- Ankylosing Spondylitis : Symptoms, Diagnosis and Treatment
- Clinical Manifestations
- Sleep Problems: Look for Health Connections
- Considering Melatonin for Sleep? Here’s a Guide to Help
- How Lupus Affects the Nervous System : Johns Hopkins
- Cognitive Dysfunction
- Organic Brain Syndrome
- CNS Vasculitis
Ankylosing Spondylitis : Symptoms, Diagnosis and Treatment
Ankylosing spondylitis (AS) is a chronic inflammatory disease causing axial arthritis, frequently resulting in inflammatory low back pain early in the disease course, with eventual severe impairment of spinal mobility due to structural changes ultimately leading to spinal fusion.
AS is the archetype of a heterogeneous group of arthritides within the rheumatic diseases known formerly as the seronegative spondyloarthropathies but now frequently referred to as spondyloarthritis (SpA).
In addition to axial arthritis, AS can result in peripheral arthritis, enthesitis, and uveitis, all shared characteristics of the SpA.
Recent population estimates indicate that the prevalence of AS in the United States is approximately 0.2-0.5%. data from multiple countries, the age- and sex-adjusted incidence of AS is 0.4-14 per 100,000 person-years.
Prevalence of AS in the population increases to approximately 5% among patients who are HLA-B27 positive. AS occurs more frequently in men than women (2:1). Age of disease onset usually peaks in the second and third decades of life.
Approximately 80% of patients with AS experience symptoms at ≤ 30 years of age, while only 5% will present with symptoms at ≥ 45 years of age.
The precise etiology of AS remains mostly unknown, though heritability is frequently cited as a significant contributor. Major histocompatibility alleles, particularly HLA-B27, may account for up to one-third of the genetic effect.
Other MHC alleles that may play a minor role in AS heritability include HLA-B60 and HLA-DR1.
Recent genome wide association studies (GWAS) of patients with AS have identified susceptibility loci, including IL23R, ERAP1, and IL1R2 among others.
Most patients with AS will experience symptoms of inflammatory back pain due to sacroiliitis and axial arthritis of the spine. This will frequently be accompanied by peripheral arthritis, enthesitis, and/or acute anterior uveitis. Cardiac involvement resulting in aortitis and arrhythmias occur less commonly.
Spinal inflammation results in symptoms of back stiffness, soreness, and pain. Symptoms tend to worsen in the early morning hours, causing sleep disturbance in many patients. Inflammatory back pain will tend to improve with stretching and physical activity and worsen with prolonged inactivity.
The natural history of AS for some patients includes structural abnormalities of the spine from development of new bone formation. These syndesmophytes frequently bridge adjacent vertebrae, resulting in impaired spinal mobility. This process tends to be slow, but when it progresses can ultimately lead to complete spinal fusion or ankylosis (i.
e. the so-called “bamboo spine”). For many patients, ankylosis classically begins at the sacroiliac joints and progresses in an ascending manner, from the lumbar spine to eventually the cervical spine. more recent data, the pattern of spinal fusion may actually occur in a saltatory manner rather than strictly in continuously ascending fashion.
There is no consensus on the diagnosis of AS, but the 1984 Modified New York classification criteria has been generally accepted for both research and clinical purposes. It requires at least 1 clinical manifestation and at least 1 radiographic parameter.
Clinical manifestations include ≥ 3 months of inflammatory back pain that improves with exercise and exacerbated by rest, limitation of lumbar motion in both frontal and sagittal planes, and limitation of chest expansion compared to the normative population.
Radiographic parameters include ≥ grade 2 sacroiliitis bilaterally or grade 3 or 4 sacroiliitis unilaterally.
Because many patients with early AS may not have radiographic evidence of sacroiliitis, the Assessment of Spondyloarthritis International Society (ASAS) has generated classification criteria for axial SpA. These recent criteria may aid clinicians in the diagnosis of axial SpA well before patients fulfill AS criteria by the 1984 Modified New York criteria.
The ASAS criteria for axial SpA mandates patients have back pain for ≥ 3 months and be < 45 years of age while fulfilling 1 of the following 2 sets of criteria:
- Sacroiliitis on imaging* and ≥ 1 SpA feature**
- HLA-B27 and ≥ 2 SpA features**,
*Sacroiliitis on imaging is active inflammation on MRI highly suggestive of sacroiliitis associated with SpA, or on definite sacroiliitis the 1984 Modified New York Criteria.
