Identifying the pathology at the prodromal phase of PD is beneficial for prognostic counseling and slowing disease progression

29 May 2023

During the 75th AAN 2023 Annual Meeting, Dr. Joyce K. Lee-Iannotti from Banner University Medical Center, Phoenix, the United States (US)  delivered a presentation on the non-motor symptoms of prodromal Parkinson's Disease (PD) and explained the importance of recognizing prodromal PD for disease prevention.1  

Prodromal PD is the initial stage of PD as people display typical signs of the disease but do not meet the clinical diagnostic criteria.1 Symptoms can accurately indicate a higher risk of developing motor symptoms and getting diagnosed with PD.1 The Braak staging indicates the severity of symptoms developed along the caudal-rostral route that determines PD progression.1 The disease begins in the olfactory bulb and lower brain (i.e., stage 1), causing hyposmia and constipation.1 Around 90% of patients experience hyposmia.1 Since patients may easily ignore the signs of olfactory bulb dysfunction or impairment, the 12-item Brief Smell Identification Test (B-SIT) and the Sniffin' Sticks tests are essential for testing olfaction.1 Constipation is another common sign when patients show abnormalities in the vagus nerve and enteric nervous system (ENS) at the early stage of disease development.1 At stage 2, patients have mood disorders and rapid eye movement (REM) sleep behavior disorder (RBD), with pathology observed in serotonergic raphe nuclei and adrenergic locus coeruleus (LC).1 Patients will eventually develop motor symptoms and experience cognitive decline as the disease progresses.1 Dr. Lee-Iannotti then discussed the symptoms and diagnosis of RBD in detail.1  

RBD dream enactment ranges from the body/limb movements that disrupt the continuity of sleep, acting out the dreams, to potentially performing harmful sleep behavior, like punching, running into walls or even jumping out of windows.1 The International Classification of Sleep Disorders (ICD) standardizes the diagnostic criteria of RBD, and in other words, a diagnosis of RBD must meet all of the ICD criteria.1 Apart from documenting the history of sleep behavior, the diagnosis heavily relies on polysomnography (PSG) for an objective assessment.1 The polysomnographic signals, including electroencephalogram (EEG), electrocardiogram (ECG), nasal flow, and multiple electromyography, are monitored, read and analyzed, comparing with normal controls using video recording.1 The abnormal motor movements of the legs and arms are also studied.1 During the diagnosis of RBD, the PSG values and movement statistics in the chin and limbs are meticulously scrutinized through the utilization of the RBD and Sleep Innsbruck Barcelona (SINBAR) protocols.1 However, irregular patterns of polysomnographic profiles can be observed in patients with prodromal PD and those with other sleeping disorders.1 Also, it remains controversial if antidepressants trigger or unmask pre-existing RBD.1   

Dr. Lee-Iannotti concluded her presentation by reiterating that the diagnosis of prodromal PD represents early detection of PD, which allows prognostic counseling and slowing disease progression with the initiation of neuroprotective therapies at the pre-onset PD stage.1   

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