Sleep Disorders

Spring 1999
Volume 10, Number 1

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Involuntary jerking or kicking of the arms or legs during sleep signal a variety of underlying medical conditions. Periodic Limb Movements of Sleep are evident on the polysomnographic record. Treatment of PLMS may significantly improve patient quality of life.

Introduction. Involuntary jerking or kicking of the arms or legs during sleep may signal a variety of underlying medical conditions. The clinician often will not be aware that such movements exist unless the bed partner of the patient complains of disrupted sleep. Alternatively, the Periodic Limb Movements of Sleep (PLMS) may be evident only on the polysomnographic record (see figure 1). Such limb movements are important to recognize as they may indicate treatable conditions which result in improved patient quality of life. Historically, PLMS was often called “nocturnal myoclonus”; a term no longer in use. The physiologic activity is clearly not myoclonic in origin. At times, polysomnogram data lists the myoclonic index (MI). This simply refers to the number of PLMS contractions per hour. There is a trend now to use the alternate label, Periodic Limb Movement Disorder (PLMD), as listed by The International Classification of Sleep Disorders: Diagnostic and Coding Manual, American Sleep Disorders Association 1997. A good general reference about PLMS can be found in Montplaisir et al 1994.

Figure 1

Clinical Description. Clusters of repetitive limb movements during sleep may be subtle and of brief duration or high amplitude lasting for several minutes. The movements last from 0.5 to 5 seconds and are quite similar to the triple flexion response. The great toe extends, the ankle dorsi-flexes and the hip and knee flex as well. Typical PLMS occurs at 15 to 40 second intervals during non-REM sleep. Approximately 70% to 90% of patients with Restless Leg Syndrome (RLS) will demonstrate PLMS on polysomnogram. Conversely, 40% to 50% of patients with PLMS complain of RLS. PLMS frequently produces arousal and sleep disruption. Prevalence of PLMS increases with age and certain medical conditions as described below. A video example of RLS and PLMS may be found in the article by Walters et al 1991.

Biologic Basis. The biologic basis of PLMS remains only partly understood. We know that the condition is associated with 2 major physiologic phenomena; low levels of dopamine in the nervous system and degeneration or dysfunction of peripheral nerves. These are all “release phenomena” that occur when the spinal cord reflexes receive less descending inhibition from cortico-spinal and other descending pathways. Such involuntary movements have been demonstrated in humans and non-human primates with spinal cord injury. There appear to be spinal locomotion generators that can produce cyclic stepping movements of the legs.4 When not under descending inhibitory control, these repetitive movements emerge. Some studies suggest that many patients with PLMS have slowing of peripheral nerve conduction or mild, sub-clinical neuropathy.3 Patients may also demonstrate abnormal conduction times when stimulated with cortical magnetic stimulation.1 These finding have led to some difficulty separating so-called primary PLMS from secondary PLMS. We also have not sorted out the possible genetic basis for PLMS and RLS. Clearly, some families have many generations effected by these phenomena. From a practical point of view, the clinician attempts to identify any underlying, treatable medical conditions at initial evaluation as described below.

Differential Diagnosis. Table 1 lists various conditions that may mimic PLMS. Evaluation should be considered in the clinical context of the patient and may include imaging studies (eg, magnetic resonance imaging scan (MRI), polysomnograph (PSG), electroencephalogram (EEG), laboratory testing).

Evaluation. Evaluation of patients with abnormal limb movements during sleep begins with a complete medical history and examination. Details about prior and current medical conditions must be obtained. A list of current and past medication exposure is critical, as one may uncover exposure to dopamine antagonists, chemotherapeutic agents, etc. Particular attention should be directed to signs and symptoms of neuropathy, myelopathy, spasticity and extrapyramidal disease. Once completed, a more focused set of laboratory tests may be ordered. This obviously is a broad spectrum and might include blood work for endocrine dysfunction, vitamin deficiencies, iron status, electromyography, and nerve conduction testing. Some patients may need neuroimaging to rule out spinal cord disease, such as demyelination or stenosis. Most patients will not have medical histories requiring such elaborate testing. They will commonly describe RLS symptoms and their spouse will report kicking in the night. Polysomnograph will reveal the classic repetitive limb movements during non-REM sleep and confirm the diagnosis.

