ic Management of Parkinsonism & Other Movement Disorders 493 |

structures is not yet fully understood, and it is not possible to

relate individual symptoms to involvement at specific sites.
M PARKINSONISM
Parkinsonism is characterized by a combination of rigidity, brady-
kinesia, tremor, and postural instability that can occur for a variety
of reasons but is usually idiopathic (Parkinson's disease or paralysis
agitans). Bradykinesia should be present before a diagnosis of Par-
kinson’s disease is made. Focal dystonic features may be present.
Cognitive decline occurs in many patients as the disease advances.
Other nonmotor symptoms include affective disorders (anxiety
or depression); confusion, cognitive impairment, or personality
changes; apathy; fatigue; abnormalities of autonomic function (eg,
sphincter or sexual dysfunction, dysphagia and choking, sweating
abnormalities, sialorrhea, or disturbances of blood pressure regula-
tion); sleep disorders; and sensory complaints or pain. The disease
is incurable, is generally progressive, and leads to increasing dis-
ability with time, but pharmacologic treatment may relieve motor
symptoms and improve the quality of life for many years.
Pathogenesis
The pathogenesis of parkinsonism seems to relate to a combina-
tion of impaired degradation of proteins, intracellular protein
accumulation and aggregation, oxidative stress, mitochondrial
damage, inflammatory cascades, and apoptosis. Studies in twins
_ suggest that genetic factors are important, especially when the
rs. in | patients under age 50. Recognized genetic
nt for 10-15% of cases. Mutations of the
4q21 or duplication and triplication of the
me are associated with Parkinson's disease,
reco gnized as a synucleinopathy. Mutations of
ft kinase 2 (LRRK2) gene at 12cen, and the
$0 cause autosomal dominant parkinsonism.
thin gene (6q25.2-q27) cause early-onset,
familial parkinsonism, or sporadic juvenile-
sveral other genes or chromosomal regions
with familial forms of the disease. Envi-
fous toxins may also be important in the
Epidemiologic studies reveal that cigarette
flammatory drug use, and high serum uric
€, whereas the incidence of the diseas: j
ing in teaching, health care, or ‘arming,
ing hese exposure or with viramin D
trace ular inclusinn bodies
gic cell: transplanted
HS previously has
on's disease
dre