Page 900 - Textbook of Pathology, 6th Edition

884 of the spinal cord, optic nerve and brain. The first attack These groups along with the list of diseases included in each
usually begins with a single sign or symptom, most group are briefly outlined below without going into the
commonly optic neuritis, followed by recovery. As the details of individual diseases for which the interested reader
disease becomes more progressive, remissions become may consult pertinent text on neuropathology and neurology.
infrequent and incomplete. The etiology of multiple sclerosis
remains unknown but a role for genetic susceptibility, Degenerative Diseases
infectious agent and immunologic mechanism has been Degenerative diseases are disorders of unknown etiology
proposed. and pathogenesis, characterised pathologically by prog-
ressive loss of CNS neurons and their processes accom-
MORPHOLOGIC FEATURES. The pathologic hallmark panied by fibrillary astrocytosis. The identification of these
is the presence of many scattered discrete areas of diseases depends upon exclusion of diseases with known
demyelination termed plaques.
etiologies such as metabolic disturbances, vascular
Grossly, plaques appear as grey-pink, swollen, sharply diseases, nutritional deficiencies or infection. A consider-
defined, usually bilaterally symmetric areas in the white able proportion of degenerative disorders are genetic in
matter. origin, with either dominant or recessive inheritance;
Microscopically, the features vary according to the age others occur sporadically. Family history is, of course, of
of the plaque: great importance.
1. ln active enlarging plaques, the histologic features are The degenerative disorders usually begin insidiously and
accumulation of lymphocytes and macrophages around have a gradual progressive course over many years. In
venules and at the plaque margin where demyelination virtually all cases, the lesions have characteristic bilaterally
is occurring. In addition, there is loss of oligodendrocytes symmetric distribution. Another striking characteristic of the
and presence of reactive astrocytosis with numerous lipid- degenerative disorders is that particular anatomic or
laden macrophages (microglia) in the plaque. The axons physiologic system of neurons may be selectively affected,
in the plaque are generally intact. leaving others entirely intact.
2. In old inactive plaques, there is no perivascular inflam- Classification of degenerative diseases into individual
matory cell infiltrate and nearly total absence of syndromes is based on clinical aspects and anatomic
oligodendrocytes. Demyelination in the plaque area is distribution of the lesions. Some of the more common
complete as there is only limited regeneration of myelin. degenerative diseases are listed in Table 30.3. Two of the
SECTION III
Gliosis is well-developed but astrocytes are less important examples—Alzheimer’s disease and parkin-
prominent. Some axonal loss may be present. sonism, are considered below.
ALZHEIMER’S DISEASE. Alzheimer’s disease is the most
Perivenous Encephalomyelitis common cause of dementia in the elderly. The condition
Perivenous encephalomyelitis includes two uncommon occurs after 5th decade of life and its incidence progressively
diseases: acute disseminated encephalomyelitis and acute increases with advancing age. The exact cause is not known
necrotising haemorrhagic leucoencephalitis. Both are monophasic but a few factors are implicated in its etiology which include
diseases characterised by perivenous mononuclear positive family history and deposition of Aβ amyloid derived
inflammatory cell infiltration. Both diseases occur following from amyloid precursor protein (APP) forming neuritic ‘senile’
a viral infection, vaccination or a respiratory illness. Both plaques and neurofibrillary tangles.
these conditions are looked upon as human counterpart of Grossly, the brain is often reduced in weight and
Systemic Pathology
experimental allergic encephalomyelitis (EAE) and are bilaterally atrophic.
considered to be allergic reaction against myelin antigen. Microscopically, the main features are as under:
Acute disseminated encephalomyelitis occurs usually i) Senile neuritic plaque is the most conspicuous lesion and
following viral infection (measles, mumps, rubella, consists of focal area which has a central core containing
chickenpox), whooping cough or vaccination. The disease Aβ amyloid.
begins abruptly with headache and delirium followed by ii) Neurofibrillary tangle is a filamentous collection of
lethargy and coma. Signs of meningeal irritation and fever neurofilaments and neurotubules within the cytoplasm
may be present. Prognosis for recovery is generally good. of neurons.
Acute necrotising haemorrhagic leucoencephalitis is a iii) Amyloid angiopathy is deposition of the same amyloid
rare disease occurring more often after a respiratory infection. in the vessel wall which is deposited in the amyloid core
The clinical course is similar to that of acute disseminated of the plaque.
encephalomyelitis except for its suddenness of onset and iv) Granulovacuolar degeneration is presence of multiple,
rapidity of progression, sometimes leading to death within small intraneuronal cytoplasmic vacuoles, some of which
48 hours. contain one or more dark granules called Hirano bodies.
PARKINSONISM. Parkinsonism is a syndrome of chronic
MISCELLANEOUS DISEASES
progressive disorder of motor function and is clinically
Included under the heading of miscellaneous diseases of the characterised by tremors which are most conspicuous at rest
CNS are degenerative, metabolic and nutritional diseases. and worsen with emotional stress; other features are rigidity