The Nervous System

Introduction

The central nervous system is composed of the cerebral hemisphere, brain stem, cerebellum and spinal cord. Microscopically, the principal cell types are neurons and neurolgia cells.

Neuron

Neuron represent the basic functions unite of the nervous system. It consists of nucleus with the large nucleolus surrounded by abundant pale cytoplasm “cell body”. A single axon and one or more dendrites project from cell body and synapse with dendrites from other neurons. Nissl substance “basophilic granules strongly stain with basic dye” are seen in cytoplasm. Neurons are permanent cells that have no mitotic capability.

Neurolgia

The name of neuroglia cells (neural glue) means the cell that hold nervous tissue together. Now the neuroglial cells have many functions not only holding the tissue together. The neuroglia cells can be distinguished from neurons, that the glial cells nuclei not show visible nucleoli on light microscopy.

a. Astrocytes

Astrocytes (star like cells) constitute the bulk of neuroglia in most regions (Fig. 1) . Astrocytes are divided into protoplasmic “in gray matter” and fibrous “in white matter”. It considers the fibrous connective tissue of the brain. Gemistocytes are enlarged astrocytes in response to mild irritation.

Fig. 1: Microscopic picture of normal astrocytes.

b. Oligodendroglia

It is found throughout the brain. They lined up along myelinated fibers in the white matter, but in gray matter they tend to cluster around the neuron “satellite cells”. The main function is the production and maintenance of CNS myelin.

c. Microglia cells

Microglia cells have small, round dark nuclei. Most authorities consider these cells to belong to the mononuclear phagocytic system.

d. Ependyma cells

Ependymal cells are cuboidal or columnar cells that line ventricles, choroid plexus and spinal canal.

Myelin

It is fatty material produced by Schwann cells.

Blood vessels

It is thin walled vessels, so it is susceptible to injury. The wall consists of thin fibrous tissue and supported by feet of astrocytes. Perivascular space called Virchow-Robin spaces are seen around arteriole and venules and lined by adventitia of blood vessels and pia matter.

Neuropathology is the part of pathology which concerns mainly with affections of the nervous system which are characterized by impairment of sensitivity and movements or dysfunction of sense organs.

The language of neuropathology

There are several terms can applied in other organs such as cloudy swelling or fatty changes not suitable to use in neuropathology. The neuropathology may need its own language.

Chromatolysis is a term used to describe neuron injury. It indicate breakdown of Nissl bodies.

Satellitosis: It is the proliferation of neuroglia cells around the degenerated neurons (Figs. 2 & 3) .

Fig. 2. Brain showing proliferation of neuroglial cells around degenerated neuron (satellitosis). Moreover, some glial cells phagocytize degenerated neuron (Neuronophagia). H&E.

Fig. 3: Brain showing proliferation of neuroglial cells around degenerated neuron (satellitosis). Moreover, some glial cells phagocytize degenerated neuron (Neuronophagia). H&E.

Status spongiosis is the term applied to the nervous tissue showed vacuolation evident by light microscope.

Gliosis is a term applied to non specific response of neurolgia cells in the CNS to many forms of injury. Moreover, microgliosis, astocytosis or astroglyosis are terms used to indicate proliferation of microglia or astrocyte respectively.

Demylination is the destruction of normally formed myelin sheath with exposing of the axon naked eye.

The following point must be kept in mind during examine a neuorologic case at necropsy or microscopically

1. necrosis of neurons in ventral horn of spinal cord will produce degeneration in associated ventral spinal root and Denervation atrophy of muscle

2. Degeneration of the axon in ventral spinal root will results in chromatolysis in their cell bodies in the ventral horn

3. Cerebellar cortex Hypoplasia or degeneration results in shrinkage of middle cerebral peduncle.

The Cerebrospinal Fluid (CSF)

CSF fills the ventricular system of the brain, the central canal of spinal cord and the subarachnoid pace.

CSF is secreted by the choroid plexuses, which are situated in the lateral ventricles. From the lateral ventricles, CSF passes through foramen of Monro into the third ventricle and through the aqueduct of sylvius in the midbrain into the fourth ventricle and then through the foramen of Luschka into the subarachnoid space. CSF then passed to the region of sagital sinus, where it absorbed into the venous system by arachnoid villi.

