Facts about Restless Legs Syndrome (RLS)

What Is Restless Legs Syndrome?

Restless legs syndrome (RLS) is a sleep disorder in which a person experiences unpleasant sensations in the legs described as creeping, crawling, tingling, pulling, or painful. These sensations usually occur in the calf area but may be felt anywhere from the thigh to the ankle. One or both legs may be affected; for some people, the sensations are also felt in the arms. These sensations occur when the person with RLS lies down or sits for prolonged periods of time, such as at a desk, riding in a car, or watching a movie. People with RLS describe an irresistible urge to move the legs when the sensations occur. Usually, moving the legs, walking, rubbing or massaging the legs, or doing knee bends can bring relief, at least briefly.

RLS symptoms worsen during periods of relaxation and decreased activity. RLS symptoms also tend to follow a set daily cycle, with the evening and night hours being more troublesome for RLS sufferers than the morning hours. People with RLS may find it difficult to relax and fall asleep because of their strong urge to walk or do other activities to relieve the sensations in their legs. Persons with RLS often sleep best toward the end of the night or during the morning hours. Because of less sleep at night, people with RLS may feel sleepy during the day on an occasional or regular basis. The severity of symptoms varies from night to night and over the years as well. For some individuals, there may be periods when RLS does not cause problems, but the symptoms usually return. Other people may experience severe symptoms daily.

Many people with RLS also have a related sleep disorder called periodic limb movements in sleep (PLMS). PLMS is characterized by involuntary jerking or bending leg movements during sleep that typically occur every 10 to 60 seconds. Some people may experience hundreds of such movements per night, which can wake them, disturb their sleep, and awaken bed partners. People who have RLS and PLMS have trouble both falling asleep and staying asleep and may experience extreme sleepiness during the day. As a result of problems both in sleeping and while awake, people with RLS may have difficulties with their job, social life, and recreational activities.

Some common symptoms of RLS include:

• Unpleasant sensations in the legs (sometimes the arms as well), often described as creeping, crawling, tingling, pulling, or painful;
• Leg sensations are relieved by walking, stretching, knee bends, massage, or hot or cold baths;
• Leg discomfort occurs when lying down or sitting for prolonged periods of time;
• The symptoms are worse in the evening and during the night.

Other possible characteristics include:

• Involuntary leg (and occasionally arm) movements while asleep;
• Difficulty falling asleep or staying asleep;
• Sleepiness or fatigue during the daytime;
• Cause of the leg discomfort not detected by medical tests;
• Family members with similar symptoms.

What Causes It?
Although the cause is unknown in most cases, certain factors may be associated with RLS:

• Family history. RLS is known to run in some families--parents may pass the condition on to their children.
• Pregnancy. Some women experience RLS during pregnancy, especially in the last months. The symptoms usually disappear after delivery.
• Low iron levels or anemia. Persons with these conditions may be prone to developing RLS. The symptoms may improve once the iron level or anemia is corrected.
• Chronic diseases. Kidney failure quite often leads to RLS. Other chronic diseases such as diabetes, rheumatoid arthritis, and peripheral neuropathy may also be associated with RLS.
• Caffeine intake. Decreasing caffeine consumption may improve symptoms.

Who Gets RLS?

RLS occurs in both sexes. Symptoms can begin any time, but are usually more common and more severe among older people. Young people who experience symptoms of RLS are sometimes thought to have "growing pains" or may be considered "hyperactive" because they cannot easily sit still in school.

How Is It Diagnosed?

There is no laboratory test that can make a diagnosis of RLS and, when someone with RLS goes to see a doctor, there is usually nothing abnormal the doctor can see or detect on examination. Diagnosis therefore depends on what a person describes to the doctor. The history usually includes a description of the typical leg sensations that lead to an urge to move the legs or walk. These sensations are noted to worsen when the legs are at rest, for example, when sitting or lying down and during the evening and night. The person with RLS may complain about trouble sleeping or daytime sleepiness. In some cases, the bed partner will complain about the person's leg movements and jerking during the night.

