Podcast
Questions and Answers
What is the primary aetiology of Polioencephalomalacia in sheep and cattle?
What is the primary aetiology of Polioencephalomalacia in sheep and cattle?
- Lead poisoning
- Genetic mutation
- Thiamine deficiency (correct)
- Bacterial infection
Which of the following histological features is associated with Polioencephalomalacia?
Which of the following histological features is associated with Polioencephalomalacia?
- Intranuclear inclusion bodies
- Cortical atrophy
- Axonal degeneration
- Astrogliosis and microgliosis (correct)
Which toxic disease is characterized by diffuse cerebral oedema?
Which toxic disease is characterized by diffuse cerebral oedema?
- Hepatic encephalopathy
- Polioencephalomalacia
- Focal symmetrical encephalomalacia
- Lead poisoning (correct)
What clinical effect can result from hepatic encephalopathy?
What clinical effect can result from hepatic encephalopathy?
Which nutritional deficiency is commonly associated with neurological lesions in kittens fed oily fish?
Which nutritional deficiency is commonly associated with neurological lesions in kittens fed oily fish?
What type of lesion is typically seen in focal symmetrical encephalomalacia?
What type of lesion is typically seen in focal symmetrical encephalomalacia?
What feature distinguishes primary tumors in the brain, such as astrocytomas, from metastatic tumors?
What feature distinguishes primary tumors in the brain, such as astrocytomas, from metastatic tumors?
What type of neurological change is characterized by the separation between grey and white matter in cases of Polioencephalomalacia?
What type of neurological change is characterized by the separation between grey and white matter in cases of Polioencephalomalacia?
Which of the following is a characteristic feature of transmissible spongiform encephalopathies?
Which of the following is a characteristic feature of transmissible spongiform encephalopathies?
Which nutrient deficiency is most commonly associated with nutritional diseases of the nervous system?
Which nutrient deficiency is most commonly associated with nutritional diseases of the nervous system?
What is the primary function of astrocytes in brain histology?
What is the primary function of astrocytes in brain histology?
Which of the following diseases is caused by mercury exposure and selectively damages certain neurons?
Which of the following diseases is caused by mercury exposure and selectively damages certain neurons?
The presence of which type of cells indicates gliosis in the brain?
The presence of which type of cells indicates gliosis in the brain?
Which disease is primarily associated with the degeneration of anterior horn cells?
Which disease is primarily associated with the degeneration of anterior horn cells?
What role do neurotransmitters play in the nervous system?
What role do neurotransmitters play in the nervous system?
In which part of the brain would one expect to find lesions related to rabies infection?
In which part of the brain would one expect to find lesions related to rabies infection?
What type of damage does methanol poisoning primarily cause?
What type of damage does methanol poisoning primarily cause?
Which of these structures does NOT contain a blood-brain barrier?
Which of these structures does NOT contain a blood-brain barrier?
Which process is responsible for the absorption of cerebrospinal fluid after it has performed its function?
Which process is responsible for the absorption of cerebrospinal fluid after it has performed its function?
Which condition is characterized by liquefactive necrosis, especially in the brain?
Which condition is characterized by liquefactive necrosis, especially in the brain?
Which cranial nerve is primarily responsible for facial expression?
Which cranial nerve is primarily responsible for facial expression?
What is a characteristic feature of Transmissible Spongiform Encephalopathy (TSE)?
What is a characteristic feature of Transmissible Spongiform Encephalopathy (TSE)?
Which of the following is NOT a typical sign of Bovine Spongiform Encephalopathy (BSE)?
Which of the following is NOT a typical sign of Bovine Spongiform Encephalopathy (BSE)?
What unique structural feature is observed in the brain histology of individuals with Creutzfeldt-Jakob disease?
What unique structural feature is observed in the brain histology of individuals with Creutzfeldt-Jakob disease?
Which type of disease is primarily associated with nutritional deficiencies?
Which type of disease is primarily associated with nutritional deficiencies?
What is a hallmark of a neurological disease caused by prions such as BSE?
What is a hallmark of a neurological disease caused by prions such as BSE?
Which characteristic is commonly associated with the histopathology of TSEs?
Which characteristic is commonly associated with the histopathology of TSEs?