Hydrocephalus

Definition

It is a marked increase in the volume of CSF with expansion of cerebral ventricles.

Classification

1. Noncommunicating “internal” hydrocephalus:

It occurs when there is an obstruction in the ventricular system that prevent CSF from passing into the subarachnoid space.

Causes:

1. Mechanical obstruction of aqueduct of sylvius and foramen of Luschka by external pressure as inflammatory exudate, tumors, cholesterol granules and parasitic cysts.

2.Brain displacement either forward or backward.

3. Congenital malformation as stenosis of aqueduct of Sylvius.

2. Communicating hydrocephalus

It occurs when CSF passes normally out of the ventricular system but either flow is obstructed in the subarachnoid space or reabsorption is reduced.

Causes

1. Over production of CSF as in case of choroid plexus papilloma.

2. Deficient absorption of CSF as incase of organized meningitis, organized subachnoid hemorrhage and dural sinus thrombosis.

Lesions

1. Prominent enlargement of ventricular system proximal to the point of obstruction (Fig 4).

2. Marked reduced white matter of dilated ventricles, although the gray matter may be relatively normal.

3. Damaged ependymal lining of ventricle associated with severe dilatation and passage of CSF into the periventricular white matter “interstitial edema”.

4. Atrophy and fenestration of the interventricular septum and hippocampus in the floor of lateral ventricles.

5. Malformation of the cranium is associated with congenital hydrocephalus.

Sequelae

It is progressive which lead to pressure atrophy of surrounding nervous tissue.

Fig. 4: Hydrocephalus characterized by prominent dilatation of ventricles.

Hydrocephalus exvacuo

It is compensatory enlargement of the ventricles and increase in CSF volume occur when brain volume is reduced.

CSF production, pressures and flow patterns are normal. It is seen, for example, in Alzheimer’s.

Malformation of the central nervous system

The CNS anomalies that originate during embryonic life are common.  Congenital anomalies aren’t necessarily to be hereditary. Many causes including intrauterine infections (especially virus), nutritional factors, toxins, toxins and trauma can induced congenital anomalies.

Acrania: It is the absence of cranium.

Amyelia: it is the absence of spinal cord.

Anencephaly: It is absence of brain which is rare.

Anophthalmia: It is the absence of both eyes.

Cerebral hypoplasia (aplasia): failure of cerebellum to develop to normal size and cellularity (Fig. 5).

Fig. 5: Brain showing cerebral hypoplasia.

Cranioschisis: Cranium bifidum, gap in the skull, usually with herniation of brain substance or meninges.

Cyclopia: It is the term applied to the presence of one eye only

Encephalocele: herniation of brain through a cranial defect.

Exencephaly: brain is outside cranial cavity (Fig. 6).

Fig. 6: Brain outside the skull (exencephaly).

Hydranencephaly: The cerebral hemispheres appears as empty sacs due to excessive cerebrospinal fluid, hydrocephalus.

Hydrocephalus: ventricles are dilated by excessive cerebrospinal fluid (Fig. 7).

Fig. 7: Brain showing congenital hydrocephalus.

Hydromyelia: cerebrospinal fluid is retained in dilated central canal of spinal cord.

Macroencephaly: brain is enlarged.

Megaloencephaly: brain is extremely enlarged.

Meningocele: herniation of meninges through bony defects in the skull (Fig. 8).

Fig. 8: Pig showing meningocele.

Microencephaly: It means a small brain.

Myelocele: Spinal cord is herniated through a bony defect in vertebral column.

Myloschisis: Spinal cord is cleft because of incomplete formation of neural tube.

Spina bifida: absence of vertebral arches, producing a defect through which spinal membranes, with or without spinal cord, protrude.

Traumatic Nervous System Lesions

Cerebral Injuries

There are many causes of traumatic injuries. Central nervous system injuries have extrinsic and intrinsic causes. The following injuries could be noticed

1. Penetrating (open) injuries

• They caused by gun shots or severe blunt trauma.

• They associated with severe brain damage.

2. Non penetrating (closed) injuries

They produced by blunt trauma.

a. Cerebral concussion

• Cerebral concussion is transient less of cerebral function (loss of consciousness) that immediately follows head injury.