Treatment. As most patients with PLMS also have RLS, treatment of RLS with dopaminergic agents often alleviates both RLS and PLMS. If patients continue to struggle with disrupted sleep, or the PLMS disrupts the bed partners sleep, a second medication may be added. Most effective is clonazepam (Klonopin) at low doses (range 0.25 to 1mg qhs). Alternative treatments include opioids (eg, codeine 30 mg qhs, propoxyphen 65mg qhs) or increased doses of the dopaminergic agent, although this group of drugs is more effective for RLS symptoms than PLMS. Some patients with severe PLMS require 2 or 3 drugs in combination. Clearly, any underlying medical problems should be addressed. If iron, magnesium or B12 deficiencies exist, replacement therapy should be initiated. Recent reports suggest a treatment goal of ferritin levels greater than 50 mcg/l. Magnesium therapy has been successful using 12.4 mmol qhs. If spasticity is present, anti-spasticity medication may be of benefit, eg, baclofen or tizanidine. Concomitant sleep apnea should be treated as this may mask or aggravate PLMS. If the patient has Parkinson’s Disease, one must consider that the limb movements reflect over dosage of dopaminergic medication, ie, dopa-induced dyskinesia, and doses reduced accordingly. In contrast, under dosage may cause PLMS and RLS. Some medications may aggravate PLMS including dopamine antagonists such as neuroleptics and metaclopramide (Reglan), some anti-depressants, and withdrawal from benzodiazepines or barbiturates.

Sleep Disorders and Parkinsonism.

Over the past few years, an interesting association between sleep disorders and parkinsonism has emerged. There are a number of common problems listed below. Particular attention is directed to the association of REM Behavior Disorder (RBD), Multi-System Atrophy (MSA), and Diffuse Lewy Body Disease (DLBD).

RBD as a precursor to Parkinson’s Disease. Originally described in the1980’s, RBD was known to be more common in males over the age of 50 and in patients with neurological problems, particularly brain stem lesions. More recently, the original authors reported that nearly 40% of the male RBD patients went on to develop parkinsonism.10 Parkinsonism was diagnosed 4 years after the diagnosis of RBD and 12 years after RBD symptom onset. Some of the patients likely have a form of MSA as a cause of their parkinsonism.

RBD as a precursor to MSA or DLBD. We are now much more accurate as to the various causes of parkinsonism. Although Idiopathic PD is still the most common, other sub-types are increasingly recognized due to distinctive clinical characteristics and more dire prognoses (see CNI Review; Winter-Spring 1999). Multi-System Atrophy includes Striato-nigral degeneration, Shy-Drager Syndrome and Olivopontocerebellar Atrophy. MSA patients often have major degeneration of brain stem and basal ganglia nuclei. Sleep disorders are common and RBD may be a precursor as with PD. When rapid onset of RBD, depression, parkinsonism, and cognitive impairment occur within a 12 month period, it is quite likely that DLBD is the correct diagnosis. This disorder is relentlessly progressive, poorly responsive to the usual PD treatments, and patients are extremely sensitive to extra-pyramidal side-effects of neuroleptics. Such patients often become very parkinsonian when given low-dose dopamine antagonists, even some of the newer atypical agents such as olanzapine (Zyprexa) or risperidone (Risperdal). The nocturnal problems usually respond to low dose clonazepam (eg, clonazepam 0.25 mg to1.0 mg) as in typical RBD. Ultimate prognosis, however, is poor. Death from aspiration pneumonia is common 8 years from symptom onset.

Severe sleep apnea in MSA. As noted above, brain stem degeneration is common in MSA. Failure to maintain normal respiration may reflect central generator dysfunction or loss of normal pharyngeal and laryngeal muscle tone contraction. Apnea may emerge as a major co-morbidity. Treatment with the standard therapies may be successful (eg, CPAP or laser UPP). Some patients develop nocturnal stridor that may require tracheotomy. We have successfully eliminated stridor in several patients using botulinum toxin injections into the adductor muscles of the larynx. Obviously, careful evaluation of these patients is needed and should include PSG and laryngoscopy.

Restless Leg Syndrome in association with PD. As noted in the article on RLS, abnormalities of dopamine are common to both PD and RLS syndromes. Patients with PD complain of RLS when under-dosed on their dopaminergic medication, especially with the wearing off phenomena during the night. This can easily be identified by asking the right questions. Treatment is successful when longer acting levodopa preparations (such as Sinemet CR) or dopamine agonists are used. The timing of doses before bed must be adjusted accordingly. If PLMS co-exists, treatment is as outlined in the PLMS article of this issue.

Sleep-wake cycle disruption with PD. Patients often complain of excessive daytime sleepiness, insomnia, or mid-sleep cycle awakening. A complex set of pharmacological, physiological and psychological factors must be addressed. The reader is referred to our recently published algorithm of PD management for further details.

Summary. 

Prognosis. The prognosis depends upon cause of PLMS and the presence of concomitant illness. If PLMS exists in isolation or with mild RLS, prognosis is usually good. If PLMS occurs in the setting of severe RLS, neuropathy or spinal cord disease, the limb movements may be difficult to suppress and will continue as a source of great frustration. Fortunately, symptom control, even in difficult PLMS, is possible with 2 or 3-drug combination therapy.

Resources. The most useful source of information for patients and physicians is the Restless Leg Syndrome Foundation, Inc. on the Web at rlsf@millcomm.com. They can be also found at: RLS Foundation, Inc., 4410 19th Street NW, Rochester, MN 55901-6624 (507) 287-6465

Address comments and questions to:

Medical Director
CNI Movement Disorders Center
701 E Hampden Avenue, Suite 530
Englewood, CO 80113

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