Figure 38-6. Schematic diagram of proposed mechanisms of α-synuclein toxicity in Parkinson disease. In this model, α-synuclein levels are elevated by (a) duplication of one copy of the α-synuclein gene; (b) point mutations in the α-synuclein gene that generate excessive accumulations of synuclein; or (c) mutations in parkin and UCH-L1 genes that reduce normal removal of synuclein by the proteosomes. The excess of synuclein polymerizes to form protofibrils, a process that is enhanced by defects in heat shock proteins (Hsps) or by the action of dopamine, which binds to synuclein. In turn, this leads to formation of Lewy bodies. This model attributes the neurotoxicity to either the protofibrils or the Lewy bodies. (Adapted by permission from Eriksen JL, Dawson TM, Dickson DW, Petrucelli L: Caught in the act: α-Synuclein is the culprit in Parkinson’s disease. Neuron 40:453–456, 2003.)
Figure 38-7. Progressive supranuclear palsy. A. T2-weighted axial MRI showing the atrophic dorsal midbrain that gives rise to the “mouse ears” (also “Mickey mouse”) appearance. B. Mid-sagittal image showing atrophy of the dorsal midbrain, giving the appearance of a hummingbird.
Figure 38-8. Familial cortical cerebellar atrophy. T1-weighted MRI in the sagittal plane showing marked atrophy of vermis and enlargement of fourth ventricle. The brainstem is only mildly atrophic and the posterior fossa is normal is size. Compare with Fig. 38-9 in which the cerebellum and pons are atrophic.
Figure 38-9. MSA-C, formerly called olivopontocerebellar atrophy. MRI in the sagittal plane demonstrating both vermian atrophy (black arrow) and smallness of the pons (white arrow). (Reproduced by permission from Bisese JH: Cranial MRI. New York, McGraw-Hill, 1991.)
Figure 38-10. Axial T2-weighted MRI showing abnormal hyperintensity reflecting wallerian change in the corticospinal tracts at the level of the internal capsule (top, arrow) and the pons (bottom) in a patient with ALS.
Chapter  38    Degenerative Diseases of the Nervous System
The Acquired Metabolic Disorders of the Nervous System
An important segment of neurologic medicine, and one that is seen with great frequency in general hospitals, are disorders in which a global disturbance of cerebral function (encephalopathy) results from failure of some other organ system—heart and circulation, lungs and respiration, kidneys, liver, pancreas, and the endocrine glands. Unlike the diseases considered in Chap. 36, in which a genetic abnormality affects the metabolic functions of many organs and tissues including the brain, the cerebral disorders discussed in this chapter are strictly secondary to derangements of the visceral organs themselves. They stand at the interface of internal medicine and neurology.