Education of both the patient and family about Parkinson’s disease is important, as this is a slowly progressive illness. Patients should be taught to avoid sofalike seats since arising from a chair is easier; to use bars in the bathroom to minimize falls; and eventually to use walkers to improve bal-ance while walking. A hip fracture in a patient with Parkinson’s disease is serious. There is a slow recovery and a 25% mortality risk.
that hypometabolism in the striatum begins prior to observable atrophy and before the onset of clin-ical symptoms. In addition to striatal neuronal loss, there is a moderate loss (10%–50%) of neu-rons in many basal ganglia nuclei and the pre-frontal cerebral cortex.
Major Clinical Features
The mean age of onset of HD is 40 years but some patients do not develop signs until past age 60 years. The clinical features are progressive disor-ders of movement, cognition, and behavior. Sud-den nonrepetitive, nonperiodic, involuntary jerking movements involving random shifting muscles or muscle groups characterize chorea, the principle movement disorder. Chorea soon becomes very frequent during waking hours, involving the arms, hands, legs, tongue, or trunk.
These movements can be voluntarily suppressed only briefly and are made worse by stress. Early in the disease, patients frequently appear fidgety and mask the involuntary limb movement by
incorpo-rating the involuntary jerk into a semipurposeful movement. Voluntary rapid eye movements from one target to another (saccadic eye movements) become slowed and uncoordinated. The inability to sustain a constant voluntary muscle contraction manifests as trouble extending their tongues for any period of time and maintaining a tight hand-shake (milkmaid’s grip). In the early stage of the disease, patients often have normal activities of daily living and may continue to be employed. As the disease worsens, dystonia and parkinsonism appears. Dysarthria develops, with hypophonic irregular speech that becomes unintelligible. At this stage the patient depends on others for help.
Dysphagia appears late and often contributes to the death of the patient.
A global decline in cognitive capabilities begins before or after the onset of chorea; only a few patients develop mild cognitive loss. The cognitive decline is characterized by loss of executive func-tions, with the inability to plan, sequence, and exe-cute complex tasks; forgetfulness from loss of recent memory; slow response times; and poor
CHAPTER 12—Disorders of the Extrapyramidal System 131
Figure 12-4 Pathology of caudate atrophy in a patient with Huntington’s disease.
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concentration. IQ score falls and dementia is pres-ent in most patipres-ents. Aphasia, apraxia, and agnosia are uncommon, but impaired visuospatial abilities develop in the late stage.
Behavioral problems often begin with personal-ity changes manifesting as irritabilpersonal-ity, compulsiv-ity, apathy, and anxiety that may appear years before the chorea. Depression develops in 1/3 of patients and may lead to suicide. Psychosis is uncommon (5%).
Juvenile HD has an onset of less than 20 years and is characterized by more prominent parkin-sonism, especially bradykinesia. Patients have marked rigidity, severe mental deterioration, prominent motor and cerebellar signs, dysarthria, myoclonus, tics, and dysphagia. Juvenile HD pro-gresses faster than adult HD.
Major Laboratory Findings
Routine blood and CSF tests are unremarkable.
Neuroimaging studies demonstrate atrophy of the caudate and may show atrophy of the putamen.
The progressive caudate atrophy parallels loss of cognitive function and putaminal atrophy with motor decline. Neuropsychiatric tests demonstrate many abnormalities, but none are diagnostic.
The clinical diagnosis is usually made based on (1) onset in mid-life with typical chorea, cognitive loss, and behavioral changes, (2) positive family history, and (3) neuroimaging demonstrating cau-date atrophy. The definite diagnosis is made by demonstrating abnormally long CAG trinu-cleotide repeat lengths (>40) in the HD gene (chromosomal locus 4p16) on genetic testing. This commercial test is useful in establishing the diag-nosis in atypical cases, symptomatic individuals without a positive family history, individuals at
risk for the illness, and prenatal screening. For pre-dictive testing to be performed, there should be (1) multidisciplinary supportive counseling before and after testing, (2) clear informed consent, and (3) confidential reporting. In general, predictive tests should not be done on minors. Although the number of CAG repeats is correlated with age of disease onset, the range of onset for each CAG length is so broad as not to be useful for individual tests and hence the length is seldom reported to the patient.
Principles of Management and Prognosis Since no treatment is available to cure or slow dis-ease progression, management aims at maximizing the quality of life for as long as possible. Depres-sion should be diagnosed early and actively treated with antidepressants. Attempts to treat the chorea seldom are beneficial to the patient. Psychosis and severe agitation can be treated with low doses of neuroleptic medications. There is no treatment for the cognitive decline.
The mean duration from diagnosis to death is 20 years, with a range of 10 to 25 years. Mean age of death is 55 years. Individuals with juvenile HD have a shorter life span.
RECOMMENDED READING
Lang AE, Lozano AM. Parkinson’s disease (parts 1 and 2). N Engl J Med 1998;339:1044–1053 and 1130–1143. (Thorough review of clinical and pathologic issues and treatment.)
Louis ED. Essential tremor. N Engl J Med 2001;345:887–891. (Reviews clinical features and treatment options.)
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Overview
Viruses, bacteria, fungi, and parasites cause CNS infections, but bacteria and viruses are the most common agents. After entering the body via the GI tract or respiratory tract or following skin inocula-tion (animal or insect bite), the infectious organ-ism sets up the initial site of replication in the GI tract, respiratory tract, or subcutaneous muscle, or vascular tissue. Most organisms reach the CNS by way of the bloodstream, but occasional organisms reach the brain via peripheral nerves or by direct entry through adjacent bone from skull fractures or infected mastoid and air sinuses.
In spite of the many infections we develop dur-ing our lifetimes, organisms rarely reach the CNS.
Important protective systems include the reticu-loendothelial system (which nonspecifically and efficiently removes microorganisms from the blood), cellular and humoral immune responses (which destroy specific microorganisms in the blood and at sites of infection), and the blood–brain barrier. The CNS evolved separately from other systemic organs and did not develop a sensitive immune surveillance system. The brain lacks lymphatic channels or lymph nodes. Instead, a blood–brain barrier has developed to prevent infectious organisms from entering the CNS. The
key element of the blood–brain barrier is tight junctions between endothelial cells, which prevent microorganisms or even small molecules from passing between endothelial cells to enter the brain or meninges. Endothelial cells in most of the body have gap junctions that are large enough to allow lymphocytes to pass from blood vessels into the lymphatic system. Molecules that reach the brain do so by passing through normal cerebral endothelial cells via specific transport systems that may require energy (amino acid transporters) or not require energy (glucose transporter), or because the molecule is lipid soluble. In addition, CNS endothelial cells have transporters that remove molecules, such as amino acids that are neurotransmitters, from the CNS. Larger mole-cules enter the CSF from blood via the choroid plexus, which acts as an ultrafilter of plasma.
When intact, the blood–brain barrier not only pre-vents entry of infectious organisms but also main-tains, under tight limits, the type and concentration of molecules free in the CNS.
However, if an infectious organism successfully enters the CNS, there are limited defenses to fight the infection. CSF has 1/1,000 the amount of anti-bodies and complement as blood. Since the brain lacks a lymphatic system, there are few WBCs and limited microglia (resident CNS macrophages) to 133