CENTRAL NERVOUS SYSTEM-I

General Features(structures & histology)

• The CNS comprises of delicate brain & spinal cord encased in a bony skull & vertebral cage.

• The average weight of the brain is about 1400 gm in men and 1250 gm in women.

• There are 4 main anatomic regions of the brain- the cerebrum, cerebellum, pons & medulla.

• There are 2 types of tissues in the nervous system:• 1. Neuroectodermal tissues which include neurons (nerve

cells) and neuroglia, and together form the predominant constituent of the CNS.

• 2. Mesodermal tissues are microglia, dura mater, the leptomeninges (pia-arachnoid), blood vessels and their accompanying mesenchymal cells.

• Histologically there are 2 main components- the neurons & neuroglia.

• The neurons are specialized cells which are involved in conduction of impulses.

• Neurons vary considerably in size and shape. Their size may range from the small granular cells of the cerebellum to large Betz cells of the motor cortex.

• Some neurons are round, others oval or fusiform but the prototype of cortical neuron is pyramidal in shape.

• A neuron consists of 3 main parts: the cell body, anaxon and numerous dendrites.

• The cell body (or perikaryon) is the main constituent of the neuron from which an axon and numerous dendritic processes extend.

• The cell bodies may be arranged in layers as in the cerebral cortex, or may be aggregated as in the basal ganglia.

• The cell body possesses a large, round, centrally-placed nucleus having finely granular nuclear chromatin and a prominent nucleolus.

• The cytoplasm contains polygonal, basophilic structures called Nisslsubstance. It consists of aggregates of RNA, sheaves of rough endoplasmic reticulum and intervening groups of free ribosomes.

• Besides Nissl substance, other special features of the cytoplasm of neuronal cell body are the presence of microtubules, synaptic vesicles and neurofilaments which are a form of intermediate filaments specific to neurons.

• Neuropil is the term used for the fibrillar network formed by processess of all the neuronal cells.

• The neuroglia are cells which support the neurons, they include astrocytes, oligodendrocytes & ependymal cells.

• The astrocytes- having multiple complex cytoplasmic processes.• In routine haematoxylin and eosin stains, an astrocyte has round or

oval vesicular nucleus, but unlike neuron, lacks a prominent nucleolus. The cytoplasm is generally scanty.

• The processes radiate from the cell body. Depending upon the type of processes, two types of astrocytes are distinguished:

• Protoplasmic astrocytes have branched processes and are found mostly in the grey matter.

• Fibrous astrocytes have long, thin processes and are present mainly in the white matter.

• The astrocytes in respond to injury undergo hyperplasia and hypertrophy termed ‘gliosis’ which is an equivalent of scar elsewhere in the body.

• Gemistocytic astrocytes are early reactive astrocytes having prominent pink cytoplasm.

• Long-standing progressive gliosis results in the development of Rosenthal fibres which are eosinophilic, elongated or globular bodies present on the astrocytic processes.

• Corpora amylacea are basophilic, rounded, sometimes laminated bodies, present in elderly people in the white matter and result from accumulation of starch-like material in the degenerating astrocytes.

• The main functions of astrocytes in health are physiological and biochemical support to the neurons and interactions with capillary endothelial cells to establish blood brain barrier.

• Oligodendrocytes- Oligodendrocytes are so named because of their short and fewer processes when examined by light microscopy with special stains (oligo=short).

• In haematoxylin-eosin stained sections, these cells appear as small cells with a darkly-staining nucleus resembling that of small lymphocyte. The cytoplasm appears as a clear halo around the nucleus.

• Oligodendrocytes are present throughout the brain in grey as well as white matter and are most numerous of all other cells in the CNS.

• In grey matter, they are clustered around the neurons and are called satellite cells. In white matter, they are present along the myelinated nerve fibres and are termed interfascicularoligodendroglia.

• The major function of oligodendrocytes is formation and maintenance of myelin.

• Ependymal cells- The ependymal cells are epitheliumlike and form a single layer of cells lining the ventricular system, aqueduct, central canal of the spinal cord and cover the choroid plexus.

• They are cuboidal to columnar cells and have ciliated luminal surface, just beneath which are present small bodies termed blepharoplasts.

• The ependymal cells influence the formation and composition of the cerebrospinal fluid (CSF) by processes of active secretion, diffusion, absorption and exchange.

• The function of cilia is not very clear but probably they play a role in the circulation of CSF.

• The ependymal cells respond to injury by cell loss and the space left is filled by proliferation of underlying glial fibres.

Cells comprising the nervous system.

• In addition, there are other cells called microglia, which constitute the mononuclear macrophage system of the brain.