To help make a diagnosis, the doctor may ask about all current and past medical problems, family history, and current medications. A complete physical and neurological exam may help identify other conditions that may be associated with RLS, such as nerve damage (neuropathy or a pinched nerve) or abnormalities in the blood vessels. Basic laboratory tests may be done to assess general health and to rule out anemia. Further studies depend on initial findings. In some cases, a doctor may suggest an overnight sleep study to determine whether PLMS or other sleep problems are present. In most people with RLS, no new medical problem will be discovered during the physical exam or on any tests, except the sleep study, which will detect PLMS if present.

How Is It Treated?

In mild cases of RLS, some people find that activities such as taking a hot bath, massaging the legs, using a heating pad or ice pack, exercising, and eliminating caffeine help alleviate symptoms. In more severe cases, medications are prescribed to control symptoms. Unfortunately, no one drug is effective for everyone with RLS. Individuals respond differently to medications based on the severity of symptoms, other medical conditions, and other medications being taken. A medication that is initially found to be effective may lose its effectiveness with nightly use; thus, it may be necessary to alternate between different categories of medication in order to keep symptoms under control.

Although many different drugs may help RLS, those most commonly used are found in the following three categories:

• Benzodiazepines are central nervous system depressants that do not fully suppress RLS sensations or leg movements, but allow patients to obtain more sleep despite these problems. Some drugs in this group may result in daytime drowsiness. Benzodiazepines should not be used by people with sleep apnoea.
• Dopaminergic agents are drugs used to treat Parkinson's disease and are also effective for many people with RLS and PLMS. These medications have been shown to reduce RLS symptoms and nighttime leg movements.
• Opioids are pain-killing and relaxing drugs that can suppress RLS and PLMS in some people. These medications can sometimes help people with severe, unrelenting symptoms.

Although there is some potential for benzodiazepines and opioids to become habit forming, this usually does not occur with the dosages given to most RLS patients.

A nondrug approach called transcutaneous electric nerve stimulation may improve symptoms in some RLS sufferers who also have PLMS. The electrical stimulation is applied to an area of the legs or feet, usually before bedtime, for 15 to 30 minutes. This approach has been shown to be helpful in reducing nighttime leg jerking.

Due to recent advances, doctors today have a variety of means for treating RLS. However, no perfect treatment exists and there is much more to be learned about the treatments that currently seem to be successful.

The Great Indian IT boom!

This would give you an inkling of what people mean when they say IT is the in thing. If you are wondering what is that structure, it is 'supposed' to be a mobile ironing vehicle which has been parked for eons against the compound wall of a house. Does the landlord have his clothes ironed for free? ;)

Sunday outing!

It was the Baptism of Paul Rosario son of one of my close family friends. I would be understating if I said 'family friends', actually they are more than friends but family. The Holy Mass was at 11 am at the Fatima Church in East Tambaram. Mass was conducted by Rev. Fr. Peter, who is the maternal uncle of Vimal Raj, father of baptism-boy.

Quite a few family members had attended the Mass and the delectable lunch which was served afterwards. Attending functions has not been my forte, but these days I seem to have changed my views on attending social/religious events. Ofcourse they help to bond with family and friends apart from giving us a break from the normal routine. A time to share experiences and views.

Hepatitis C: Prevalence, complications, management

Hepatitis C virus (HCV) infection is the most common blood-borne infection worldwide and an important health care problem (National Center for Health Statistics, 1996; National Institutes of Health, 1997), as it represents the leading indication for liver transplantation. Hepatitis C virus (HCV) is the major cause of transfusion non-A, non-B hepatitis and continues to be a major cause of human liver disease throughout the world. Approximately 20-30% of patients with chronic hepatitis C develop cirrhosis (Hoofnagle, 1997). The course of hepatitis C is variable among individuals, but it eventually can lead to chronic hepatitis, decompensated cirrhosis, and hepatocellular carcinoma.

The prevalence of HCV around the world ranges from 0.4 to 2%. Hepatitis C is gradually being recognised as a major health problem even in developing countries. Among Indian blood donors, the seroprevalence varies from 0.48% in Vellore, TN to 1.85% in New Delhi. Although it is not well established, hepatitis-C infections do not easily take place through the sexual route and is therefore regarded as a problem confined largely to drug injectors.