What effect does myelin damage have in relation to TSEs?
What effect does myelin damage have in relation to TSEs?
What is a notable sign of nutritional disease in animals?
What is a notable sign of nutritional disease in animals?
Which of the following is a common pathological finding in brain tissue affected by prion diseases?
Which of the following is a common pathological finding in brain tissue affected by prion diseases?
What type of virus is primarily associated with Canine Distemper?
What type of virus is primarily associated with Canine Distemper?
Which of the following diseases is associated with severe neurological deficits and can be linked to nutritional deficiencies?
Which of the following diseases is associated with severe neurological deficits and can be linked to nutritional deficiencies?
Which type of agent is known to cause inclusion bodies in viral encephalitides?
Which type of agent is known to cause inclusion bodies in viral encephalitides?
Which viral infection is a significant concern in the context of rabies transmission?
Which viral infection is a significant concern in the context of rabies transmission?
Study Notes
Polioencephalomalacia (CCN)
- Affects sheep and cattle
- Characterized by malacia of the gray matter, particularly the cerebral cortex
- Caused by thiamine deficiency
- Gross lesions include discoloration, separation between gray and white matter
- Histological findings include extensive neuronal degeneration and necrosis, hemorrhage, astrogliosis, and microgliosis
Toxic Diseases
- Lead Poisoning:
- Diffuse cerebral edema
- Non-specific CNS lesions
- Intranuclear inclusions in renal tubule epithelium
- Focal Symmetrical Encephalomalacia (FSE):
- Caused by enterotoxaemia due to Clostridium perfringens type D
- Necrosis and hemorrhage
- Hepatic Encephalopathy:
- Secondary to liver damage
- High levels of ammonia and amines
- Astrocytosis
Neoplasia
- Primary tumors are rare and seldom metastasize
- Effects of neoplasia:
- Tissue destruction
- Space-occupying lesions
- Astrocytoma:
- Commonly found in brachycephalic dogs
- Located on cerebral hemispheres
- Solitary mass
- Anencephaly:
- Caused by genetic derangements, nutritional deficiencies, or infections
Myelination
- Primary Demyelination: Involves intact axons with damaged oligodendrocytes
- Secondary Demyelination: Necrosis of axons with intact oligodendrocytes and damaged neurons
Traumatic Injuries
- Space-Occupying Lesions:
- Skull fracture
- Laceration
- Contusion
- Haematoma (haematocyst)
- Epidural
- Subdural
- Routes of Spread:
- Haematogenous
- Adjacent structures
- Trauma/surgery (open wounds, penetrating wounds)
- Neural spread (viral travel via nerve)
Infectious Disease
- Meningitis:
- Bacterial: Suppurative/purulent meningitis (e.g., Streptococcus meningitis in pigs)
- Viral:
- Viral Encephalitides Features:
- Inclusion bodies:
- Single (e.g., herpesvirus)
- Multiple (e.g., rhabdovirus, canine distemper)
- Intranuclear/intracytoplasmic/both
- Perivascular cuffing (PVC):
- Occurs in Virchow-Robins space/perivascular space
- Non-specific to viruses but indicative of viral infection
- Usually mononuclear cells, rarely neutrophils
- Inclusion bodies:
- Vasculo-endothelial changes:
- Degeneration and necrosis of endothelium
- Necrosis of blood vessels (fibrinoid)
- Neuronal necrosis: Neuronophagia by microglial cells (Gitter cells)
- Glial proliferation: Astrocytic and microglial cell response
- Demyelination:
- In white matter (secondary to oligodendrocyte damage)
- In gray matter (caused by prions, as seen in bovine spongiform encephalopathy (BSE))
- Viral Encephalitides Features:
Rabies
- Emerging infectious disease
- Affects all mammals
- Lyssavirus from the Rhabdoviridae family, Mononegavirales order
- Vaccine options: Human diploid cell vaccine (HDCV), Purified chick embryo cell vaccine (PCEC), Rabies Vaccine Adsorbed (RVA), Rabies Immune Globulin (RIG)
- Reservoir: Megachiroptera (fruit-eating bats), Microchiroptera (insectivorous, frugivorous bats)