• The brain is covered by tough fibrous sheath called the durameter and leptomeninges which includes piameter & arachnoid-meter.

• The common disorders of CNS includes the following-

1. Developmental anomalies- Spina bifida, Meningocele, Meningomyelocele

2. Infections & inflammations- Meningitis, Encephalitis, Abcess

3. Cerebrovascular disease- Thrombosis,embolism, hemorrhge

4. Demyelinating disorder- Multiple sclerosis

5. Tumors- Meningioma, astrocytoma, medulloblastoma.

HYDROCEPHALUS• It is defined as an increase volume of cerebrospinal fluid(CSF) within the brain. It is

divided into internal & external hydrocephalus.

• In the internal type there is irregular dilatation of the ventricular spaces with increased intracranial pressure and in the external type there is localized collection of CSF in the subarachnoid space.

• Source and Circulation of CSF

• CSF is mainly produced by choroid plexus in the lateral, third and fourth ventricle, and a small part is formed on the surface of the brain and spinal cord.

• The total volume of CSF is about 120-150 ml.

• CSF formed in the lateral ventricles flows through the foramina of Munro to the third ventricle and from there by the aqueduct of Sylvius to the fourth ventricle. The fluid then passes through the foramina of Magendie and Luschka of the fourth ventricle to reach the subarachnoid space of the brain. It then spreads through the subarachnoid space over the surface of the spinal cord. It is absorbed into the blood by the arachnoid villi present along the dural venous sinuses.

Normal circulation of CSF

• Types and Etiopathogenesis• Hydrocephalus is classified into primary and secondary

types, the former being much more common, both types have distinct etiology and pathogenesis.

• PRIMARY HYDROCEPHALUS- Primary hydrocephalus is defined as actual increase in the volume of CSF within the skull along with elevated intracranial pressure.

There are 3 possible mechanisms of primary hydrocephalus:1. Obstruction to the flow: Stenosis of aqueduct, arnold-

chairi malformation, tumors adjacent to ventricles2. Overproduction of CSF: Due to tumors like choroid plexus

papilloma3. Deficient reabsorption of CSF: As in meningitis.

• SECONDARY HYDROCEPHALUS- Secondary hydrocephalus is much less common and is defined as compensatory increase of CSF due to loss of neural tissue without associated rise in intracranial pressure (normal pressure hydrocephalus) e.g. from cerebral atrophy and infarction.

• MORPHOLOGIC FEATURES- Grossly, there is dilatation of the ventricles depending upon the site of obstruction. There is thinning and stretching of the brain. The scalp veins overlying the enlarged head are engorged and the fontanelle remain open.

• Histologically, severe hydrocephalus may be associated with damage to ependymal lining of the ventricles and periventricular interstitial oedema.

INFECTIONS

• The brain and spinal cord is prone for a wide range of infections.

• The infections reach the brain through-i)blood stream(hematogenous), ii)local spread from adjacent infective foci andiii) along nerve roots(viral infections).

• The general pattern of inflammations include-meningitis(inflammation of meninges), encephalitis(inflammation of the brain) and meningoencephalitis(both).

Meningitis

• It is inflammatory condition involving the meninges. Meningitis may involve the dura called pachymeningitis, or the leptomeninges (pia-arachnoid) termed leptomeningitis.

• The latter is far more common, and unless otherwise specified, meningitis would mean leptomeningitis.

• Pachymeningitis is invariably an extension of the inflammation from chronic suppurative otitis media or from fracture of the skull. An extradural abscess may form by suppuration between the bone and dura. Further spread of infection may penetrate the dura and form a subdural abscess.

• Other effects of pachymeningitis are localised or generalised leptomeningitis and cerebral abscess.

• Leptomeningitis, commonly called meningitis, is usually the result of infection but infrequently chemical meningitis and carcinomatousmeningitis by infiltration of the subarachnoid space by cancer cells may occur.

• Infectious meningitis is broadly classified into 3 types: -acute pyogenic, -acute lymphocytic (viral, aseptic) and- chronic (bacterial or fungal)

• Acute Pyogenic Meningitis

• Acute pyogenic or acute purulent meningitis is acute infection of the pia-arachnoid and of the CSF enclosed in the subarachnoid space. Since the subarachnoid space is continuous around the brain, spinal cord and the optic nerves, infection spreads immediately to whole of the cerebrospinal meningesas well as to the ventricles.

• ETIOPATHOGENESIS- The causative organisms vary with age of the patient:

• 1. Escherichia coli infection is common in neonates with neural tube defects.

• 2. Haemophilus influenzae is commonly responsible for infection in infants and children.

• 3. Neisseria meningitidis causes meningitis in adolescent and young adults and is causative for epidemic meningitis.

