Ms. Mazorra facilitates the Atypical Parkinsonian Support Group at the University of California, Los Angeles (UCLA) and is Medical Professional Liaison for CurePSP. Dr. Cadogan is Professor, Adjunct Series, UCLA School of Nursing, Los Angeles, California.
The authors have disclosed no potential conflicts of interest, financial or otherwise.
Address correspondence to Mary P. Cadogan, DrPH, RN, GNP-BC, Professor, Adjunct Series, UCLA School of Nursing, Factor 5-952, Box 956919, Los Angeles, CA 90095-6919; e-mail: firstname.lastname@example.org. Ms Mazorra may be reached via e-mail at email@example.com.
Mr. A. is a 72-year-old retired schoolteacher who was referred to a university-affiliated movement disorders clinic for evaluation of suspected Parkinson’s disease (PD) that was not responding to treatment with increasingly high doses of carbidopa/levodopa (Sinemet®). In fact, Mr. A.’s wife reported that her husband’s symptoms had never responded to Sinemet, and she was alarmed that her husband’s condition was deteriorating rapidly. Although Mr. A. was able to report some of his medical history, his responses to questions were extremely slow and his speech was soft and difficult to understand. He suggested that his wife provide the details of his medical history.
Mrs. A. reported that her husband’s symptoms began more than 4 years prior to that day’s visit with several unexplained falls. He tended to fall backward, and the falls became very frequent, progressing to multiple falls each week. He was seen by his primary care physician who learned that Mr. A. was also having trouble driving and had been involved in a few car accidents for which he was at fault. In addition, Mrs. A. noted that her husband was losing interest in his usual activities, was much less communicative with family, seemed to lack awareness of safety issues, and appeared to be unconcerned about the impact of his changing behavior on others. He was initially treated with Sinemet for presumed PD and an antidepressant agent for depression.
In the few years following the start of treatment with Sinemet, Mr. A.’s symptoms progressed. He continued to fall and sustained a few fractures. Most bothersome to him, however, were visual problems that included “double vision” and persistent problems with dry and irritated eyes. He was seen by his ophthalmologist and underwent bilateral cataract surgery, but his vision problems worsened to the point that he was no longer able to read. This was devastating to him as he had been an avid reader.
During that same time, Mr. A. began to lose weight because he was having difficulty feeding himself. Much of his food ended up on his clothes, but even the food that reached his mouth presented challenges because he began to have some swallowing problems. Mr. A.’s physicians were puzzled because he did not have tremors or the fine motor problems that often cause problems with self-feeding, and his visual acuity was normal when tested in the office. Mrs. A. was told that magnetic resonance imaging (MRI) of Mr. A.’s brain showed some changes commonly seen with both aging and PD but no evidence of a stroke or other findings that might explain his rapid decline.
After listening to Mrs. A. describe the course of her husband’s illness, the nurse practitioner in the movement disorders clinic thought she might know what was causing Mr. A.’s problems and sought additional information through a carefully targeted physical examination. In particular, Mr. A.’s visual assessment provided strong clues for a new diagnosis. Mr. A. had a wide-eyed stare, his eyes were dry and slightly inflamed, and his blink rate was markedly decreased. When asked to voluntarily look up and down, Mr. A. was noted to have moderate limitations in upward gaze and significant limitations in downward gaze. In addition, when asked to close his eyelids, Mr. A. appeared to struggle with the task and even used his hand to assist with the process. In addition, as described by his wife, Mr. A. was found to have marked postural instability with significant impairments in gait and balance when he was evaluated. In consultation with the clinic physician, the brain MRI was repeated and showed severe midbrain atrophy and a characteristic “hummingbird sign” often associated with progressive supranuclear palsy (PSP).
Definition of PSP
The name progressive supra-nuclear palsy itself provides important information about the disorder. Progressive describes the worsening of symptoms over time and the fatal course of PSP. Supranuclear refers to the fact that the main problem affecting eye movements in PSP occurs not in the brainstem nuclei that directly control eye movements but is related to degeneration of structures in the higher (supra) centers of the brain that control the oculomotor nuclei (Zampieri & Di Fabio, 2006). Palsy describes the weakness and/or paralysis of eye muscle movement. PSP was originally known as Steele-Richardson-Olzewski syndrome, named after the three physicians who first described characteristic features of the disorder at a neurology conference more than 40 years ago (Steele, Richardson, & Olzewski, 1964). It is estimated that approximately half of all PSP patients have the classic Steele-Richardson-Olzewski syndrome (Stamelou et al., 2010). However, ongoing research has demonstrated that there may be at least four other distinct atypical presentations of PSP that share both overlapping and distinct clinical features with the more classic Steele-Richardson-Olzewski syndrome (Williams & Lees, 2009). In addition, PSP has some clinical and pathological features in common with other parkinsonian syndromes (e.g., rigidity, bradykinesia, postural instability) that make diagnosis of PSP challenging for clinicians not familiar with it (Wenning, Krismer, & Poewe, 2011).
Neuropathology of PSP
As noted in the individual example, Mr. A.’s brain MRI demonstrated midbrain atrophy and a classic “hummingbird sign” that refers to the thinning of the rostral midbrain that results in an appearance similar to the head and beak of a hummingbird (Boeve, 2012). In addition to the midbrain atrophy, atrophy of the pallidum, thalamus, and subthalamic nucleus, as well as mild symmetric frontal atrophy, are common in PSP (Houghton & Litvin, 2007; Song, Huang, & Halliday, 2011). Characteristic histopathological findings in classic PSP include accumulation of a specific tau protein isoform (4R-tau) that appear in neurons as flame-shaped neurofibrillary tangles and in glial cells as tufted astrocytes within the globus pallidus, subthalmic nucleus, substantia nigra, and brainstem. The severity and specific distribution of tau pathology appears to account for clinical differences in typical and atypical presentations of PSP (Bouchard & Suchowersky, 2011).