- Furious rabies: Characterized by fever, irritability, restlessness, anxiety, muscle pain, salivation, vomiting, painful muscle spasms (hydrophobia, aerophobia)
- Dumb rabies: Similar to furious rabies but progresses into paralysis and death
- Diagnosis:
- History of being bitten (animal, severity, site of bite)
- Animal:
- If survives >10 days, not rabies
- If dead, send brain to lab for Negri bodies, IFA, virus isolation
- Dogs: ovaline hippocampus
- Other species: cerebellum, spinal cord, trigeminal ganglia
- Human:
- Difficult to diagnose early stage of infection
- Clinical picture, skin biopsy, corneal impression
- Immunofluorescence, immunohistochemistry, Sellers stain
- Laboratory Tests:
- Inclusion bodies (carmine red cytoplasm, paranuclear)
- Brush border slide/smear of bladder transitional epithelium (Dif-Quick stain)
Canine Distemper
- Also known as "Barking Pig Syndrome"
- Natural host: Fruit bats (Pteropus sp)
- Incubation period in pigs: 4-14 days
- Clinical signs:
- Neurological:
- Encephalitis
- Head pressing, agitation/biting bars
- Tetanic spasms, seizures
- Hind limb lameness
- Respiratory:
- Harsh, non-productive cough (“barking”)
- Rapid, forced, open-mouthed respiration
- Neurological:
- Gross Pathology:
- Lungs: edema, pneumonia, hemorrhage, thickened septa
- Brain (at obex): Congestion in small vessels, perivascular cuffing, vasculitis
- Histopathology:
- Vasculitis: syncytial cells, cytolysis, necrosis
- Immunohistochemistry indicates lung involvement
Nipah Virus Encephalitis
- Prion properties:
- Small size (20-30 nm)
- No nucleic acid
- Extremely resistant to inactivation (UV, formaldehyde, heat)
- Transmissible via intracerebral, subcutaneous inoculation of infected brain tissue
- Clinical Signs:
- Apprehension
- Low head carriage
- Arched back
- Wide-based stance
Transmissible Spongiform Encephalopathy (TSE)
- Transmissible neurological syndromes
- Novel infectious particles (prions)
- Affect humans and other animals
- Characteristics:
- Confined to central nervous system (CNS)
- Long incubation period
- Progressive, uniformly fatal course
- Brain histology:
- Reactive gliosis
- Vacuolation of neurons
- Deposition of amyloid protein
- Absence of inflammatory response
- Examples:
- Bovine spongiform encephalopathy (BSE)
- Scrapie (goats and sheep)
- Feline spongiform encephalopathy (FSE)
- Creutzfeldt-Jakob disease (human)
- Spongiform encephalopathy (primate)
Nutritional Diseases
- Thiamine Deficiency:
- Thiamine is an essential component in energy metabolism
- Deficiencies lead to impaired pyruvate utilization (increased plasma pyruvate levels, ATP shortage)
- Lesions:
- Bilateral symmetrical
- Edema, hemorrhage, necrosis
- Gliosis
- Vitamin E/Selenium Deficiency:
- Affects young animals
- Causes white matter lesions, neuronal necrosis, gliosis
Fundamentals
- Blood Brain Barrier
- Protection around the central nervous system (CNS), similar to a membrane
- Newborns have a less developed BBB compared to adults
- Degenerates with age
- 7 areas without BBB
- Pituitary gland
- Median eminence
- Area postrema
- Preoptic recess
- Paraphysis
- Pineal gland
- Endothelium of choroid plexus
- Identifying Abnormalities
- 8 criteria for identification of abnormalities
- Classification of Lesions
- 10 groups for classification of lesions
- Differential Diagnosis
- Process involves considering different possible causes (aetiological) and appearances (morphological)
- Diagnosis achieved through a process of confirmation or elimination.
- Final Diagnosis
- Made after considering the presence or absence of abnormalities, their location, and conducting a differential diagnosis.
Similarities between Nervous System and Other Body Systems
- Neurones are surrounded by a membrane
- Neurones contain a nucleus that carries genes
- Neurones have a cytoplasm filled with mitochondria and other organelles
Differences between Nervous System and Other Body Systems
- Specialized projections: dendrites and axons
- Dendrites carry information to the cell body
- Axons carry information away from the cell body
- Communication between neurones occurs through an electrochemical process.
