Neurodegenerative disease movement disorders

It is now widely accepted that the term Parkinson s syndrome refers to a collection of neurodegenerative diseases, all of which are characterized by movement disorders. It also applies to drug-induced disorders of the parkinsonian type. A schematic representation of this syndrome is shown in Figure 13.1. 

Parkinson s disease (PD), Alzheimer s disease (AD), multi-infarct dementia and motoneuron disease (e.g. amyotrophic lateral sclerosis, ALS) represent typical neurodegenerative diseases for which no known etiology has been put forward. Parkinson s disease is characterized by reduced size and velocity of movements. In AD, cognitive impairment is the cardinal clinical symptom. In motoneuron disease, a degeneration of the central pyramidal, the peripheral motor system or both is the reason for the clinical picture. A significant overlap exists between these three disorders. 

Parkinson s disease is a common neurodegenerative syndrome characterized by loss of dopaminergic neurons in the substantia nigra, formation of filamentous intraneuronal inclusions (Lewy bodies) and an extrapyramidal movement disorder. Mutations in the a-synuclein gene are linked to familial Parkinson s disease, and a-synuclein accumulates in Lewy bodies and Lewy neurites. Normal and mutant forms of a-synuclein were expressed in Drosophila and produced adult-onset loss of dopaminergic neurons, filamentous intraneuronal inclusions containing a-synuclein and locomotor dysfunction. The Drosophila model thus recapitulates the essential features of the human disorder and makes possible a powerful genetic approach to Parkinson s disease. 

HD is an autosomal dominant, late-onset neurodegenerative disorder with an incidence of about 1 in 10,000 in most populations of European origin. The disease is progressive and characterized by frequent involuntary, rapid movements (chorea) and dementia with a median survival time of 15 to 18 years after the onset of symptoms. The mean age of onset is in the decade between 35 and 44 years, but approximately 25% of patients first display symptoms after the age of 50, and about 10% of patients have juvenile HD with the age of onset before 20 years. In the first few years of the disease, symptoms include mood disturbances, cognitive deficits, clumsiness, and impairment of voluntary move-ment. The next stage of the disease is associated with... 

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