Researchers in India have identified, for the first time, two patients with chronic liver disease - a 46-year-old man and a 52-year-old woman, both from eastern India - who were found to be infected with hepatitis C virus genotype 6 strains. These strains have been previously reported only from Hong Kong and Southeast Asia.

Magnitude of hepatitis C virus infection in India: Prevalence in healthy blood donors, acute and chronic liver diseases. Link

Several advances in the management of chronic HCV infection have occurred in the last decade. More recent research has propelled a shift from interferon alfa monotherapy to combination therapy with pegylated interferon (peginterferon) and ribavirin as the standard treatment for chronic hepatitis C. Numerous clinical studies and review articles have been published in the recent literature, the aim of which is to investigate the efficacy of peginterferon versus standard interferon as monotherapy and combination therapy with ribavirin. Clearly defining the terminology of the treatment endpoints to better understand the clinical findings in these studies is important. An earlier review article used the following definitions:

* End-of-treatment response occurs on the basis of having no detectable HCV RNA (virologic response) at the end of the treatment.

* Sustained response occurs based on reference range ALT levels and no detectable HCV RNA at the end of the treatment and throughout the observation period after stopping the therapy. Sustained virologic response (SVR) is defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy.

* Nonresponse to treatment is when ALT levels remain abnormal at all time points evaluated during the study period or ALT levels become elevated (or HCV RNA appears) after having been in the reference range (or having no detectable HCV RNA) on treatment.

* A histologic response is defined as a reduction in the Knodell score of 2 or more points compared to the baseline (Lindsay, 1997).

Future targets of therapy

Combining peginterferons with ribavirin considerably improves efficacy but at the expense of poor tolerability attributable to ribavirin, and a significant proportion of patients in these trials did not respond to treatment. Given the significant adverse effects attributed to interferon-ribavirin therapy, patients need to be screened carefully to assess their candidacy for this therapy. Future therapeutic developments may include 1 or more of the following approaches: understanding the HCV genomic organization, elucidating the viral life cycle and HCV replication strategy, and understanding the immune mechanisms required for viral propagation or infectivity (Sookoian, 2003). Therapies under development and evaluation for patients with hepatitis C include adjunctive use of the antiviral agent amantadine and the immunomodulatory agent thymalfasin as well as novel small molecules, which include the ribavirin analogs, viramidine and levovirin, and BILN 2061, an inhibitor of HCV serine protease (Foster, 2004).

Lipoprotein(a) and cardiovascular disease

Lipoprotein(a) (Lp[a]) is an atherogenic lipoprotein that consists of LDL-C (ie, cholesterol, phospholipids, and apolipoprotein B-100) linked covalently by a disulfide bond to apolipoprotein(a). Apolipoprotein(a) is homologous to plasminogen, a proenzyme promoting clot lysis. Unlike plasminogen, apolipoprotein(a) promotes thrombosis by competitive inhibition of plasminogen. Lp(a) binds to endothelial cells, monocytes, and macrophages. It is believed to provide the link between thrombosis and atherosclerosis.

The level of Lp(a) is unrelated to the level of other lipoproteins or apolipoproteins. Lp(a) levels are genetically determined. The actual level is a function of synthesis in the liver rather than of degradation or catabolism. Lp(a) levels are decreased in chronic liver disease and increased in end-stage renal disease, hypothyroidism, and acromegaly. Both testosterone and estrogen decrease Lp(a) levels. Furthermore, Lp(a) is an acute-phase reactant, increasing after an acute event.

Population studies have shown a skewed distribution among white and Asian populations. African Americans have a normal distribution of Lp(a) levels; however, plasma levels are 2-4 times higher than in whites. Lp(a) does not appear to convey the same risk of coronary artery disease (CAD) as among whites. Increased levels of Lp(a) have been associated with increased risk of CAD among South Asians.

Risks of Lp(a)

The literature on the risk of Lp(a) is not always concordant. However, a meta-analysis of 27 prospective studies with a mean follow-up period of 10 years showed that patients with Lp(a) levels in the upper tertile had a 70% increased risk of coronary heart disease (CHD).

