Background and Objectives: Restless legs syndrome (RLS) is a common, underdiagnosed neurological movement disorder of undetermined etiology. The primary treatments for restless legs syndrome are pharmacological. To date, no randomized controlled trials have examined the effectiveness of an exercise program on the symptoms of RLS.Methods: Study participants (N ‫؍‬ 41) were randomized to either exercise or control groups. 28 participants (average age 53.7; 39% males) were available and willing to begin the 12-week trial. The exercise group was prescribed a conditioning program of aerobic and lower-body resistance training 3 days per week. Restless legs symptoms were assessed by the International RLS Study Group (IRLSSG) severity scale and an ordinal scale of RLS severity at the beginning of the trial, and at 3, 6, 9, and 12 weeks.Results: Twenty-three participants completed the trial. At the end of the 12 weeks, the exercise group (N ‫؍‬ 11) had a significant improvement in symptoms compared with the control group (N ‫؍‬ 12) (P ‫؍‬ .001 for the IRLSSG severity scale and P < .001 for the ordinal scale). Conclusions Background and ObjectivesRestless Legs Syndrome (RLS) is a common neurological movement disorder affecting a large segment of the population. Studies of the prevalence of RLS suggest the condition affects approximately 10% of the adult population, although one study found a prevalence of 24% in patients presenting to a primary care office.1-3 Although RLS is common, it is seldom diagnosed. The 2001 Sleep in America Poll found a prevalence of 13% in the adult population, but only 3% of those had actually been diagnosed with RLS. 4 Factors associated with higher incidence of RLS include older age, multiparity, sedentary lifestyle, positive family history, and obesity.1,2 Secondary causes of RLS include iron deficiency, renal failure, neuropathy, pregnancy, and certain medications. 5 RLS is associated with depression, anxiety, and negative quality of life. 6,7 The diagnosis of RLS is clinical. Minimal criteria for the diagnosis are: 1) a compelling urge to move the limbs, usually associated with paresthesias/dysesthesias; 2) motor restlessness as seen in activities such as floor pacing, tossing and turning in bed, and rubbing the legs; 3) symptoms worse or exclusively present at rest (ie, lying, sitting) with variable and temporary relief by activity; and 4) symptoms worse in the evening and at night. 8 RLS tends to cluster in older, overweight adults, 6,9,10 who are at increased risk for comorbid conditions. Physical activity and exercise may be important in the reduction of the risk for comorbid conditions; however, the effects of exercise on RLS severity are unknown. Furthermore, the current treatment for RLS is primarily pharmacological in nature. The vast majority of clinical trials have concentrated on the use of dopaminergic agents, anticonvulsants, and benzodiazepines.11-13 These agents often have significant side effects. Little research has been undertaken to determine whether lifestyle changes, ...

The use of valproic acid (VPA) (also known as Depakote, Depakene, and others) frequently results in elevated plasma ammonia. In some people, hyperammonemia may be clinically significant, resulting in hyperammonemic encephalopathy, which may be severe. Valproic acid-induced hyperammonemic encephalopathy may occur in people with normal liver function, despite normal doses and serum levels of VPA. We describe 2 cases of valproic acid-induced hyperammonemic encephalopathy in patients with supratherapeutic VPA levels, although the condition has been described in people with normal VPA lev- Valproic acid (VPA) is effective in the treatment of seizure disorders, bipolar disorder, migraine headache prophylaxis, neuropathic pain, restless legs syndrome, dementia-related agitation, and social anxiety disorder, among other conditions. VPA has numerous drug interactions and toxicities; severe toxicities include hepatic damage, pancreatitis, teratogenicity, thrombocytopenia, and hyperammonemia. Here we depict 2 case reports of VPAinduced hyperammonemic encephalopathy (VHE), both occurring in patietns with no history of underlying liver disease. In one instance, the patient was able to function, but with significant cognitive limitations. In the second case, the patient was comatose. Both of the patients we describe also had supratherapeutic VPA levels, but VHE is a welldocumented potential complication of the use of VPA in the medical literature, and it may occur in people with normal VPA levels.1 Because of the wide spectrum of symptoms associated with VHE, physicians should consider hyperammonemia in the differential diagnosis of any patient taking VPA who shows changes in behavior, cognition, or orientation. Case ReportsCase 1 A 51-year-old woman was transferred from a psychiatric hospital to an emergency department to evaluate the recent deterioration in her mental status. She had been admitted to the psychiatric hospital for an exacerbation of posttraumatic stress disorder and was placed on extended-release VPA at 1,000 mg nightly. After 7 days of treatment she was no longer responsive to verbal stimuli. Her medical history was significant for migraine headaches, posttraumatic stress disorder, and major depression. Her medications included topiramate (for migraine prophylaxis), quetiapine, and VPA. In the emergency department, she was nonresponsive to verbal or painful stimuli; her vital signs were normal. Her pupils were equal at 5 mm and her ammonia level was 232 mol/L (N ϭ 10 to 47); her VPA level was 145 g/mL (N ϭ 50 to 100); and aspartate aminotransferase and alanine aminotransferase were normal at 17 IU/L and 19 IU/L, respectively. The remainder of laboratory tests, including all liver tests, were normal. For the first 24 hours, the patient remained nonresponsive; her This article was externally peer reviewed.

