Neuropathology Own Notes PDF

NEUROPATHOLOGY ∞ PROF NOORDIN ∞ Blood-brain barrier (protection) Fundamentals - Newborn < adults Identification of abnormality...

NEUROPATHOLOGY ∞ PROF NOORDIN ∞ Blood-brain barrier (protection) Fundamentals - Newborn < adults Identification of abnormality - Degenerates when old age - 8 criteria - 7 areas without BBB - Presence ◦ Pituitary gland - Absence - Location ◦ Median eminence Classification of lesion ◦ Area postrema - 10 groups ◦ Preoptic recess Differential diagnosis ◦ Paraphysis - Aetiological ◦ Pineal gland - Morphological ◦ Endothelium of choroid plexus - Via confirmation / elimination process Final diagnosis CRANIAL NERVES I Oh Olfactory Smell Similarities with other body systems II Oh Ocular (Optic) Vision Neurones are surrounded by a membrane III Oh Oculomotor Control eye movement Neurones have a nucleus that contains genes IV To Trochlear Control eye movement Neurones contain cytoplasm, mitochondria and other Face sensation, organelles V Touch Trigeminal mastication VI A Abducens Control eye movement Differences with other body system VII Female Facial Facial expression Specialised projections : dendrites & axons Vestibulocochlear Vestibular : Balance VIII Vagina - Dendrites bring information to cell body (Acoustic) Cochlear : Hearing Oral sensation, taste, - Axon take information away from cell body IX Gives Glossopharyngeal salivation Communicate with each other through an electrochemical Involuntary nervous process X Vincent Vagus system (maintain heart Form specialized connections “synapses” and produce rate, food digestion) special chemicals “neurotransmitters” that are released Accessory Shoulder elevation, XI A at synapse (Spinal accessory) head turning Brain does not have lymphatics XII Hard-on Hypoglossal Tongue movement - Advantage : no infection from lymphatics - Disadvantage : unable to drain fluid in edema cases Resident macrophage = microglials Liquefactive necrosis (especially for brain) Neuropathology Nerve cell (neurone) + supporting cells (Glial cells) Enclosed in a bony box (non-expandable) - Any lesion that takes up space will cause problem - Even a benign tumour is dangerous Meninges (covers brain and spinal cord) - 3 membranes (protect and nourish CNS) ◦ Dura mater  Aka pachymeninges (limits infection) Frontal lobe Decision, Memory ◦ Arachnoid mater Parietal lobe Sensation (feeling)  Pia mater + arachnoid = leptomeninges Occipital lobe Vision  Subarachnoid space (contain Temporal lobe Hearing (language, speech) Olfactory lobe Smell cerebrospinal fluid) is in between arachnoid mater and pia mater  Leptomeningitis : inflammation of both A tiny lesion in an ‘eloquent’ area may present striking membranes clinical problems ◦ Pia mater A large infarct in a ‘silent’ area is missed  Blood vessels connected to CNS = Diverse lesions (infarcts, abscesses, tumours) in one site nourishment may produce similar problems, while similar pathologic processes at different sites will present different pictures  Cortical lesions produce contralateral visual, tactile and motor problems Cerebellum is mostly responsible for coordination and the basal ganglia for muscle tone Consciousness is lost with damage to the pontine and midbrain reticular formation Cells of nervous tissue are selectively vulnerable to diseases / conditions - Alzheimer’s affect hippocampus and cholinergic nucleus of Maynert - Mercury (Hg) selectively damages cerebellar granular neurons - Methanol poisons the retina - Poliomyelitis destroys only the anterior horn cells Region from diagnostic tests for viral diseases - BSE : obex - Canine distemper : demyelination in cerebellum - Rabies : hippocampus - Nipah virus : any part of brain Topics Brain - Congenital anomalies Emerging diseases in Malaysia - Traumatic injuries Ebola - Infectious