Nocturnal Leg Cramps Research Articles

Transient Pulmonary Infiltrates Possibly Induced by Quinine Sulfate

Quinine sulfate, which has been available for many years, has not been implicated definitively in the development of pulmonary toxicity. A variety of adverse effects, however, have been reported with quinine administration. A 45-year-old woman with longstanding rheumatoid arthritis experienced wheezing, severe anxiety, breathlessness, cough, orthopnea, mild fever, chills, and pleuritic chest discomfort after taking a single dose of quinine for nocturnal leg cramps. Radiographic imaging demonstrated diffuse, bilateral pulmonary infiltrates suggestive of pulmonary edema. No cause other than acute quinine ingestion could be identified despite thorough cardiac and infectious disease evaluations. Clinicians should be aware of a possible association between quinine sulfate and pulmonary toxicity.

EFFECTIVENESS OF QUININE IN TREATING MUSCLE CRAMPS: A DOUBLE‐BLIND, PLACEBO‐CONTROLLED, PARALLEL‐GROUP, MULTICENTRE TRIAL

SUMMARYTo determine the efficacy and safety of quinine in treating nocturnal muscle cramps we performed a double‐blind, placebo‐controlled, parallel‐group, multicentre trial in 17 general practice centres in Germany. Ninety‐eight patients aged 18–70 years with more than six muscle cramps in two weeks were enrolled. A two‐week run‐in period without treatment was followed by two weeks of treatment with 400 mg quinine or placebo per day and a wash‐out period of two weeks without treatment. The primary outcome measure was the reduction in the number of muscle cramps between the run‐in and treatment periods. The intensity of cramps, number of nights with cramps, sleep disturbance and intensity of pain were recorded as secondary outcome measures. At baseline the median number of cramps was 12 in two weeks in both groups. The median reduction between the run‐in and therapy phases was eight (95% CI 7–10) versus six (95% CI 3–7) muscle cramps during quinine and placebo treatment; 36 (80%) participants in the quinine group and 26 (53%) in the placebo group had a reduction of at least 50% in the number of muscle cramps. Frequency, intensity and pain at night showed a statistically significant difference in favour of quinine. The improvement was more evident according to physician assessment than patient assessment; this is corroborated by the high placebo response rate. No significant differences were found between the two groups with respect to side‐effects. Short term treatment with 400 mg quinine per day can effectively prevent nocturnal leg cramps in adults without relevant side‐effects.

Nocturnal leg cramps

Nocturnal leg cramps

Treatment alternatives for nocturnal leg cramps.

Treatment alternatives for nocturnal leg cramps.

Does snoring predict sleepiness independently of apnea and hypopnea frequency?

Obstructive apneas and hypopneas during sleep are a well recognized cause of excessive daytime sleepiness. Snoring is also associated with excess sleepiness, although it is not known whether this reflects an independent effect of snoring or whether snoring is simply a marker for obstructive sleep apnea. To further explore the relation of snoring to sleepiness, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study. The study sample comprises 2,737 men and 3,040 women with a mean age of 64 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Snoring history was obtained via a self-completion questionnaire. The respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, was measured during in-home polysomnography. The ESS score increased progressively with increasing RDI, from a mean of 7.1 (4.2) in subjects with RDI < 1.5 to 8.8 (4.8) in subjects with RDI >/= 15 (p < 0.001). A progressive increase in ESS score was also seen across five categories of snoring frequency, from 6.4 (4.2) in current nonsnorers to 9.3 (4.8) in subjects who snored six to seven nights per week (p < 0.001). The prevalence of excessive daytime sleepiness, defined as an ESS score >/= 11, increased from 15% in never-snorers to 39% in those who snored six to seven nights per week. The relation of snoring to sleepiness was seen at all levels of RDI, with no significant change in the relation of snoring to ESS score after adjustment for RDI in multivariate models. The effects of snoring and RDI on sleepiness were little affected by adjustment for age, sex, race, body mass index, or questionnaire evidence of insufficient sleep time or nocturnal leg jerks or cramps. We conclude that both snoring and RDI are independently associated with excess sleepiness in community-dwelling, middle-aged and older adults.

Quinine-Induced Hemolytic-Uremic Syndrome

Quinine is still frequently used by practitioners for the treatment of nocturnal leg cramps, despite the lack of Food and Drug Administration (FDA) approval. We report the 15th case of quinine-induced hemolytic-uremic syndrome (HUS) in the medical literature. The likely mechanism by which quinine induces HUS is via quinine-dependent antibodies to blood cellular constituents. These antibodies likely cause endothelial damage and the resultant nephropathy, microangiopathic hemolytic anemia, and thrombocytopenia that define HUS. Although there is no set guideline for the treatment of quinine-induced HUS, most authorities consider plasmapheresis as the standard of care, especially in severe cases. Our patient required the longest known treatment duration (16 plasmapheresis treatments over a 37-day period) for disease resolution. The prognosis of quinine-induced HUS is excellent, with no deaths reported in the literature.

