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Disease processes which afflict the central nervous system are similar to those which occur elsewhere in the body. However, there are three special features of the nervous system that modify the expression of disease. These features are
All three features profoundly influence the response of the nervous system to a host of diseases and they will be discussed briefly.
The cells of the nervous system can respond to injury in only a limited number of ways. They can swell, shrink, die, disappear or recover. The neuron is most sensitive to injury and is generally the target of an injurious agent. The astrocytic, microglial, neutrophilic, lymphocytic or vascular response is usually secondary, but may be so vigorous at times that it overshadows the primary neuronal damage. The oligodendrocyte is almost as sensitive to injury as the neuron, followed by the astrocyte, microglial and capillaries in that order. There is a paucity of connective tissue in the brain. Proliferation of astrocytes with production of glial fibers is analogous to the fibrosis and scarring of other organs.
The neuron is highly vulnerable to injurious influences and tends to react to disease in three ways (acute necrosis, degeneration, axonal changes).
Is usually associated with ischemia or an overwhelming acute toxic or infectious disorder. The neuron becomes shrunken and angular and the nucleus becomes pyknotic. The Nissl substance (endoplasmic reticulum) in the cytoplasm disappears (chromatolysis) and the cytoplasm assumes a homogeneous, brightly eosinophilic appearance. These changes are followed ultimately by fragmentation of the cell processes, disruption of the membranes and autolysis or phagocytosis.
May be associated with a variety of chronic disorders. As in acute necrosis, degeneration is characterized by contraction of the cell body. However, the cytoplasm becomes basophilic rather than eosinophilic (reflecting clumping and increased prominence of Nissl substance). Also lipofuscin pigment is common within the cytoplasm of degenerating neurons. Remember, these changes are reversible as long as the nucleus is intact. However, if the degenerative process continues, the nucleus ultimately becomes pyknotic and fragments. From this point on, the changes are basically the same as those of acute necrosis.
occurs when the axon is injured or severed, thus resulting in a series of alterations in the cell body. At first, the neuron swells and loses its angularity. The nucleus is displaced to the periphery opposite the axon hillock. The Nissl substance disappears (this occurs first near the center of the cell and the process is referred to as "central chromatolysis"). Up to this point the cell is still alive and the changes are reversible. Thus, the axonal reaction signifies a neuron in crisis. (Remember, very similar changes may result from ischemia which is not sufficiently intense or sudden to cause acute necrosis. These changes may also occur after many types of acute toxic or infectious injury). Death of the neuron or loss of the axon is always accompanied by degeneration of the myelin sheath. The converse is not true, however. The term demyelinization customarily refers to a situation in which there is loss of myelin with preservation of the cell body and axon. The myelin progressively loses it affinity for myelin stains and ultimately appears as an unstained area surrounding the axon. Neuronal Inclusion Bodies may occur in either the nucleus or cytoplasm of neurons. "Cowdry's Type A" is an intranuclear inclusion, eosinophilic (with H & E), which is usually single and displaces the nucleolus. It is surrounded by a clear halo and is considered relatively specific for viral infections. "Cowdry's Type B" inclusions are less specific. They are intranuclear, eosinophilic, and often multiple. The nucleolus is not displaced. Intracytoplasmic inclusions referred to as Negri Bodies may be observed in cases of rabies. Negri bodies are eosinophilic with internal granules which stain purple with methylene blue and basic fuchsin. It must be remembered that groups of tiny spherical bodies without a limiting membrane are encountered in the neurons of nonrabid animals. These bodies are easily confused with Negri bodies. However, they are more eosinophilic. The bodies have been described in the cat, dog, fox, skunk and laboratory mice. So called "feline inclusions" have been described in the neurons of normal cats. These inclusions cannot be differentiated from Negri bodies on morphologic basis. In canine distemper, cytoplasmic or nuclear inclusions can be found in neurons.
The astrocyte functions in response to injury in a manner similar to that of fibroblasts in other tissues. In acute injury, the astrocyte swells, the cytoplasm becomes deeply eosinophilic and oxidative enzymes increase. These large, swollen, reactive astrocytes are referred to as gemistocytes. Subacute and chronic processes may incite astrocytic proliferation with the formation of new cells and glial fibers. This process is referred to as gliosis or scarring. Astrocytes imbibe much fluid in cerebral edema.
These cells are normally found between the axons of the white matter where they are believed to elaborate and maintain the myelin sheath. They are also found clustered around neurons in the gray matter. In the white matter, oligodendrocytes often proliferate in early processes of demyelination, whereas they are scant in the later stages. In the gray matter, the oligodendrocytes swell in response to nearly all types of injury to the neuron. In addition, these cells (along with microglial) may accumulate around a damaged neuron. This process is referred to as satellitosis.
These cells act as macrophages in the central nervous system. As the hardiest of the specialized cells of the CNS, they may remain alone in a focus of injury to phagocytize dead tissue and to engulf the lipids from degenerating myelin. Lipid-laden microphages are referred to as gitter cells. Microglia accumulate around damaged neurons as satellites and may eventually remove the damaged cell by neuronophagia.
These cells line the ventricles and central spinal canal (also reflected over the choroid plexus). Ependymal cells are easily damaged and do not regenerate.
Each locus within the nervous system correspond to a different bodily process. Therefore, the clinical effect of a lesion depends largely on its location within the nervous system. Location of a lesion may be far more important than its size. For example, a small infarct in the frontal cortex may be of no apparent significance, whereas, a lesion of the same size in the medulla oblongata may cause instant death. In general, as one proceeds caudally from the cerebral cortex where there is a dispersal of neurons over a fairly large area, toward the medulla oblongata, where all of the neurons lie together in a relatively compact area, pathologic processes have increasingly dire consequences. From a clinical standpoint, certain signs or symptom complexes enable the neurologist to infer the exact location of the causative lesion. Since many disorders tend to be selective for certain sites in the brain, this knowledge may in turn suggest the probable diagnosis.
The brain is rather rigidly encased by the skull. Even though this provides great protection against injury, it becomes detrimental when there is any expansion of the intracranial contents. Such expansion may result from space-occupying lesions, edema and abnormal accumulation of cerebrospinal fluid.
Many noxious agents can act on the developing fetus in utero causing malformations. Most major lines of differentiation in the CNS are laid down early (during the first trimester), so that any agent acting during this period of time may cause total absence (agenesis/aplasia), partial absence (hypoplasia), or severe disturbance in structure and organization (dysplasia). At a later time, an injurious agent can act to destroy an already formed part of the brain. Injurious agents acting during the last trimester of gestation tend to evoke rather prominent inflammatory changes. Malformations of the CNS are rather common in domestic animals. Some of these are inherited, whereas other are caused by various noxious agents.
2.5.2.1 ANENCEPHALY
refers to total absence of the entire brain (this probably does not occur). The term is used even though a small portion of the brain persists. Usually in anencephaly, there is absence of the cerebral hemispheres with failure of forebrain fusion.
2.5.2.2 AMYELIA
Refers to total absence of the spinal cord which usually occurs in association with anencephaly.
2.5.2.3 ENCEPHALOCELE
Refers to protrusion of the brain (along with the meninges) through a defect in the cranium. The term spinal bifida refers to the defect in the skull. Encephaloceles are related to suture lines and are almost always median. The skin forms the hernia sac. Meningocele refers to protrusion of the meninges. (Refer to 2x2 slides #8, 9, 10, 11 & 12).
2.5.2.4 PROSENCEPHALY
Occurs as the result of failure of bilateral separation of the primitive single telecephalic cavity into two hemispheres. There is usually a single central ventricle, absence of the longitudinal fissure, the corpus callosum, olfactory bulb and optic tracts. Severe cases may have a central proboscis and a single eye (cyclopia). Less severe cases may show narrowing of the interpupillary space, small eyes and a flattened nose. The brain stem and cerebellum are usually normal. Prosencephaly with cyclopia is not uncommon in domestic animals, especially pigs. A wide range of cyclopia-type malformations occur endemically in lamb fetuses. The malformation can be reproduced experimentally in many different ways. (Refer to 2x2 slide #1).
2.5.2.5 HYDRANENCEPHALY
Refers to complete or almost complete absence of the cerebral hemispheres in a cranium of normal size and formation. The leptomeninges are in their normal position and form sacs enclosing cerebrospinal fluid (the fluid occupies space normally occupied by the parenchyma). In other words, the cerebral hemispheres are largely represented by large cystic spaces or sacs. There is no ependymal lining. Hydranencephaly occurs in all species, but it occurs most commonly in calves in association with cerebellar hypoplasia (Refer to 2x2 slide #3). The defect has been observed in lambs of ewes vaccinated during pregnancy for bluetongue.
2.5.2.6 LISSENCEPHALY (MACROGYRI/AGYRI)
In this defect, there is a lack of formation of secondary or tertiary gyri so that large, smooth gyri analogous to those of the brains of lower organisms are formed (macrogyri). If there is an absence of primary gyri as well, the cortical surface is perfectly smooth and the condition is referred to as lissencephaly. In any case, there is much dysplasia and distortion of cortical architecture (Refer to 2x2 slide #14).
2.5.2.7 SYRINGOMYELIA
Refers to a tubular cavitation of the spinal cord which extends over several segments. This is a rather rare anomaly, except in the Weimaraner breed of dog. Typically, affected dogs are unable to completely extend the hind limbs so that their normal posture or attitude is crouched and the hind limbs are moved together in progression (symmetrical hopping gait). Even though the defect is familial, lesions are not observed until about the 8th month of life; however, the functional defect is present when the animal first begins to walk. Grossly, cavitations are usually found in the lumbar segments and they may or may not be visible to the naked eye. Microscopically, the cavitations are usually found in the central gray matter (dorsal and lateral to the central canal) and they are not lined by ependymal cells.
2.5.2.8 HYDROMYELIA
Refers to a simple dilatation of the central canal of the spinal cord (Refer to 2x2 slide #20). The cavity is connected with the central canal and lined by ependymal cells.
2.5.2.9 OPTIC NERVE HYPOPLASIA
Is manifested as a decrease in size or disruption of continuity of the optic nerve. The optic chiasm may or may not be involved. The condition is nearly always bilateral and the globes as a rule are microphthalmic (Refer to 2x2 slide #15).
2.5.2.10 HYDROCEPHALUS
Refers to an increased or abnormal accumulation of cerebrospinal fluid (CSF) in the cranial cavity. The condition may be congenital or acquired. In internal hydrocephalus, the fluid is within the ventricular system. In external hydrocephalus, the fluid is in the arachnoid space. In communicating hydrocephalus, the excess fluid is present in both locations. The external and communicating types of hydrocephalus are quite rare in animals, whereas internal hydrocephalus is common. Evidence suggests that hydrocephalus may follow
- (1) increased production of CSF,
- (2) obstruction of the normal flow of CSF or
- (3) defective absorption of CSF.
CSF is produced by the choroid plexuses and the flow of fluid is from the lateral ventricles through the foramen of Monro to the 3rd ventricle and, via the aqueduct of Sylvius, to the 4th ventricle. Exit of fluid from the ventricular system is via the foramen of Luschka to the subarachnoid space. Congenital hydrocephalus occurs in all species but is most commonly observed in pups, foals, calves and piglets and is frequently associated with malformation of the cranium. Acquired hydrocephalus is usually less severe than the congenital defect and there is usually no malformation of the cranium. The causes are almost always obstructive; however, minor degrees of ventricular dilatation occurs in association with cortical atrophy in aged dogs. Grossly, the lateral and 3rd ventricles are most severely affected in hydrocephalus. They are dilated and the CSF is under increased pressure. There is parenchymal atrophy affecting chiefly the white matter and the cerebral cortices (the gray matter is markedly resistant to the effects of pressure exerted by the fluid but subcortical white matter degenerates rapidly). The septum pellucidum is the structure most sensitive to the effects of fluid accumulation. (Refer to 2x2 slides # 16, 17, 18 & 19).
