Neuropsychiatric Dimensions of Movement Disorders in Sleep

April 1, 2006

Sleep-associated movement disorders are common in the general population. When patients complain of sleep disturbance, psychiatrists should consider,and question for, features of nocturnal movement disorder.

Special Report: Neuropsychiatry

With the change of state from wakefulness to sleep, muscle activity and tone decrease, and they are lost completely during rapid eye movement (REM) sleep. Therefore, one would anticipate few, if any, movement problems associated with sleep. In spite of these physiologic changes, however, normal sleep is not totally free of movement. The average sleeper moves about 40 to 50 times a night andthis number changes in certain situations.For example, sleep deprivationresults in a sleep with fewer movements.1

In addition to total body movements,limb jerks and twitches also occur innormal sleepers. They typically occurduring sleep onset (sleep starts or hypnicjerks) or in association with REMsleep.2 Such movements in sleep areincreased in persons who have movementdisorders while awake, such asthose with Parkinson disease (PD) orTourette syndrome (TS).

When considering disorders ofmovement during sleep, the physicianshould ascertain whether abnormalmovements also occur during awakeperiods. Abnormal movements that arepresent during the day, such as the motordisturbance of PD or TS, are usuallyquiescent during sleep, while those occurringprimarily in sleep (eg, nocturnalepilepsies, parasomnias, restless legssyndrome [RLS], periodic limb movementsof sleep [PLMS]) rarely intrudeinto awake periods. Some disorders,such as seizures, manifest predominantlyduring sleep, but may occasionallyoccur during periods ofwakefulness. A classification of sleeprelatedmovement disorders is presentedin Table 1. I will discuss the more salientof these disorders in this article.

SLEEP-SPECIFIC MOVEMENT DISORDERS


Periodic limb movements of sleep

Previously referred to as “nocturnalmyoclonus,” PLMS are regarded as adistinct nosologic entity, even thoughthey overlap a great deal with RLS andother sleep disorders. These movementsprimarily occur in the lower limbs andare classically described as phasic extensionsof the big toe and dorsiflexion atthe ankle, occurring with a periodicityof 20 to 40 seconds. Flexion at the kneeand hip may occur, and movements may involve the upper limbs. Both lowerlimbs are usually involved but not necessarilysymmetrically or simultaneously.Sometimes only one leg is involved, orthe phenomenon may alternate from oneleg to the other.3 The electromyographiccharacteristics of the movements arevaried and are usually of longer durationthan those of classic myoclonus,typically 1.5 to 2.5 seconds long (range,0.5 to 5 seconds). There may be an initialmyoclonic jerk followed by a toniccontraction, or a polyclonic contractionwith or without a tonic component.

PLMS are common in healthy elderly persons, with 45% of 65- to 76-year olds,women more often than men,having 5 PLMS per hour at night4; thecondition is rare before the age of 30.PLMS occur in a number of sleep disorders,particularly RLS, but alsonarcolepsy, REM sleep behavior disorder(RSBD), and obstructive sleep apnea.PLMS also occur in awake subjectswith RLS but only rarely in controls.5

The clinical significance of PLMScontinues to be debated, since manystudies have failed to demonstrate anassociation between PLMS and symptomsof sleep disturbance.6,7 It is possiblethat people who complain ofinsomnia caused by leg movementsmay have a lower threshold of arousal.

The pathogenesis of PLMS is notclear. Lesion, imaging, and laboratorystudies indicate neuronal hyperexcitabilitywith involvement of brainstemand spinal cord structures, in particular,the central pattern generator for gait.8 There is also evidence of decreased dopaminergictransmission.9 PLMS have alsobeen associated with neuroleptic-inducedakathisia.10 Tricyclic and selective serotoninreuptake inhibitor antidepressantsmay induce or worsen PLMS,11 presumablyvia serotonergic influences on dopaminergictransmission.

Several authors have highlighted alink between PLMS and psychiatricdisorders. A recent community surveyof 18,980 persons documented a 3.9%prevalence of PLMS and high associationswith stress, having a mental disorder,and certain lifestyle and healthfactors, such as high caffeine intake anddiabetes.12 Patients with PLMS havebeen reported to have high rates of ahistory of depression.6 Increased ratesof PLMS are reported in patients withattention-deficit/hyperactivity disorder(ADHD)13 or posttraumatic stress disorder,and in those who have frequentnightmares.14

In patients who present with symptomsof sleep disturbance, such as excessivedaytime sleepiness, insomnia, orfrequent awakening, the clinician isfaced with deciding whether to treatpatients with a high PLMS index. A trialof treatment can be undertaken in thesepatients once other sleep disorders havebeen excluded and possible exacerbatingfactors such as caffeine, hypnotics,and stress have been curtailed. Dopaminergicdrugs, dopamine agonists,opiates, benzodiazepines, and anticonvulsantsare all used, with dopaminergicdrugs or dopamine agonists regardedas first-line treatment.15

Restless legs syndrome

RLS is a common disorder, the mostcomprehensive account of which wasprovided by Ekbom.16 The main symptomis an unpleasant and uncomfortablesensation frequently localized inthe legs, with the shins being moreaffected than the calves (hence, thedesignation “anxietas tibiarum”). Thesymptoms are typically bilateral andmay sometimes affect the thighs or feetand less often the buttocks and lowerback. The descriptors typically used are“creeping,” “pulling,” “stretching,”“restless sensations,” “aching,” andoccasionally, “painful.” The affectedperson may attempt to obtain relief byrubbing the skin, massaging the legs,stretching and kicking, swinging thelegs, or standing and walking.