Should people with nocturnal leg cramps drink tonic water and bitter lemon?

A literature search from 1993 to 1997 using MEDLINE and key-words beverages, muscle cramp, and quinine was performed. Three beverages containing quinine were examined in grocery stores. Analysis indicate that leg cramps are a common phenomenon associated with many comorbid disorders especially peripheral vascular and neurologic disorders. Thus, evaluation of a patient's complaining of leg cramps appropriately includes vascular, neurologic, and musculoskeletal examinations. Laboratory investigation of the symptom of leg cramps warrants as a minimum, assessment of thyroid function and determination of platelet counts and serum levels of electrolytes, calcium, and magnesium. A few small studies suggest that quinine is effective in decreasing the frequency of nocturnal leg cramps but not their severity or duration. Quinine consumed in commercial beverages has been reported to cause potentially fatal immunologically mediated hypersensitivity reactions. The concentration of quinine in commercial beverages varies greatly. Although commercial beverages containing quinine generally are labeled "Contains quinine," they typically lack both nutritional information about the amount of quinine and warnings of the health risks. It appears that 325 milligrams of quinine taken by mouth at bedtime typically relieves nocturnal leg cramps, but lower starting doses are appropriate for senior citizens and individuals with impaired renal function. In general, quinine in any form should be avoided by pregnant women and people with hepatic failure. Quinine consumed for the treatment of leg cramps should be prescribed and monitored by physicians, and people who consume quinine in commercial beverages must be warned of the health risks.

Prevalence and pathologic associations of sleep paralysis in the general population.

Previous epidemiologic data on sleep paralysis (SP) came from small specific samples. The true prevalence and associated factors of SP in the general population remain unknown. A representative sample of the noninstitutionalized general population of Germany and Italy age > or =15 years (n = 8,085) was surveyed by telephone using the Sleep-EVAL questionnaire and the Sleep Questionnaire of Alertness and Wakefulness. Overall, 6.2% (5.7 to 6.7%) of the sample (n = 494) had experienced at least one SP episode in their lifetime. At the time of the interview, severe SP (at least one episode per week) occurred in 0.8% of the sample, moderate SP (at least one episode per month) in 1.4%, and mild SP (less than one episode per month) in 4.0%. Significant predictive variables of SP were anxiolytic medication, automatic behavior, bipolar disorders, physical disease, hypnopompic hallucinations, nonrestorative sleep, and nocturnal leg cramps. SP is less common in the general population than was previously reported. This study indicates that the disorder is often associated with a mental disorder. Users of anxiolytic medication were nearly five times as likely to report SP, even after we controlled for possible effects of mental and sleep disorders.

SHOULD PEOPLE WITH NOCTURNAL LEG CRAMPS DRINK TONIC WATER AND BITTER LEMON?

A literature search from 1993 to 1997 using MEDLINE and keywords beverages muscle cramps, and quinine was performed. Three beverages containing quinine were examined in grocery stores. Analysis indicated that leg cramps are a common phenomenon associated with many comorbid disorders especially peripheral vascular and neurologic disorders. Thus, evaluation of a patient's complaining of leg cramps appropriately includes vascular, neurologic, and musculoskeletal examinations. Laboratory investigation of the symptom of leg cramps warrants as a minimum, assessment of thyroid function and determination of platelet counts and serum levels of electrolytes, calcium, and magnesium. A few small studies suggest that quinine is effective in decreasing the frequency of nocturnal leg cramps but not their severity or duration. Quinine consumed in commercial beverages has been reported to cause potentially fatal immunologically mediated hypersensitivity reactions. The concentration of quinine in commercial beverages varies greatly. Although commercial beverages containing quinine generally are labeled “Contains quinine,” they typically lack both nutritional information about the amount of quinine and warnings of the health risks. It appears that 325 milligrams of quinine taken by mouth at bedtime typically relieves nocturnal leg cramps, but lower starting doses are appropriate for senior citizens and individuals with impaired renal function. In general, quinine in any form should be avoided by pregnant women and people with hepatic failure. Quinine consumed for the treatment of leg cramps should be prescribed and monitored by physicians, and people who consume quinine in commercial beverages must be warned of the health risks.