2.5.2.11CEREBELLAR HYPOPLASIA
Is most commonly observed in cats, dogs and calves. Morphologically, the cerebellum may be normal in size and appearance or it may be represented by a very small nubbin of tissue. In those cases where the cerebellum is grossly normal, the hypoplastic defect can be detected only on microscopic examination (there is a loss of purkinje cells, the granular layer is narrowed and deficient in cells and the molecular layer is usually normal).
In some instances, cerebellar hypoplasia may be inherited. However, it has been clearly demonstrated that certain viral agents are capable of producing this defect. Panleukopenia virus produces cerebellar hypoplasia and ataxia if kittens are inoculated in utero or shortly after birth (periods when the cerebellum is still growing and differentiating rapidly). The virus effect is primarily on the external germinal layer of the cerebellum. Early in the disease, intranuclear neuronal inclusion bodies may be present. The virus can pass the placenta and the kittens will carry the virus for months after birth, especially in the kidneys. The rat virus and the hamster osteolytic virus are capable of causing cerebellar hypoplasia in cats, rats and hamsters. Modified hog cholera virus can affect the cerebellum of the fetal pig causing cerebellar hypoplasia along with a host of other defects. Cerebellar hypoplasia has also been recorded in calves born to dams infected with the bovine virus diarrhea virus (Refer to 2x2 slides #2, 3, 4, 5, 6 & 7).
2.5.2.12 GLOBOID CELL LEUKODYSTROPHY
Is the result of inherited deficiency of the catabolic enzyme galactocerebroside-ß-galactosidase. Macrophages (microglial cells) are transformed into globoid cells when PAS-positive inclusion tubules of galactocerebroside accumulate within them. The condition has been recorded in dogs and cats. In dogs, clinical signs may develop as early as the 2nd and as late as the 7th month of life. Significant pathologic changes are restricted to the CNS. Grossly, the involved regions of fixed white matter are gray and soft compared to normal white matter. Microscopically, white matter exhibits degenerative changes, but changes in gray matter are minimal. Destruction of white matter is bilaterally symmetrical. The characteristic feature of the disease is the presence of PAS-positive globoid type macrophages. (Refer to 2x2 slide #21)
2.5.2.13 ARNOLD-CHIARI MALFORMATION
Is considered to be a developmental defect of the cerebellum and brain stem with displacement of the tongue of the cerebellar vermis, medulla and caudal 4th ventricle through the foramen magnum into the spinal canal. The condition is oftentimes associated with hydrocephalus.
Inflammation of the central nervous system may be limited to the coverings of the brain or spinal cord (meningitis). If only the dura is involved, the term pachymeningitis applies, whereas the term leptomeningitis refers to inflammation of the pia-arachnoid. Choroiditis applies to inflammation of the choroid and ependymitis refers to inflammation of the ependyma. Inflammatory processes may involve the parenchyma of the brain (encephalitis) or of the spinal cord (myelitis) or both (encephalomyelitis). Well-defined abscesses may also occur in the central nervous system. Most infections of the CNS are secondary to infection elsewhere in the body. However, direct introduction may occur with trauma, skull fractures, congenital bone defects or surgery. Also, direct entrance by growth along peripheral or cranial nerves occurs occasionally in certain viral infections (rabies, etc.). Most organisms enter the bloodstream and then localize in the lungs, kidneys, lymph nodes or other tissues. They then enter the CNS secondarily, usually by bloodstream metastasis from these primary foci. The inflammatory reaction of the CNS to injury is modified by the paucity of connective tissue. Encapsulation occurs at a very slow rate and granulation tissue formation is modified by astrocytic and microglial participation. Also, the structure of the nervous tissue and meninges limits the anatomic types of exudates that may occur. Fibrinous exudate or inflammation is confined to the meninges and larger perivascular spaces. Fibrin is usually indicative of a bacterial infection but there are exceptions (malignant catarrhal fever, etc.). Suppurative and granulomatous inflammations are the usual response of the brain parenchyma to bacterial and mycotic infections. Viral infections of the CNS are usually characterized by an inflammatory response designated as nonsuppurative. This response is composed typically of neuronal degeneration, perivascular cuffing by mononuclear cells and foci of glial proliferations. Canine distemper and visna of sheep are 2 viral diseases characterized by demyelination.
2.6.2.1 MENINGITIS:
Meningitis is usually purulent (bacterial in origin), but it may also be lymphocytic (viral) or granulomatous. In any case, meningitis most often conforms to the distribution of cerebrospinal fluid and thus involves the arachnoid and pia mater (leptomeningitis) and the subarachnoid space including the Virchow-Robin spaces and ventricles. Once an infectious agent gains access to the leptomeninges (usually via the bloodstream) there is very little resistance to spread in the meningeal space. Thus, the inflammatory process becomes more or less diffuse in most cases. The cerebrospinal fluid is an excellent culture medium for many bacteria. Most animals with bacterial or purulent meningitis will die within a few days; however, if the animal survives for a prolonged period of time, the infection may spread to the brain parenchyma (meningoencephalitis). A wide variety of infectious agents are capable of invading the CNS. Colibacillosis of a protracted course commonly causes meningitis and polyarthritis in neonatal calves and lambs (this is not a common occurrence in piglets). Streptococcal infection in neonatal calves, lambs and pigs (but not in foals) will frequently produce a combination of purulent leptomeningitis, choroiditis and polyarthritis. Pasteurella hemolytica and P. multocida (organisms commonly responsible for fibrinous pneumonia and septicemia in ruminants) may localize in the meninges resulting in a fibrinopurulent leptomeningitis in calves and lambs. On gross examination of the meninges, purulent exudate may be difficult to detect or it may be overlooked (the color of the exudate is not very different from that of the normal brain). In very acute or early cases, exudation may be detectable only as congestion and cloudiness of the meninges. In severe or more prolonged cases, purulent exudate is best observed in fissures where the arachnoid space is rather wide. Choroiditis commonly complicates leptomeningitis. The ventricular fluid is cloudy and flakes of exudate overlie the plexuses as well as the walls of the ventricles. If the aqueduct becomes obstructed with exudate, ependymitis and internal hydrocephalus may develop.
2.6.2.2 ABSCESSES OF THE CENTRAL NERVOUS SYSTEM:
Brain abscesses may develop as a result of embolism, by direct implantation or by direct invasion of the brain from an adjacent structure. Leptomeningitis rarely leads to abscessation, whereas choroiditis commonly leads to periventricular abscesses. Abscesses in the spinal cord are usually hematogenous in origin. Hematogenous abscesses may actually occur anywhere in the CNS. However the two most common sites are
- (1) the hypothalmus and
- (2) the cerebral cortex at the junction of gray and white matter (Listeria monocytogenes is an exception).
Abscesses arising from direct invasion of the brain may also develop in any location. However, the two most common sites of invasion are
- (1) the cribiform plate and
- (2) the inner ear.
In general, abscesses are more common in white matter than gray matter (although they usually begin in the gray matter). In the early stages, the abscess margins are irregular and poorly defined. The surrounding brain tissue is edematous and infiltrated with neutrophils. In later stages, brain abscesses tend to encapsulate. The capsule seems to be formed more from condensation of vessels than by proliferating fibroblasts, but both contribute.
When abscesses are multiple, death is the outcome after a rather short course. If they are single or isolated, survival may be prolonged. The course is usually shorter with medullary abscesses, even when they are small. Many brain abscesses act as "space occupying" lesions.
2.6.2.3 THROMBOEMBOLIC MENINGOENCEPHALITIS (HEMOPHILUS INFECTION):
Thromboembolic meningoencephalitis is an acute infectious disease, primarily affecting the CNS, that is characterized by fever, depression, weakness, ataxia, blindness, polyarthritis, coma and death. The disease is oftentimes peracute and clinical signs may not be observed. Hemophilus somnis is most often isolated from affected animals. The organism produces a septicemia. Grossly, the most characteristic lesions are single or multiple hemorrhagic foci (infarcts) located in any part of the brain. However, gross lesions may be found in many organs and tissues (heart, kidneys, etc.). Microscopically, the basic and characteristic lesion is vasculitis with thrombosis and septic infarction in the brain as well as in other organs. In less acute cases, the disease is characterized by signs referable to the septicemia and the polyarthritis. Treatment with antibiotics may yield some success. In general, morbidity is low but mortality may reach 100%.
2.6.2.4 LISTERIOSIS
Listeriosis is a sporadic bacterial disease caused by Listeria monocytogenes. It is most commonly manifested by:
- (1) encephalitis or meningoencephalitis in adult ruminants,
- (2) septicemia with focal hepatic necrosis in young ruminants and monogastric animals and
- (3) septicemia and myocardial degeneration or focal hepatic necrosis in fowl.
Abortion and prenatal infection may occur in all susceptible mammals. Listerial encephalitis occurs chiefly in adult ruminants. Gross lesions are usually not observed in the brain; however, occasionally grayish foci of malacia may be found in cross-sections of the medulla. Listeria has an affinity for the brain stem and lesions are most severe in the medulla and pons. There is evidence that infection reaches the brain by passing along cranial nerves (especially the trigeminal). Microscopically, the primary lesion is circumscribed collections of mononuclear cells, with or without neutrophils, in close proximity to blood vessels. Well-defined microabscesses may occur, but they are most common in sheep.
2.6.2.5 ENTEROTOXEMIA DUE TO CLOSTRIDIUM PERFRINGES TYPE D
In sheep (lambs) that survive the acute form of enterotoxemia type D, brain lesions may occur. The lesions are of two morphologic patterns and in each they are bilaterally symmetrical. The more common pattern is hemorrhage and softening of the basal ganglia, internal capsule, dorsal lateral thalmus and substantia nigra. The second patters is characterized by lysis and liquefaction of the white matter of the frontal gyri, which spares only the common "U" fibers. The overlying gray matter is edematous.
It is important to remember that Clostridium perfringes Type D is an economically important disease only in sheep (particularly lambs). However, this disease may occur in calves. In both species, most cases of the disease are peracute in lambs and calves i.e., these animals are found dead without having exhibited any clinical signs. If the affected animals survive for 1 to 2 days they may develop diarrhea. In affected lambs, blood glucose may have reached levels of 400 mg% and spilled over into the urine (glycosuria). The presence of glycosuria may or may not provide good data for establishing the diagnosis of this disease in lambs, because bacterial growth and fermentation of carbohydrates in urine within the first few hours after death may effectively eliminate any glucose which may have been present. Thus, the absence of glucose in the urine of lambs that have been dead for a few hours does not definitively rule out this disease. Glycosuria is not a feature of the disease in calves.
A large number of viruses may cause encephalitis or encephalomyelitis in animals. Characteristically, viral agents produce what is referred to as a "nonsuppurative" inflammation, but this pattern of inflammation is by no means entirely specific for viruses. The natural routes by which viruses infect the CNS are
The blood stream seems to be the route of entry employed by most viral agents.
Acute viral encephalitis is characterized by fairly uniform histologic changes. Gross lesions are minimal, consisting of slight edema and sometimes petechiae. Microscopically, degeneration of neurons, reactivity of glial cells and perivascular changes (cuffing, etc.) are considered to be the hallmarks of viral infections of the CNS. The basic process involves chiefly the gray matter; however, lesions in white matter occur consistently. There is progressive degeneration and destruction of the neurons. Inclusion bodies have been identified in some of the encephalitides (rabies, canine distemper, etc.). They may form in neurons, astrocytes, microglial, and other mesenchymal cells (inclusions are not identified in oligodendrocytes in animals). In nearly all cases of encephalitides, there is proliferation of microglial cells. The gliosis may be diffuse or focal. The blood vessels are surrounded by lymphocytes and plasma cells (perivascular cuffing). Despite the general uniformity of the histologic picture of acute encephalitis, there are variations in this pattern in regards to certain viral diseases.