**SpA features include inflammatory back pain, arthritis, enthesitis, uveitis, dactylitis, psoriasis, Crohn’s disease/ulcerative colitis, good response to NSAIDs, family history of SpA, HLA-B27, and elevated CRP.
Depending on whether symptoms include axial arthritis, peripheral arthritis, or enthesitis, effective treatment modalities will vary. All patients with AS should undergo physical therapy to improve spinal mobility and physical functioning.
Non-steroidal anti-inflammatory drugs (NSAIDs) are nearly always used in conjunction with physical therapy to alleviate symptoms of inflammatory back pain.
Any NSAID will usually be effective, when used at near maximum recommended doses; however, indomethacin has been considered the NSAID of choice based mostly on anecdotal evidence.
If NSAIDs fail to improve symptoms of sacro-iliitis, intra-articular corticosteroid injections of the sacroiliiac joints may be considered.
The introduction of TNF inhibitors, including etanercept, infliximab, adalimumab, and golimumab, have contributed further to alleviating the symptoms of axial arthritis. data from clinical trials, patients with active AS reported not only reduced inflammatory back pain but improved physical functioning, fatigue, and quality of life. As is true for all treatment modalities for AS, TNF inhibitors have not been demonstrated to slow the disease progression of patients with AS destined to incur spinal fusion.
For symptoms of peripheral arthritis, the disease-modifying antirheumatic drugs (DMARDs) including sulfasalazine and methotrexate are frequently effective and well-tolerated. Leflunomide has not demonstrated to be that effective in AS, un rheumatoid arthritis and psoriatic arthritis.
The prognosis for many patients with AS will be complete spinal ankylosis, while others will experience intermittent flares between bouts of clinical remission. The long-term goal in the treatment of AS is to preserve as much physical functioning, decrease work absenteeism, and maintain a high quality of life.
- Braun J, Sieper J. Ankylosing spondylitis. Lancet 2007;369(9570):1379-90.
- Reveille JD. Epidemiology of spondyloarthritis in North America. Am J Med Sci 2011;341(4):284-6.
- Dillon CF, Hirsch R. The United States National Health and Nutrition Examination Surveyand the epidemiology of ankylosing spondylitis. Am J Med Sci 2011;341(4):281-3.
- Rudwaleit M, van der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009;68(6):777-83.
Sleep Problems: Look for Health Connections
A wide variety of health issues (as well as the medications that treatthem) can have a surprising connection to the quality of your sleep. Here’show some common conditions are linked with sleep problems:
Allergies: Allergies to dust mites, mold, pollen and other substances cause sneezing, congestion and itchy, watery eyes that can lead to more nighttime wakeups and poor sleep quality.
“If you have mild obstructive sleep apnea (pauses in breathing), a stuffed-up nose could make it worse because you will have to breathe through your mouth more often,” says Johns Hopkins sleep expertVsevolod Y. Polotsky, M.D., Ph.D.
Meanwhile, allergy medicines containing pseudoephedrine can keep you from falling asleep while those containing antihistamines such as diphenhydramine can leave you feeling extremely drowsy the following day.
Alzheimer’s disease: Insomnia and daytime sleeping are more common in the later stages of Alzheimer’s disease . Maintaining a regular daytime schedule and, if needed, medications can help sleep quality.
Asthma: For about 60 percent of people with asthma, airway changes at night (called “nocturnal asthma”) can lead to coughing, wheezing and breathlessness that interrupt sleep. The asthma drug theophylline can contribute to sleep problems and more frequent nighttime awakenings, as can using the quick-relief inhaler drug albuterol more often than your doctor recommends.
Benign prostatic hyperplasia: Up to 14 million American men have an enlarged prostate gland; as a result, nearly one in three men older than age 60 wake up two or more times each night to use the bathroom. Medications can help.