• It is a diffuse brain injury and in mild type the brain shows no gross or histological lesions.

b. Cerebral contusion

• It is characterized by grossly detectable lesions (usually due to hemorrhage) that is more focally in nature and superficial in location.

c. Cerebral laceration

• It is characterized by tearing of cerebral tissue resulting in acute subarachnoid or subdural hemorrhages.

Spinal Cord Injuries

The basic injury of spinal cords are similar to those in the brain including concussion, contusion and laceration. Moreover, compression of the spinal cord can be caused by intramedullary or extramedullary forces as intervertebral disc herniation and cervical stenotic myopathy.

Circulatory Lesions

Anemia may accompany general anemia

Hyperemia  may be passive or active (Fig. 9 ) accompany inflammation as in the course of infectious diseases.

Fig. 9: Brain showing congestion of cerebral blood vessels. H&E.

Hypoxia, ischemia and infarction

Although brain constitute only 2% of the body weight, it receives 15% of the resting cardiac output. The brain may be deprived of oxygen in

1. Anoxic anoxia in case of low inspired O₂.

2. Anemic anoxia in case of reduced hemoglobin.

3. Histotoxic anoxia in case of cyanide poisoning.

4. Ischemic anoxia in case of cessation of blood flow

In clinical practice two general types of acute ischemic injury are recognized:

1. Ischemic (hypoxic) encephalopathy

It occurs when there has been a generalized reduction of cerebral perfusion with wide spread bilateral ischemic damage as in atherosclerosis, cardiac arrest. The lesions depend upon duration and severity of the ischemia and length of survival.

2. Cerebral infarction

It is focal ischemic necrosis that follow severe reduction or cessation of blood flow to a localized area.

Most vascular occlusions are either

a.Thrombotic occlusions usually associated with atherosclerosis and arteritis.

b. Embolic occlusions.

Macroscopic picture

Anemic infarcts not detectable before 6-12 hours. After 48 hours, there is softening of the brain tissue and finally forming cyst.

Hemorrhagic infarcts is red in color and usually result from break down of emboli (Fig.10).

Fig. 10: Gross picture of hemorrhagic infarction. It is usually red in color.

Microscopic picture

1. Necrotic neuron and oligodendroglia are seen.

2. There is hypercellularity by microgliosis and astroglyosis.

3. The center of the infarct has coagulative and liquifactive necrosis which reabsorbed leaving cyst surrounded by astrocytes.

N.B. Cells and tissue structure of CNS, in decreasing order of susceptibility to ischemia are neurons, oligodendroglia, astrocytes, microglia and blood vessels.

Hemorrhage

Hemorrhages may be mechanical in origin; in this case the blood may be found accumulating in subdural space giving rise to hemocephalus externa. Petechial hemorrhage is frequent in acute infections and toxemia that injury capillaries (Figs 11&12).

Epidural hemorrhage and subdural hemorrhages may be due to severe trauma to the head which lead to repute of one or more branches of meningeal arteritis (Fig. 13).

Cerebral hemorrhage usually associated with arteriosclerosis and hypertensive diseases.

Fig. 11: Brain showing petechial hemorrhages.

Fig. 12: Extravagation of erythrocytes from  cerebral blood vessels (hemorrhages). H&E.

Fig. 13: Brain showing epidural hemorrhages.

Cerebral Edema

The brain is sensitive to edema not only because it has little room to expand, but also because the brain has no lymphatic system to carry away excess fluid. The edema resulted from the escape of fluid in abnormal quantities from the circulation or the failure of recirculation of tissue fluid.

Fluid and electrolytes movement into and out of the brain is depend upon blood brain barrier which depend on the interaction between astrocytes and capillary endothelial.

The cerebral edema occurs in response to several injuries including degeneration, inflammatory disorders, traumatic injuries and neoplasm. The edema occurs in both white and gray matter but more severe in the later.

Classification

1. Vasogenic edema

It occurs in association with primary and metastatic tumors, abscess, hematoma, infarction and contusions resulted in damage in the wall of cerebral blood vessels leading to escape of plasma and proteins under the effect of hydrostatic pressure.

Macroscopic picture

The white matter more affected than gray matter. The edematous area is swollen soft beside gyral flattening over the affected region.