Using a nested case-control design, the Lipid Research Clinics Coronary Primary Prevention Trial reported that an elevated Lp(a) level was an independent risk factor for CHD during a follow-up period of 7-10 years. In contrast, in the Physicians’ Health Study, using a nested case-control design, Lp(a) levels did not predict future myocardial infarction after 60 months.

The Framingham Heart Study reported an 11.4% prevalence of Lp(a) levels greater than 30 mg/dL in the cohort population. Lp(a) was an independent risk factor for CHD events among men aged 55 years or younger. The attributable risk of 9.3% was similar to a total cholesterol level of 240 mg/dL or higher (10.3%) or an HDL-C level of less than 35 mg/dL (10.3%).

In a Swedish study of 1216 patients with established coronary disease, an Lp(a) level of 30 mg/dL or greater was present in 30% of the population and found to be an independent predictor of death over a mean follow-up period of 6.7 years. Other predictors of death included a high fibrinogen level, a low antithrombin III level, depressed left ventricular function, and a high coronary obstruction score.

To assess the predictive role of Lp(a) in the Cardiovascular Health Study, 3972 ambulatory men and women aged 65 years or older who were free of cardiovascular disease were monitored for 7.4 years. For men only, elevated levels of Lp(a) were associated with a 2.92 times increased risk of stroke, a 2.09 times increased risk of death due to vascular diseases, and a 1.60 times increased risk of all-cause mortality.

Children who have an Lp(a) level of 30 mg/dL or greater are more likely to have a parental history of heart attack or angina before age 50 years.

The Familial Atherosclerosis Treatment Study examined 146 men aged 62 years or younger with known CAD and apolipoprotein B levels of 125 mg/dL or higher. Baseline coronary disease severity, its progression, and events over a 2.5-year period were best correlated with Lp(a) levels. However, once LDL-C levels were lowered, Lp(a) was not as predictive for atherogenic outcomes.

In the Prospective Cardiovascular Münster Study, men with Lp(a) levels of 20 mg/dL or greater were shown to have 2.7 times more cardiovascular events over a 10-year period compared to men with lower levels. The risk was magnified in concert with other risk factors, including a high LDL-C, low HDL-C, and hypertension.

Elevated levels of Lp(a) are associated with other risks as well:

* Saphenous vein graft stenosis after coronary bypass surgery is related to Lp(a). With a level of 31.6 mg/dL, 92% of patients developed vein graft stenosis.
* An elevated Lp(a) level has been shown to be a risk factor for venous thromboembolism.
* An interaction between elevated levels of Lp(a) and factor V Leiden, protein C deficiency, antithrombin deficiency, and hyperhomocystinemia seems to exist.
* Lp(a) levels of greater than 30 mg/dL are associated with an increased risk of atherosclerotic cardiovascular disease.

Clinical guidelines

Rather than being viewed as a major risk factor, Lp(a) is considered an “emerging” risk factor for cardiovascular disease by the Adult Treatment Panel (ATP) III; thus, routine measurement is not advocated. The ATP III recognized that a high Lp(a) level could count as a second risk factor, justifying a lower goal for LDL-C levels, although that was considered a controversial approach.

Recommendations for assessment of Lp(a)

Measurement of Lp(a) levels should be reserved for persons with a strong family history of premature CAD and those with genetic causes of hypercholesterolemia. Consider measuring levels in patients with a normal lipid profile and established CAD.

Lp(a) is not stable at room temperature; thus, an analysis should be immediately performed or centrifuged and frozen for later determination. Measurement of Lp(a) is performed using immunologic methods, and assays for measurement of Lp(a) levels are variable. Since accurate methodology is not available in most clinical chemistry laboratories, samples must generally be sent to special laboratories.

In general, dietary interventions and exercise are ineffective in reducing Lp(a) levels. However, increased fish, almond, and red wine consumption appears to be modestly effective. Statins have been reported to have variable effects on Lp(a). Nicotinic acid in doses of 3-4 g daily can also lower Lp(a) levels as much as 30%. However, whether niacin reduces the associated risks is unknown. Both tamoxifen and estrogen lower Lp(a) levels. LDL apheresis is considered the most effective means to lower Lp(a) levels as much as 50%.