The symptoms of RLS appear onlywhen the limbs are at rest, and arealmost invariably worse in the eveningor at night. Typical situations for theworst symptoms are lying in bed orsitting for prolonged periods. In severecases, long trips or even a visit to thetheater can become impossible. Theuntreated patient has the worst symptomsbetween 11 PM and 4 AM, and theleast symptoms between 6 AM and 12noon. Sleep deprivation results fromdifficulty in initiating sleep and maintainingsleep after arousals.

Eighty percent of RLS sufferers havea PLMS index greater than 5,17 and thepresence of PLMS is supportive of thediagnosis of RLS. Sleep studies of RLSpatients also show increased sleeplatency and reduced total sleep time,sleep efficiency, and slow-wave sleep.Sleep efficiency is often below 50%.Neurologic findings are normal.

The prevalence of RLS ranges from2.5% to 15% of the general population,increasing with age.18 Some studieshave reported a higher prevalence inwomen, but this is not a consistent finding.Family history of RLS is positivein 34% to 92% of cases.19,20

The differential diagnosis of RLSincludes peripheral neuropathy, peripheralclaudication, leg cramps, akathisia,and in children, ADHD.21 Sachdev22 describesseveral features for differentiatingbetween akathisia and RLS. In particular,akathisia sufferers report an innerfeeling of restlessness with a compulsionto move in response to this feeling,with only partial amelioration of thesubjective restlessness. Patients withRLS, on the other hand, report sensorysymptoms in the legs, which may be deepand which typically occur when the legshave been in a recumbent position.

Akathisia does not have the characteristicworsening at nighttime seen inRLS, and akathisic patients feel worstwhen they are standing or sitting in onespot. PLMS and dyskinesia whileawake are uncommon in patients withakathisia, who often have a tremor ofextrapyramidal rigidity owing to neurolepticmedication. RLS can be idiopathicor secondary to a number of conditions,including pregnancy, iron deficiency,and renal failure; in these cases, RLSusually remits with resolution of theunderlying condition.

Several new medications have led toimprovements in treatment for RLS.Dopamine agonists such as pramipexole(Mirapex)23 and cabergoline (Dostinex)24 are the first choices for treatment, withlonger half-life, better tolerance, and lessrisk of the augmentation effect than withL-dopa.

Anticonvulsants, particularly gabapentin(Neurontin), are useful if pain isa prominent feature, while benzodiazepinessuch as clonazepam (Klonopin)may be useful but have significantadverse effects. Low-potency opioidsor opioid agonists are another pharmacologicoption. Other strategies includeamelioration of iron deficiency, considerationof withdrawing potential exacerbatingagents such as neuroleptics andantidepressants, and avoiding caffeine,alcohol, and nicotine (Table 2).

Nocturnal paroxysmal dystonia

Patients with nocturnal paroxysmal dystonia,irrespective of age or sex, have bizarremovements during sleep that superficiallyresemble seizures. The episodestend to recur chronically and appear torespond to carbamazepine at low doses.25

Narcolepsy and cataplexy

Narcolepsy is an idiopathic syndromecharacterized by excessive daytimesleepiness and often disturbed nocturnalsleep, along with pathologic manifestationsof REM sleep. Narcolepsyis often associated with cataplexy(sudden muscle hypotonia precipitatedby intense emotions), hypnagogic andhypnopompic hallucinations, and sleepparalysis. Other associated disordersinclude bruxism, PLMS, sleepwalking,sleeptalking, and RSBD. Daytime sleep(“microsleeps”) lasting seconds tohours occurs in 40% of patients. Duringthis time, complex automatic behaviors,subjectively experienced asamnestic periods, may manifest.

Narcolepsy is a rare disorder, witha prevalence of between 0.02% and0.18% of the population.26 It usuallyemerges in the second or third decade,but can have its onset in childhood.Cataplexy occurs in 75% of cases butmay not manifest for several years,rendering differential diagnosis a challenge.An abnormality of the hypothalamichypocretin system resulting indecreased central hypocretin-1 and alterations of monoaminergic transmission-in particular dopamine andnoradrenaline--is thought to be involvedin the pathophysiology of thedisorder. The HLA haplotypes DR2and DQB1*0602 confer an increasedrisk of narcolepsy, and mutations of thegene coding for catechol-O-methyltransferasehave been described inpatients with narcolepsy.27

PRIMARY NEUROPSYCHIATRICMOVEMENT DISORDER


Parkinson disease

Abnormal movements intrinsic to PD,such as tremor and rigidity, persist butdecrease in frequency and amplitudewith sleep. RSBD, PLMS, and RLShave all been described in PD patients.Interestingly, RSBD has been reportedto predate the development of PD andother neurodegenerative disorders28 andsuggests a common origin.

Tourette syndrome

Questionnaires indicate that sleep problems,including parasomnias, arefrequent in TS.29 Movement disordershave also been noted, but the literatureis conflicting about almost every aspect.

CONCLUSION

Sleep-associated movement disordersare common in the general populationand are more frequent in elderly personswith neuropsychiatric disorders. Psychiatristsencountering patients complainingof sleep disturbance should consider,and question for, features of nocturnalmovement disorder. This is particularlyimportant for patients taking antidepressantor antipsychotic medication,since these may worsen abnormalmovements in sleep. It is equally importantto consider the high rates of depressivefeatures in patients with PLMS,RLS, and narcolepsy, which warrantscreening for depression in thesepatients and a close liaison with psychiatricservices.

Dr Sachdev is professor of neuropsychiatry atthe University of New South Wales in Sydney,Australia. He has indicated that he has no conflictsto disclose concerning the subject matterof this article.

References:

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