Chronic obstructive pulmonary disease (COPD): Lung disorders such as emphysema, chronic bronchitis and asthma can lead to coughing, chest pain and difficulty breathing that compromises sleep quality for nearly 50 percent of the more than 12 million Americans with COPD . Oxygen levels in your blood may drop, causing daytime tiredness. In addition, up to 15 percent of people with COPD may have sleep apnea. Some COPD medications such as albuterol and prednisone can also bring on sleep problems.
Congestive heart failure: More than five million Americans have congestive heart failure , which weakens the heart’s ability to pump and also increases your risk of sleep apnea and sleep-disrupting shaking of the arms and legs called periodic limb movements. Treatments for heart failure can help; you may also need apnea treatments such as a continuous positive airway pressure breathing machine.
Depression and anxiety: “Everyone has a bad night of sleep once in a while, perhaps because you’re stressed or worried about an event in your life.
But if sleep problems persist, depression or anxiety could be involved,” says Johns Hopkins sleep expert R. Nisha Aurora, M.D., M.H.S.
“Treating depression and anxiety can help your sleep quality, and treating sleep problems can improve these mental-health issues. You and your doctor may have to look at both.”
Diabetes: High blood sugar levels can prompt your kidneys to excrete more glucose into your urine, leading to more nighttime bathroom trips.
In addition, many people with diabetes are also overweight, which can raise your risk of sleep apnea.
Pain from diabetes-related nerve damage (peripheral neuropathy) and night sweats due to shifting blood sugar levels may affect your sleep quality too.
Gastroesophageal reflux: Studies show that as many as three four people with heartburn have night symptoms at least once a week. Lying down worsens the painful backwash of stomach acid into the esophagus. Avoiding large meals and alcohol before bed and raising the head of your bed about six inches may help.
Parkinson’s disease: Insomnia, nightmares, acting out dreams during sleep, sleep apnea and falling asleep without warning during the day are among the sleep problems that people with Parkinson’s disease may experience. Medications may help, though some Parkinson’s disease drugs can contribute to insomnia; your doctor may suggest taking them earlier in the day.
Considering Melatonin for Sleep? Here’s a Guide to Help
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It’s understandable that you may be struggling to fall asleep these days. Our world has been turned upside down, so it is especially hard to unplug from the day and get the high-quality sleep your body needs.
“Almost every single patient I’m speaking with has insomnia,“ said Dr. Alon Y. Avidan, a professor and vice chair in the department of neurology at the David Geffen School of Medicine at the University of California, Los Angeles, and director of the U.C.L.A. Sleep Disorders Center. “Especially now with Covid-19, we have an epidemic of insomnia. We call it Covid-somnia.”
An increase in anxiety in both children and adults is affecting our ability to fall asleep. Additionally, our lifestyles have changed drastically as people observe sheltering in place guidelines. With more people staying indoors, it can mean they are not getting enough light exposure.
“Without light exposure in the morning,” Dr. Avidan said, people “lose the circadian cues that are so fundamentally important in setting up appropriate and normal sleep-wake time.”
There are nonmedical ways to help you sleep better: Meditation, turning off screens early in the night, warm showers and cool bedrooms can help your body rest better.
But if these options don’t work, or if you are ready for the next step, you may have considered trying melatonin supplements.
These pills are commonplace enough that you have most ly heard of them and seen them in your local pharmacy.
Here’s what you need to know about the pros and cons of using melatonin supplements for sleeping difficulties.
Melatonin is a hormone that helps regulate sleep timing.
It is produced in the pea-size pineal gland, which is nestled in the middle of your brain and syncs melatonin production with the rising and setting of the sun.
According to the National Sleep Foundation, the gland remains inactive during the day but switches on around 9 p.m. (when it’s generally dark) to flood the brain with melatonin for the next 12 hours.
Melatonin itself doesn’t make you fall asleep; it just tells your body that it’s time to fall asleep by lowering alertness and reducing your core body temperature. It works in tandem with the body’s circadian rhythms to let you know when you should rest and when you should be awake.
“Melatonin is the hormone of darkness and you need it to start falling asleep,” Dr. Avidan said. “The reverse also happens. If you expose yourself to too much light at night, you actually delay the production and release of melatonin.” This is why experts suggest you avoid computers and smartphones before bedtime.
You can buy synthetic melatonin supplements over the counter. They are generally considered safe and nonhabit-forming. Dr. Avidan says melatonin supplements can be effective for most people: “For all practical purposes, it probably helps.”
