Chapter 21 - Progressive Supranuclear Palsy

Abstract

Progressive supranuclear palsy (PSP) is an age-dependent neurodegenerative condition, and the clinical progression of PSP has similarities to amyotrophic lateral sclerosis—with progressive loss of speech, swallowing, and ambulation in the setting of largely intact cognitive function. The presence of a vertical supranuclear gaze palsy and prominent postural instability with falls in the first year of symptoms leads to a diagnosis of clinically probable PSP , and the presence of the balance disorder with slowing of vertical saccades or an isolated supranuclear gaze palsy leads to a diagnosis of clinically possible PSP. Magnetic resonance imaging (MRI) is helpful in excluding structural lesions and in established PSP often shows midbrain and superior cerebellar peduncular atrophy, which can be used to distinguish PSP from Parkinson's disease (PD) and multiple system atrophy (MSA) associated with parkinsonism. Pathologically, PSP involves the deposition of neurofibrillary tangles (NFTs), gliosis, and cell loss in a specific distribution, particularly affecting the subthalamic nucleus, globus pallidus, substantia nigra (pars compacta and reticulata), pretectal area of the midbrain, and basis pontis. The pathological differential diagnosis of PSP includes FTDP-17T, corticobasal degeneration (CBD), and other neurodegenerative tauopathies. Cerebrospinal fluid tau analysis may become a biomarker, which might be useful in diagnosing PSP or in tracking the response to disease-modifying therapies. The molecular genetics and treatment methods of PSP are also discussed in the chapter.