Slow viral infections of the CNS have received considerable attention in recent years. These viral infections are characterized by long latency and slow attrition. In animals, visna, mink encephalopathy and scrapie are typical examples of slow viral infections. In both scrapie and mink encephalopathy, an agent (most likely a virus) is indicated. They are both characterized by swollen, vacuolated neurons. In man, Creutzfeldt-Jakob disease and kuru are slow viral infections with pathologic alterations similar to scrapie and mink encephalopathy. The following are some important viral diseases of animals.
Dogs that survive the visceral phase of canine distemper may succumb to nervous complications (encephalitic phase). The encephalitis is nonsuppurative and demyelination is a prominent feature. Lesions are diffuse in both the brain and spinal cord. However, they are most prominent and severe in the cerebellum, about the 4th ventricle and in the optic tracts.
There are three arboviruses that cause encephalitides in horses in this country (eastern, western and Venezuelan). These viruses are maintained in nature by an arthropod, bird or rodent reservoir. Mosquitoes act as biological vectors. Reservoir hosts tend to develop viremia with blood titers adequate to infect mosquitoes. However, there is some evidence to suggest that horses with the western virus do not develop a viremia adequate to infect mosquitoes (horse is a dead-end host). Horses with the eastern and Venezuelan viruses may develop viremia adequate for infecting mosquitoes. Clinical signs include fever, depression, impaired vision, irregular gait, wandering circling, yawning, grinding of the teeth, pendulous lower lip, inability to swallow, paralysis and death. Grossly, there are no characteristic lesions. Microscopically, the most severe lesions are found in the gray matter, especially in the cerebral cortex, thalmus and hypothalmus. Neuronal degeneration is a prominent feature. In the early stages (1 to 2 days), neutrophils are most prominent; later, lymphocytes are numerous.
Hog cholera is an acute, highly contagious viral disease affecting swine of all ages. The disease is characterized by sudden onset, high morbidity and high mortality. Death usually occurs within 2 weeks of clinical signs, but some pigs may survive for long periods. The gross lesions most commonly observed are petechial hemorrhages in kidneys and the periphery of lymph nodes (petechial hemorrhages may also be found in the urinary bladder, laryngeal mucosa, stomach, lungs and epicardium). Splenic infarcts are considered to be the single most useful diagnostic lesion. The hog cholera virus combines with bacteria (and possibly other factors) to produce craterous mucosal defects (button ulcers) in the cecum and colon in subacute or chronic stages of the disease. The virus exerts its effects primarily on endothelial cells of small blood vessels and reticuloendothelial cells. Microscopically, the virus causes a diffuse, nonsuppurative encephalitis, but lesions are most prominent in the medulla, pons, midbrain and thalmus. Perivascular cuffing by lymphocytes, mononuclear cells and plasma cells occurs. There are many glial nodules. Prominent hemorrhage may be found around blood vessels (demyelination does not occur).
Scrapie of sheep is a progressive, fatal disease characterized by intense pruritus, altered gait and debility. The etiologic agent has not been completely elucidated. It has been suggested that the transmissible agent is a small specific molecule which combines with an incomplete DNA/polysaccharide subvirus, or an incomplete replicating factor. The disease has a prolonged incubation period. Clinical signs include restlessness, dilated pupils, aimless movement, stiffness, pruritus, incoordination, etc. No significant gross lesions are found. Microscopically, the characteristic lesion is the presence of large vacuoles in the cytoplasm of neurons, associated with gliosis (there are no inflammatory lesions as such). The bilaterally symmetrical lesions are limited primarily to the medulla, pons, midbrain and spinal cord.
Mink encephalopathy is a chronic progressive disease caused by a filterable agent (most likely a virus). Neurons, especially those in the cerebellar peduncles, may contain vacuolated cytoplasm very similar to scrapie. In addition, neuronal degeneration and gliosis are prominent features.
Visna, as a naturally occurring disease, has only been reported in sheep in Iceland. However, the etiologic agent (most likely a virus) is an important animal model for naturally occurring multiple sclerosis in man. Visna is a chronic demyelinating encephalomyelitis with a prolonged latency. Pleocytosis is a prominent feature of the disease (normal sheep are expected to have no more that 50 cells per cubic millimeter of CSF. In visna, the number of cells is elevated to 1000 or more and consists chiefly of lymphocytes). There are no gross lesions and the microscopic change is one of demyelinating encephalitis involving chiefly the white matter. There is an associated gliosis and subependymal and perivascular infiltration of lymphocytes.
(Name two diseases in animals characterized by a demyelinating encephalitis. How would you define the following terms: PLEOCYTOSIS, LATENCY, DEMYELINATION, COMPARATIVE PATHOLOGY, ANIMAL MODELS?)
Avian encephalomyelitis is a picornavirus disease of birds characterized by ataxia and tremors of the head, neck and limbs. The virus is transmitted through the eggs laid by infected hens. Signs usually occur in chicks at 7 to 10 days of age (Signs are occasionally present at hatching or delayed until several weeks of age.). The disease in adult birds is unapparent. In chicks, no gross lesions are observed. Microscopically, lymphocytic perivascular cuffing, neuronal degeneration and endothelial hyperplasia are prominent features. In addition, lymphocytic foci are present in the liver, pancreas, gizzard and proventriculus.
Rabies is an acute diffuse viral encephalitis and all warm-blooded animals are susceptible. The primary reservoir vectors in the U.S. are skunks and foxes. Transmission is usually by bite wounds (nonbite transmission has occurred in man and animals exposed in bat caves when the population of bats is high). Bats are the only vector in which rabies is not self-limiting by virtue of being constantly fatal. asymptomatic bats may have viruses in salivary glands and not in the brain. It should be remembered that the virus may be present in the saliva and be transmitted by an infected animal several days prior to the onset of clinical signs. Infection takes place by the deposition of infected saliva in or near nerves. The virus travels centripetally along peripheral nerves to the CNS and then centrifugally along peripheral nerves from the CNS to salivary glands.
2.7.8.1 STREET VIRUS
Refers to the virus as it occurs in nature. It has a variable incubation period and causes characteristic inclusion bodies (negri bodies).
2.7.8.2 FIXED VIRUS
Refers to the virus in which properties are fixed by repeated intracerebral passage. Inclusions are not produced and there is no affinity for salivary glands (Flurry chicken embryo vaccine).
Grossly, no lesions are observed. Microscopically, rabies is characterized by nonsuppurative encephalomyelitis with ganglioneuritis and parotid adenitis. The most severe lesions are found from the pons to the hypothalmus and in the cervical portion of the spinal cord (there is relative sparing of the medulla). In dogs, brain lesions are usually severe, whereas in other species (ruminants, etc.), lesions are usually rather mild. The reaction is typically one of perivascular cuffing, focal gliosis and neuronal degeneration. Neuronal intracytoplasmic inclusion bodies may be present (inclusions are most prominent in the hippocampus of carnivores and purkinje cells of herbivores). However, inclusion bodies may be found in neurons any place in the CNS. In addition, inclusions may be found in ganglion cells of the adrenal medulla, salivary glands and retina. Inclusion bodies may not be found in animals killed instead of being allowed to die. Nonspecific homogeneous inclusion bodies may be found in neurons of cats and other animals. Large neurons in sheep and cattle may contain nonspecific inclusions in the medulla and spinal cord. If there is no ganglioneuritis in the paravertebral ganglia, the possibility of the animal having rabies is remote (Pigs with Teschen disease may have ganglioneuritis, however.).
The diagnosis of rabies should always be confirmed by laboratory examination. A diagnosis based on the presence (or absence) of inclusion bodies may not be reliable. In many laboratories, mouse inoculation procedures are employed. Mice injected intracerebrally with a 10% suspension of infected brain tissue will die within 6 to 21 days. Identification of infection in affected mice is then made by demonstrating negri bodies or by neutralization tests. The fluorescent antibody staining technique is the test of choice in most laboratories (the F.A. test is oftentimes used in combination with mouse inoculation).
2.7.8.3 PSEUDORABIES (AUJESZKY DISEASE):
Pseudorabies is a viral disease (Herpesvirus) that occurs in a number of animal species. The disease is probably of greatest importance in cattle in which infection is nearly always fatal. Swine are the natural host and principal reservoir. In swine, infections are usually unapparent except in suckling or young piglets (Which usually develop a fatal encephalomyelitis) and in pregnant sows (which may abort or produce still-born or mummified fetuses). Susceptible suckling piglets develop acute pyrexia, paralysis, coma and die within 24 hours. Adult swine may excrete the virus in the absence of clinical signs. Also, infected swine may transmit the disease to cattle and sheep (via nuzzling cattle and sheep with their snout). In cattle, intense pruritus develop in the skin at the site of contact with infected swine. Paralysis develops and death may occur rather suddenly.
The virus reaches the CNS by traveling along nerve fibers. Lesions occur in nerve fibers, ganglia and CNS of all species. In general, lesions are most severe in the spinal ganglia, temporal cerebral cortex and basal ganglia of the brain. In swine, lesions may be very mild or unrecognizable. When they are present, lesions consist of perivascular changes and slight neuronal degeneration. A few intranuclear inclusions may be observed. In addition, foci of necrosis may be found in the liver, lungs, adrenal medulla, tonsils, lymph nodes and pharyngeal mucosa. In cattle, there is moderate lymphocytic perivascular cuffing and foci of microglial proliferation in the brain. Most neurons are normal or exhibit very mild chromatolysis.
The degenerative diseases of the central nervous system are characterized by progressive loss of neurons (with or without a known cause). To some extent this is a wastebasket of diseases and conditions that do not fit well under sections that have been or will be discussed in this handout.
Malacia refers to softening and the term is used to indicate necrosis of tissue in the CNS. When myelin sheath is primarily or selectively injured to leave the axon naked by intact, the term demyelination should be used. Actually, malacia, to some degree, is associated with most injuries to the CNS (encephalitis, trauma, anoxia, etc.). Malacia or softening of the gray matter is known as poliomalacia and softening of the white matter is known as leukomalacia.
2.8.2.1 POLIOENCEPHALOMALACIA OF SHEEP AND CATTLE:
Polioencephalomalacia is a noninfectious disease of cattle, sheep, goats and deer characterized by multifocal or diffuse yellow areas of malacia (necrosis) in the brain. Clinical signs include anorexia, incoordination, depression, blindness, convulsions and death (there is no fever). Evidence indicates that animals with polioencephalomalacia are in a state of thiamine depletion. Thiamine functions as a coenzyme in carbohydrate metabolism and its lack can be expected to cause increases in blood concentrations of pyruvic, lactic and alpha-ketoglutaric acids and a decrease in activity of the enzyme transketolase. The dependency of neurons and glial cells of the brain on CHO catabolism accounts for the prominent neurologic signs. Gross lesions are confined to the CNS and changes in the cerebral cortex are most striking. There is focal or diffuse necrosis (soft & yellow) of the gray matter. In advance cases, the gray matter is completely destroyed. The adjacent white matter is spared. (Cerebral cortical necrosis similar to that of polioencephalomalacia is observed in lead poisoning (subacute or chronic cases), salt poisoning and cases of anoxia). Certain clinical cases respond dramatically to the administration of thiamine within a matter of hours (however, the established role of thiamine in the disease has not been completely established). Microscopically, neurons in affected areas are shrunken, acidophilic and surrounded by clear spaces. The necrosis and edema are usually most severe in the deeper laminae of the cerebral cortex (cerebral cortical necrosis). In chronic cases, healing with intense gliosis is observed.