Epidemiology and Clinical Course
PSP is the second-most-common parkinsonian neurodegenerative disorder following Parkinson’s disease (Houghton & Litvin, 2007). The estimated prevalence of PSP is 6 to 6.5 per 100,000 individuals (Nath et al., 2001). The average onset is ages 60 to 65, and men are more likely to be affected than women (Rajput & Rajput, 2001). Findings from a recent study of 197 PSP patients indicate a median survival of 8 years, with shorter survival estimates for men and for those with disease onset at an older age (Chiu et al., 2010). Other predictors of shorter survival include patients experiencing falls at disease onset and those who developed speech problems or diplopia within the first year or swallowing problems within the first 2 years (Houghton & Litvin, 2007).
PSP is difficult to recognize in its early stages because of similarities with other disorders such as PD and because the classic visual and MRI signs of PSP may not be evident in the early stages. Although approximately 8% of patients have observable gaze palsy initially, in most cases, it may take 3 to 4 years to develop the classic sign of either upward or downward gaze palsy (Houghton & Litvin, 2007). For many PSP patients, horizontal gaze palsy may also occur as the disease progresses (Warren & Burn, 2007). Of note, reflex eye movements such as those seen in the “doll’s eye maneuvers” (when the head is turned rapidly to the side while eyelids are held open, the eyes move together towards the opposite side) are preserved in PSP (Houghton & Litvin, 2007). Progression of gait and balance abnormalities is more predictable, with most patients becoming unable to stand unassisted and requiring the use of a wheelchair after 5 years (Zampieri & Di Fabio, 2006).
Despite the variability of clinical presentation that may occur in PSP, the National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy (NINDS-PSP) have developed criteria for possible, probable, and definite PSP. Possible PSP is a gradually progressive disorder, with onset at age 40 or older, and either vertical supranuclear palsy or slowing of vertical saccades (i.e., slowing of voluntary eye movements when requested to move eyes rapidly between two stimuli), and prominent postural instability with falls in the first year of disease onset that cannot be explained by other diseases (Litvin et al., 1996). NINDS-PSP criteria for probable PSP are similar to those for possible PSP but require the presence of vertical supranuclear palsy rather than just slowing of vertical saccades. Criteria for definite PSP can be made at autopsy only and require the clinical correlates of possible or probable PSP along with histopathological evidence of PSP.
Individual Example Update
After being diagnosed with probable PSP at the movement disorders clinic, Mr. A.’s condition continued to deteriorate in a predictable manner. Because there are no effective disease-modifying treatments for PSP, the early goals of care were to maintain functional ability as much as possible through use of assistive devices such as smooth-soled shoes to improve ease of initiating steps, a weighted front-wheeled walker to decrease backward falls, use of prism glasses to improve downward gaze, and speech therapy to maximize communication ability. Unfortunately, Mr. A. did not receive much benefit from these strategies. However, one of the most important interventions was the referral made to a PSP support group where Mr. and Mrs. A. met other patients and families coping with the devastating effects of PSP. Also through this group, they became aware of excellent resources available through the CurePSP® organization on its website at http://www.psp.org.
Soon after the initial diagnosis of PSP was made, both Mr. and Mrs. A. found the CurePSP online forum particularly helpful, as they were able to ask questions of experts and others about management of PSP symptoms and about the experience of living with PSP. As her husband’s disease progressed, Mrs. A. obtained significant benefit from the monthly telephone support group available for patients or caregivers who are housebound. While it was difficult to learn of the poor prognosis for PSP, it was beneficial to be able to anticipate and plan for the future. The couple spent a great deal of time focusing on spiritual needs, which improved quality of life for each of them.
Within a year of his visit to the movement disorders clinic, Mr. A. was no longer ambulatory and developed swallowing problems. He received swallowing therapy and thickened liquids to prevent aspiration. By the following year (Year 6 after disease onset), Mr. A. was completely dependent on a caregiver for all of his needs. He remained cognitively intact but was able to communicate mostly through limited hand gestures. As part of advance care planning, Mr. A. indicated he did not want a feeding tube inserted and did not want cardiopulmonary resuscitation initiated if his heart stopped. Mr. A. was enrolled in hospice, and despite careful hand feeding, he developed aspiration pneumonia and died peacefully 3 days later with his family at his side.
As demonstrated in the individual example, Mr. A.’s experiences were similar to others who are ultimately diagnosed with PSP. Early in the course of his illness, Mr. A. had a classic history of multiple, unexplained (often backward) falls that progressed in frequency and severity. Due perhaps to the absence of other signs at that time and possible lack of familiarity with PSP among health care providers, Mr. A. was treated for PD with increasingly high doses of Sinemet. His failure to respond to Sinemet, the fact that his pattern of falls is not typically seen in PD, as well as the absence of other classic PD signs (e.g., tremor) should raise suspicion of PSP. His subsequent development of characteristic visual signs and evidence of progressive disease meet the NINDS-PSP criteria for probable PSP. Like the majority of PSP patients, aspiration pneumonia was the immediate cause of Mr. A.’s death.
Although PSP is a rare and ultimately fatal disease, early diagnosis may improve the success of supportive interventions to maintain functional stability and improve quality of life. In addition, patients and their families may benefit from information about potential treatment developments, such as those targeting different aspects of tau dysfunction (Stamelou et al., 2010), that could be available in the future. Similarly, possible involvement of PSP patients in clinical treatment trials may be available. Although current PSP patients may have limited treatment options, much progress has been made in understanding and classifying PSP since the disorder was first recognized. Nurses and other health professionals have an important role to play in assessment and supportive management of PSP.
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