Contractures in End-Stage Alzheimer's Disease May Respond to Low-Dose Corticosteroid Treatment: Report of Three Cases

Dear Editor:

Severe contractures (defined as range of motion <50% of normal) contribute to morbidity and mortality in patients with end-stage Alzheimer's Disease (AD) by increasing the risk of falls, pain, pressure wounds, and infections (see Fig. 1). AD patients with contractures frequently have uncontrolled pain ¹ and benefit from the use of multimodal pain therapy. Targeted at central pathways, such therapies, including dexamethasone and methadone, can reduce pain intensity via their effects at nerve terminals and the dorsal root ganglia as well as in peripheral nerves. ²

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FIG. 1.

AD patient with static contracture right knee at start of treatment (above) and three weeks after initiating methadone 2.5 mg TID, dexamethasone 4 mg daily (below).

An inflammatory component contributes to pain intensity in acute postoperative pain—for which dexamethasone is an accepted component of multimodal therapy. Regardless of concurrent pain intensity, inflammation contributes to the pathogenesis of contractures. We therefore undertook a therapeutic trial of low-dose dexamethasone alone or as an adjunct to treat contractures whether or not concurrent pain per se was well controlled in three patients with end-stage AD after other agents had failed.

In this case series the use of low-dose dexamethasone improved static contractures from an average range of motion of <10% normal to a final average of 50% normal. Less-severe contractures improved from <50% range of motion to 80% normal. The patients were observed to use their affected joints in comfort positioning, displaying previously lost active extension and purposeful movement. These changes positively affected their quality of life.

Although the patients of this case series received low-dose corticosteroids for compassionate therapeutic trials to reverse established contractures, their positive responses are consistent with earlier, pilot observations. A landmark study by Clavet et al. on the development of contractures in prolonged-stay ICU patients correlated concurrent corticosteroid therapy with a reduced risk of contracture development. ³ This protective effect indicates that inflammatory mediators play a role in the development of contractures. The improvement of severe, static flexion contractures in the present case series suggests that an inflammatory process is involved in the maintenance of contractures as well. Attempts at contracture prevention by physical therapy and/or neuromuscular blockade and stretch treatment for range of motion have yielded no protective benefit. ³

Dexamethasone, a potent anti-inflammatory agent, has the potential to inhibit connective tissue remodeling and aid in the prevention or reversal of painful contractures in AD, alone or as part of a multimodal pain regimen. In fact, pain intensity was not uniformly severe or even moderate in the three patients reported herein, suggesting that the benefits of dexamethasone upon contractures may be independent of its effect upon pain intensity per se. An additional benefit hinted at by our observations may include increased cognitive function. Whether this is because end-stage AD patients with contractures experience prefrontal and thalamic gray matter atrophy as a result of chronic pain, ⁴ and that central nervous system inflammation such as involves microglial activation may accelerate cognitive decline, ⁵ remains unknown. In summary, the use of low-dose corticosteroids may provide benefit for end-stage AD patients with contractures who display comorbidities consistent with central neuroinflammation, e.g., microglial activation.