This study investigated the frequency and the burden of negative sentiment of nocturnal symptoms from patients’ perspective in a large dataset (15,119 dialogues) using a social listening technique. SOV of motor symptoms was the highest in nocturnal symptoms same with overall symptoms indicating that motor symptoms were still the most concerning problems of doctors and patients. The most prominent nocturnal motor symptom was rigidity, a condition whereby patients have restricted or no movement, often to the extent that they cannot turn over or get out of bed. This is consistent with the profile of PD, as rigidity is one of the most difficult symptoms to adequately alleviate [21].
Compared with the highest SOV of nocturnal motor symptoms, SOV of nocturnal non-motor symptoms increased larger across 3 years, which is same with overall symptoms, indicating patients paid more and more attentions to non-motor symptoms. Amongst nocturnal non-motor symptoms, insomnia, pain, and RBD featured with high SOV and CAGRs in our data. Such nocturnal non-motor symptoms may arise for multiple reasons. Firstly, different with motor symptoms improved by dopaminergic drugs, nocturnal symptoms become more prevalent with disease progression [7, 22] but improvement by dopaminergic drugs is limit. Thus, attentions for improvement of non-motor symptoms are growing [23]. Secondly, interplay exists between motor and non-motor symptoms [10]. For example, insomnia and nocturnal pain are associated with nocturnal motor symptoms [24]. Lower than optimum dopaminergic dosages may cause insufficient control of nocturnal akinesia, tremors, which exacerbate nocturnal non-motor symptoms [5, 25, 26]. In addition, undesired effects of dopaminergic drugs, or the use of inappropriate medication or dosages may also play a role. The dosage and pharmacokinetics of levodopa are associated with the development of complications [23]. Reliance on higher doses of levodopa rather than using adjunctive medications or modifying delivery regimens may exacerbate or induce nocturnal symptoms [5].
Although SOV of motor symptoms is highest, non-motor symptoms evoked higher negative sentiment scores no matter whether they occurred in the daytime or at night (see Fig. 2). Whilst any symptom that impairs daily functioning can be expected to evoke negative sentiment, non-motor symptoms like depression may be particularly debilitating. One reason is that many non-motor symptoms are not reported or enquired about. They are often not recognized by the consulting clinician and may thus go untreated [6, 13]. Further, the pathological and biochemical mechanisms for many non-motor symptoms involve dopaminergic and non-dopaminergic (i.e. noradrenergic, serotoninergic and cholinergic) systems. As major therapy for Parkinson’s disease, effect of dopaminergic drugs on improving non-motor symptoms is unclear [27, 28]. Non-motor symptoms are more resistant and troubling. It is worth noting that for symptoms occurring at day and night, negative sentiment toward PD symptoms was more pronounced when they occurred nocturnally (see Fig. 3). Control over nocturnal symptoms may not be as good as daytime symptoms due to nocturnal wearing-off, or reduced attention on nocturnal symptom control.
These symptoms disrupt sleep initiation or maintenance even deteriorate daytime symptoms resulting in higher negative sentiment.
Implications for managing nocturnal symptoms
With an increasing SOV and a higher negative sentiment of nocturnal symptoms from the patients’ perspective, it is important for healthcare providers to spend more time focusing on the management of these symptoms. Considering the nocturnal inaccessibility of patients, approaches to measure nocturnal symptoms could be more varied. Some wearable devices could provide a continuous objective measurement (COM) to track symptoms over 24 hours [29–31], which is good for clinicians seeking to evaluate 24-hour symptoms objectively. Communication through various technologies may be beneficial for healthcare providers and patients alike. Increased use of patient-doctor consulting platforms, or even specialized mobile applications for chronic disease management [32] could be utilized to enhance nocturnal symptoms detection and treatment for patients with PD.
Due to increasing SOV and a higher negative sentiment of nocturnal symptoms in Parkinson’s disease, 24-hour continuous treatment is important. Firstly, the replacement of lost dopamine with dopaminergic drugs in 24 is necessary. Adjunctive medications [33–35], infusion systems such as DuoDopa (carbidopa/levodopa) [36], continuous dopamine delivery treatments like the transdermal rotigotine patch [37–41], and oral extended release versions of dopamine agents [42, 43] have shown significant promise in ameliorating wearing-off effects and symptom fluctuations, in nocturnal as well as daytime symptoms. In a randomized, placebo‑controlled study (the RECOVER trial, quality score, 93%), patients with unsatisfactory control of early morning motor symptoms were evaluated on the PDSS-2 and UPDRS III. The study demonstrated that rotigotine could significantly improve early morning motor symptoms and nocturnal symptoms [37], comparable to levodopa continuous infusion [44]. Rotigotine patches are thus highly recommended for the management of nocturnal symptoms [45]. In addition, deep brain stimulation (DBS) is another option which is active over a 24-hour period. However, to date the proven benefits of DBS are limited to motor symptoms and is most commonly restricted to use in patients in relatively advanced stage [45, 46]. Secondly, for symptoms which can’t be improved by dopaminergic drugs, especially for non-motor symptoms, there is no standard pharmacological treatment now. Their management is based on careful assessment of triggering or contributing factors and consideration of other factors, including economic influences, local availability of the drug, local drug approval, the treating physician’s experience and judgment and so on [28].Non-pharmacological treatments are helpful in conjunction with 24-hour drug treatment. Improved sleep hygiene and cognitive-behavioral therapy may be useful for insomnia [24]. Regular exercise and physical therapy can also assist with issues such as joint rigidity and flexed posture [35]. Focused education on symptoms for both patients and families or caregivers is highly recommended. The adoption of non-pharmacological therapies alongside pharmacological treatment early in the disease course is also recommended [47]. The importance of effective multi-specialty management for patients with PD should not be underestimated.
Limitations
Although powerful, utilizing a social listening technique has some limitations. First, the relative lack of full demographic information constrains the conclusions that can be drawn from the data – general conclusions about the reporting PD population may be valid, but not conclusions about specific groups of PD patients. Further, whilst the candid nature of the interactions makes more information accessible, the available details are constrained by what patients recall, lending itself to potential inaccuracies and skewed data. An ability to further identify and segment patient populations will be an important target in future studies.