Microscopic picture

1. Extracellular accumulation of fluid especially in Virchow Robin space, subarachnoid space and round neuron.

2. Microvacuolation and separation of myelin sheath.

3. Demylination and axonal degeneration in long stimuli edema.

2. Cytotoxic edema

It is the accumulation of excess intracellular fluid resulted from disturbs energy depend ionic pumps.

Causes

• It is associated with disturbance in metabolism and membrane function of the cells as in case of ischemia and water intoxication.

• The blood brain barrier remain intact.

• It occurs primary in gray matter.

Microscopic picture

The cells appear swollen and vacuolated.

3. Interstitial edema

It is associated with increased hydrostatic pressure accompanying communicating hydrocephalus when excess fluid crosses the ependymal lining of the ventricles and accumulates in the periventriclar white matter.

Reaction of cells to injury

1. Neuron

a. Reaction of neuron following injury to axons that extend to periphery:

The neuronal lesion affect lower motor neuron that have cell bodies in CNS. Microscopically, central chromatolysis is characterized by swelling of cell body, loss of Nissl substance and eccentric location of nucleus (Fig. 14) . The axon distal to the point of injury shows irregular swelling, fragmentation beside degeneration of myelin sheath (wallerian degeneration).

b. Response of neuron following injury to axons that remain within the central nervous system:

It varies, some cells show central chromatolysis, other show rapid degeneration or simple atrophy with gradual degeneration of various organelles, or show no changes. Wallerian degeneration within the CNS is similar to that described above (Fig. 15 ) .

Fig. 14: Cerebrum showing neuronal degeneration. The nucleus become small and dark basophilic. H&E.

Fig. 15: Wallerian degeneration of the white muscle. H&E

c. Ischemic cell changes:

Microscopically, following H&E staining, the cell body stain light eosinophilic, shrunken and has cytoplasmic vacuolation. The nucleus is reduced in size, triangular shape and stain dark blue beside undetectable nucleolus. Unstained perinuclear space is detected.

2. Astrocytes

In severe cases astrocytes swell, loss their processes and degenerate.

In less severe, increase size of astrocytes and their nuclei beside increase number of cells.

The cytoplasm id homogenous pink (gemistocyte). Astrogliosis is proliferation of astrocytes and is seen in toxic and hypoxic condition, edema and many viral diseases.

3. Microglia

It is more resistance to injury than the neural cells. The degeneration stimulate glial cell to hypertrophy, hyperplasia and surround the degenerated neuron (Satellitosis) or phagocytize the neuron (neuronophagia).

4. Oligodendroglia

Degeneration of cells with swollen vacuolated cytoplasm and small dark nucleus are seen.

Neurofunctional disturbances

1. Nervous depression

It is attributed to chemical changes in protoplasm of nerve cells and fibers due to chemical, plant and bacterial toxins. Other causes are neoplasm and parasites.

The degree and duration of loss of function of CNS depend upon the cause and extent of injury.

The clinical signs of nervous depression include dullness, which is called somnolence. The animal stands with drooping head and closed eyes or walking dragging its feet on ground.

The somnolence followed by stupor. The animal lean its body against object with legs widely separated or lies without movement except moving his head and leg from time to tome.

The lethargy is characterized by the animal is sleeping but response to strong stimulation.

2. Loss of consciousness

It occurs due to pressure upon brain as in case of hemorrhage, brain tumor, hydrocephalus and inflammatory exudate.

If loss of consciousness is complete, a state of coma is said too exist. The animal lied motionless, its reflex are gone (palpebral, corneal papillary and cutaneous). Cardiac and respiratory function are maintained.

Fainting (syncope): it is acute loss of consciousness with weak imperceptible pulse.

3. Nervous excitement

It results from congestion and inflammation of the brain and its covering. The chief symptoms are:

1. The animal become extremely antagonistic to the usual means of restrian.

2.  Fights and may injury self.

3.  Biting the attendant, frothing at the mouth and the eye have widely look.

4. The conjunctiva is red.

Neuromuscular functional disturbances

In general there are two types

1. Spasm

It is characterized by sudden, violent, involuntary contraction of muscle. It may be

a. Tonic spasm: is persistent continuous contraction.

b. Clonic spasm: is intermittent  contraction of muscle.

• Tremors are mild clonic spasm of group of muscles as epidemic tremors in chicks.

• Convulsion is clonic spasm of whole body muscles as in dog infested with ascarids.