2.8.2. 2 MYELOMALACIA OF AFGHAN HOUNDS:
Malacia of the spinal cord has been reported in afghan hound. The etiologic mechanism has not been elucidated but the condition is apparently congenital (probably hereditary). Massive necrosis of the spinal cord is the prominent alteration.
2.8.2.3 AVIAN ENCEPHALOMALACIA:
Chicks fed a diet deficient in vitamin E may exhibit one or more of three classical deficiency disorders:
- (1) encephalomalacia,
- (2) exudative diathesis,
- (3) nutritional muscular dystrophy.
Various dietary supplements, unrelated to the vitamin E content of the diet, can prevent any one of the diseases without affecting the course of the other two (synthetic antioxidants can prevent encephalomalacia; inorganic selenium can prevent exudative diathesis; cystine can prevent nutritional muscular dystrophy). Encephalomalacia occurs with diets borderline in vitamin E that also contain polyunsaturated fats (cod-liver oil, soybean oil, etc.) in the process of undergoing oxidative rancidity. The disease is characterized by sudden prostration with the legs outstretched, toes flexed, and the head retracted. In early stages, the gait is uncoordinated. Lesions are found in the cerebellum and sometimes in the cerebrum. Softening is prominent and necrotic reddish or brownish areas may be observed with the naked eyes. Microscopically, the lesions are consistent with those of malacia. Exudative diathesis is a frequent occurrence on corn or soybean meal diets when these are grown on selenium deficient soil. Nutritional muscular dystrophy is found when the diet is deficient in both vitamin E and sulfur-containing amino acids.
2.8.2.4 LEUKOENCEPHALOMALACIA IN HORSES ASSOCIATED WITH MOLDY CORN:
Moldy corn toxicosis in the horse occurs when horses are forced to subsist on moldy corn for one month or more. Clinically, the condition is characterized by drowsiness, impaired vision, partial or complete pharyngeal paralysis, weakness, staggering and a tendency to circle. Chronic cases with static signs are dummies. There is necrosis of the white matter of the cerebral hemispheres (the surface of the brain is normal on gross inspection but palpable softness may be detected in the cortex overlying large areas of malacia). The malacic foci are soft, pulpy, grayish depressions with small hemorrhages. Microscopically, the white matter is spread apart by fluid (edema) and the myelin sheath, axons and glia degenerate to form structureless, acidophilic semifluid masses to which the microglial cells react. Perivascular cuffing is not a prominent feature. Foci of malacia also occur in the spinal cord (but in contrast to the brain, the necrosis chiefly affects the gray matter).
2.8.3.1 THIAMINE DEFICIENCY:
Thiamine deficiency is an important natural disease only in the cat, fox and mink. The deficiency is induced by the presence of thiamine splitting enzymes (thiaminase) naturally present in many species of fish and via the destruction of thiamine by cooking foods at 212o F or above. Thiamine deficiency does not occur in ruminants since they are able to fulfill their requirement via ruminal synthesis. Thiamine deficiency may occur in horses poisoned by bracken fern (Pteridium aquilinum) and by horsetail (Equisetum arvense). In horses, the condition is characterized by incoordination, recumbency and bradycardia. CNS lesions have not been fully elucidated. Clinical signs in cats usually occur within 2-4 weeks of being fed the deficient diet. Initially, there is anorexia, salivation, incoordination and convulsions (at this stage, the cat will respond fully to thiamine treatment; however, after 2-3 days of neurologic signs, the animal passes into a irreversible phase of semi-coma and, ultimately, death occurs). Lesions consist of edema, perivascular dilation, hemorrhage and necrosis of brain tissue. The periventricular gray matter is most severely involved and the lesions are bilaterally symmetrical.
2.8.4.1 STAR THISTLE POISON (NIGRO PALLADIAL MALACIA)
Star thistle poisoning has been observed in horses in California. Malacic lesions are present and the pallidus and substantia are specifically affected.
2.8.5.1 LEAD POISONING:
Lead is considered to be the most consistently important poison in farm animals (the main sources of lead are outlined in your textbook). In general, lead poisoning is rather common in man and animals. the element is usually obtained via ingestion (only a small amount of the ingested dose is absorbed). In acute cases, absorbed lead is stored in the liver and kidneys, whereas in chronic cases, bones are the sites of deposit. Lead is slowly excreted in the milk, urine and bile.
In cattle, acute lead poisoning usually leads to death in 12-24 hours. Calves tend to stagger, develop muscular tremors and rapidly become recumbent. Convulsions are intermittent until death. Adult cows who less tendency to early recumbency. There is head pressing, apparent blindness with death in convulsions. Central nervous system lesions are minimal or absent in acute cases (there may be mild to moderate edema). In subacute or chronic cases, laminar cerebral cortical necrosis may be observed (necrosis of the cerebral cortex gray matter). This necrosis is believed to be associated with ischemia and/or anoxia.
In dogs, acute lead poisoning is characterized by edema of the white matter of the brain and spinal cord with degenerative changes in the myelin sheaths (especially prominent in the deeper white matter of the cerebrum and cerebellum). There is also degeneration and necrosis of neurons in the subthalmus and head of the caudate nucleus. In horses, lead poisoning is usually chronic. The diagnosis of lead poisoning should be based on chemical analysis.
2.8.5.2 MERCURY POISONING:
The syndromes produced by the organic and inorganic salts of mercury are different. Inorganic salts tend to exert principal effects on the kidneys, whereas organic salts tend to involve the central nervous system. Mercury binds to cell membrane protein sulfhydryl groups, causing rapid increased cell permeability with subsequent ion shifts and inactivation of membrane transport systems (mitochondria are not primarily affected). Grossly, lesions are minimal or absent. Occasionally, the cerebral cortices are pale and soft and on cut surfaces there may be no sharp line of demarcation between gray and white matter. Microscopically, there is diffuse neuronal degeneration and gliosis. Peripheral nerves may show pronounced demyelination. Occasionally, malacia of the brain and spinal cord occurs. In general, organic mercury tends to affect the granular cells of the cerebellum most severely in all species.
2.8.5.3 SALT POISONING (NaCl):
Salt may be toxic when excessive amounts are consumed. In the U.S., swine and sheep are most frequently affected. However, death has been attributed to salt poisoning in cattle, horses, dogs and poultry. Toxicosis will not occur if animals are always provided with free access to water of low saline content. In swine, clinical signs consist of blindness, deafness, head pressing and convulsions. The convulsions are characteristic in their pattern and in the regularity of the time intervals in which they occur. Convulsions begin as tremors of the snout and rapidly extend as clonic spasms of the neck muscles with jerky opisthotonus which causes the pig to walk backward and sit down. Microscopically, eosinophilic meningoencephalitis and encephalomalacia characterize the disease in swine. Necrosis of the gray matter of the cerebral cortex (similar to that described for polioencephalomalacia of sheep and cattle) may also occur. There is an abundance of eosinophils in the meninges and around blood vessels. The relative pure population of eosinophils in combination with laminar necrosis of the cerebral cortex is considered to be "pathognomonic" for salt poisoning in swine.
- What lesions would you expect to find in a horse poisoned by star thistle? Give the location of such lesions within the brain. In what organs would you expect to find large amounts of "stored" lead in acute toxicosis? Describe the clinical signs and lesions associated with lead poisoning in cattle. Upon what organs or tissues would you expect organic and inorganic mercury to exert major effects? What characteristic clinical signs would you expect pigs poisoned with salt to exhibit? What characteristic microscopic lesions would you expect to observe in cases of salt poisoning? Define the following: OPISTHOTONUS, CLONIC SPASMS, TONIC SPASMS, PATHOGNOMONIC, GRANULAR CELLS.
The neurons of the brain are highly susceptible to anoxic or hypoxic changes (complete ischemia produces irreversible damage in a neuron in 3 to 4 minutes). The oligodendrocytes are nearly as susceptible or sensitive to a lack of oxygen as neurons, followed by astrocytes, microglia and blood vessels. The neurons are not a uniform population and there are regional differences in their susceptibility to anoxia (neurons of the cerebral cortex and purkinge cells are most sensitive. Within the cerebral cortex, neurons of the deeper laminae are more sensitive than those of the superficial laminae, etc.). Pathologically, anoxia produces neuronal necrosis and softening of the gray matter (the malacic changes are very similar to those described for polioencephalomalacia in sheep/cattle).
The brain and spinal cord are well protected from external injurious forces by their bony encasements. Thus, the nature of traumatic injuries is determined by a number of factors including vulnerability of the CNS parenchyma, physical rigidity of the bones, ability of the part to move in response to the applied force, the mass and velocity of the force, etc. The injurious force may cause concussion, contusion or laceration of soft tissue; bony structures may be dislocated, fractured, etc.
Is a loss of consciousness and reflex activity following a sudden, non-fatal blow to the head. The loss of consciousness is sudden but transient. There is a sudden violent movement of cerebrospinal fluid and blood; unconsciousness is believed to be due to a transient anemia caused by a certain amount of blood being prematurely jarred from capillaries into larger vessels (if the head is firmly immobilized, a considerable blow can be applied with relatively minor effect, the force being absorbed by the skull. On the other hand, a blow of much less magnitude will cause concussion if the head is capable of moving in response to the blow.
Is an injury in which there is disruption of the architecture of nervous tissue. In general, the causes of lacerations are the same as those of contusions.
The architecture of the nervous tissue is retained but there is hemorrhage in the meninges and around parenchymatous vessels. The applied force (blow) and brain displacement are more severe than that causing concussion. Contusions may be focal or diffuse injuries. Typically, in diffuse injuries, some of the most severe hemorrhages occur on the surface of the brain opposite to the point of impact (contrecoup). Focal injuries usually result in hemorrhages at the point of impact.
are important because of concurrent injuries to the underlying meninges and brain parenchyma (contusions/lacerations). In addition, fractures provide pathways of infection into the cranial vault. Fractures are injuries produced by considerable force.
Traumatic injuries may result in vertebral subluxation or fractures. Such injuries may cause considerable damage to the spinal cord. SUBLUXATIONS are largely restricted to the cervical portion of the vertebral column where there is relative mobility of the ligaments. Comparable forces are more likely to cause fractures in the thoracic and lumbar spin because of the lack of mobility. Fracture dislocations of the vertebral column occur chiefly in the caudal cervical region and near the thoraco-lumbar junction. Slight injuries to the spinal cord may allow for recovery, whereas more severe injuries may result in severe necrosis, etc.
The intervertebral disc consists of
Spinal cord injury may occur when there is partial or complete rupture of the annulus fibrosus or when there is bulging (without rupture) of the annulus fibrosus and nucleus pulposus into the vertebral canal. Intervertebral disc abnormalities are preceded by degenerative changes in the annulus fibrosus and nucleus pulposus. They usually occur in the terminal thoracic and lumbar segments, but occasionally affect the cervical spine. Disc abnormalities occur with frequency only in dogs. Chondroystrophoid breeds (Dachshunds, Pekinese, Beagles, etc.) develop disc abnormalities at an early age. The condition occurs in aged dogs of all breeds. Clinical signs tend to vary with the nature, extent and position of the injury to nervous elements. In some cases, no symptoms are produced, but in other instances, severe and rather sudden pain and reflex immobility results. Thoracolumbar disc protrusion is characterized by an arched back, abdominal tenseness and reluctance to move and down stairs. Also, there may be flaccid paraplegia with urinary or fecal retention or incontinence. Protrusion of disc in the cervical region is characterized by extreme pain on moving the head or neck. Weakness of the front legs may be noted. The protruded discs may result in hemorrhage, malacia or inflammation. The intervertebral disc material may enter vessels (embolus) with lodgement and infarction of the spinal cord parenchyma.
