Led by Florence Portet of the Montpellier University Hospital Center in France, researchers at Columbia University in New York City searched for extrapyramidal symptoms in 388 people who participated in the seven-year, longitudinal Washington Heights Hamilton Heights Inwood Columbia Aging Project (Tang et al., 2001). The current study focused on people who did not have AD at their first visit, but were later diagnosed with the disease. Extrapyramidal symptoms were present in more than 10 percent of people after diagnosis with Alzheimer’s; in some cases, the EPS appeared before the AD diagnosis was even confirmed. By their final visit to the center (participants were followed for an average of 3.6 years), more than one fifth of these participants showed evidence of extrapyramidal signs such as tremors and muscle rigidity. Cognition in people who had EPS along with AD declined more steeply than those who had AD alone.

Without pathological data from autopsies, one can only surmise what might link Alzheimer’s and EPS. “What struck me the most is the parallels that are in this paper with what we know about dementia with Lewy bodies,” said David Salmon of the University of California in San Diego, who was not associated with the report. DLB, which includes parkinsonian motor symptoms such as rigidity, is present in 15 to 25 percent of people with AD, Salmon noted, similar to the percentage of people with EPS in the current study (see ARF Related news story.)

The authors noted that one possible explanation for the extrapyramidal symptoms in this subgroup of people with AD could be that the plaques and tangles classically associated with AD might be invading extrapyramidal areas or the substantia nigra, the movement-associated brain area where dopaminergic neurons die in people with Parkinson’s. The death of neurons in those locations could also explain the symptoms. Alternatively, the protein α-synuclein, which accumulates in PD and forms Lewy bodies, could also be abnormal, Salmon suggested. “Maybe [these abnormalities] are just not at the level to lead to a full parkinsonian syndrome,” he said. The extrapyramidal symptoms likely have the same root as the Alzheimer’s symptoms, Salmon said. While it is possible that some people are unlucky enough to develop both AD and PD, he said, parkinsonism and DLB are present in people with AD at higher levels than the individual disease rates would suggest.

As for ALS, extrapyramidal symptoms are not part of the classic definition of this disease, either, but perhaps they should be. Pierre-François Pradat led a group of researchers at the Pitie-Salpetriere Hospital in Paris, France, in assessing EPS in 39 consecutive cases of ALS. “Our experience, based on more than 7,500 patients examined at the Paris ALS Center since 1989, has convinced us that careful examination of patients with typical ALS reveals that some signs and symptoms are due to a combination of pyramidal and extrapyramidal involvement,” Pradat wrote in an e-mail to ARF.

For the study, the scientists recruited people who did not experience significant motor problems in their legs, but nonetheless found that more than half exhibited extrapyramidal signs such as muscle rigidity. People with EPS, despite having functional legs, had more trouble with day-to-day activities such as getting dressed and climbing stairs. “ALS is a multisystem degenerative condition affecting the extrapyramidal system,” Pradat wrote. “Mild extrapyramidal symptoms should not exclude the diagnosis of ALS.”

It’s becoming clearer to the field that neurodegenerative diseases lie across a broad spectrum and their overlapping symptoms can confound early diagnosis of neurodegenerative disease. The current studies show that extrapyramidal symptoms are a factor worth considering in the clinic. “It is important to know, because there may be different implications for treatment,” Salmon said. —Amber Dance.

References
Portet F, Scarmeas N, Cosentino S, Helzner EP, Stern Y. Extrapyramidal signs before and after diagnosis of incident Alzheimer disease in a prospective population study. Arch Neurol. 2009 Sep;66(9):1120-6. Abstract

Pradat PF, Bruneteau G, Munerati E, Salachas F, Le Forestier N, Lacomblez L, Lenglet T, Meininger V. Extrapyramidal stiffness in patients with amyotrophic lateral sclerosis. Mov Disord. 2009 Sep 4. [Epub ahead of print] Abstract