diseases Rabies - Nutritional diseases Canine distemper - Toxic diseases Nipah virus - Neoplasia Mononegavirales Spinal Cord & Peripheral Nerves Immature Nervous System GLIAL CELLS Congenital Anomalies Gliosis = proliferation / hypertrophy Normal CSF physiology Produced by choroid plexus & brain parenchyma Astrocytes Usually secondary Lateral ventricle Increase in NH3 toxicity  foramen of Monroe Decrease in necrosis 3rd ventricle Unprofessional phagocytes  aqueduct of Sylvius Gemistocytes (hypertrophy) 4th ventricle  foramina of Magendie and Luschka Astrogliosis (proliferation) Subarachnoid space Ultimately absorbed by arachnoid villi and through open channels around cranial & spinal nerves 1. Hydrocephalus - Hypersecretion of CSF in brain (due to choroid plexus papilloma – rare) - Obstructive hydrocephalus Astrocyte Gemistocyte ◦ Foramina of Monroe (colloid cyst, tuberous sclerosis) Microglial cells ◦ Third ventricle (craniopharyngioma, pilocytic Phagocytic astrocytoma, germ cell tumours) Microgliosis (proliferate) ◦ Aqueduct (aqueductal stenosis or atresia, Gitter cells posterior fossa tumours) - Eventual result of neuronophagia (phagocytosis of ◦ Foramina of Luschka or impairment of flow neurons) from the fourth ventricle - Fibrosis of subarachnoid space (meningitis, subarachnoid haemorrhage, meningeal dissemination of tumours) - Obliteration of subarachnoid space - Congenital / acquired - Types ◦ External Microglia Gitter Cells ◦ Internal ◦ Communicating Oligodendrocyte - Defective filtration of CSF : postulated for low- Indirect : proliferate (satelitosis) pressure hydrocephalus (rare) Direct : demyelination 2. Anencephaly - Genetic derangements - Nutritional - Infectious Myelination Primary : intact axon (damage of oligodendrocyte) Secondary : necrosed axon (intact oligodendrocyte, damaged neuron) Traumatic injuries - Haematogenous Space-occupying lesions - Adjacent structures - Skull fracture - Trauma / surgery (open wound, penetrating such as - Laceration bullet wound, arrow) - Contusion - Neural spread (viral travel via nerve) - Haematoma (haematocyst) ◦ L. monocytogenes in poor silage (Listeriosis) ◦ Epidural  Perivascular cuffing, microabscesses ◦ Subdural ◦ Rhabdovirus (Rabies virus travels via neuron) Agents - Bacterial (pus) ◦ Suppurative / purulent meningitis due to strep meningitis in pigs - Viral (Viral Encephalitides Features) ◦ Inclusion bodies  Single (herpes virus) Epidural Subdural  Multiple (rhabdovirus, canine distemper)  Intranuclear / intracytoplasmic / both Shaken Baby Syndrome  Eosinophilic, basophilic  Rabies (Rhabdovirus) inclusion bodies known as Negri bodies : intracytoplasmic  Herpes virus causes Aujeszky’s disease in pigs : intranuclear  Both - Paramyxovirus - CMV (canine distemper) - Nipah - Newcastle Disease ◦ Perivascular cuffing (PVC)  Occur in Virchow-Robins space / perivascular space  Non-specific to virus but indication of viral infection; sign of inflammation  Usually mononuclear cells, rarely neutrophils - Aggregation of lymphocytes ◦ Vasculo-endothelial changes  Degeneration & necrosis of endothelium  Necrosis of blood vessels = fibrinoid (appears like fibrin, but not) ◦ Neuronal necrosis  Neuronophagia by microglial cells  Gitter cells ◦ Glial proliferation  Astrocytic, microglial cells response ◦ Demyelination in white matter  In grey matter is due to prion (BSE)  Primary : oligodendrocyte damage  Secondary : neurone damage  Mechanism - Myelin damage  anti-myelin antigen (prevents new myelin formation) Infectious disease RABIES Primary / Secondary Emerging Route of infection  - A known agent appearing in a new geographical Paramyxovirus (Morbilivirus group) area; only applicable when Aka Hard Pad disease (hyperkeratosis of paws & nose) ◦ Non-classical rabies is detected anywhere in Clinical signs