Equine wobbles is a locomotor disturbance that occurs primarily in young horses, being attributable to slight nonprogressive injury to the spinal cord. The causes and pathogenesis may vary. In the majority of cases, the condition is associated with malalignment and hypermobility of the cervical vertebrae and degeneration of the cervical articular processes. There is apparent relaxation of the intervertebral ligaments resulting in increased mobility of the articulations. This causes unnatural stretching and compression of the spinal cord as it passes over the articulations (in some cases, the vertebrae may be deformed which increases the liability of the spinal cord to injury). The articular changes usually occur between the 3rd and 4th cervical vertebrae, but may extend from C2-C3 to the anterior thoracic vertebrae. Gross lesions in the involved spinal cord may or may not be visible to the naked eye. when lesions are present, they appear as brownish-yellow foci of malacia (softening). Remember, the spinal cord should be fixed in formalin for 24-48 hours before slicing. Also, it may be necessary to slice the cord at intervals of not more than 2-3 mm in order to detect small malacic foci. Microscopically, there is demyelination to the white matter (a moth-eaten appearance) characterized by microcavitations which represent areas of liquefactive necrosis. In the region of the primary focus (lesion), demyelination may be present in all fiber tracts. Anterior to the primary focus, demyelination is present in ascending fibers which are found mostly in the dorsal funiculi. Caudal to the primary focus, the degenerating fibers are concentrated in the ventral and ventrolateral funiculi. Clinical signs are characteristically first observed in the hind limbs. In some cases, however, the forelegs are also involved. The onset is insidious and a drunken, weaving gait may be the only signs. The signs may be accentuated by walking the animal in a tight circle, turning abruptly on a lead or by forcing the head and neck into flexwhile backing.
Osseous metaplasia of the dura (formation of bony plaques) may occur in the cranial or spinal dura. These plaques oftentimes contain bone marrow. The condition occurs most frequently in larger breeds of dogs after maturity. These bony plaques may cause pressure on the spinal cord as well as spinal root nerves. Pain and gradual paresis may develop. Many dogs with bony plaques do not exhibit symptoms.
Neuritis of the cauda equina is characterized clinically by tail paralysis and loss of sphincter tone (urinary bladder and rectum). Lesions are confined primarily to the cauda equina, but peripheral and spinal nerves may be involved (polyneuritis). The inflammation begins as a serous neuritis followed by hyperemia, hemorrhage and fibrinous exudation. In the chronic stage, fibrosis and adhesions are prominent.
Cholesteatosis is considered to be a degenerative lesion of the choroid plexus (it is not a true neoplasm). The development of cholesteatosis appears to be related to inflammatory changes. Cholesterol crystals are characteristically found in these lesions, but it is not known whether the cholesterol is primary or secondary. The lesions occur almost exclusively in old horses and are found most often in the lateral ventricles. Microscopically, cholesterol clefts along with fibrosis are observed in advanced lesions.
Granulomas of the spinal cord can be caused by a variety of agents. However, the comments that follow will deal only with oil granulomas associated with contrast media. Many contrast media used in myelography are known to cause tissue reactions and other complications when injected into the subarachnoid space. Those media prepared in an oil base may cause a chronic leptomeningitis with the formation of granulomas.
Due to the wandering pattern of nematode larvae, they sometimes migrate into the brain and spinal cord. Several nematode species appear to have an affinity for nervous tissue. However, identification of individual worms in tissue sections is often difficult. Nematode larvae which migrate somatically are the ones most likely to go astray. This is especially true when they wander in alien or aberrant hosts. The subject of cerebral nematodiasis will be discussed in your parasitology course. The comments that follow will be confined to Baylisascaris procyonis (formally referred to as Ascaris columnaris).
2.11.1.1 Baylisascaris procyonis
Parasitizes the skunk and raccoon as definitive hosts. However, introduction of the larvae into aberrant hosts (rabbits, nutria, squirrels, etc.) may result in severe neurologic disturbances (the larvae apparently have an affinity for nervous tissue). The larvae reaches the brain via the bloodstream and grow very rapidly during the first 3 weeks while migrating actively throughout the nervous tissue. This active migration is extremely destructive (5 to 6 larvae in the brain of mice is usually fatal, whereas, over 100 Toxocara canis larvae are usually innocuous). However, T. canis larvae do not grow once they reach the brain. It is apparent from this discussion that man should use extreme caution when handling contaminated materials, etc.
A tentative diagnosis of B. procyonis can be made on the basis of the size of larvae found in nervous tissue. This species measures from 60 to 70 microns at the greatest diameter, whereas, migrating larvae of other ascarids (T. canis, T. cati, A. suum, etc.) are much smaller (less than 30 microns in diameter). Gross lesions are usually not observed. Microscopically, larvae (with bilateral cuticular alae) may or may not be associated with foci of malacia and inflammatory cell infiltration. The inflammatory cells consist primarily of heterophils, lymphocytes and glial cells.
Nosematosis (encephalitozoonosis) is a widespread protozoan infection of rabbits (and occasionally rats, mice, guinea pigs and dogs) caused by Nosema cuniculi. However, under certain conditions, a paralytic and systemic disease is produced which is mildly contagious in a rabbitry. The brain and kidneys are primarily involved and infection is believed to be spread via the urine and transplacentally. Microscopically, granulomas made up of epithelial cells surrounding a necrotic center are found. Typical organisms are demonstrable in the center of the granulomas with special stains (Giemsa, silver impregnation methods, etc.). Individual organisms appear as short, plump, rod-shaped bodies with rounded ends measuring about 1 to 2 microns.
Toxoplasma gondi is a small crescent shaped parasite (protozoan) which appears to have the characteristics of coccidia. There is an intestinal epithelial cell cycle for the production of oocysts only in the cat and other felidae. The organism undergoes schizogony and microgametogomy in the feline ileum. Oocysts are shed in the feces and are infectious after sporulation occurs. The asexual forms can propagate in macrophages and myocytes of different mammalian species. Upon entering a secondary host, the endozoites are spread to various tissues after infecting circulating monocytes. In natural occurring cases, only the encysted parasites are likely to be seen. The thick wall is composed of a dense outer layer of host cell origin and an inner thin membrane of parasitic origin. The host reaction consists of necrosis of infected cells along with an accumulation of macrophages and neutrophils. (In dogs, active infection in the brain is often associated with cases of canine distemper.)
Blastomycosis is a chronic disease caused by Blastomyces dermatitidis and characterized by granulomatous lesions in the lungs, brain and other organs. Lesions contain yeast-like organisms with double contoured walls. Reproduction is by budding.
Cryptococcosis is a subacute or chronic disease of many animal species as well as man. The causative organism, Cryptococcus neoformans, is a yeast-like fungus which may live in a nonparasitic state in nature. In dogs, the condition usually involves the meninges and paranasal sinuses. In cats, lesions are common in the nasal cavity and pharynx. However, generalized infection (systemic) may occur in all species. The cut surface of affected tissues has a mucinous quality. The organisms occur in tissue as oval or spherical, thick-walled, yeast-like bodies surrounded by a wide gelatinous capsule. The cell inside the capsule is usually from 5 to 20 microns in diameter and the capsule increases the overall size to a maximum of 30 microns.
Meningiomas are tumors that originate within the meninges, usually in close association with the dura. They grow by expansion, compressing but seldom invading the brain parenchyma. Grossly, meningiomas are well-circumscribed and encapsulated (a few may infiltrate). They are usually characterized by whorls and solid cords of spindle-shaped cells of uniform size and shape.
Primary neoplasms of the brain and spinal cord are gliomas (astrocytomas, oligodendrogliomas, ependymal cell tumors, medulloblastomas). The neoplasms act as space-occupying lesions and may cause displacement of intracranial structures. Glial tumors have been reported most frequently in the dog. It appears that brachycephalic breeds are most frequently affected.
Is the most common of the glial neoplasms. This type may be found in the brain or spinal column and it has been reported in cats, dogs and cattle. Grossly, astrocytomas may vary in appearance depending on the degree of malignancy. They are oftentimes difficult to detect grossly (being similar in color to normal brain tissue). Microscopically, the patterns are diverse. They may consist of protoplasmic or fibrillar astrocytes or they may show a transition between these two cell types. All degrees of cell differentiation may be noted.
Have been reported only rarely in domestic animals. Grossly, the mass is usually well-demarcated, being grayish and soft. Microscopically, the tumor is densely cellular with almost no stroma. The cells resemble normal oligodendrocytes in size and shape.
Are derived from ependymal cells that normally line the ventricles and spinal canal. They are gray and fleshy. Hemorrhage may be present. Microscopically, there is a great variation in patterns. Some may exhibit a well-differentiated papillary structure and others may consist of solid sheets of poorly differentiated ependymal cells.
Are rare in animals, but well known in children. The tumor is composed of cells of unknown parentage (there is no such cell as a medulloblast). There is evidence to suggest that the tumors arise from the undifferentiated cells found in neonatal life beneath the cerebellar pia matter which are thought to be precursors of the cerebellar cortex. These tumors consist of masses of small dark staining cells that are round, elongated or pyriform with oval or elongated nuclei. The cells are arranged radially around blood vessels or in true rosettes. Mitotic figures are common. In animals, these tumors have been reported in the cerebellum, cerebrum and pons.
Neoplasms from other sites in the body may reach the CNS by hematogenous metastasis or by direct invasion. Local invasion occurs from neoplasms of the sinuses and nasal mucosa most commonly. Hematogenous metatasis is likely in any neoplasm that disseminates widely. Metastasis may occur in any location but there is a predilection for the junction of gray and white matter.
SLIDE 1:
OVINE HEAD: CYCLOPIA (MULTIPLE CONGENITAL DEFECTS) - Observe the single eye, absence of nostrils, absence of nasal bones, hyperplasia of gums and dome-shaped head. (Discuss the development of prosencephaly in animals. What plant is capable of producing this defect in lamb feti?).
SLIDE 2: BOVINE BRAIN: CEREBELLAR HYPOPLASIA - Observe the remnant of the cerebellum and the collapsed posterior portion of the cerebrum. This condition was caused by bovine virus diarrhea virus. The collapsed cerebrum represents hydranencephaly.
SLIDE 3: BOVINE BRAIN - CEREBELLAR HYPOPLASIA - Observe the remnant of cerebellum and the collapsed posterior portion of the cerebrum. Compare abnormal and normal brains.
SLIDE 4: CANINE BRAIN: CEREBELLAR HYPOPLASIA - Observe the small cerebellum with unilateral surface defect. (Should this lesion be classified as cerebellar atrophy? How would you differentiate between cerebellar atrophy and cerebellar hypoplasia?).
SLIDE 5: EQUINE BRAIN - CEREBELLAR HYPOPLASIA - Note the cerebellum which is only slightly smaller than normal. (How would you confirm the diagnosis of cerebellar hypoplasia? What characteristic features would you expect on microscopic examination?).
SLIDE 6: FELINE BRAIN (MICRO): CEREBELLAR HYPOPLASIA - This microscopic section demonstrates the paucity of cells in the granular layer. (What microscopic changes would you expect to see in the molecular and purkinje cell layers? What viral agent is capable of producing this defect in kittens? On what portion of the brain would you expect the viral agent to exert its effect? Name one other viral agent that's capable of producing this defect in kittens.).
SLIDE 7: BOVINE BODY: CEREBELLAR HYPOPLASIA - This calf is exhibiting some of the clinical manifestations associated with cerebellar hypoplasia. Note the extended neck, abnormal posture, etc. (What viral agent is capable of producing this condition in calves? What lesions and clinical signs would you expect to observe in an adult cow infected with the viral agent you named above?).
SLIDE 8: BOVINE HEAD: ENCEPHALOCELE - Observe the sac-like structure protruding from the frontal portion of the skull. This structure contains remnants of the cerebrum and fluid. (How would you differentiate between an encephalocele and a hernia? How would you define the following terms: ENCEPHALOCELE, MENINGOCELE, CEPHALOCELE, SPINAL BIFIDA?)
