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PARKINSON’S DISEASE AND RELATED DISORDERS
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Parkinson’s disease (PD) is the second commonest neurodegenerative disease, exceeded only by Alzheimer’s disease (AD). Its cardinal clinical features were first described by the English physician James Parkinson in 1817. It is noteworthy that James Parkinson was a general physician who captured the essence of this condition based on a visual inspection of a mere handful of patients. It is estimated that approximately 1 million persons in the United States, 1 million in Western Europe, and 5 million worldwide suffer from this disorder. PD affects men and women of all races, all occupations, and all countries. The mean age of onset is about 60 years. The frequency of PD increases with aging, but cases can be seen in patients in their 20s and even younger. Based on the aging of the population and projected demographics, it is estimated that the prevalence of the disease will dramatically increase in the next several decades.
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Clinically, PD is characterized by rest tremor, rigidity, bradykinesia (slowing), and gait impairment, known as the “cardinal features” of the disease. Additional features can include freezing of gait, postural instability, speech difficulty, autonomic disturbances, sensory alterations, mood disorders, sleep dysfunction, cognitive impairment, and dementia (Table 449-1).
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Pathologically, the hallmark features of PD are degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), reduced striatal dopamine, and intracytoplasmic proteinaceous inclusions known as Lewy bodies that primarily contain the protein alpha synuclein (Fig. 449-1). While interest has primarily focused on the dopamine system, neuronal degeneration with inclusion body formation can also affect cholinergic neurons of the nucleus basalis of Meynert (NBM), norepinephrine neurons of the locus coeruleus (LC), serotonin neurons in the raphe nuclei of the brainstem, and neurons of the olfactory system, cerebral hemispheres, spinal cord, and peripheral autonomic nervous system. This “nondopaminergic” pathology is likely responsible for the development of nondopaminergic clinical features listed in Table 449-1 characterized by their lack of satisfactory response to dopaminergic replacement therapy. There is evidence that Lewy body pathology first begins in the peripheral autonomic nervous system, olfactory system, and dorsal motor nucleus of the vagus nerve in the lower brainstem, and then spreads in a predictable and sequential manner to affect the upper brainstem and cerebral hemispheres (Braak staging). These studies suggest that degeneration of dopamine neurons develops in a mid-stage of ...