Clinicopathological characteristics of freezing of gait in autopsy-confirmed Parkinson's disease.

Abstract

Twenty-five percent to sixty percent of Parkinson's disease (PD) patients reportedly have freezing of gait, leading to impaired mobility, falls, and decreased quality of life. Several factors have been associated with gait freezing in PD patients. We analyze for these factors in autopsy-proven PD patients. We performed a chart review of 58 patients with pathologically confirmed PD based on substantia nigra Lewy bodies. Freezing of gait was defined as a score of 1 or more on Item 14 of the Unified Parkinson's Disease Rating Scale or if documented on examination. Serial office notes and scales were used to determine onset and progression of motor and non-motor symptoms. Patients had been followed up for an average of 20 visits over 9 y. The mean onset of gait freezing was 9.3 y from initial motor symptoms. Patients with earlier gait freezing more commonly had initial gait difficulties and developed postural instability, dyskinesias, memory impairment, hallucinations, and vivid dreams earlier during the disease course. Early onset of hallucinations was correlated with more rapid progression of gait freezing. Maximal equivalent levodopa dose was not correlated with earlier onset or progression of gait freezing. Progressive and more severe gait freezing trended toward higher-severity Lewy body disease on postmortem examination. Early onset and rapid progression of freezing of gait in this cohort were correlated with early cognitive impairment and hallucinations that are potential clinical hallmarks of cortical Lewy bodies. The gradual worsening and severity of gait freezing correlated with the density of cortical Lewy body-containing neurons.