Anesth Analg 2005;101:726-727
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000159376.47974.71
ANESTHETIC PHARMACOLOGY
Physostigmine for the Acute Treatment of Restless Legs Syndrome
Calvert C. Alpert, MD,
D. Patrick Tobin, CRNA, and
Stephen F. Dierdorf, MD
Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston, South Carolina
Address correspondence and reprint requests to Stephen F. Dierdorf, MD, Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, 165 Ashley Avenue, Suite 525, PO Box 250912, Charleston, South Carolina 29425. Address e-mail to dierdorf{at}musc.edu.
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Abstract
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We present a case report of an acute episode of restless legs syndrome that interfered with the performance of a diagnostic imaging procedure of the cervical spine. The patient had a 19-yr history of restless leg syndrome with periodic limb movements during sleep. Treatment with additional sedation and opioids did not alleviate the leg movements. IV administration of 1 mg of physostigmine eradicated all extraneous leg motion.
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Introduction
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Restless legs syndrome (RLS) is a neurologic disorder that may affect 5% to 10% of the population. The incidence increases with aging and RLS may affect 15% of geriatric patients. RLS is characterized by dysesthesias of the extremities, particularly the legs, and an uncontrolled urge to move the extremities. During sleep periodic limb movements can be severe, causing chronic sleep disturbances and sleep deprivation (1). A variety of drugs have been recommended for treatment of RLS, including dopamine agonists, benzodiazepines, anticonvulsants, opiates, ketamine, magnesium, and amantadine. Improvement has been reported with chronic therapy with most of these drugs. There have been no reports, however, of the acute treatment of RLS when excessive movement interfered with a diagnostic procedure. We report a case of the acute treatment of a patient with RLS during magnetic resonance imaging (MRI) of the cervical spine.
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Case Report
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A 77-yr old man with severe degenerative disease of the cervical spine with the recent onset of paresthesias and numbness in the upper extremities was scheduled for MRI of the cervical spine. At the age of 58 yr, he had an onset of RLS that progressed to the extent that it interfered with sleep. His mother and older brother also had RLS. Treatment with anti-Parkinson drugs produced no relief. Chronic treatment with oral methadone (10 mg at 2 pm and 10 mg at 9 pm) provided the most effective, although incomplete, relief of symptoms.
Deep sedation for cervical MRI was planned. After the slow IV administration of 5 mg of midazolam, the patient complained of pruritus of the legs. IV administration of 12.5 mg of diphenhydramine did not reduce the itching. An infusion of propofol, 50–75 µg · kg–1 · min–1 was begun. Supplemental oxygen was administered via nasal cannulae and the oxygen saturation was maintained between 96% and 98% with spontaneous ventilation. Other monitors included a noninvasive arterial blood pressure device, a continuous electrocardiogram, and end-tidal capnography. Despite a satisfactory level of sedation, rhythmic and pronounced leg movements interfered with the quality of the diagnostic procedure. A 30-mg bolus dose of propofol and 2 doses of hydromorphone (1 mg) had no effect. Glycopyrrolate 0.2 mg and physostigmine 1 mg IV were administered 10 min after hydromorphone. Sixty to 90 s after the administration of physostigmine, all leg movement ceased and the procedure was successfully completed.
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Discussion
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RLS is a sensorimotor disturbance characterized by unpleasant sensations in the legs and the irresistible urge to move them (akathisia). Walking or stretching usually relieves the symptoms. Typically, RLS is worse at night and it can cause severe sleep disturbances. Periodic limb movements during sleep are also common in patients with RLS (2). RLS may be primary (idiopathic) or secondary. The etiology of primary RLS has been linked to an abnormality in the dopamine system that may be related to a relative deficiency of iron in the central nervous system. Iron is required for dopamine synthesis and iron depletion in the brain may cause a dopamine deficiency (3). Although patients with Parkinson’s disease have an increased incidence of RLS, there is no evidence to suggest that patients with RLS are more likely to develop Parkinson’s disease. RLS may be a manifestation of altered somatosensory processing, as it has been reported in patients with spinal cord lesions and normal patients during recovery from spinal anesthesia (4). Reduction of sensory input during sleep may explain why RLS occurs at rest (5). Secondary causes of RLS include iron deficiency anemia, diabetes mellitus, polyneuropathy, spinal cord lesions, and uremia. RLS has been reported in 6% to 62% of patients undergoing chronic renal dialysis. RLS generally abates after successful renal transplantation (6).
The current recommended treatment for primary RLS is anti-Parkinson drugs. Levodopa may be effective, but its relatively short half-life and side effects limit its usefulness. Dopamine agonists, such as ropinirole, pramipexole, cabergoline, and pergolide, have fewer side effects and a better pharmacokinetic profile than levodopa. Other drugs used for the treatment of RLS include benzodiazepines, carbamazepine, gabapentin, valproic acid, opiates, magnesium, clonidine, and ketamine (7,8). Patients with severe RLS refractory to oral medications may respond to chronic intrathecal infusion of opiates and local anesthetics (9). These treatment modalities have been directed at chronic therapy of RLS. This report is the first to describe the necessity for the acute treatment of RLS. It is possible that sedation with midazolam and propofol triggered the dysesthesias and periodic limb movements in our patient. Physostigmine for the treatment of RLS has not been previously reported. It was felt by the authors that physostigmine might reverse the effects of the sedative drugs and alleviate the periodic limb movements. Physostigmine is an anticholinergic that crosses the blood-brain barrier and reverses the effects of a variety of hypnotics. Presumably, physostigmine permits acetylcholine to accumulate at cholinergic receptors in the reticular activating system, thereby increasing arousability. Although we do not know the precise mechanism for the efficacy of physostigmine for the treatment of RLS, it could be that physostigmine altered central neurotransmitter balance and eliminated the leg movement. Dopaminergic effects of physostigmine have not been reported.
In summary, we present a case of a patient with RLS with severe limb movements that interfered with an important diagnostic procedure. The periodic limb movements were eliminated by the administration of physostigmine. The possibility of an additive or synergistic effect between physostigmine and other drugs administered to our patient, specifically hydromorphone, can not be discounted. Further investigation in other patients with RLS is certainly warranted.
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Footnotes
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Accepted for publication February 1, 2005.
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References
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Abstract
Introduction
