Progressive Supranuclear Palsy: Neurology and Treatment

Introduction to Progressive Supranuclear Palsy

Progressive Supranuclear Palsy (PSP) is an uncommon neurodegenerative disorder that leads to severe executive dysfunction. Traditional clinical findings in PSP reveal that executive functions are the most severely affected, including lack of initiative, increasing information processing time, decreased verbal fluency, and loss of mental flexibility. PSP is often regarded as a typical parkinsonian disease, alongside multiple system atrophy and corticobasal degeneration. Onset of signs typically occurs after age 40, with peak onset around age 63. It is uncertain whether men and women are affected at the same rate. Although genetics may confer some vulnerability to the illness, PSP cases are generally sporadic and not usually inherited (Ghosh, Carpenter & Rowe, 2013).

Clinical Presentation and Neurological Findings

Clinical findings in PSP may be subtle at initial presentation but become more pronounced as the illness advances. The executive dysfunctions associated with PSP involve supranuclear pathways and include impaired voluntary saccades — usually affected first — and reduced vigilance, as patients recognize fewer targets over time. Both the velocity and range of these eye movements are reduced, and movements in the vertical plane are more severely affected early in the disease course. Delayed latencies and eye movements driven solely by lower motor neurons, such as the vestibulo-ocular reflex, are preserved. Patients may also display square-wave jerks, which are brief, horizontal, saccadic intrusions during fixation (Burbank, 2006). Altered sensory processing often gives patients a startled or surprised facial appearance and can cause dry eyes. Additional ocular findings include blepharospasm, photophobia, and apraxia of eyelid opening.

Though patients are most likely to exhibit slowed information processing, key neurological findings are also evident on examination and should be carefully assessed. Decreased verbal fluency is typical, and patients may demonstrate loss of mental flexibility as the illness progresses. In PSP, altered memory retrieval indicates memory difficulties caused by dysfunction in the frontostriatal system. Combined with the inability to direct gaze downward, gait apraxia causes frequent falls in patients with PSP. These falls are typically backward, and patients often make little attempt to correct themselves — a pattern described as a "toppling bowling pin" appearance. Rigidity of the neck and other axial musculature is common and can be identified during assessment of the vestibulo-ocular reflex. Patients may also experience changes in personality and behavior, most often manifesting as anxiety, apathy, or disinhibition (Olanow, Stocchi & Lang, 2011). Finally, PSP patients may display frontal release signs — such as the applause sign and the grasp reflex, including the inability to clap exactly three times on command — all of which indicate that executive dysfunction in PSP can be extremely severe.

Cognitive and Performance Impairments

PSP patients experience behavioral and cognitive changes reflecting abnormal functioning of the frontal lobes. Cognitive changes in executive function include a decline in frontal lobe performance, such as slowed information processing and retrieval, impaired reasoning, concrete thinking, and difficulty planning or shifting between tasks. Behaviorally, patients often display apathy — including social withdrawal and decreased motivation — as well as impulsivity, perseveration, and an inability to change topics or switch tasks. Depressive disorders are also common.

In most cases, visual performance is at least as impaired as walking performance, though visual problems typically do not appear until three to five years after the onset of gait difficulties. Because the primary problem with vision involves directing the eyes accurately, reading frequently becomes challenging. Patients find it difficult to move their gaze to the beginning of the next line immediately after reaching the end of the previous one. This is fundamentally different from simple refractive problems requiring reading glasses. An eye care professional unfamiliar with PSP may misinterpret a patient's inability to read continuous text despite normal ability to identify individual letters on a standard eye chart. Some patients have undergone unnecessary cataract extraction in a futile attempt to address such visual difficulties. Another common visual problem is the inability to maintain eye contact during conversation (Josephs et al., 2005). This can create the false impression that the affected person is disengaged, hostile, or cognitively impaired. The same oculomotor disturbance can produce a sensation of "tunnel vision" and create hazards when driving.