Pisa syndrome may be a relatively frequent and often disabling complication in Parkinson’s disease, especially in the advanced disease stages, according to research published in the November 17 issue of Neurology.

Variables associated with Pisa syndrome include Hoehn and Yahr stage, ongoing combined treatment with levodopa and dopamine agonist, and veering gait, said Michele Tinazzi, MD, PhD, Associate Professor of Neurology at the University of Verona, Italy, and colleagues.

Pisa syndrome, which is characterized by lateral trunk flexion, has been described in patients with dementia and other neurodegenerative diseases. It was first described as a side effect of antipsychotic treatment and also has been associated with medications such as antiemetics, antidepressants, central cholinesterase inhibitors, and lithium carbonate. Pisa syndrome’s pathophysiologic explanation, however, is uncertain, and case series have produced conflicting findings, the researchers said.

A Cross-Sectional Study of Patients With Parkinson’s Disease

To assess the prevalence of Pisa syndrome in patients with Parkinson’s disease and the association between Pisa syndrome and demographic and clinical variables, Dr. Tinazzi and colleagues conducted a cross-sectional study of consecutive outpatients with Parkinson’s disease who attended 21 tertiary movement disorders centers in Italy.

The investigators enrolled patients between February 2012 and July 2013. Patients diagnosed with Pisa syndrome (ie, lateral trunk deviation of 10° or more that was almost completely reverted by passive mobilization or supine positioning) completed an ad hoc questionnaire and neurologic examination. The researchers diagnosed Parkinson’s disease according to the United Kingdom Parkinson’s Disease Society Brain Bank criteria and excluded patients who had other postural deformities, concomitant neurologic diseases known to affect posture, history of major spinal surgery or muscle or skeletal disease, treatment with drugs that can induce Pisa syndrome in the six months before enrollment, and clinical features that were consistent with a diagnosis of atypical parkinsonism.

A neurologist at each center recorded patients’ sex, age, age at Parkinson’s disease onset, BMI, disease duration, Parkinson’s disease phenotype (ie, rigid-akinetic, tremor-dominant, or mixed type), laterality of motor symptoms at disease onset, latency between disease onset and the start of antiparkinsonian therapy, and pharmacologic treatment at disease onset and at their latest visit.

The researchers also evaluated falls in the previous month; comorbidities; quality of life, as assessed by Parkinson’s Disease Questionnaire–8; and disease severity, as assessed by Unified Parkinson’s Disease Rating Scale, Parts I–IV. Clinical asymmetry and Hoehn and Yahr scale staging also were assessed. Investigators measured trunk deviation using a wall goniometer. Patients underwent a spine x-ray to disclose orthopedic conditions that could lead to lateral bending of the trunk.

Pisa Syndrome Was Associated With Age

Of the 1,631 patients who met the eligibility criteria, 143 patients fulfilled the diagnostic criteria for Pisa syndrome, representing a prevalence of 8.8%. Trunk flexion ranged from 10° to 50°, with an average of 17°. Pisa syndrome appeared on average seven years after the onset of Parkinson’s disease, and the patients had had Pisa syndrome for a mean of 2.6 years.

The investigators found that patients with Pisa syndrome were older and had lower BMI, a significantly longer disease duration, more severe disease, and worse quality of life, compared with patients who did not have Pisa syndrome. In addition, patients with Pisa syndrome had higher levodopa equivalent daily dose. Osteoporosis, arthrosis, veering gait, and falls were more common in the Pisa-syndrome group, compared with the group without Pisa syndrome. Multivariate logistic regression analysis confirmed that Hoehn and Yahr stage, ongoing antiparkinsonian treatment, associated medical conditions, and veering gait were associated with Pisa syndrome.

Most patients were aware of their leaning posture, and half adopted a head compensation to correct their visual alignment. Those with more severe Pisa syndrome (ie, trunk flexion of 20° or greater) were not significantly different from those with mild Pisa syndrome, in terms of demographic or clinical variables.

“The association of poor quality of life with Pisa syndrome in our cohort supports its clinical effect as motor manifestation of Parkinson’s disease; however, this was not confirmed by multivariate logistic regression analysis, suggesting that Pisa syndrome might not be the principal determinant of poor quality of life, but other factors associated with longer disease duration are also contributing,” the researchers said.

The study did not confirm a finding of previous studies that patients with Pisa syndrome lean away from their dominant Parkinson’s disease side.

These results may inform future studies that investigate the pathophysiologic mechanisms of Pisa syndrome in Parkinson’s disease and help identify “at-risk patients who may benefit from tailored therapeutic strategies,” said Dr. Tinazzi and colleagues.

“Early detection and treatment of Pisa syndrome may prevent fixed, irreversible deformities, thereby avoiding complications that may arise from such a disabling condition,” concluded the researchers.

—Jake Remaly

Pisa Syndrome May Be a Relatively Common Complication in Parkinson’s Disease