• Epilepsy is alternating attack of tonic and clonic spasm accompanied by loss of function.

Sequelae

It the spasm persist for long time lead to muscular atrophy or fibrosis.

2. Paralysis

It is the inability of muscle to contract. There are three types of paralysis:

a. Hemiplegia: It is unilateral paralysis of the body caused by damage to the brain cortex at opposite side by hemorrhage or thrombus.

b. Paraplegia: It is bilateral paralysis of the posterior parts of the body and limbs. It is caused by injury of spinal cord.

c. Paresis: It is incomplete loss of motion.

N.B. Ataxia: It is a pathological condition where the muscles maintain their ability to contract but not coordinated.

Infection

The nervous system is susceptible to a large number of infectious agents of all types. Because the nervous system is so well insulated from outside, organisms infecting it usually come from other organs.

There are four routs of infection of the nervous system

1- By hematogenous route: it is the most common route of entry as arboviruses.

2- By extension of established infection through nasal or olfactory tissues.

3- Carried along the course of nerves, such as rabies and herpes simplex.

4- Direct implantation of infection. It is almost traumatic as in case of surgery, fracture of skull.

Infection of the nervous system are classified according to the infected tissue into:

1- Meningeal infections (meningitis), which may involve the dura matter (pachymeningitis) or the pia-arachnoid (leptomeningitis).

2- Cerebral and spinal parenchyma (encephalitis or myelitis), leukoencephalomyelitis is inflammation of the white matter of brain and spinal cord. Polioencephalomyelitis is inflammation of the gray matter.

In many cases, both the meninges and brain parenchyma are affected (meningioencephalitis).

  The CNS inflammation is characterized by perivascular cuffing, Gliosis and neuronal Satellitosis and neuronophagia.

Meningitis

Infectious meningitis can be classified as acute bacterial (pyogenic), acute viral (lymphocytic and chronic bacterial mycotic).All types of inflammation except the catarrhal can be observed in meningitis.

a. Acute pyogenic meningitis

It causes by bacteria as E. coli, H. influenza and usually associated with trauma, otitis or through hematogenic infection.

Macroscopic picture

• CSF is cloudy and sometimes purulent.

• Congestion and thickening of meninges beside meningeal abscess or diffuse pus may be seen (Fig 16).

Figure 16: Meninges showing gross picture of acute suppurative meningitis.

Microscopic picture

• Congestion of subarachnoid space, around blood vessels, lepto and pachymeninges by inflammatory cells mainly neutrophils.

• Gram stain reveal varying numbers of causative organism.

b. Acute lymphocytic meningitis

It is associated with several viral diseases.

Macroscopically, slight meningeal swelling is seen.

Microscopically, meningeal infiltration by lymphocytes is noticed.

c. Chronic meningitis

It is associated with bacterial and mycotic affections.

Macroscopically, focal meningeal thickening  beside gelatinous exudate are seen in subarachnoid space.

Microscopically, focal or diffuse infiltration of meninges by macrophages, fibroblasts and plasma cells are seen. Caseous necrosis may be seen.

Meningoencephalitis

It is the inflammation of brain and meninges. It can classified into

1. Acute non suppurative meningoencephalitis

Causes

It is associated with viral diseases as rabies, Equine encephalomyelitis, Hog cholera and bovine malignant catarrhal fever.

Macroscopically, slight edema of meninges and congestion of meningeal and cerebral blood vessels. Moreover, increase of CSF may be noticed.

Microscopically, perivascular lymphocytic infiltration and gliosis are characteristic. Moreover, degenerated neuron, satellitosis and neuronophagia are seen (Fig 17) beside lymphocytic perivascular cuffing (Fig 18)

Fig. 17: Acute non suppurative meningoencephalitis showing satellitosis and neuronophagia.. H&E.

Fig. 18: Lymphocytic meningoencephalitis showing perivascular lymphocytic cuffing. H&E.

2. Acute suppurative meningoencephalitis

Causes

pyogenic microorganisms as staphylococci, Corynbacteria, Pasteurella and Listeria.

Macroscopically, congestion of meninges and brain beside accumulation of pus in pia, arachnoid and brain ventricles and parenchyma are seen.

Microscopically, infiltration of meninges, subarachnoid space and brain parenchyma by neutrophils, beside congestion of meningeal and cerebral blood vessels are seen. Moreover, liquifactive necrosis is seen (Figs 19 & 20 ). .