Malaysia - Conjunctivitis (keratoconjunctivitis, chorioretinitis, ◦ Classical rabies happens in Sabah & Sarawak optic neuritis) - A known agent or its close relative occurring in a - Enamel hypoplasia hitherto unsusceptible species - Hyperkeratosis (paw & nose) ◦ All mammals are susceptible to rabies - Diarrhoea, vomiting - A previously unknown agent detected for the first - Fever time - Pneumonia, rhinitis ◦ If a new lyssavirus is detected from any species - Symptoms exacerbated by secondary bacterial anywhere in Malaysia infections Lyssavirus from Rhabdoviridae of the Mononegavirales - Encephalomyelitis order - Ataxia, hyperaesthesia, myoclonus - Most virus from this order affects nervous system - Paralysis / paresis Vaccine - Progressive deterioration of mental abilities / motor - Human diploid cell vaccine (HDCV) skills - Purified chick embryo cell vaccine (PCEC) - Seizures (chewing gum fit) = could also be rabies - Rabies Vaccine Adsorbed (RVA) - Rabies Immune Globulin (RIG) Reservoir - Megachiroptera : less-specialised & fruit-eating (flying foxes) - Microchiroptera : more specialised & echolocating, insectivorous (insect), frugivorous (fruit), very few feed on blood & fish Furious rabies - Fever, irritability, restlessness, anxiety - May progress to muscle pain, salivation, vomiting - Few days – a week : stage of excitement ◦ Painful muscle spasms (triggered by swallowing saliva, drinking = similar to bone in throat) ◦ Drool, fear water & air (hydrophobia, aerophobia) ◦ Few days later, lapses into coma and death Sample Dumb rabies - Gastric mucosa - Begins like furious form - Renal pelvis (collecting tubules) - Progress into excitement, retreats steadily and - Urinary bladder downhill, with some paralysis to death Lab test / Diagnosis - Diagnosis may easily be missed - Inclusion bodies (carmine red cytoplasm, Diagnosis paranuclear) - History of being bitten (animal, severity, site of bite) - Brush border slide / smear of bladder transitional - Animal epithelium ◦ If survive >10 days, not rabies - Dif-Quick stain ◦ If dead, send brain to lab (Negri bodies, IFA, - 90% of bladder cells +ve in early stages virus isolation) - Almost absent after 21 days post-onset ◦ Dogs : ovaline hippocampus ◦ Other spp : cerebellum, spinal cord, trigeminal ganglia - Man ◦ Difficult to diagnose early stage of infection ◦ Clinical picture, skin biopsy, corneal impression - Immunofluorescence, immunohistochemistry ◦ Sellers stain CANINE DISTEMPER NIPAH VIRUS ENCEPHALITIS  Aka Barking Pig Syndrome Prion properties Natural host : Fruit bats (Pteropus sp) - Very small (20-30 nm) Incubation period (pigs) : 4-14 days - No nucleic acid Clinical signs - Extremely resistant to inactivation via - Neurological (boars & sows) ◦ UV, formaldehyde, heat ◦ Encephalitis - Transmissible via intra-cerebral, sub-cut inoculation ◦ Head pressing, agitation / biting bars of infected brain tissue ◦ Tetanic spasm, seizures ◦ Hind limb lameness - Respiratory signs (piglets) ◦ Harsh, non-productive cough ‘barking’ ◦ Rapid, forced, open-mouthed respiration Clinical signs - Apprehension - Low head carriage - Arched back Gross pathology - Wide-based stance - Lungs ◦ Oedema ◦ Pneumonia ◦ Haemorrhage ◦ Thickened septa - Brain (@ obex) ◦ Observe congestion in small vessels ◦ Perivascular cuffing (does not invade) ◦ Vasculitis (invades blood vessels) Histopathology - Vasculitis : syncytial cells, cytolysis, necrosis BSE - Immunohistochemistry indicates lung involvement TRANSMISSIBLE SPONGIOFORM ENCEPHALOPATHY (TSE) Transmissible neurological syndromes Novel infectious particles (prion) Man & other animals Characteristics Creutzfeldt-Jakob disease - Confined to CNS - Long incubation period - Progressive, uniformly fatal course - Brain histology ◦ Reactive gliosis ◦ Vacuolation of neurones ◦ Deposition