Elderly Woman With Refractory Restless Legs Syndrome
From Medscape Neurology & Neurosurgery. Posted 06/29/2005
Chief Complaint
Meredith is an 86-year-old woman who is referred to a sleep medicine specialist for further treatment of refractory Restless Legs Syndrome (RLS).
History of Symptoms
Meredith describes "electric currents" or "shocklike feelings" in her legs, and to a lesser extent in her arms, when she lies down to rest in the evening. These unpleasant sensations are associated with an irresistible urge to move her legs, which partially relieves the symptoms but prevents her from falling asleep. She additionally experiences leg jerks during sleep and occasionally during wakefulness. In addition to disrupting her sleep, she believes that her symptoms impair her daytime functioning. She describes fatigue and lack of energy, an inability to sit and relax, difficulties with concentration and attention, and feelings of anxiety and depression. Meredith states that her symptoms, which began in her 50s, were initially intermittent but have progressively worsened over the years.
Treatment History
Meredith has a long treatment history for this malady. When her symptoms became more frequent, she sought help from a neurologist who diagnosed RLS. Blood tests for iron demonstrated a ferritin level below 50 ng/mL. The neurologist prescribed iron 325 mg once daily along with vitamin C 500 mg once daily to aid with absorption of the iron. Her ferritin level after 6 months increased but remained below 50 ng/mL nonetheless. Her iron and vitamin C supplement regimen was raised to twice daily for an additional 6 months. Ferritin levels drawn at that time were greater than 50 ng/mL. Her symptoms, although improved with a higher ferritin level, remained severe.
The neurologist prescribed clonazepam 0.5 mg at bedtime. The medication appeared to reduce Meredith's sense of anxiety associated with the RLS, but the core symptoms of her RLS persisted. She continued to experience unpleasant sensations associated with an irresistible urge to move her legs. Furthermore, she continued to jerk her legs at night. Higher doses of clonazepam resulted in intolerable daytime fatigue and the medication was tapered and discontinued.
Next, the physician tried carbidopa-levodopa 25-100 mg, 1 tablet, 1 hour before bedtime. This medication was effective in relieving the symptoms of RLS during the first half of the night, but the symptoms reemerged during the second half of the night. As a result, her neurologist switched her from carbidopa-levodopa 25-100 mg to sustained-release carbidopa-levodopa 50-200 mg at 1-2 hours before bedtime. This regimen was effective for several months, but eventually her symptoms returned, occurred earlier in the day, affected the arms to a greater degree, and became more intense. The neurologist increased her dosage to 2 tablets at 1 hour before bedtime, but her symptoms only temporarily improved and the medication was discontinued.
Pramipexole 0.125 mg 2 hours before bedtime was started. The dose was increased by 0.125 mg every week until an effective dose of 0.375 mg was reached. This dose was effective for several years, but Meredith's symptoms eventually returned. Attempts to increase the dose further caused nightmares and the medication was discontinued. Given the efficacy of pramipexole, the neurologist believed that a trial with another dopamine agonist was warranted. He started ropinirole 0.25 mg at 1-2 hours before bedtime, but it was associated with nausea and was discontinued.
The physician next decided to try gabapentin 300 mg 1-2 hours before bedtime, and this dose was gradually increased to 900 mg shortly before bedtime; however, this resulted in intolerable daytime sedation, weight gain, and cognitive impairment. No clear improvement in the symptoms was noted and the medication was discontinued.
A brief trial of hydrocodone-acetaminophen at bedtime did not result in improvement of the RLS.
The neurologist then prescribed codeine 30 mg shortly before bedtime. This dose was partially effective, and the patient gradually self-increased her dosage to 90 mg shortly before bedtime. Her symptoms improved, but the neurologist was uncomfortable with further increasing the dose of opiates. The medication was continued and the patient was referred to a sleep medicine specialist.
Other Pertinent History
Allergies: Carbamazepine.
Past medical history: Single seizure.
Past surgical history: None.
Current medications: None.
Review of systems: Not contributory.
Social history: Meredith is widowed, with 5 children. She is a retired seamstress. She denies tobacco, alcohol, and illicit drug use.
Family history: She reports no other family members with RLS.
Physical examination: Her physical exam, including a detailed neurologic assessment, is unremarkable.
Laboratory tests: Complete blood cell count and chemistry panels, including creatinine level, folate level, and iron studies, are normal.
Impression
Meredith suffers from severe, medically refractory RLS. Essential diagnostic features of RLS include an urge to move the legs or arms after lying down in the evening, with movement attenuating the symptoms. Supportive clinical features include a family history of RLS, a therapeutic response to dopaminergic drugs, and the presence of periodic limb movements during sleep or occasionally during wakefulness. Associated features include a variable clinical course, symptoms that are typically more severe when the age of onset is greater than 50 years, a major sleep disturbance, and an unremarkable neurologic examination.[1]
Meredith has tried a number of classes of medication that were either ineffective or resulted in intolerable side effects. Specifically, iron supplements failed to adequately improve her symptoms. Clonazepam, a benzodiazepine, reduced the anxiety associated with RLS but did not improve the periodic limb movements and resulted in intolerable daytime sedation. Carbidopa-levodopa, although temporarily effective, resulted in rebound. Sustained-release carbidopa-levodopa was effective but over time resulted in augmentation, which is characteristic of this class of medication.[2]
Dopamine agonists, such as pramipexole and ropinirole, have a lower incidence of augmentation than carbidopa-levodopa.[3] In this case, they appeared to be effective but resulted in intolerable side effects of nightmares and nausea. Hydrocodone-acetaminophen, a low-potency opioid, was ineffective. Codeine, a high-potency opioid, appeared to be effective without side effects, but the patient seemed to require a higher dose than what the neurologist was comfortable prescribing.
Outpatient Course
The sleep specialist discontinued codeine and started transdermal fentanyl 25 mcg/hour. The medication was partially effective, and the dose was increased to 50 mcg/hour and ultimately to 75 mcg/hour. Meredith has been stable on this dosage for 1 year.
References
• Allen RP, Pacchietti D, Hening WA, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003;4:101-119.
• Allen RP, Earley CJ. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep. 1996;19:205-213.
• Comella CL. Restless legs syndrome: treatment with dopaminergic agents. Neurology. 2002;58(suppl1):S87-S92.
Funding Information
Supported by an independent educational grant from GlaxoSmithKline.
Anil N. Rama, MD, PhD, Staff Physician, Department of Neurology, The Permanente Medical Group, Inc., San José, California
Clete A. Kushida, MD, PhD, Assistant Professor, Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California; Director, Stanford University Center for Human Sleep Research, Stanford, California
Disclosure: Anil N. Rama, MD, MPH, has disclosed that he has a relationship with Orphan Medical.
Disclosure: Clete A. Kushida, MD, PhD, has disclosed that he has received grants for clinical research from, has received grants for educational activities from, and has served as an advisor or consultant to GlaxoSmithKline. Dr. Kushida has also disclosed that he has served on the medical advisory board and has received research grants from Pfizer, has received grants for clinical research from Cephalon, and has received clinical research grants from Respironics.
Resource: Medscape Neurology & Neurosurgery. 2005;7(1)
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