Fig. 19: Brain showing suppurative meningoencephalitis represented by infiltration of the meninges and brain with neutrophils besides congested blood vessels. H&E.

Fig. 20: Brain showing suppurative meningoencephalitis represented by infiltration of the meninges and brain with neutrophils besides congested blood vessels. H&E.

3. Fibrinous meningoencephalitis

It is associated with some bacterial infections as pasteurellosis in sheep and cattle and pleuropneumonia like organism in swine.

Macroscopically, there is abundant fibrin in subarachnoid and covered meninges beside severe congestion of blood vessels (Fig. 21).

Microscopically, there is fibrin threads in subarachnoid space, ventricles and Vrishow Robin space. Congestion of blood vessels and infiltration of the affected tissues by inflammatory cells mainly neutrophils are seen.

Fig. 21: Brain, gross picture of fibrinous meningioencephalitis.

4. Serous meningioencephalitis

Causes: It may mild irritants as sunstroke or mild viral infections.

Lesions: Include congestion and increase CSF.

Encephalopathy and Encephalomalacia

Encephalopathy is a general term used to indicate degeneration of neurons, axon, myelin sheath and vessels.

Encephalomalacia is necrosis of brain (Figs 22 & 23) . (leukomalacia is necrosis of white matter, while poliomalacia is necrosis of gray matter) and myelomalacia is necrosis of spinal cord.

• Encephalomalacia is most liquifactive in CNS, but may be coagulative or caseous too.

Fig. 22: Brain showing gross picture of encephalomalacia.

Fig. 23: Brain showing encephalomalacia represented by cavities. H&E.

1. Liquifactive necrosis

Macroscopically, areas of softening or liquefaction may be seen (Figs 24 & 25 ) . Moreover, cavities filled with fluid or empty may be seen.

Microscopically, cavities surrounded by glial cells are seen. Degenerated neurons beside neuronophagia and satellitosis are noticed.

Fig. 24: Brain showing liquifactive necrosis.

Fig. 25: Brain showing liquefactive necrosis. The parenchyma infiltrated with neutrophils. H&E.

2. Caseous necrosis

Cause: Mycobacterium tuberculosis.

Microscopically, the brain parenchyma is focally lost their cellular details and tissue architecture. The necrotic tissue is surrounded by glia cells.

3. Coagulative necrosis

Causes: Bacterial toxins and chemical poisons.

Microscopically, swollen more eosinophilic neurons are seen. Moreover, cytoplasmic tigrolysis and nuclear chromatolysis and karyorrhexis are seen. There is satellitosis and neuronophagia.

Necrosis of the peripheral nerves (Wallerian degeneration)

The degenerative and necrotic changes include swelling of myelin and break down in to lipid which are phagocytized by microglia. The axon swell and become fragmented (Fig 26).

Fig. 26: Wallerian degeneration Demylination of salmic nerve. H&E.

Disturbances in Cell Metabolism

Cloudy swelling and hydropic degeneration usually associated with hypoxemia or mild toxic or infections.

Hyaline degeneration seen in dura matter of old animals.

Cholesterol granuloma (Cholesteatoma)

Cholesterol granuloma occur In old horses. They are more frequent in the plexus of the fourth ventricle than in lateral ones. Cholesteatoma of the lateral ventricles frequently cause hydrocephalus through obstruction of foramina of Monro. Interstitial tissue is edematous and infiltrated lightly by macrophages containing lipids and hemosiderin. The crystals of the cholesterol are deposited in the tissue spaces and act as foreign body which stimulates a low grade productive inflammatory process.

It occurs associated with repeated hemorrhage in choroid plexus especially in aged horse.

Macroscopically, the choroid plexus show firm, nodular grayish areas. Crystals can be expressed from cut surface by slight pressure.

Microscopically, the choroid plexus is partially replaced by cholesterol granuloma (cholesterol cleft and macrophages).

Large one in choroid plexus may result in internal hydrocephalus.

Demylination

It is disappearance of myelin sheath leaving naked but intact axon. It occurs in some vitamins deficiencies as vitamin B complex or with trauma.

