Reviews for Primary Care - Fall 2007 - (Page 44) Insomnia and Neurological Disorders continued tremor, eye blinking, dyskinesias, and other phenomena, such as periodic limb movements in sleep, restless legs syndrome, fragmentary myoclonus, and respiratory dysfunction in sleep.32 The underlying biological basis of sleep disruption in PD is probably related to the alteration of dopaminergic, noradrenergic, serotonergic, and cholinergic neurons in the brainstem.33 Typical polysomnographic features in PD include an increase in stage 1 sleep, a reduction of both slow wave sleep (SWS) and REM sleep, and an increase in nocturnal myoclonus. Almost two thirds of patients with PD may have sleep initiation insomnia. Close to 90% of these patients often have sleep maintenance insomnia associated with frequent awakenings.2,34 Potential causes of insomnia in PD are related to the disease itself and in some situations, related to the medical therapy used in PD. Patients with PD often have difficulties turning and changing positions during the night secondary to bradykinesia. Leg cramps, leg jerks, and dystonic spasms of the limbs, face, and back also are very common. The most commonly reported sleep disorders include frequent awakening (sleep fragmentation) and early awakening.30 One study found a strong correlation between depression and sleep disorders in patients with PD, which underlines the importance of identifying and treating both conditions in these patients.30 Sleep maintenance problems and difficulties with sleep initiation are the earliest and most frequent sleep disorders observed in these patients.33 Sleep fragmentation and spontaneous daytime dozing occurred much more frequently in PD patients than in controls.35 Sleep fragmentation in PD may be the result of increased skeletal muscle activity, disturbed breathing, and REM-to–non-REM variations of the dopaminergic receptor sensitivity.33 Sleep-related motor complaints include nocturnal akinesia, dystonia, and painful cramps.33 The chronic-release formulation of levodopa/carbidopa (Sinemet® CR; Merck & Co., Inc., Whitehouse Station, NJ) has been demonstrated to improve nocturnal akinesia and increase sleep efficiency in patients with PD with underlying sleep-related motor disturbances.33 Circadian rhythm disturbances in PD may be related to mesocorticolimbic dopaminergic abnormalities and mesostriatal system abnormalities.33 Abnormalities of dopaminergic neurons in the ventral tegmentum area often lead to electroencephalographic desynchronization and an abnormal sleep-wake schedule disorder.36 Factors that are often responsible for sleep disruption in PD are probably the result of tremors, dystonia, rigidity, dyskinesia, REM behavior disorder (RBD), periodic leg movements of sleep, REM onset blinking, and increased awakening.28 These patients often have difficulties in changing position and an inability to initiate movement. Patients with PD who are already on medications may have additional sleep difficulties. Low-dose dopaminergic agonists are often sedating. On the other hand, high-dose dopaminergic agonists may lead to increased hallucinations, nightmares, and increased arousal. Levodopa is often associated with increased sleep latency but an increased sleep continuity.37,38 Attempts to explain the sleep-wake disruption in PD have been linked to reduction in serotonergic neurons of the dorsal raphe, noradrenergic neurons of the locus ceruleus, and cholinergic neurons of the pedunculopontine nucleus.33 The polysomnographic hallmark of PD includes reduced sleep efficiency, increased wakefulness after sleep onset, increased sleep fragmentation, reduction of SWS and REM sleep, disruption of non-REM–to-REM cyclicity, loss of REM-related muscle atonia, and increased electromyography (EMG) activity, which is the basis for RBD.39 Figure 3 demonstrates a polysomnographic example of RBD showing the pathological increase in limb EMG tone during REM sleep. Treatment of sleep disorders in patients with PD deserves special consideration. Patients with PD who suffer from insomnia are often treated by improving sleep hygiene abnormalities. Hypnotic therapy for sleep disturbances in PD patients should be approached with considerable care because of the risks of falling, agitation, drowsiness, and hypotension.40 Some patients may benefit from pharmacologic treatment with small-dose dopaminergic preparation (ie, levodopa/ carbidopa 25/100), and small doses of sedating tricyclic antidepressants (TCAs) may be tried. Problems with bradykinesia and nocturia are often improved by providing patients with a portable bedside commode. For patients with restless legs syndrome symptoms, evening and nocturnal doses of a dopaminergic agonist such as carbidopa/levodopa or a dopamine (D3) agonist are useful.41 Patients with RBD are often treated with clonazepam (0.5 mg at bedtime).41 Diffuse Lewy Body Dementia Patients with diffuse Lewy body dementia (DLBD) are found to have an increased rate of RBD.42,43 DLBD is the second most common cause of dementia, following Alzheimer’s disease.44 DLBD is characterized by dementia, extrapyramidal symptoms, and psychosis (specifically visual hallucinations). Neuropathology demonstrates the effects of Lewy body deposition and neuronal degeneration in the substantia nigra, locus ceruleus, and raphe nuclei.44,45 Patients are found to have an increased rate of 44 VOL. 1 NO. 1 2007 REVIEWS FOR PRIMARY CARE
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