Randomized, Double‐Blind, Placebo‐Controlled Study of the Safety and Efficacy of Vitamin B Complex in the Treatment of Nocturnal Leg Cramps in Elderly Patients with Hypertension

Nocturnal leg cramps is a common and troublesome problem in elderly individuals, and their etiology is unknown. Treatment with quinine is a common practice, but the effectiveness of the drug is doubtful and adverse drug effects are common. This randomized, double-blind, placebo-controlled study was conducted to evaluate the safety and efficacy of vitamin B complex capsules (fursulthiamine 50 mg, hydroxocobalamin 250 micrograms, pyridoxal phosphate 30 mg, and riboflavin 5 mg) in 28 elderly patients with hypertension who had severe nocturnal leg cramps that disturbed their sleep. Self-reported ratings of leg cramp frequency, duration, and intensity were used to evaluate severity of nocturnal leg cramps. Both the patients taking vitamin B capsules (n = 14) and those taking placebo (n = 14) received medications three times daily, and were examined regularly at 2-week intervals for 3 months. After 3 months, 86% of the patients taking vitamin B had prominent remission of leg cramps, whereas those taking placebo had no significant difference from baseline. Treatment with vitamin B complex significantly reduced the frequency, intensity, and duration of nocturnal leg cramps. Because quinine is not without potential for side effects, and vitamin B complex is a relatively safe and effective alternative, clinicians should reconsider the treatment of choice for nocturnal leg cramps.

Quinine for nocturnal leg cramps: a meta-analysis including unpublished data.

With respect to the use of quinine for the treatment of nocturnal leg cramps, to determine whether the findings of a previously performed meta-analysis of published data are altered with the addition of unpublished data, and whether publication bias is present in this area. A meta-analysis of eight (four published and four unpublished) randomized, double-blind, placebo-controlled trials, seven of which had a crossover design. Randomized trials that were available as of July 1997. Ambulatory patients (659) who suffered from regular nocturnal leg cramps. When individual patient data from all crossover studies were pooled, persons had 3.60 (95% confidence interval [CI] 2.15, 5.05) fewer cramps in a 4-week period when taking quinine compared with placebo. This compared with an estimate of 8.83 fewer cramps (95% CI 4.16, 13.49) from pooling published studies alone. The corresponding relative risk reductions were 21% (95% CI 12%, 30%) and 43% (95% CI 21%, 65%), respectively. Compared with placebo, the use of quinine was associated with an increased incidence of side effects, particularly tinnitus. Publication bias is present in the reporting of the efficacy of quinine for this indication, as almost all published studies reported larger estimates of its efficacy than did unpublished studies. This study confirms that quinine is efficacious in the prevention of nocturnal leg cramps. However, its benefit may not be as large as reported from the pooling of published studies alone. Given the side effect profile of quinine, nonpharmacologic therapy (e.g., regular passive stretching of the affected muscle) is the best first-line treatment. For persons who find this ineffective and whose quality of life is significantly affected, a trial of quinine is warranted. Prescribing physicians must closely monitor the risks and benefits in individual patients. Publication bias is present in this area even though there is controversy about the role of quinine in the treatment of leg cramps. To minimize the possibility of this bias, persons performing medication-related meta-analyses should seek high-quality unpublished data from drug regulatory agencies and pharmaceutical companies.

Understanding and measurement of muscle tone as related to clinical muscle pain

Measurable sources of muscle tension include viscoelastic tone, physiological contracture (neither of which involve motor unit action potentials), voluntary contraction, and muscle spasm (which we define as involuntary muscle contraction). The latter two depend on motor unit action potentials to generate the tension. Total muscle tension is most accurately measured as stiffness. Thixotropy of muscle is an ubiquitous and functionally important phenomenon that is not commonly recognized. A clinical pain condition associated with increased muscle tension is tension-type headache, which is largely muscular in origin; it is often caused by myofascial trigger points, but not by a pain-spasm-pain cycle, which is a physiologically and clinically untenable concept. Clinical conditions associated with painful muscle spasm include spasmodic torticollis, trismus, unnecessary muscle tension, nocturnal leg cramps, and stiff-man syndrome.