SLIDE 9: CANINE HEAD - ENCEPHALOCELE - Observe the protruded portion of the brain in this newborn pup.
SLIDE 10: CANINE HEAD - ENCEPHALOCELE - Observe the protruded brain along the midline.
SLIDE 11: FELINE (MANX) VERTEBRAL COLUMN: SPINAL BIFIDA & MENINGOCELE - Observe the well-defined opening in the vertebral column (spinal bifida). The meninges protruded through this opening (meningocele). (How would you define spinal bifida occulta? Would you expect to observe more congenital defects in the Manx than in other breeds of cats? Why?).
SLIDE 12: FELINE (MANX) SPINAL CORD: DYSPLASIA OF SPINAL CORD ASSOCIATED WITH SPINAL BIFIDA & MENINGOCELE - This dysplastic spinal cord is from the kitten demonstrated in slide #11. Note the distortion of the surface.
SLIDE 13: CANINE SPINAL CORD: SYRINGOMYELIA - Observe the abnormal cavitation in the spinal cord. (In what breed does this condition commonly occur? What clinical signs would you expect to see in an affected animal? What portion of the spinal cord is most commonly affected? How would you differentiate between syringomyelia and hydromyelia?).
SLIDE 14: CAPRINE BRAIN: LISSENCEPHALY/MACROGYRI/AGYRI - Observe the relative smooth surface of this brain. There was a failure of complete development of the gyri. (How would you differentiate between lissencephaly, macrogyri and agyri?).
SLIDE 15: CANINE BRAIN - HYPOPLASIA OF THE OPTIC NERVES & CHIASM - Observe the very small underdeveloped optic nerves and chiasm. Compare normal with abnormal.
SLIDE 16: EQUINE HEAD - HYDROCEPHALUS - Observe the well-defined dome-shaped head. (Would you expect the condition in this animal to be congenital or acquired? What changes would you expect to see in the cerebrum and cerebellum?).
SLIDE 17: CANINE HEAD: HYDROCEPHALUS - Observe the dome-shaped head.
SLIDE 18: CANINE HEAD/BRAIN: HYDROCEPHALUS - Observe the collapsed cerebrum. The lateral ventricles were filled with fluid. (How would you differentiate between internal, external and communicating hydrocephalus? Trace a drop of cerebrospinal fluid from the lateral ventricles to the arachnoid space. Discuss the possible causes of internal hydrocephalus. Why is it difficult to diagnose hydrocephalus in newborn animals?).
SLIDE 19: CANINE BRAIN: HYDROCEPHALUS - Observe the thin-walled, dilated ventricle with only a small portion of the cerebral cortex remaining. (How would you differentiate this condition from hydranencephaly? What brain structure is most sensitive to the effects of fluid accumulation?).
SLIDE 20: EQUINE SPINAL CORD: HYDROMYELIA - This dilated portion of the lumbar spinal cord was filled with fluid. (Define hydromyelia. How would you differentiate hydromyelia from syringomyelia?).
SLIDE 21: CANINE BRAIN (MICRO): GLOBOID CELL LEUKODYSTROPHY - Observe the large foamy macrophages in this microscopic section. (Give the causative mechanism for this condition. What material would you expect to accumulate in affected macrophages? What cell in the brain is considered to be phagocytic? What is a "gitter cell?" What specific enzyme is considered to be deficient in globoid cell leukodystrophy? At what age would you expect clinical signs to develop in affected dogs? Describe the gross and microscopic changes that you would expect to see in affected dogs.).
SLIDE 22: BOVINE BRAIN: SUPPURATIVE MENINGITIS - Observe the cloudy meninges and pale exudate. The condition in this 2-week-old calf was caused by E. coli. (Would you classify this condition as leptomeningitis or as pachymeningitis? Define the following terms: LEPTOMENINGITIS, PACHYMENINGITIS, MYELITIS, CHOROIDITIS, EPENDYMITIS, ENCEPHALOMYELITIS, MENINGOENCEPHALOMYELITIS. Give a likely pathogenesis for the meningitis observed. What specific lesions would you expect to observe in the intestinal tract of this calf?).
SLIDE 23: BOVINE BRAIN: SUPPURATIVE MENINGITIS - Observe the cloudy and discolored meninges. This condition was associated with septicemic colibacillosis.
SLIDE 24: EQUINE BRAIN: SUPPURATIVE MENINGOENCEPHALITIS - The lesions were caused by E. coli. Observe the severely congested brain parenchyma and the small foci of exudate beneath the meninges.
SLIDE 25: EQUINE BRAIN: CHOROIDITIS AND EPENDYMITIS - Observe the purulent exudate in the lateral ventricle. (Is it possible for this condition to develop subsequent to a suppurative leptomeningitis? How? Explain how it is possible for hydrocephalus to develop subsequent to this condition. The choroiditis and ependymitis observed in this foal was caused by Actinobacillus equuli. What lesion would you expect to see in the kidneys?).
SLIDE 26: EQUINE BRAIN (MICRO): SUPPURATIVE MENINGITIS - Observe the inflammatory cells associated with the meninges. (What cell type would you expect to be most prominent in this process?).
SLIDE 27: BOVINE BRAIN: ABSCESSATION OF THE CEREBRUM - This large cerebral abscess was caused by Corynebacterium pyogenes. (Name other bacteria capable of causing brain abscesses. Name the 2 most common sites in the brain for abscesses of hematogenous origin to develop. Why would death occur rather acutely subsequent to abscesses in the medulla oblongata? Would you consider Listeria monocytogenes to be a likely cause for the abscess observed in this animal? Why?).
SLIDE 28: PORCINE SPINAL CORD: ABSCESSATION OF THE SPINAL CORD - Observe the well-defined abscess and distorted spinal cord. (What clinical signs would you expect in this pig? Give a likely pathogenesis for this abscess.).
SLIDE 29: PORCINE SPINAL CORD: ABSCESSATION OF THE SPINAL CORD - Observe the purulent exudate and swollen segment. (Give a likely etiologic agent. What type of necrosis is manifested in this slide?).
SLIDE 30: PORCINE SPINAL CORD: ABSCESSATION OF THE SPINAL CORD - Observe the well-defined and thickened wall of the abscess. (Describe how a capsule is formed around a CNS abscess.).
SLIDE 31: BOVINE BRAIN: THROMBOEMBOLIC MENINGOENCEPHALITIS - Locate the well-defined foci of hemorrhage (infarcts). The meninges are congested. (Name the likely etiologic agent for this disease. In what organs and tissues besides the brain would you expect to find lesions? How would you treat this condition?).
SLIDE 32: BOVINE BRAIN: THROMBOEMBOLIC MENINGOENCEPHALITIS - Observe hemorrhagic infarcts along the ventral aspect of the brain. (Is there a tendency for lesions to localize in certain portions of the brain in this disease? Explain. Would you expect an increased body temperature in this animal? Why?).
SLIDE 33: BOVINE BRAIN: THROMBOEMBOLIC MENINGOENCEPHALITIS - Observe the well-defined hemorrhagic infarcts in incised portions of the cerebrum. (Give a likely pathogenesis for this disease. How would you differentiate this disease from listeriosis on the basis of distribution of lesions within the brain?).
SLIDE 34: BOVINE BRAIN: THROMBOEMBOLIC MENINGOENCEPHALITIS - This brain is from a steer that survived for several days after the onset of clinical signs. Observe the exudate. (Give the exact location of the exudate. What complication would you expect to occur subsequent to exudation in this location? Can you locate foci of hemorrhage in the brain parenchyma?).
SLIDE 35: BOVINE BRAIN (MICRO): THROMBOEMBOLIC MENINGO-ENCEPHALITIS - Observe the affected blood vessel as well as the infiltration of inflammatory cells. (How would you describe the blood vessel observed in this slide? What cell type would you expect to be most numerous in this disease? Define the following terms: CHEMOTAXIS, VASCULITIS, THROMBOSIS, INFARCTION, EMBOLISM.).
SLIDE 36: BOVINE BRAIN: THROMBOEMBOLIC MENINGOENCEPHALITIS - This is a close-up view of the blood vessel observed in slide #35. Observe the more or less homogeneous and thickened wall of this vessel. Also observe partial closure of the vessel lumen as well as inflammatory cells within and around the vessel wall. (What "characteristic" lesion would you expect to observe in this disease?).
SLIDE 37: BOVINE BRAIN (MICRO): THROMBOEMBOLIC MENINGO-ENCEPHALITIS - Observe the heavy infiltration of inflammatory cells. (Can you identify the most prominent cell type?).
SLIDE 38: BOVINE JOINT: THROMBOEMBOLIC MENINGOENCEPHALITIS - Observe the exudate in the joint of this steer (What other joints would you expect to be involved in this animal? What treatment would you recommend to the owner? Define the following terms: MORTALITY, MORBIDITY, PREVALENCE.).
SLIDE 39: BOVINE BRAIN: LISTERIOSIS - This illustration denotes the distribution of lesions within the brain. (What portions of the brain would you expect to find lesions? Give the etiologic agent for listeriosis.).
SLIDE 40: BOVINE BRAIN: LISTERIOSIS - Observe the rather well-defined area of malacia in this brain stem (grayish discoloration). (Are gross lesions a common finding in this disease? Discuss the problems encountered in an attempt to culture the listeria organism.).
SLIDE 41: BOVINE BRAIN STEM: LISTERIOSIS - Observe the hemorrhagic foci of malacia. This cow survived for several days after the onset of clinical signs. (What lesions would you expect to find in baby calves with listeriosis? Give a likely route by which the listeria organisms reach the brain.).
SLIDE 42: BOVINE BRAIN (MICRO): LISTERIOSIS - This microscopic section is characterized by a heavy infiltration of inflammatory cells. (What cell types would you expect to observe in cases of listeriosis?).
SLIDE 43: BOVINE BRAIN (MICRO): LISTERIOSIS - Observe the areas of malacia and perivascular cuffing in this microscopic section.
SLIDE 44: BOVINE BRAIN (MICRO): LISTERIOSIS - This is a close-up view of the inflammatory cells observed in slide 43.
SLIDE 45: OVINE BRAIN: ENTEROTOXEMIA - Observe the well-defined bilateral foci of malacia in the brain of this lamb. What clinical signs and lesions would you expect to see in this animal? Discuss the clinical significance of glycosuria in lambs and calves with this condition. Outline the different morphologic patterns that may occur in the brain of lambs with this disease.
SLIDE 46: OVINE BRAIN: ENTEROTOXEMIA - Observe the bilateral and symmetrical foci of malacia associated with C.prefringes Type D.
SLIDE 47: CANINE BODY: CANINE DISTEMPER - This dog is exhibiting some of the clinical signs associated with canine distemper. Observe the nose and eye exudate. (Name two infectious diseases that are sometimes confused with clinical cases of distemper. How would you differentiate the two diseases that you named above from canine distemper on the basis of histopathologic findings?).
SLIDE 48: CANINE BRAIN: CANINE DISTEMPER - Observe the vacuolated areas (malacia) in the myelinated tracts. (Name a disease in sheep that is characterized by similar lesions.).
SLIDE 49: CANINE BRAIN: CANINE DISTEMPER - Observe the inflammatory reaction (gliosis, etc.) associated with canine distemper. (How would you define the term "gliosis?").
SLIDE 50: CANINE BRAIN: CANINE DISTEMPER - Observe the well-defined neuronal nuclear inclusion body. (How would you differentiate a Cowdry Type A from a Cowdry Type B inclusion body? Would you expect to find inclusions in the cytoplasm of neurons? What lesions would you expect to find in the lungs of this dog?).
SLIDE 51: CANINE BRAIN: CANINE DISTEMPER - This is a close-up view of the inclusion body observed in slide #50. (Define the following terms: CHROMATOLYSIS, PYKNOSIS, KARYORRHEXIS.).