Disturbances of Pigmentation

Melanosis

It is seen in pia matter in sheep and cattle. This pigmentation may accompany general melanosis or some melanosis may be found independently among tissues of leptomeningis. This is considered as developmental abnormality (Fig. 27).

Fig. 27: Meninges showing melanosis (black pigment inside melanophore). H&E.

Lipofuscin (wear and tear pigments)

It is noticed as brown pigments in neurons and glia cells in old ruminants.

Sidrosis

Is mostly found in Purkinje cells.

Calcification

Is seen in meninges, hyalinized choroid plexus, blood vessels and necrotic areas.

Disturbance in growth

• Cartilaginous and osseous metaplasia are common in dura matter in dogs.

• Hyperplasia of glia cells in hypoxic and toxic condition.

• Atrophy senile atrophy of brain and spinal cord are seen in old animals.

I. Tumors arising from the nervous tissue

Tumors of CNS of animals aren’t rare as was once believed. Such tumors occur in some animals “especially in dogs” with a frequency and variety that is similar to that in human. We can classified the CNS neoplasms into:

1. Neuroglial tumors

Generally called gliomas and divided into

A. Astrocytoma

It is gray white infiltrative tumor

Susceptible animals

It is reported in dog and cat and bovine. It is the most common of neuroglial tumors in dog.

Gross and microscopic picture

The less malignant is soiled but the more malignant is soft and gelatinous. The less malignant tumor consists of population of astrocytes described as protoplasmic, fibrillary or gemistocytic beside unclassified astrocytes. Between the neoplastic cells there are characteristic fibrillary backgrounds of astrocytes (Fig. 28) . The anaplastic astrocytoma is grossly distinguishable from astrocytoma. The tumor is not easily demarcated from surrounding tissue.

Microscopic picture shows that the cells have anaplastic features such as hypercellularity, nuclear and cytoplasmic pleomorphism and hyperchromatic nuclei. The tumor has characteristic proliferation and hyperplasia of vascular endothelium.

B. Glioblastoma multiform

It is characterized by varying in appearance; some regions may be white and firm others yellow and soft. Moreover, foci of necrosis, cysts and hemorrhage are common. Microscopically, necrosis, which may or may nor have pseudopallisading around it distinguishes them from anaplastic astrocytoma. The others cellular feature as anaplastic astrocytoma (Fig. 29) .

C. Oligodendroglioma

It occurs in dog, but also reported in cattle and cat.  

Lesions

It is well circumscribed, gray to pink and gelatinous. It contains focal hemorrhage, cysts and calcification. Microscopically, the tumor is composed of sheats of regular cells surrounded by clear halo of cytoplasm (Fig. 30) . Calcification occurs in up to 90% of these tumors.

Fig. 28: Brain showing low grad astrocytoma characterized by hypercellularity and pleomorphism besides the characteristic fibrillary backgrounds of astrocytes.

Fig. 29: Brain showing microscopic picture of glioblastoma multiform characterized by anaplastic features such as hypercellularity, nuclear and cytoplasmic pleomorphism and hyperchromatic nuclei. Moreover, necrosis, which may or may nor have pseudopallisading around it distinguishes them from anaplastic astrocytoma. H&E.

Fig. 30: Brain showing oligodendroglioma represented by mass or sheet of cells with large pleomorphic cells with large nucleus and clear cytoplasm. H&E.

E. Ependymoma

It is one of the rare tumors in animals. It reported in dog, cat, cattle and bovine.

Lesions

It is soft gray white to red in color. It occurs primary in lateral ventricles and less frequent in third and fourth bone (Fig. 31) . Microscopically, The tumor is high cellular and well vascularizedز The cells have hyperchromatic nuclei with scant to undetectable cytoplasmز The nuclei are round to oval or carrot shaped and arranged around blood vessels or may form ependymal canals and perivascular pseudo rosettes (Figs 32 & 33)

Fig. 31: Gross picture of ependymoma characterize by gray or pink mass are seen.

Fig. 32: Microscopic picture of ependymoma characterize by  high cellular and well vascularized. The cells have hyperchromatic round to oval or carrot shaped nuclei with scant to undetectable cytoplasm. The cells arranged around blood vessels or may form ependymal canals and perivascular pseudo rosettes. H&E.