- Form specialized connections called "synapses" that release special chemicals called "neurotransmitters".
- The brain lacks lymphatics
- Advantage: limits infection from lymphatics
- Disadvantage: difficulty draining fluid in edema cases
- Resident macrophages within the brain are called microglials.
- Brain tissue is more susceptible to liquefactive necrosis (especially in brain)
Neuropathology
- Comprised of nerve cells (neurons) and supporting cells (glial cells).
- The brain and spinal cord are enclosed in a bony box (non-expandable) -- any lesion that occupies space in the CNS can cause problems.
- Even a benign tumor is dangerous
- The CNS is covered by the meninges: 3 membranes that provide protection and nourish the CNS
- Dura mater (aka pachymeninges) -- limits infection.
- Arachnoid mater
- Pia mater + Arachnoid mater = leptomeninges
- Subarachnoid space (contains cerebrospinal fluid) is located between the arachnoid mater & pia mater
- Leptomeningitis: inflammation of both meninges
- Pia mater
- Blood vessels connecting to CNS provide nourishment
Cranial Nerves
- I Olfactory - Smell
- II Ocular (Optic) - Vision
- III Oculomotor - Control of eye movement
- IV Trochlear - Control of eye movement
- V Trigeminal - Face sensation, mastication (chewing)
- VI Abducens - Control of eye movement
- VII Facial - Facial expression
- VIII Vestibulocochlear (Acoustic) - Vestibular (balance), Cochlear (hearing)
- IX Glossopharyngeal - Oral sensation, taste, salivation
- X Vagus - Involuntary nervous system (maintains heart rate, digestion)
- XI Accessory (Spinal Accessory) - Shoulder elevation, head turning
- XII Hypoglossal - Tongue movement
Brain
- Frontal lobe - Decision making, Memory
- Parietal lobe - Sensation (feeling)
- Occipital lobe - Vision
- Temporal lobe - Hearing (language, speech)
- Olfactory lobe - Smell
- Clinical problems are dependent on the location of the lesion
- A tiny lesion in an "eloquent" area may present striking clinical problems
- A large infarct in a "silent" area may be missed
- Diverse lesions (infarcts, abscesses, tumors) in one site may produce similar problems, while similar pathologic processes at different sites will present different pictures.
- Contralateral problems : Cortical lesions produce contralateral visual, tactile, and motor problems.
- Consequences of lesions
- Cerebellum is mostly responsible for coordination
- Basal ganglia responsible for muscle tone
- Consciousness is lost with damage to the pontine and midbrain reticular formation
- Selective vulnerability of cells
- Alzheimer's affects hippocampus and cholinergic nucleus of Meynert.
- Mercury (Hg) selectively damages cerebellar granular neurons.
- Methanol poisons the retina.
- Poliomyelitis destroys only the anterior horn cells.
Region of Diagnostic Tests for Emerging Viral Diseases
- Bovine Spongiform Encephalopathy (BSE) - Obex
- Canine Distemper - Demyelination in the cerebellum
- Rabies - Hippocampus
- Nipah Virus - Any part of the brain
Gliosis
- Gliosis : Proliferation or hypertrophy of glial cells
- Astrocytes :
- Usually secondary (arising from an underlying condition)
- Increase in ammonia toxicity
- Decrease in necrosis
- Unprofessional phagocytes
- Gemistocytes (hypertrophy of astrocytes)
- Astrogliosis (proliferation of astrocytes)
Normal Cerebrospinal Fluid (CSF) Physiology
- Produced by the choroid plexus and the brain parenchyma.
- Lateral ventricle
- Flows through the foramen of Monroe
- Third ventricle
- Flows through the aqueduct of Sylvius
- Fourth ventricle
- Flows through the foramina of Magendie and Luschka.
- Subarachnoid space
- CSF is ultimately absorbed by arachnoid villi and through open channels around cranial & spinal nerves
Congenital Anomalies
- Emerging Diseases in Malaysia
- Ebola
- Rabies
- Canine distemper
- Nipah Virus
- Mononegavirales
Spinal Cord & Peripheral Nerves
- Not discussed in this document.
Immature Nervous System
- Not discussed in this document.
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