• 4. Streptococcus pneumoniae is causative for infection at extremes of age and following trauma.

• The routes of infection in acute pyogenic meningitis are as follows:

1. Most commonly by the blood stream.

2. From an adjacent focus of infection.

3. By iatrogenic infection such as introduction of microorganisms at operation or during lumbar puncture.

• MORPHOLOGIC FEATURES- Grossly, pus accumulates in the subarachnoid space so that normally clear CSF becomes turbid or frankly purulent. The turbid fluid is particularly seen in the sulci and at the base of the brain where the space is wide. In fulminant cases, some degree of ventriculitis is also present having a fibrinouscoating on their walls and containing turbid CSF. In addition, purulent material may interfere with CSF flow and result in obstructive hydrocephalus.

• Microscopically, there is presence of numerous polymorphonuclear neutrophils in the subarachnoid space as well as in the meninges, particularly around the blood vessels. Gram-staining reveals varying number of causative bacteria.

• Acute Lymphocytic (Viral, Aseptic) Meningitis• Acute lymphocytic meningitis is a viral or aseptic meningitis,

especially common in children and young adults.• Among the etiologic agents are numerous viruses such as

enteroviruses, mumps, ECHO viruses, coxsackie virus, Epstein-Barr virus, herpes simplex virus-2, arthropode-borne viruses and HIV. However, evidence of viral infection may not be demonstrable in about one third of cases.

• MORPHOLOGIC FEATURES- Grossly, some cases show swelling of the brain while others show no distinctive change.

• Microscopically, there is mild lymphocytic infiltrate in the leptomeninges.

• Chronic (Tuberculous and Cryptococcal) Meningitis• There are two principal types of chronic meningitis—one bacterial

(tuberculous meningitis) and the other fungal(cryptococcal meningitis).• Both types cause chronic granulomatous reaction and may produce

parenchymal lesions.• Tuberculous meningitis occurs in children and adults through

haematogenous spread of infection from tuberculosis elsewhere in the body, or it may simply be a manifestation of miliary tuberculosis. Less commonly, the spread may occur directly from tuberculosis of a vertebral body.

• Cryptococcal meningitis develops particularly in immunocompromisedpersons, usually as a result of haematogenous dissemination from a pulmonary lesion. Cryptococcal meningitis is especially an important cause of meningitis in patients with AIDS.

• MORPHOLOGIC FEATURES- Grossly, in tuberculous meningitis, the subarachnoid space contains thick exudate,particularly abundant in the sulci and the base of the brain. Tubercles, 1-2 mm in diameter, may be visible, especially adjacent to the blood vessels.

• The exudate in cryptococcal meningitis is scanty, translucent and gelatinous.

• Microscopically, tuberculous meningitis shows exudate of acute and chronic inflammatory cells, and granulomas with or without caseation necrosis and giant cells. Acidfast bacilli may be demonstrated. Late cases show dense fibrous adhesions in the subarachnoid space and consequent hydrocephalus.

• Cryptococcal meningitis is characterised by infiltration by lymphocytes, plasma cells, an occasional granuloma and abundant characteristic capsulated cryptococci.

Acute supporative meningitis

• Clinical Profile: The general clinical features include-

• fever,

• severe headache,

• vomiting,

• drowsiness,

• stiffness of the neck,

• convulsions and coma.

• Diagnosis: The diagnosis is made based on the examination of CSF.

• CSF finding in various forms of meningitis:

CSF findings Normal Pyogenicmeningitis

Aseptic meningitis

Chronicmeningitis

Nakedappearance

Clear and colourless

Cloudy/purulent Clear Clear with formation of cob web

Pressure 60-150 mm water

Elevated Elevated Elevated

Predominat cells 0-4 lymphocytes/μl

Neutrophils Lymphocytes Lymphocytes

Protein level 15-45 mg/dl Markedlyincreased

Normal Inreased

Sugar content 50-80 mg/dl Markedly decreased

Normal Decreased

Bacteriological study

Sterile Organisms detected

Sterile AFB+ve bacilli

Encephalitis

• It is inflammation of the brain parenchyma due to bacterial, viral & fungal infections.

• The most common clinical entities are-1. Brain abcess, which are localized supporative

inflammatory conditions of the brain,2. Tuberculoma, a manifestation of tuberculosis of brain,3. Neurosyphilis, which is seen in tertiary form of syphilis.• Most common viral agents causing encephalitis are-

HIV, Herpes zoster virus, Cytomegalovirus, Poliovirus.• The common fungal organisms include- Cryptococci,

Aspergillus, Histoplasma etc.

Tuberculous encephalitis of brain

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