SLIDE 52: CANINE LUNG: CANINE DISTEMPER - Observe the well-defined inclusion bodies in bronchial epithelial cells. (In what cell type would you expect to find the inclusion bodies associated with infectious canine hepatitis? What is the importance of Brucella bronchiseptica in cases of canine distemper? What animals besides members of the family canidae may be infected with the distemper virus? Discuss the diagnosis of distemper as outlined in your textbook. What is the relationship between canine distemper, measles, and rinderpest?).
SLIDE 53: EQUINE BODY: EASTERN EQUINE ENCEPHALOMYELITIS - Observe clinical signs of depression, abnormal posture, etc. (What characteristic gross lesions would you expect to see in the brain of this horse? What microscopic lesions would you expect to see? What areas of the brain are most severely affected?).
SLIDE 54: EQUINE (ILLUSTRATION): EASTERN EQUINE ENCEPHALOMYELITIS - This slide denotes the distribution of lesions within the CNS.
SLIDE 55: EQUINE BRAIN: EASTERN EQUINE ENCEPHALOMYELITIS - Observe the degenerating neurons and evidence of gliosis. There is also an infiltration of inflammatory cells.
SLIDE 56: EQUINE BRAIN: EASTERN EQUINE ENCEPHALOMYELITIS - This is a close-up view of slide #55. Observe the inflammatory reaction.
SLIDE 57: EQUINE BRAIN: EASTERN EQUINE ENCEPHALOMYELITIS - This is a close-up view of slides #55 & 56. Observe the neutrophils and mononuclear cells.
SLIDE 58: EQUINE (MAP): EASTERN EQUINE ENCEPHALOMYELITIS - This map denotes the distribution of diagnoses cases of EEE in the 1973 outbreak in the State of Michigan. (What conclusions can you make from this type distribution? Can EEE be transmitted to man? What is a biological host? What time of the year would you expect an outbreak such as this to occur?).
SLIDE 59: PORCINE KIDNEY: HOG CHOLERA - Observe the multiple hemorrhages over surfaces of kidneys. (How would you explain the presence of hemorrhages in visceral organs? What portion of the vascular system would you expect to find the earliest and most pronounced lesions? Discuss the microscopic lesions associated with this disease. What gross lesion(s) would you expect to find in the spleen of this pig? What characteristic lesion(s) would you expect to find in the colon of pigs dying from hog cholera after a more prolonged course? How would you differentiate hog cholera from swine erysipelas on the basis of gross and microscopic lesions? How would you differentiate Teschen disease from hog cholera on the basis of histopathologic findings?).
SLIDE 60: PORCINE BRAIN (MICRO.): HOG CHOLERA - Observe the infiltration of inflammatory cells. This disease is characterized by a diffuse, nonsuppurative encephalitis. (What portion of the brain would you expect to find the most prominent lesions? What characteristic lesion would you expect to find in the brain on gross examination? Name one CNS malformation that may be caused by the hog cholera virus.).
SLIDE 61: OVINE BODY: SCRAPIE - Sheep exhibiting some of the clinical signs associated with scrapie. (Discuss the clinical signs you would expect to see in an animal with scrapie. In what age group would you expect this disease to occur? Discuss the etiologic agent responsible for scrapie?).
SLIDE 62: OVINE BRAIN (ILLUSTRATION): SCRAPIE - Observe the location in which lesions usually occur. (What sites in the brain would you expect lesions to occur most frequently? What characteristic lesions would you expect to occur in the brain of sheep with scrapie? Name a disease in animals that is characterized by lesions similar to those of scrapie. What two diseases of man are characterized by lesions similar to those of scrapie? Give reasons why the scrapie virus is considered to be an important research tool.).
SLIDE 63: OVINE BRAIN (MICRO): SCRAPIE - Observe the well-defined vacuolated neurons associated with scrapie. (How would you define "slow viral infection?" Give ways in which the agent responsible for scrapie differs from classical viruses observed in other animal diseases.).
SLIDE 64: OVINE BRAIN (MICRO): SCRAPIE - (Can you identify vacuolated neurons? Name two diseases that we have discussed which are characterized by bilaterally symmetrical lesions in the brain. Are the lesions of scrapie found in the brain considered to be an inflammatory type reaction?).
SLIDE 65: OVINE BRAIN (MICRO): SCRAPIE - This is a close-up view of a well-defined vacuolated neuron.
SLIDE 66: CHICK BODY: AVIAN ENCEPHALOMYELITIS - This chick is exhibiting some of the clinical signs associated with avian encephalomyelitis. Characteristic muscular tremors can only be appreciated in the live bird.
SLIDE 67: CHICK BRAIN (MICRO): AVIAN ENCEPHALOMYELITIS - This is an example of encephalitis associated with the disease. Observe the well-defined glial nodules, etc.
SLIDE 68: CHICK PANCREAS: AVIAN ENCEPHALOMYELITIS - Observe the well-defined lymphoid nodules in the pancreas. (In what organs would you expect to find lymphoid nodules? What are the classical clinical signs observed in chicks? How is this disease transmitted to young chicks? What clinical signs would you expect to observe in adult birds?).
SLIDE 69: MOUSE BRAIN: RABIES - Observe the well-defined cytoplasmic inclusion bodies within neurons. (List the primary reservoir vectors for rabies in this country. Discuss the occurrence of rabies in bats. Is it possible for apparently normal dogs - no observable signs - to transmit rabies via bite wounds? Briefly describe how the rabies virus reaches the brain and salivary glands. Define the following terms: STREET VIRUS, FIXED VIRUS, CENTRIPETALLY, CENTRIFUGALLY, NEGRI BODY, FLUORESCENT ANTIBODY TEST, ASYMPTOMATIC. What characteristic microscopic lesions would you expect to find in the brain of a dog with rabies? In what sites in the brain would you expecto find the most severe lesions? Give reasons why a diagnosis of rabies in the cat based on the presence of inclusion bodies may not be reliable. Briefly discuss the ways by which rabies can be diagnosed.).
SLIDE 70: BOVINE BRAIN (ILLUSTRATION): POLIOENCEPHALOMALACIA - This illustration denotes the manner in which lesions are oftentimes distributed in the brain. However, lesions may be diffuse over the cerebral cortex. (Describe the manner in which the lesions of thromboembolic meningoencephalitis and listeriosis is distributed in the brain.).
SLIDE 71: BOVINE BRAIN: POLIOENCEPHALOMALACIA - Observe the well-defined areas of malacia (yellowish discoloration) over the cerebral cortex. (Name two CNS diseases of cattle in which you are able to make a tentative diagnosis on the basis of gross lesions. Name at least four diseases and/or conditions characterized by cerebral cortical necrosis. Define the following terms: POLIOMALACIA, LEUKOMALACIA, INFECTIOUS, CONTAGIOUS & THIAMINE.).
SLIDE 72: BOVINE BRAIN: POLIOENCEPHALOMALACIA - Observe the well-defined malacic areas in this incised portion of the cerebrum. Compare normal and abnormal areas. (What well-defined pathologic lesions do you see in the white matter? Can you identify the lateral ventricle and hippocampus in this incised section of brain? Would you expect thiamine deficiency to occur in a 10 month old steer due to a deficiency of the vitamin in the ration? Discuss the possible role of thiamine as the cause of polioencephalomalacia).
SLIDE 73: BOVINE BRAIN: POLIOENCEPHALOMALACIA - This microscopic section denotes the laminar type necrosis associated with this disease. Compare normal and abnormal areas in this slide.
SLIDE 74: BOVINE BRAIN: POLIOENCEPHALOMALACIA - This microscopic section denotes malacia and intense glial reaction in the deeper laminae of the cerebral cortex. (Is this condition acute or of prolonged duration?).
SLIDE 75: BOVINE BRAIN: POLIOENCEPHALOMALACIA - Observe the collapsed gyri in the brain of this calf with polioencephalomalacia. Refer also to slides #76 & 77. (Is this condition acute or chronic? What microscopic changes would you expect to see? Can you identify apparent normal areas in the cortex?).
SLIDE 76: BOVINE BODY: POLIOENCEPHALOMALACIA - This calf is exhibiting some of the clinical signs of polioencephalomalacia. (Discuss clinical signs that you would expect to be associated with this disease. How would you differentiate polioencephalomalacia from thromboembolic meningoencephalitis on the basis of (1) fever, (2) treatment, (3) identification of the responsible agent.) How would you treat the animal observed in this slide?).
SLIDE 77: BOVINE BODY: POLIOENCEPHALOMALACIA - This is the very same calf that you saw in slide #76. Large doses of thiamine were given and there was apparent recovery. The calf was euthanized four months after the onset of clinical signs and thiamine treatment. Prior to euthanasia, the calf was in good health but apparently blind.
SLIDE 78: CANINE SPINAL CORD: MYELOMALACIA - (Afghan hound) Observe the well-defined malacic cavity in the spinal cord of this dog.
SLIDE 79: DUCKLING BODY: AVIAN ENCEPHALOMALACIA - These birds are exhibiting some of the clinical signs associated with encephalomalacia; abnormal posture or prostration, etc. (Discuss the causes of this disorder as well as exudative diathesis and nutritional muscular dystrophy. How would you prevent the three disorders caused by a deficiency of vitamin E?).
SLIDE 80: DUCK BRAIN: AVIAN ENCEPHALOMALACIA - Observe the well-defined areas of malacia in the cerebrum of this bird. See the reddish-yellowish areas.
SLIDE 81: DUCK BRAIN: AVIAN ENCEPHALOMALACIA - Observe extensive areas of malacia; hemorrhage is also a prominent feature. (How would you explain the absence of well-defined gyri?).
SLIDE 82: DUCK BRAIN: AVIAN ENCEPHALOMALACIA - Compare normal and abnormal brains. Malacia is a prominent feature.
SLIDE 83: FELINE BRAIN: THIAMINE DEFICIENCY - Observe reddened meninges and small foci of hemorrhage. The brain is actually discolored. (How many diseases can you name with bilaterally symmetrical lesions in the brain? Under what circumstances would you expect thiamine deficiency to occur in cats & horses? Discuss clinical signs in cats with thiamine deficiency. Discuss the prognosis and treatment of a cat with thiamine deficiency.).
SLIDE 84: FELINE BRAIN: THIAMINE DEFICIENCY - Observe the well-defined malacic areas in the cortex. Note the hemorrhagic foci. (In what part of the brain would you expect to find the most severe lesion? What lesions would you expect to see in the brain on microscopic examination?).
SLIDE 85: FELINE BRAIN: THIAMINE DEFICIENCY - This microscopic section denotes the hemorrhage and glial cell proliferation found in the periventricular gray matter.
SLIDE 86: CANINE SKULL: TRAUMATIC INJURY - This slide denotes extensive hemorrhage beneath the skin and over the cranium. The skull was fractured (see slide #87). The dog was hit by an automobile. (Define concussion & contusion. What does the term contrecoup mean to you?).
SLIDE 87: CANINE SKULL: TRAUMATIC INJURY - Observe the well-defined skull fracture (see slide #86 & 90).
SLIDE 88: DUCK SKULL: TRAUMATIC INJURY - This duck received a blow to the head via a stick. Note the absence of a small plate of bone that penetrated the brain parenchyma (see slide #89).
SLIDE 89: DUCK SKULL/BRAIN: TRAUMATIC INJURY - Observe the lacerated brain parenchyma subsequent to a skull fracture (see slide #88).
SLIDE 90: CANINE BRAIN: TRAUMATIC INJURY - This brain is from the same dog illustrated in slide #86 & 87. The brain was lacerated by fractured edges of the skull bones. Observe the hemorrhage.
