Page 850 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

836 C H A P T E R 22 Central Nervous System Table 22–3 Some Causes of Dementia or Cognitive Impairment
metals, including lead (often causing a diffuse encephalopa- Primary Neurodegenerative Disorders
thy), as well as arsenic and mercury; industrial chemicals, Alzheimer disease
including organophosphates (in pesticides) and methanol Frontotemporal lobar degeneration
(causing blindness from retinal damage); and environmental Lewy body dementia
pollutants such as carbon monoxide (combining hypoxia Huntington disease
with selective injury to the globus pallidus). Spinocerebellar ataxia (certain forms)
Ethanol has a variety of effects on the brain. While acute Infections
intoxication is reversible, excessive intake can result in pro- Prion disease
found metabolic disturbances, including brain swelling HIV associated neurocognitive disorder
and death. Chronic alcohol exposure leads to cerebellar Progressive multifocal leukoencephalopathy
dysfunction in about 1% cases, with truncal ataxia, unsteady Viral encephalitis
gait, and nystagmus, associated with atrophy in the ante- Neurosyphilis
rior vermis of the cerebellum. Chronic meningitis
Ionizing radiation, commonly used to treat intracranial Vascular and Traumatic Diseases
tumors, can cause rapidly evolving signs and symptoms Multifocal cerebral infarction
including headaches, nausea, vomiting, and papilledema, Severe hypertensive cerebrovascular disease
even months to years after irradiation. Affected brain Cerebral autosomal dominant arteriopathy with subcortical infarction
regions show large areas of coagulative necrosis, adjacent
edema, and blood vessels with thickened walls containing and leukoencephalopathy (CADASIL)
intramural fibrin-like material. Chronic traumatic encephalopathy
Metabolic and Nutritional Diseases
NEURODEGENERATIVE DISEASES Thiamine deficiency (Wernicke-Korsakoff syndrome)
Vitamin B12 deficiency
Degenerative diseases of the CNS are disorders character- Niacin deficiency (pellagra)
ized by the cellular degeneration of subsets of neurons that Endocrine diseases
typically are related by function, rather than by physical Miscellaneous
location in the brain. Many of these disorders are associ- Neuronal storage diseases
ated with the accumulation of abnormal proteins, which Toxic injury (from mercury, lead, manganese, bromides, others)
serve as histologic hallmarks of specific disorders (Table
22–2). An important but unanswered question is why these of neuronal dysfunction: those that affect the cerebral corti-
abnormal proteins tend to accumulate in and preferentially cal neurons result in loss of memory, language, insight, and
affect particular kinds of neurons, since the involved pro- planning, all components of dementia; those that affect the
teins typically are widely expressed throughout the nervous neurons of the basal ganglia result in movement disorders;
system. those that affect the cerebellum result in ataxia; and those
that affect motor neurons result in weakness. Although
Subtle differences among subtypes of neurons are pre- many degenerative diseases have primary targets, other
sumed to explain why particular neurons are affected in brain regions are often affected later in the course of the
specific disorders. Understandably, the clinical manifesta- illness; thus, while Huntington disease often has move-
tions of degenerative diseases are dictated by the pattern ment disorders as an early symptom, later cortical involve-
ment typically results in the development of cognitive
Table 22–2 Protein Inclusions in Degenerative Diseases changes as well. Dementia is defined as the development of
memory impairment and other cognitive deficits severe
Disease Protein Location enough to decrease the affected person’s capacity to func-
tion at the previous level despite a normal level of
Alzheimer disease Aβ Extracellular consciousness. It arises during the course of many neuro-
Tau Neurons degenerative diseases; it also can accompany numerous
other diseases that injure the cerebral cortex (Table 22–3).
Frontotemporal Tau Neurons Dementia is an increasing public health concern as the
lobar degeneration population ages.

Progressive Tau Neurons and Alzheimer Disease
supranuclear palsy glia
Alzheimer disease (AD) is the most common cause of
Corticobasal Tau Neurons and dementia in the elderly population. The disease usually
degeneration glia manifests with the insidious onset of impaired higher intel-
lectual function and altered mood and behavior. Later, this
Parkinson disease α-Synuclein Neurons progresses to disorientation, memory loss, and aphasia,
findings indicative of severe cortical dysfunction, and over
Multiple system α-Synuclein Glia and some another 5 to 10 years, the patient becomes profoundly dis-
atrophy neurons abled, mute, and immobile. Death usually occurs from
intercurrent pneumonia or other infections. Age is an
Frontotemporal TDP-43 Neurons
lobar degenerations

Amyotrophic lateral TDP-43 Neurons
sclerosis SOD-1 (familial disease) Neurons

Huntington disease Huntingtin Neurons

Spinocerebellar Ataxins (various) Neurons
ataxias

SOD-1, superoxide dismutase-1; TDP-43, TAR DNA-binding protein 43.