of amyloid protein ◦ Absence of inflammatory response Examples - BSE (bovine), scrapie (goats & sheep), FSE (feline), Creutzfeldt-Jakob disease (man, familial), SE Scrapie: Counter-immunoperoxidase (primate) Presence of astrocytes NUTRITIONAL DISEASES 1. Polioencephalomalacia (CCN) TOXIC DISEASES Sheep & cattle 1. Lead poisoning Malacia of grey matter (! Cerebral cortex) Diffuse cerebral oedema Aetiology Non-specific CNS lesion - Thiamine deficiency Intranuclear inclusion in renal tubule epithelium Gross 2. Focal symmetrical encephalomalacia (FSE) - Discolouration Enterotoxaemia (Clostridium perfringes type D) - Separation between grey and white matter Necrosis & haemorrhage Histology - Extensive neuronal degeneration & necrosis 3. Hepatic encephalopathy - Haemorrhage Secondary to liver damage - Astrogliosis, microgliosis High levels of NH3 and amines 2. Thiamine deficiency Astrocytosis Kittens fed oily fish Aetiology NEOPLASIA - Thiamine = essential component in energy Primary tumours are rare & seldome metastasize metabolism Effects - Insufficiency will lead to impaired pyruvate - Tissue destruction utilisation (increase in plasma pyruvate levels, - Space-occupying lesion ATP shortage) 1. Astrocytoma Lesions Brachycephalic dogs - Bilateral symmetrical Especially on cerebral hemispheres - Oedema, haemorrhage, necrosis Solitary mass - Gliosis 2. Meningioma General signs Derived from leptomeninges - Weight loss, weakness Solitary / multiple - Impaired feed utilisation Location Predisposing factor - Base of brain - Fern - Surface of ◦ First to emerge during spring cerebellum ◦ Contaminate hay - Cerebrum ◦ Used as bedding - Spinal cord - Plowing exposes rhizomes 3. Eosinophilic Meningoencephalitis Pigs Aetiology - High salt (>2%), restricted water supply - Disappears after water replenishment Pathogenesis - Cerebral oedema Lesions - PVC by eosinophils - Loss of cortical neurons 4. Swayback (Enzootic Ataxia) 3. Other tumours New-born lambs Ependymoma Aetiology Oligodendroglioma - Low copper in diet of dam Medullaoblastoma Pathogenesis Neurofibroma - Improper myelin formation Schwannoma - Lack of cytochrome oxidase, superoxide dismutase, caeruloplasmin Lesions - Demyelination - Microgliosis Ependymoma SPINAL CORD DISEASES Regenerate if Relay nerve impulses to & fro centres in brain - Fibre ends are apposed Lesion interferes with (dependent on affected site) - Neuron is intact - Motor function - Viable endoneurium & perineureum - Sensation - Nerve growth factor (NGF) Spinal cord compression (signs) a) Degeneration (Wallerian) and Necrosis - Minor motor/sensory deficit Removal performed by macrophages - Paraplegia (lower limbs) Severe injury  fibrosis - Quadriplegia (all four limbs) Causes : trauma, prolonged compression, burns, - Loss of bladder control toxin - Many aetiology b) Tumour a) Vertebral fracture / dislocation Neurofibroma, Marek’s disease Due to trauma Effect : compression of spinal cord Lesions ◦ Haemorrhage ◦ Degeneration ◦ Necrosis ◦ Severe cases : total transection of cord b) Vertebral malarticulation / malformation Cervicospinal arthropathy (Wobblers, spinal ataxia) Young thoroughbred horses REGENERATION OF PERIPHERAL NERVES Misaligned / hypermotility of cervical vertebrae ◦ C3-C4 (C1-C7) ◦ Hyperflexion led to excessive pressure on cord ◦ Great Danes & Doberman : C7 misaligned & stenosed canal c) Meningeal abscess Epidural / subdural Compression Omphalophlebitis, tail-biting d) Neoplasia Primary : meningioma, neurofibroma, osteosarcoma Secondary : mammary carcinoma e) Disc protrusion Associated with degenerative disease Dachshund, Pekingese, Cocker Spaniel Compressed spinal cord / blood vessel damage PERIPHERAL NERVES DISEASES PATHOLOGY OF IMMATURE NERVOUS SYSTEM In summary Same general principle holds true for immature nervous - an early