SLIDE 91: CANINE BRAIN: TRAUMATIC INJURY - Observe the yellowish discoloration (malacia) along the ventrolateral aspect of the brain. This dog lived several days after falling down a flight of stairs. This condition may also be referred to as "traumatic encephalopathy." (Give possible reasons for the yellowish discoloration.).
SLIDE 92: CANINE VERTEBRAL COLUMN: TRAUMATIC INJURY - Observe the pellet lodged along the spine. A young man received a rifle for Christmas and this resulted.
SLIDE 93: PORCINE VERTEBRAL COLUMN: TRAUMATIC INJURY - Observe the fractured spine with disrupted continuity of the spinal cord. This pig was kicked by a frightened horse.
SLIDE 94: EQUINE VERTEBRAL COLUMN: TRAUMATIC INJURY - Observe the fracture with compression of the spinal cord.
SLIDE 95: CANINE VERTEBRAL COLUMN: INTERVERTEBRAL DISC PROTRUSION - Observe the disc material within the vertebral canal. This placed pressure on the spinal cord. Compare normal and abnormal disc. (What is an intervertebral disc? Define the following: CHONDRODYSTROPHY, PARAPLEGIA, ANNULUS FIBROSUS, NUCLEUS PULPOSUS, URINARY INCONTINENCE, FLACCID, SYMPTOMS, SIGNS & DEGENERATION.).
SLIDE 96: CANINE VERTEBRAL COLUMN: INTERVERTEBRAL DISC PROTRUSION - Observe the elevated disc which extends into the vertebral canal. Considerable hemorrhage is associated with the spinal cord. (What is an "ascending myelitis?" What clinical signs would you expect to be associated with protruded discs in the lumbar spine? Discuss the occurrence of protruded discs in dogs.).
SLIDE 97: CANINE SPINAL CORD: INTERVERTEBRAL DISC PROTRUSION - Observe the severely hemorrhagic spinal cord associated with protruded disc. (What lesions would you expect to observe on microscopic examination?).
SLIDE 98: CANINE VERTEBRAL COLUMN (ILLUSTRATION): PROTRUDED INTERVERTEBRAL DISC - This illustration denotes the effect of a protruded disc on the spinal cord. (Can a protruded disc damage spinal nerves?).
SLIDE 99: EQUINE VERTEBRAL COLUMN: EQUINE WOBBLES - Observe the narrowed vertebral canal at the level of C2-C3. There was slight but significant pressure on the spinal cord. (What other terms are used to denote the condition commonly known as equine wobbles? What specific alterations would you expect to find in the vertebral column of this horse?).
SLIDE 100: EQUINE VERTEBRAL COLUMN: EQUINE WOBBLES - Observe the severely narrowed vertebral canal in this young horse. Note the compressed spinal cord. (What segment(s) of the spinal cord would you expect to find lesions?).
SLIDE 101: EQUINE VERTEBRAL COLUMN: EQUINE WOBBLES - Observe the severely narrowed vertebral canal. The neck is flexed. (How would you remove the spinal cord from a horse?).
SLIDE 102: EQUINE SPINAL CORD: EQUINE WOBBLES - Observe the compressed area in this spinal cord.
SLIDE 103: EQUINE SPINAL CORD: EQUINE WOBBLES - Observe the well-defined foci of hemorrhage and malacia in these pieces of the cervical spinal cord. (What clinical signs would you expect to see in this animal? How would you localize the primary foci of malacia in the spinal cord of this horse: Why are tissues fixed in formalin?).
SLIDE 104: EQUINE SPINAL CORD: EQUINE WOBBLES - This segment of the spinal cord is severely involved. Note the discolored areas.
SLIDE 105: EQUINE SPINAL CORD: EQUINE WOBBLES - Observe the well-defined cavitations in this microscopic section from a horse with wobbles. Swollen axons may be observed.
SLIDE 106: CANINE SPINAL DURA: OSSEOUS METAPLASIA OF THE DURA - Observe the bony plaques in the dura. Apparently some pressure was placed on the spinal cord.
SLIDE 107: CANINE SPINAL DURA: OSSEOUS METAPLASIA OF THE DURA - Observe thickened dura. Bony plaques are located along the ventral aspect of the spinal cord. (Define metaplasia.).
SLIDE 108: CANINE SPINAL DURA: OSSEOUS METAPLASIA OF THE DURA - Note bony plaque adjacent to a spinal root nerve. (How could such a lesion affect the health of this dog?).
SLIDE 109: CANINE SPINAL DURA: OSSEOUS METAPLASIA OF THE DURA - This microscopic section demonstrates the presence of bony plaques in the dura. Note the bone marrow.
SLIDE 110: FELINE BODY: OSSEOUS METAPLASIA OF THE DURA - This cat had severe osseous metaplasia of the dura with compression of spinal root nerves.
SLIDE 111: EQUINE SPINAL CORD: NEURITIS OF THE CAUDA EQUINA - Observe the markedly thickened dura. Spinal nerves are compressed and adhered. Some hemorrhage is present. (What significant clinical signs would you expect to see in this horse? In what nerves would you expect to see lesions?).
SLIDE 112: EQUINE SPINAL CORD: NEURITIS OF THE CAUDA EQUINA - The thickened dura has been incised. Spinal nerves are compressed. (How would you differentiate this condition from osseous metaplasia of the dura?).
SLIDE 113: EQUINE BRAIN: CHOLESTEATOSIS - Observe the granulomatous mass located in a lateral ventricle.
SLIDE 114: EQUINE BRAIN: CHOLESTEATOSIS - Observe well-defined masses in the lateral ventricle of this horse. (What lesions would you expect to find on microscopic examination of such a mass? What alteration(s) could such a mass cause in the brain parenchyma? What does the term "cholesteatoma" mean to you? In what age animal would you expect to find such a lesion?).
SLIDE 115: EQUINE BRAIN: CHOLESTEATOSIS - Observe the cholesterol clefts associated with a mass in the lateral ventricle of a horse. (How would you identify cholesterol clefts in tissue sections? What is a granuloma?).
SLIDE 116: CANINE SPINAL CORD: OIL GRANULOMAS - An oil base media was injected into the subarachnoid space of this 10 year-old Poodle in an attempt to confirm the diagnosis of intervertebral disc(s). No discs were found and improvement was noted after a few weeks of treatment. However, the dog was returned to the clinic 3 months after the contrast medium was infected with a history of difficulty walking. The dog was euthanized. (What lesions do you observe in this slide? Define the following terms: EUTHANASIA, MYELOGRAPHY, OIL GRANULOMA. How would you identify the presence of oil in tissue sections?).
SLIDE 117: CANINE SPINAL CORD: OIL GRANULOMAS - Observe cavitations and oily material in the spinal cord of this dog. (How would you differentiate this condition from syringomyelia?).
SLIDE 118: RABBIT BRAIN: CEREBROSPINAL NEMATODIASIS - Observe the well-defined nematode larvae (B. procyonis) within an area of malacia. This microscopic section (as well as slides #119, 120, 121 & 123) was taken from rabbits that were involved in an epizootic of cerebral nematodiasis. Eighty (80) diseased rabbits died or were killed. the morbidity was high in groups of recently purchased rabbits and in the offsprings of 12 breeder rabbits. The breeder rabbits which had been on the farm for more than a year survived the outbreak. Wild birds and animals had access to the housing facility, but skunks and raccoons were never observed. B. procyonis larvae were found on histopathologic examination and live larva were recovered. (What conclusions can you draw from the outbreak of cerebral nematodiasis described above? How would you identify nematode larvae in tissue sections: Give reason(s) why B. procyonis is considered to be more dangerous than other migrating ascarid larvae.).
SLIDE 119: RABBIT BRAIN: CEREBRAL NEMATODIASIS - This is a close-up view of slide #118. Observe well-defined ascarid larvae.
SLIDE 120: RABBIT BRAIN: CEREBRAL NEMATODIASIS - This cross section of B. procyonis denotes the well-defined lateral alae. (How would you differentiate B. procyonis from other migrating nematodes (ascarids) in tissue sections? What specific microscopic changes would you expect to find in the brain of this rabbit?).
SLIDE 121: RABBIT BRAIN: CEREBRAL NEMATODIASIS - Observe the inflammatory cells located around blood vessels. (Define the following: HETEROPHIL, TENTATIVE DIAGNOSIS, ALAE, GLIAL CELLS.).
SLIDE 122: RABBIT BRAIN: CEREBRAL NEMATODIASIS - This larva was recovered alive from the brain of a rabbit. Observe the lateral alae.
SLIDE 123: RABBIT BRAIN: CEREBRAL NEMATODIASIS - This larvae was recovered from the brain of a rabbit. (What clinical signs would you expect to observe in cases of cerebral nematodiasis?).
SLIDE 124: MOUSE BRAIN: CEREBRAL NEMATODIASIS - Pneumostrongylus tenuis associated with the meninges of a moose. This parasite (adult) occurs in the brain of the white-tailed deer without eliciting significant clinical signs or causing overt disease. However, in moose, wapiti, caribou, reindeer and mule deer, the parasite may cause severe damage to nervous tissue.
SLIDE 125: RABBIT BODY: NOSEMATOSIS - These rabbits are exhibiting signs associated with nosematosis. Observe the abnormal posture, etc. (How would you make a diagnosis of this disease in the live animal? How is this disease transmitted from animal to animal? What gross lesions would you expect to find in the brain of infected rabbits?).
SLIDE 126: RABBIT BRAIN: NOSEMATOSIS - Observe the aggregates of organisms as well as the glial proliferation.
SLIDE 127: RABBIT BRAIN: NOSEMATOSIS - This is a close-up view of slide #126. Observe the well-defined groups of organisms. (Would you expect to observe organisms in tissue sections stained with Hematoxylin & Eosin?).
SLIDE 128: RABBIT BRAIN: NOSEMATOSIS - Observe the intense inflammatory reaction. There is a tendency for organisms to evoke a granulomatous reaction when activated. (In what organ besides the brain would you expect to find lesions?).
SLIDE 129: CANINE BRAIN: TOXOPLASMOSIS - Observe the encystic parasite and the proliferation or accumulation of inflammatory cells. (Discuss the occurrence of toxoplasma organisms in the intestinal tract of cats.).
SLIDE 130: CANINE BRAIN: BLASTOMYCOSIS - Observe organisms and intense inflammatory reaction.
SLIDE 131: CANINE BRAIN: BLASTOMYCOSIS - Note the thick walled organisms and inflammatory response. (How would you differentiate this organism from Histoplasma capsulatum, Coccidioides immitis, and Cryptococcus neoformans in tissue sections?).
SLIDE 132: CANINE BRAIN: CRYPTOCOCCOSIS - Observe the large granulomatous mass in the sulcus associated with the pia matter. (What technique would you employ in order to make a tentative diagnosis of this disease at the time of necropsy?).
SLIDE 133: CANINE BRAIN: CRYPTOCOCCOSIS - Observe the well-defined gelatinous mass in the brain stem. (Would you expect lesions in this location to cause more severe disturbances than one located in the anterior portion of the cerebrum? Why?).
SLIDE 134: CANINE BRAIN: CRYPTOCOCCOSIS - Observe multiple granulomatous masses associated with root nerves. (Based strictly on gross examination or observations, what specific neoplasm would you consider in your differential diagnosis? How would lesions in this location affect the rectum and urinary bladder?).
SLIDE 135: CANINE BRAIN: CRYPTOCOCCOSIS - Observe the well-defined organisms which are surrounded by clear spaces. (Discuss the microscopic changes that you expect to see in this disease. What changes would you expect to observe in a typical gross specimen of the brain?).
SLIDE 136: CANINE BRAIN: MENINGIOMA - Observe the well-defined neoplastic mass associated with the meninges but compressing the brain parenchyma. (In what portion of the cerebrum is this tumor located? How would this tumor affect the health of the dog? What is a benign neoplasm? How would you differentiate a benign from a malignant neoplasm?).