Introduction:Restless legs syndrome (RLS) is a common neurological disorder affecting 10% of the population. Most antidepressants exacerbate symptoms; however, correlational studies have noted symptom improvement with bupropion. The purpose of the current study was to examine whether, in a controlled study, bupropion would improve the symptoms of RLS, or at least not exacerbate them.Methods: This was a double-blinded, randomized controlled trial. Twenty-nine participants with moderate to severe RLS received 150 mg sustained-release bupropion once daily, and 31 control participants received a placebo. Participants were followed for 6 weeks and completed standardized tools, including the International Restless Legs Syndrome Study Group (IRLSSG) severity scale.Results: The primary outcome was change from baseline in IRLSSG severity score; lower scores were associated with improved symptoms. At 3 weeks, IRLSSG scores were 10.8 points lower in the bupropion group and 6.0 points lower in the placebo group (P ‫؍‬ .016). At 6 weeks, IRLSSG scores were10.4 points lower in the bupropion group and 7.6 points lower in the placebo group (P ‫؍‬ .108). Bupropion was more effective than placebo in the treatment of RLS at 3 weeks; however, this difference was not statistically significant at 6 weeks.Conclusions: The data from our study suggest that bupropion does not exacerbate the symptoms of RLS and may be a reasonable choice if an antidepressant is needed in individuals with RLS. Larger studies that include titration of bupropion should be considered to determine if bupropion is appropriate for primary treatment of RLS, particularly considering the lower cost and favorable side effect profile compared with currently recommended first-line dopamine agonists. (J Am Board Fam Med 2011;24: 422-428.)

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Acute methemoglobinemia may be caused by topical anesthetics and other oxidizing medications commonly prescribed by Family Physicians. Without knowledge of this potentially lethal condition, delay in diagnosis and treatment is likely. Methemoglobinemia should be considered in any patient presenting with cyanosis, particularly after the use of oxidizing medications.We describe a case of methemoglobinemia in a patient who presented with cyanosis after endoscopy. This case followed otherwise uncomplicated upper gastrointestinal (GI) endoscopy. The diagnosis was delayed several hours because the physicians treating the patient did not consider the possibility of acute methemoglobinemia. Case ReportThe patient was a 26-year-old white woman who was sent to the emergency department for evaluation of cyanosis immediately after esophagogastroduodenoscopy. Before the onset of cyanosis, the procedure had been uncomplicated. Benzocaine spray had been applied, and the patient was routinely sedated with meperidine and midazolam. While in recovery, the nurses noted that the patient became cyanotic and mildly short of breath.The patient was transferred to the emergency department, where she was markedly cyanotic. She was initially given naloxone and flumazenil without improvement in her cyanosis. Her blood pressure was 72/48 mm Hg, and she was tachypneic. Cardiac and pulmonary exams were otherwise unremarkable. Hemoglobin and hematocrit were 12.6 g/dL and 0.384, respectively. The results of a basic chemistry panel were normal. Arterial blood gas on room air showed pH of 7.349, pCO 2 was 40.8 mm Hg, pO 2 was 97.5 mm Hg, and HCO 3 was 21.8 mEq/L. Oxygen saturation (SaO 2 ) by pulse oximetry was 83%. The patient was placed on 100% oxygen, but there was no improvement in the SaO 2 . A chest radiograph was unremarkable and results of a ventilation-perfusion scan were normal. At that time, a pulmonologist was consulted. He recommended checking a methemoglobin level, which was subsequently found to be elevated at 23.6%.Because the patient was tachypneic and hypotensive, she was admitted to the intensive care unit and given 90 mg of intravenous methylene blue (2 mg/kg) over 5 minutes. Repeat methemoglobin level 3 hours later was near zero. The patient was discharged the following day in stable condition without any further complications.