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Neurodegenerative Diseases Parkinson’s Disease
Table 1: Non-motor Symptoms at Different Disease speculated that RBD occurs following degeneration of the lower
Severities in 1,072 Patients Screened in Italy
brainstem nuclei, which is characteristic of Braak Stages 1 and 2 of PD
progression and may represent a pre-clinical marker of PD.
6
RBD is
Non-motor Symptom Disease Severity as Hoehn and Yahr Score
diagnosed by the presence of limb or body movements while
1 1.5–2 2.5–3 4–5
dreaming in addition to at least one of the following: potentially
Pain 50.9 58.6 67.1 79.6
Urinary 43.1 51.7 68.3 89.9
harmful sleep behaviours, dreams that appear to be ‘acted out’ and
Sleep dysfunction 47.9 60.6 75.4 81.6
sleep disorders that disrupt the sleep continuum. Bed partners often
Fatigue 37.7 56.5 68.9 81.6
report odd vocalisations and abnormal body movements exhibited by
Apathy 24.6 26.8 36.6 49.0
people with RBD. However, morbidity associated with RBD can stretch
Loss of attention 37.7 40.4 51.7 65.3 beyond the sleep disturbance associated with PD, including
Skin 14.4 19.8 34.5 32.7
ecchymosis, lacerations, fractures and even dislocations. In those
Psychiatric 61.1 63.3 73.2 83.7
who experience violent limb and body movements, the risk of injury
Respiratory 9.6 15.5 22.8 30.6
to bed partners should also be considered.
Gastrointestinal 45.5 54.4 76.9 73.5
Sources: Antonini et al., Neurol Sci, 2008;29(2):61–5 and Barone et al., Mov Disord,
Autonomic Dysfunction
2009;24(11):1641–9.
Autonomic dysfunction in PD consists of a variety of adverse NMS that
not receiving dopaminergic medications. The activity of dopamine in present due to changes in the activity of the autonomic nervous
the meso-limbic pathways, along with overall dysfunction in the system. Nearly all people with PD experience one or more of the
dopaminergic and serotonergic systems, has been implicated in symptoms associated with autonomic dysfunction. Failure in
various types of psychosis and most likely contributes to the autonomic function is caused by both the failure of the
psychosis seen in PD patients. Psychosis in PD is primarily parasympathetic nervous system – leading to symptoms such as
characterised by hallucinations (primarily visual hallucinations), constipation, dry mouth, urinary retention and erectile dysfunction –
delusions and other sensory disturbances such as illusions. PD and sympathetic nervous system failure – with symptoms such as
psychotic events can range from occasional subtle non-disturbing orthostatic hypotension (OH) and thermoregulatory dysfunction.
hallucinations, mild illusions and vivid dreams to a psychotic state
with disturbing hallucinations and paranoid delusions.
14
When PD OH is a particularly disabling NMS of PD that is thought to occur in
patients experience visual hallucinations, they most often consist of 20–50% of patients.
18
While people with PD can experience OH at
people or animals and rarely of inanimate objects. any stage of the disease, it is more common in those with advanced
disease. Studies indicate that OH occurs in people with PD due to
Sleep Disturbances peripheral sympathetic cardiovascular denervation, which leads
Sleep disturbances are frequent non-motor manifestations of PD and to impaired sympathetic input to the cardiovascular system.
19
involve a complex aetiology, which is often multifactorial in nature. Symptoms are generalised weakness, dizziness, clouded mentation
Potential contributing factors can include underlying neurodegenerative and even syncope.
processes, loss of sleep due to motor and non-motor features of the
disease and sleep-altering effects of drug therapies. Constipation is very common in PD. Studies show that constipation
is reported as a prominent complaint before the onset of motor
Evidence suggests that the neurodegenerative changes that occur symptoms in approximately 50% of patients. In light of these
in PD can lead to sleep disturbances very early in the disease findings, a prospective study in 7,000 men followed up for a period
process. Such changes may affect sleep structure, leading to sleep of 24 years found that those patients with an initial finding of
fragmentation and the loss of duration of rapid-eye movement (REM) constipation (defined as less than one bowel movement per day)
sleep. In fact, longitudinal data to date indicate that REM sleep were at a three-fold increased risk of developing PD 10 years after
behaviour disorder (RBD) can precede the motor symptoms of PD, and the initial report of constipation symptoms.
20
However, it should be
that RBD may herald the onset of motor symptoms in up to 40% of stressed that all PD medications, including levodopa, have been
patients.
15
Interestingly, the severity of sleep disturbance is positively implicated in further slowing of gastrointestinal motility and the
correlated with disease severity, Unified Parkinson’s Disease Rating exacerbation of gastrointestinal dysfunction, making effective
Scale (UPDRS) motor scores, levodopa dose, severity of rigidity and management challenging.
severity of bradykinesia. These correlations underline the complex
interplay between sleep disturbance and other manifestations and Urinary and/or bladder dysfunction affects over 50% of PD patients
symptoms of PD. with symptoms including increased urinary frequency, urgency and
urge incontinence; another 17–27% of patients report urinary
Excessive daytime sleepiness (EDS) can be observed in approximately hesitancy and/or a weak urinary stream. Urinary symptoms in patients
50% of PD patients.
16
Daytime sleepiness is strongly correlated with the with PD appear to correlate with both severity and duration of
use of dopaminergic therapies, which are widely used to treat the motor disease.
21
Among PD medications, anticholinergics can significantly
symptoms of PD. Levodopa and other dopamine agonist therapies have worsen urinary symptoms.
been associated with both EDS and the sudden onset of sleep, and there
appears to be a positive correlation with the dose of dopaminergic Erectile dysfunction is a common symptom experienced by male PD
agents and the occurrence of EDS and sudden onset of sleep.
17
patients.
22
Additional sexual symptoms secondary to dopaminergic
treatment may also occur in PD patients. Increased libido, hyper-
RBD is characterised by the loss of REM sleep in combination with sexuality and aberrant sexual behaviour have been reported in
nocturnal jerking and/or violent limb and body movements. It is patients receiving dopamine agonist therapies.
26 EUROPEAN NEUROLOGICAL REVIEW
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