ø First described in UK in 1732
Ø Mode of spread not known
Ø Rapid lateral communicability in endemic
areas
Ø Initial multiplication in lymphoid tissue
andlower intestine
Ø May take 2 years to reach CNS

66. Bovine Spongiform encephalopathy
Ø Scrapie, wasting disease, kuru
Ø Vacuoles in the grey matter due to vaculation of
neurons, oligodendrocytes and astrocytes
Ø Hypertrophy of astrocytes
Ø Amyloidosis
Ø 27-30 kd infectious proteins (prions) devoid of
RNA or DNA, named “PrP 27-30” (abnormally
folded) derived by larger precursor (Sp33-37)
encoded by host gene

67. Bovine spongiform encephalitis

68. Bovine Spongiform encephalopathy

70. Bovine spongiform encephalitis
Ø Histopathology

71. Listeriosis
Ø Listeria monocytogenes – moncytosis –
mostly cattle and sheep
l Septicemia with miliary visceral abcesses
l meningio-encephalitis
l Infection of uterus with abortion

72. Listeriosis
Gram positive bacteria called listeria
monocytogenes
Listeriosis is world wide in distribution
3 syndrome are produced
a) Infection of pregnant uterus and abortion
b) septicemia with milliary visceral abscess
c) Encephalitis

73. Cause septicemia ,meningitis and abortion
in humans
Associated with silage feeding
Bacteria invade trigeminal nerves and cross
BBB
Affinity for brain stem ,medulla ,pons

74. Clinical signs
Mental confusion , depression ,head
pressing , moving in circles” circling
disease “
Medullary meninges thickened
Characteristic parenchymal lesions is a
microabscess
Vasculitis

75. Clinical and pathological changes
Ø Animals are agitated,excited and have
seizures
Ø Self trauma rubbing against
posts,treesand nibbling at feet and legs
Ø Abrasion of skin,loss of
wool,emaciation,paralysis and death
Ø No inflammatory changes and gross
lesions

76. Continued….
Ø Presence of large intra-neuronal vacuoles
in mid-brain
Ø Astrogliosis
Ø Frequent falling, aggressive behavior,
recumbency
Ø Hyperesthetic and dysmetira