Abstract
Freezing of gait (FOG) is a common disorder in Parkinson's disease (PD) and could be attributed to a reduction in brain noradrenaline. The aim of this study was to determine the relationship between aromatic l-amino acid decarboxylase (AADC) activity in the locus coeruleus (LC) and FOG in PD using high-resolution positron emission tomography with an AADC tracer, 6-[18F]fluoro-l-m-tyrosine (FMT). We assessed 40 patients with PD and 11 age-matched healthy individuals. PD was diagnosed based on the UK Brain Bank criteria by two movement disorder experts. FOG was directly observed by the clinician and assessed using a patient questionnaire. FMT uptake in the LC, caudate, and putamen was analyzed using PMOD software on coregistered magnetic resonance images. FOG was present in 30 patients. The severity of FOG correlated with the decrease of FMT uptake in the LC regardless of disease duration and the severity of other motor impairments, indicating dysfunction of the noradrenergic network in FOG.
Highlights
Freezing of gait (FOG) is a debilitating and common symptom in Parkinson’s disease (PD)
FOG was defined as a score of one or more on item 3 of the Freezing of Gait Questionnaire (FOG-Q) [1], Parkinson’s Disease or if documented on examination by a movement disorder specialist
FOG is more common in advanced stages of PD, it may occur early in the course of the disease and in untreated patients [3, 6]
Summary
Freezing of gait (FOG) is a debilitating and common symptom in Parkinson’s disease (PD). More than 80% of patients with PD experience FOG during the course of the disease [1]. Patients feel as if their feet are “sticking or glued to the ground” for several seconds when initiating gait, turning, or walking through narrow spaces. FOG may be attributed to the loss of noradrenergic neurons in the locus coeruleus (LC) and their projections to the frontal lobe [7]. Such an association was suggested by the observation that l-threo-3,4-dihydroxyphenylserine (l-DOPS or droxidopa), a precursor of noradrenaline, improves FOG in some patients with PD [8, 9]. To elucidate the relationship between FOG and catecholamine synthesis in the LC, we utilized positron emission tomography (PET) with 6-[18F]fluoro-l-m-tyrosine (FMT), a sensitive tracer for aromatic l-amino acid decarboxylase (AADC) [10, 11]
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