However, he cautions, melatonin’s success depends on three things:
- When you take it.
- How much you take.
- If the amount you take is the actual dose written on the box.
These products work best for two kinds of short-term sleep problems.
First, melatonin supplements are useful when you have a circadian rhythm disorder such as jet lag or sleep pattern disruptions resulting from shift work. When used to treat these conditions, melatonin supplements signal to the brain that it is nighttime and the body should start winding down.
In these instances, said Dr. Bhanu Kolla, an associate professor in psychiatry and psychology and a consultant in sleep medicine at the Center for Sleep Medicine at the Mayo Clinic, it is best to use low doses of melatonin supplements. Consult with a doctor if you have any questions or concerns.
The second use for melatonin supplements is when you have difficulty falling asleep and staying asleep. Over all, Dr. Kolla said, melatonin supplements, if taken before bedtime, reduce the time to fall asleep.
In one study published in PLOS One, people who took melatonin supplements fell asleep seven minutes faster and increased overall sleep time by eight minutes.
Researchers found that overall sleep quality was improved too.
For those addressing sleep regulation issues, experts suggest taking 0.5 milligrams two to three hours before bed. For people with insomnia who need help falling asleep, you can take 5 milligrams 30 minutes before bedtime.
“We try to recommend low doses,” said Dr. Rachel Marie E. Salas, an associate professor of neurology and nursing at Johns Hopkins Medicine. “Again, this is not a prescribed medication, so there is a great deal of variability.”
Most people end up taking melatonin supplements without consulting a physician, Dr. Kolla said. “If you have any major health conditions such as liver failure, renal failure or are pregnant,” he said, it is always best to consult your physician before taking melatonin supplements.
Melatonin supplements can cause dizziness and headaches. Occasionally, people might feel a little groggy during the day, but over all, Dr. Kolla said, melatonin is safe to take. Because melatonin can cause daytime drowsiness, the Mayo Clinic warns that you shouldn’t drive or operate machinery within five hours of taking it.
In contrast to most available sleep medications, melatonin seems not to be habit-forming and typically produces no hangover effects.
Before you buy melatonin, it’s important to make sure you are getting it from a reputable place. “The F.D.A. does not regulate supplements,” Dr. Kolla said. “So you’re trusting the manufacturer in terms of the dosing.”
A 2017 study in the American Academy of Sleep Medicine found that the melatonin content of dietary supplements often varies widely from what is listed on the label. The study found that even within the same batch of product, variability of the melatonin varied by as much as 465 percent.
Without governmental oversight, there really isn’t a way to ensure the levels of melatonin advertised on the package are accurate. Therefore, Dr.
Kolla recommends looking for a GLP (good laboratory practice) or GMP (good manufacturing practice) label on the product. Both labels refer to federal regulations designed to affirm a product has the quality and purity that appear on its label.
He says this provides “some assurance that you are getting close to what the label says you’re getting.”
Taking melatonin supplements alone to treat insomnia won’t be as effective as taking melatonin and also working on improving your sleep hygiene, Dr. Avidan said. Sleep hygiene refers to creating an ideal environment that promotes conditions good for sleep.
- Powering down electronics and avoiding the news two hours before bedtime.
- Maintaining a regular sleep schedule.
- Eschewing alcohol and caffeine at night.
- Trying to get as much natural sunlight during the day as possible to orient your internal clock.
Dr. Avidan suggests that people both try these habits and take melatonin for two to three weeks to see if it helps.
While melatonin “can help with the promotion of sleep, for many it does not,” Dr. Salas said.
If you are stumped as to why melatonin isn’t working for you, Dr. Salas recommends talking to your physician.
She says it may also be time to contact a sleep specialist, as there could be other, more serious sleep issues. Dr.
Avidan says he and his colleagues are currently taking virtual appointments for anyone living in the United States, so it’s worth inquiring whether a sleep specialist can see you remotely.
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How Lupus Affects the Nervous System : Johns Hopkins
Lupus can affect both the central nervous system (the brain and spinal cord) and the peripheral nervous system. Lupus may attack the nervous system via antibodies that bind to nerve cells or the blood vessels that feed them, or by interrupting the blood flow to nerves.
