The clinical spectrum of freezing of gait in atypical parkinsonism

Abstract

Freezing of gait (FOG), commonly seen in advanced Parkinson's disease (PD), has been classified as its fifth cardinal feature. However, its presence frequently leads to a misdiagnosis of PD. FOG is actually more common in atypical parkinsonism (AP): including vascular Parkinsonism (VP), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), dementia with Lewy bodies (DLB), and higher level gait disorders (HLGDs). VP is the result of multiple small vessel infarcts (lacunar state or Binswanger's disease), particularly involving the frontal, parietal, and basal ganglia regions. Approximately 50% have FOG (often referred to as lower body parkinsonism). FOG is also common in neurodegenerative forms of AP, present in 45-57%. Of these, FOG is present in 53% of PSP, 54% MSA, 54% DLB, 25% CBD, and 40% HLGD. It is generally seen in the late stages. There are two syndromes closely associated with AP that are dominated by FOG; pure akinesia (PA) and primary progressive freezing gait (PPFG). PA is characterized by akinesia of gait (including FOG), writing, and speech. Tremor, rigidity, dementia, and response to levodopa are notably absent. PPFG is defined by early FOG (often the initial feature) that progresses to include postural instability. It is accompanied by bradykinesia, rigidity, postural tremor, dementia, and levodopa unresponsiveness. Both syndromes are heterogeneous but PSP seems to be the most common cause. CBD and DLB can also present as PPFG. FOG is a common feature of AP and although typically occurring late in disease may also be an early symptom.

Primary Progressive Freezing: does it stand on its own?

“…He did not respond to treatment with levodopa. Considering that freezing is a common feature among gait disorders [7], particularly in patients with Parkinsonism [10], other diagnoses must be excluded. In Parkinson's disease (PD) freezing of gait increases with disease duration, affecting 60% of patients after 10 years of disease and 80% after 20 years [11].…”

“…Several studies suggest that PPF is part of the spectrum disease of progressive supranuclear palsy (PSP) [1,2,7,8,12], particularly the Pure-akinesia subtype [1,12]. In these patients, although freezing of gait may be the presenting feature, they latter show micrography, abnormalities of speech, axial rigidity, vertical supranuclear gaze palsy and postural instability [13].…”

“…Primary progressive freezing was first described in 1993 [6] and various names were used to describe it [1,7]. Furthermore, distinct criteria were used (some studies consider parkinsonian features as part of the clinical syndrome [1,2] while others consider only isolated freezing of gait [7]).…”

“…Furthermore, distinct criteria were used (some studies consider parkinsonian features as part of the clinical syndrome [1,2] while others consider only isolated freezing of gait [7]). This entity was considered part of the Parkinson-plus syndromes [1,2] but recent papers [2,3,8] suggested that it is caused by other neurodegenerative diseases, such as progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, pallidonigroluysian degeneration [7], primary lateral sclerosis [9].…”

The clinical manifestations and pathophysiology of cerebral small vessel disease

“…Approximately 50% of atypical parkinsonism patients have FOG [31,32] . Most patients exhibit bilateral bradykinesia and rigidity, characterized predominantly by a shuffling gait [33,34] .…”