Fig. 33: Microscopic picture of ependymoma characterize by  high cellular and well vascularized. The cells have hyperchromatic round to oval or carrot shaped nuclei with scant to undetectable cytoplasm. The cells arranged around blood vessels or may form ependymal canals and perivascular pseudo rosettes. H&E.

Fig. 34: Histological section of choroid plexus papilloma characterized by papillae have connective tissue stalks covered cuboidal cells. H&E.

Fig. 35: Brain showing meduloblastoma made up of densely packed cells with scant cytoplasm and elongated hyperchromatic nuclei. Rossete formation is often a feature.  H&E.

Fig. 36: Meningothelial meningioma showing polygonal shaped cells, which form sheets or whorls. Nuclei are large and centrally placed and may be clear vacuoles in nuclei. The cytoplasm is pale. H&E.

F. Choroid plexus papilloma

It forms papillary growth from meninges and ventricles. It occurs in dogs, and reported in horse and cattle. Microscopically, the papillae have connective tissue stalks covered cuboidal cells (Fig. 34). The malignant one resembles metastatic adenocarcinoma.

2. Tumor of neuronal origin

a. Neuroblastoma

It is rare tumor. Microscopically, it resembles peripheral neuroblastoma and composed of undifferentiated cells with characteristic rosettes.

b. Gangliocytoma

Tumor containing more differentiated neuronal cells. Grossly, gangliocytoma are well-circumscribed masses with focal calcification or cysts. Microscopically, it forms from clumps of cells separated by stroma .

3. Tumor of primitive or undifferentiated cells.

The most important member of this group is medulloblastoma.

Medulloblastoma

It is recorded in bovine and canine species. It has been found in young calves and dogs in which the recorded signs include high stepping gait, ataxia and uncoordinated movements.

Lesions

Single mass of cerebellum with occasional extension to fourth ventricle, meninges and brain stem. Hemorrhage and necrosis may be seen. Microscopic picture, It is made up of densely packed cells with scant cytoplasm and elongated hyperchromatic nuclei. Rossete formation is often a feature (Fig. 35)

4. Tumors of meninges

Meningioma

It is the most common reported mesodermal tumor in animals. It is occurs frequently in dog and cat but reported in other species.  The term is applied to neoplasm that arises from meninges.

Classification of meningioma

A. Meningothelial meningioma

It composed of polygonal shaped cells, which form sheats or whorls. Nuclei are large, spherical and centrally placed with conspicuous nucleoli and may be clear vacuoles in nuclei. The cytoplasm is pale (Fig. 36).

b. Fibroblastic meningioma

It composed of spindle shape arranged in whorls (Fig. 37) . Psammoma (round laminated calcification) bodies may occurs (Fig. 38) .

c. Syncytial meningioma

The cells are arranged in sheats or pseudoalveoli. The nuclei are regular and oval. The cytoplasm is finely granular without distinct margin.

5. Neoplasms of peripheral nervous system

Schwannoma (neurilemmoma (

It arises from Schwann cells. Schwannoma is composed of elongated spindle shaped cells arranged in palisading (Fig. 39).

Fig. 37: Histological section of fibroblastic meningioma showing spindle shape cells arranged in whorls.

Fig. 38: Histological section of fibroblastic meningioma showing infrequent meningothelial whorls. Psammoma (round laminated calcification) bodies are seen. H&E.

Fig. 39: Schwannoma is composed of elongated spindle shaped cells arranged in palisading. H&E.

Neurofibroma

It is composed of spindle shapes cells arranged in circular whorls or wavy fasciculi.

 Teratoma

Teratoma is a tumor consisting of at least to and often all three embryonic germ layers. It is a rare tumor but observed in all animal species specially dog and horse. It occurs mostly in ovary and testis. Ovarian teratoma is usually well differentiated and benign. It consists of cyst, which lined by stratified squamous epithelium and skin appendages and contains cartilage, bone, teeth and hair (Figs. 40 &41) .  Testicular teratoma are always malignant (Figs. 42, 43).

Fig. 40: Histological section of neurofibroma. It is composed of spindle shapes cells arranged in circular whorls. H&E.

Fig. 41: Ovary of cattle showing teratoma represented by presence of hair in ovary.

Fig. 42: Microscopic picture of ovary teratoma showing cartilaginous structure and keratin. H&E.

Fig. 43: Testes showing teratoma represented by presence of multiple tissue as skin tissue and keratin.H&E.