Quinine and nocturnal leg cramps

Quinine and nocturnal leg cramps

Clinical Epidemiology of Nocturnal Leg Cramps in Male Veterans

AbstractThis article describes patients with nocturnal leg cramps concerning their age, medical problems, and medications, and reviews any medical evaluation performed for the complaint of nocturnal leg cramps. Provided is a retrospective chart review of 50 patients who took quinine sulfate for nocturnal leg cramps. These patients were identified through computerized pharmacy records. A control group was chosen from age-matched patients who took medications other than quinine during the study period. In a university- affiliated Veterans Administration hospital, patients with nocturnal leg cramps had a significantly higher median number of medical problems than controls. Cardiovascular diseases and neurological diseases were significantly more common in patients with nocturnal leg cramps (cases) than in those without (controls) (82% versus 64% and 36% versus 18%, respectively). The most striking differences between patients with cramps and controls were peripheral vascular disease (34% versus 12%, P = 0.09) and peripheral neurological deficit (12% versus 0%, P =0.012). Patients with nocturnal leg cramps were prescribed significantly more medications than were controls, but no specific medication or type of medication was prescribed more frequently to patients with cramps (other than quinine). Results suggested that men with nocturnal leg cramps have greater medical comorbidity and are prescribed more medications than age- matched control patients. Unlike in previous studies, no evidence was found that specific medications, such as diuretics, betaagonists, or calcium-channel antagonists are associated with nighttime cramps. The significantly in-creased frequency of peripheral vascular disease and peripheral neurologic deficits in patients with nocturnal leg cramps raised the possibility that these problems contribute to the occurrence of cramps. Although the size of the study and its methodologic limitations preclude definitive conclusions, areas for research to clarify the clinical epidemiology of nocturnal leg cramps are suggested.

Clinical epidemiology of nocturnal leg cramps in male veterans.

This article describes patients with nocturnal leg cramps concerning their age, medical problems, and medications, and reviews any medical evaluation performed for the complaint of nocturnal leg cramps. Provided is a retrospective chart review of 50 patients who took quinine sulfate for nocturnal leg cramps. These patients were identified through computerized pharmacy records. A control group was chosen from age-matched patients who took medications other than quinine during the study period. In a university-affiliated Veterans Administration hospital, patients with nocturnal leg cramps had a significantly higher median number of medical problems than controls. Cardiovascular diseases and neurological diseases were significantly more common in patients with nocturnal leg cramps (cases) than in those without (controls) (82% versus 64% and 36% versus 18%, respectively). The most striking differences between patients with cramps and controls were peripheral vascular disease (34% versus 12%, P = 0.09) and peripheral neurological deficit (12% versus 0%, P = 0.012). Patients with nocturnal leg cramps were prescribed significantly more medications than were controls, but no specific medication or type of medication was prescribed more frequently to patients with cramps (other than quinine). Results suggested that men with nocturnal leg cramps have greater medical comorbidity and are prescribed more medications than age-matched control patients. Unlike in previous studies, no evidence was found that specific medications, such as diuretics, betaagonists, or calcium-channel antagonists are associated with nighttime cramps. The significantly increased frequency of peripheral vascular disease and peripheral neurologic deficits in patients with nocturnal leg cramps raised the possibility that these problems contribute to the occurrence of cramps. Although the size of the study and its methodologic limitations preclude definitive conclusions, areas for research to clarify the clinical epidemiology of nocturnal leg cramps are suggested.

Quinine for nocturnal leg cramps?

When we reviewed the management of nocturnal muscle cramps over 12 years ago,1,2 we concluded that there was little evidence of efficacy for any treatment, but what there was favoured quinine. Here we re-examine the data, including material published since our original article, and assess whether the position has changed.

Prescribing of quinine and cramp inducing drugs in general practice

Quinine is widely prescribed as the treatment of choice for nocturnal leg cramps despite doubts about its clinical efficacy. Several commonly prescribed agents, including nifedipine, cimetidine, salbutamol, terbutaline, and diuretics in general, may also cause leg cramps as a side effect.1 2 In addition, quinine may cause severe visual problems in acute self poisoning.3 We examined the prescribing of quinine by general practitioners in the Greater Glasgow Health Board. In addition, the age and sex profiles of patients given quinine and the proportion of these patients concurrently prescribed other drugs associated with leg cramps were determined in a sample of practices. By using the Scottish prescribing analysis database provided by …

Quinine for nocturnal leg cramps

Quinine for nocturnal leg cramps

Quinine is effective for preventing nocturnal leg cramps

Quinine is effective for preventing nocturnal leg cramps

Meta-analysis of efficacy of quinine for treatment of nocturnal leg cramps in elderly people.

To assess quantitatively the efficacy of quinine (as quinine sulphate) compared with placebo in the treatment of nocturnal leg cramps. A meta-analysis of six randomised, double blind, crossover trials. Randomised trials that were available as of April 1994. A total of 107 general ambulatory patients who suffered from regular nocturnal leg cramps from six clinical trials. Data from individual patients were used to calculate point estimates and 95% confidence intervals for each of the outcome measures reported by these studies. Treatment with quinine resulted in a significant reduction in the number of cramps for a four week period compared with placebo (8.83 fewer cramps; 95% confidence interval 4.16 to 13.49). Treatment with quinine reduced the number of nights with cramps by 27.4% (24.0% to 30.8%) compared with placebo. Treatment did not produce a significant change in the severity or duration of individual nocturnal leg cramps. Side effects were uncommon. The results indicate that quinine can prevent nocturnal leg cramps in general ambulatory populations. Given the possible serious side effects of treatment with quinine, the benefits and risks in patients taking this drug should be closely monitored.