effect in gestation = shape of the brain system with a few exceptions - later, malformed cell multiplication leading to Neurologic disorders result from damage inflicted on normal shape albeit with variable size of different growing brain and spinal cord parts of the brain - Before - Latest part of development, may affect the specific - During unit of a structure - Immediately after birth Damage inflicted have serious effect on A. Feline Panleukopaenia - Multiplication - In adult : intestinal and haemogram disturbances - Migration / maturation of neurons ◦ Destroys the cell of the crypt and bone - Formation of myelin marrow - Free flow of CSF - In kittens: cerebellum is being affected Consequences ◦ happens just before / immediately after birth - Deficiency in nerve cell numbers ◦ at this point, normal shape but with missing - Dysplasia of nervous tissue details - Deficiency of myelin Prior to birth, the Purkinje cells and other neurons - Hydrocephalus migrate from the sub-ependymal plate areas of the Due to different growth rate, certain agent produce fourth ventricle different lesions in different system between the mature - Migrate outwards and immature body system despite the similar - Virus do not attack this layer, usually attack pathogenesis in both systems rapidly-dividing cells (GIT) Example: Effect of feline parvovirus on kittens infected At around the time of birth, a second pattern of while in utero (cerebellar hypoplasia) and adult (villous migration occurs from the external germinal layer that atrophy and bone marrow suppression) lies along the external cerebellar surface Central nervous system organogenesis - Migrate inwards - Organogenesis and neuronal - To form granular layer ◦ Stage whereby the adult brain shape begins to - Rapidly dividing : virus will tend to attack this layer form Cells of this layer undergo remarkably intense period of ◦ Subdivided into 2 main stages mitotic activity in the neonatal period and migrate into  Maturation period for axonal & dendritic the substance of the brain to form the granular layer of growth the cerebellum  Period of size growth : intense This bulk layer of the cerebellar mass (granular layer) is multiplication & myelination attacked by the virus leading to hypoplasia - The mature adult phase The growth and development have their very own spurt B. Swayback/Enzootic Ataxia Similarly, brains of different animal species grow at a state of copper (Cu) deficiency seen in only different rates and mature at different times neonatal or young lambs Likewise, the growth rate and maturation period of occurs while the lamb is in utero various parts of the brain differ considerably too - Ex: cellular multiplication always precede C. Hypomyelogenesis congenita/trembling pigs/Border myelination disease Depending on time of contact by an agent in utero, Cattle : cerebellar ataxia (hypomyelogenesis different changes in different part may occur congenita) This variation in susceptibility associated with growth Pigs : trembling pigs/dancing pigs spurts has led to the concept of “Vulnerable Periods of Lambs : Border disease/ hairy shaker disease or Development” which is a very important concept in hypomyelogenesis congenita understanding the pathology of the foetus Hairy shakers are born with hairy hair coats and Consideration with tremors - cellular pathology of the foetus and the adult is The shaking is due to the patchily distributed (lack) almost similar of myelin - a particular malformation in the foetus may be produced by one of a number of widely differing D. Bovine Viral Diarhoea agents Adult : Virus affects gut - the target organ for a pathogen in the foetus may Foetus : Virus affects the nervous tissue affecting be vary different from the target organ for that cerebellum and eye pathogen in the adult