Nocturnal symptom complex in PD and its management

Sleep disturbances are a key aspect of nonmotor complications of Parkinson’s disease (PD), and virtually all patients with PD suffer from various levels of nocturnal disability, causing sleep disruption.1-4⇓⇓⇓ The pathology is diverse and includes degeneration of central sleep regulatory centers, such as the forebrain ventrolateral preoptic area, the thalamus, and the nucleus tractus solitarius, as is evident from studies in canine models of narcolepsy.2,5⇓ Paradoxically, dopaminergic drugs also play a part in the pathogenesis of sleep disruption in PD, and this may manifest itself as abnormal sleepiness or a hypoactivity response.2,6,7⇓⇓ Subjectively, nocturnal symptoms in PD can be categorized as insomnia, motor, urinary, and neuropsychiatric, often with secondary daytime somnolence.8 Thus far, these symptoms have not been systematically quantified because there have been no instruments that specifically evaluate the multifactorial nature of sleep disorders in PD. The newly developed Parkinson’s Disease Sleep Scale (PDSS) aims to measure nocturnal symptoms of PD in a semiquantitative manner.8,9⇓ Recognition and targeted treatment of these symptoms would allow smooth 24-hour control of PD symptoms. In PD, degeneration of dopaminergic neurons in the CNS affects central sleep regulatory centers. Midbrain dopamine neurons have extensive connections with the striatum and also directly with the thalamus.10 These neurons are believed to modulate thalamocortical neuronal excitability which, in turn, influences the sleep–wake cycle (figure 1). 2 In a primate model, systemic administration of 1-methyl,4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a dopamine neurotoxin, produced general and daytime sleepiness.11 The sleep-wake cycle also appears to be controlled by glutamatergic influences exerted on the basal ganglia circuitry from the subthalamic nucleus (STN), the pedunculopontine nucleus, and the laterodorsal tegmental nuclei.12-14⇓⇓ Various other neuropeptides/chemicals that modulate wakefulness and rapid eye movement (REM) sleep include serotonin, norepinephrine, histamine, acetylcholine, …