The most common manifestation of neuro-lupus is cognitive dysfunction, which is characterized by clouded thinking, confusion, and impaired memory. Eighty percent of lupus patients who have had lupus for ten years or more will experience this condition.
Single positron emission computed tomography (SPECT) scans of SLE patients with cognitive dysfunction show abnormalities in blood flow, indicating that the condition may be the result of decreased oxygen delivery to certain parts of the brain. Unfortunately, there is no real treatment for cognitive dysfunction. Normally, it does not get worse over time.
However, some people find that counseling and other forms of cognitive therapy help them to cope with associated symptoms.
About 20% of patients with lupus have migraine- headaches. These headaches are different from “lupus headaches,” which are due to active lupus and require a lumbar puncture (spinal tap) or blood vessel study (MRA or CT-angiogram) for diagnosis.
A true lupus headache usually requires corticosteroids for treatment. Non-lupus migraine headaches should be treated with a migraine prevention diet. [A copy of this diet can be found in the article “Migraine Prevention Diet” under this heading.
] However, when diet alone becomes insufficient, medications such as nortriptyline can be used to reduce headache frequency and severity.
Fibromyalgia is a chronic pain sensitization disorder characterized by widespread tenderness, general fatigue, and non-restful sleep. Doctors do not currently know the cause of fibromyalgia, but it is believed to result from a rewiring of pain pathways that lead to the spinal cord and brain.
As a result, the central nervous system experiences an increased sensitivity to pain signals. Many people with lupus have fibromyalgia; in fact, much of the pain that people with lupus feel is due to this condition. To check for fibromyalgia, your doctor may touch several points on the muscles of your body.
People with fibromyalgia often feel pain when light pressure is applied to these areas, whereas people without the condition feel little discomfort.
Three drugs are currently approved by the FDA for the treatment of fibromyalgia: pregabalin (Lyrica), duloxetine (Cymbalta), and milnacipran HCl (Savella). While these drugs can help to reduce discomfort by about 25%, there are many things that you can do on your own to help ease and manage the symptoms of fibromyalgia.
Some people believe that limiting their daily activities helps to reduce pain and fatigue. In fact, doctors recommend that people with fibromyalgia continue to engage in regular daily activities. Scheduling short daily rest times may help you to keep a normal schedule.
However, spending too many hours resting may make your symptoms worse.
In addition, since responses to stress can cause physical symptoms such as headache, increased pain, and muscle tension, try to practice stress management skills. There are some stressors that you can control, and there are some that are simply your hands. Focus on what you can control, and direct your energy toward future growth.
Try to practice a healthy lifestyle. Research has shown that light stretching activities such as Tai Chi and yoga can help to relax muscles and improve some of the pain associated with fibromyalgia.
In addition, molecules called endorphins that are released by your brain after exercise—usually about 30 minutes of moderate or intense activity—help you to achieve a ‘natural high,’ and many people report that exercise simply makes them feel better overall.
Other lifestyle elements, such as a supportive social network and a healthy diet, can also help to ease feelings of emotional and physical discomfort and promote an overall sense of well-being. If you feel you need more help in managing your fibromyalgia, your doctor can assist you in devising coping strategies.
Organic Brain Syndrome
Organic brain syndrome is a general term referring to physical disorders that cause impaired brain function. Other names are cerebritis, encephalopathy, and acute confusional state.
This condition is usually diagnosed through lumbar puncture (spinal tap) or EEG (the recording of brain waves), and before the diagnosis is made, the doctor will ly rule out certain causes, such as drug use, infection, cancer, or metabolic problems.
If the condition is confirmed to be caused by lupus, high dose steroids will be used to combat its effects.
CNS vasculitis is a very rare SLE complication caused by inflammation of the blood vessels of the brain. It is diagnosed by a blood vessel study (brain MRA or CT-angiogram) and requires treatment with high dose steroids.
- Wallace, Daniel J. “Heady Connections: The Nervous System and Behavioral Changes.” The Lupus Book: A Guide for Patients and Their Families. 1st ed. New York: Oxford University Press, 1995. 99-115.
- “How Lupus Affects the Body: Nervous System.” Lupus Foundation of America. 1 July 2009. .