Progressive Supranuclear Palsy-An Unusual Cause of Memory Loss and Falling.

Abstract

To the Editor: A woman in her 60s was referred to a memory disorders clinic with a 1-year history of memory loss. She also had multiple falls, mostly backward falls. Other problems included urinary incontinence, toe dystonia, depression, and behavioral abnormalities. She was originally diagnosed with atypical Parkinson's disease (PD) and had some response to levodopa with carbidopa. Examination found fluent speech with decreased content and slow irregular prosody, mild vertical gaze deficit, ptosis, and forward head tilt when gazing down. Review of the clinical presentation and brain magnetic resonance image (MRI) changed the diagnosis to progressive supranuclear palsy (PSP). PSP is an uncommon neurological disorder that clinically may resemble PD, but the pathophysiology is distinct from PD. PSP is a tauopathy, while PD is a ubiquitinopathy. PSP is in the same family as frontotemporal lobe degeneration. In PSP, abnormal tau is present in brain areas that are consistent with the clinical signs. One estimate of PSP prevalence in the United States is 1.39 per 100,000.1 This woman at first was felt to be a routine case of falling and memory loss, a common presentation in a geriatrics clinic. The lower extremity stiffness and tremor led to a preliminary diagnosis of atypical Parkinson's disease, but the brain MRI results led to the presumptive diagnosis of PSP. MRI showed mild to moderate cerebral volume loss, more prominent in the frontal lobes, and mild deformity and narrowing of the midbrain due to atrophy in a shape that suggested a bird, particularly a hummingbird, consistent with PSP (Figure 1). An expert committee defined criteria for the diagnosis of PSP. Major criteria are a gradual progressive disorder with onset after age 40, vertical supranuclear palsy (weakness in up-down gaze, especially down gaze) or slowing of vertical saccades (normal eye jerking when changing point of gaze), and postural instability with falls within the first year of disease onset.2 There is clinical similarity between PSP and PD. Both conditions include postural instability with falls,3 axial and limb rigidity, tremors, autonomic dysfunction, mood disorders,4, 5 and ophthalmic symptoms,6 but there are clinical differences that help separate the conditions. Eye signs are a cornerstone sign of PSP. Typically, downward gaze difficulty occurs early in the disease.7 Other distinguishing eye signs are slow blink rate and lid retraction, which produces a facial worried expression, different from PD's “masked face” or hypomimia countenance.7 Falls are more likely in the first 3 years with PSP, whereas the median for falls onset in PD is 9 years.3 The falling in PSP is more likely to be backward, probably because of retrocollis (tendency to tilt the head backward). Olfactory dysfunction is relatively specific for PD and can differentiate it from PSP.8 Therapeutic response to levodopa is more likely in PD.5, 9 The Food and Drug Administration has not approved any medication for PSP. Clinical trials of coenzyme Q10 have not been published. No evidence has been found of efficacy of any nondrug therapy. A combination of eye and balance rehabilitation was shown to have some positive effect in gaze control, gait, and general mobility in one study, but the effect was not shown to have benefit in terms of number of falls, quality of life, or mortality.10 One year after the examination, the woman was found to have fewer falls, presumably due to education about rising and sitting, safety measures (wheelchair seat belt), and compensating for neck rigidity. When she did fall, she was reported to have less injury, presumably due to padding of the floor and sharp edges. Her care burden had increased, and she was being moved to a facility with a higher level of care. Levodopa with carbidopa was believed to help reduce her tremors. Botulinum toxin was used for her toe dystonia. Memory loss and falling may be due to PSP. The diagnosis of PSP has a poor prognosis. There are no evidence-based therapies available, although physical therapy with balance training and family education may be helpful. The clinical picture of PSP overlaps with that of PD. Certain characteristics can help separate them, including the unique PSP brain MRI, eye signs, and falling history. Conflict of Interest: Dr. Hajjar receives salary support from a grant from Taibah University, Saudi Arabia. Author Contributions: The authors wrote the manuscript jointly. Sponsor's Role: Taibah University had no role in preparation of this paper.