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Cardiac and Neuro Sarcoidosis (Drs. Culver, Tavee, and Tchou 3/28/12)

Online Health Chat with Dr. Daniel Culver; Dr. Jinny Tavee, MD and Dr. Patrick Tchou

March 28, 2012

Introduction

Cleveland_Clinic_Host: Sarcoidosis is an inflammatory disease that affects multiple organs. While it commonly affects the lungs and lymph glands, it also often involves the heart and nervous system.

Cardiac sarcoidosis causes easily recognizable clinical problems in a small number of sarcoidosis patients, however, granulomas are present in the heart muscle in up to one quarter of patients. Cardiac sarcoidosis may cause heart block, rhythm disturbance, heart failure, or even sudden death. With the use of new or technologies, cardiac involvement is increasingly being recognized.

Neurological involvement in sarcoidosis occurs in 5-10% of patients and can affect any nervous system structure. While some neurologic manifestations resolve spontaneously, the majority signify chronic disease which often requires treatment.

Daniel Culver, DO is a Staff Physician in the Department of Pulmonary, Allergy, and Critical Care Medicine at Cleveland Clinic's main campus. His clinical interests include sarcoidosis, pulmonary alveolar proteinosis, critical care, and interstitial lung diseases. Dr. Culver is a fellow of the American College of Chest Physicians and a member of several professional associations, including the American Thoracic Society, the American Osteopathic Association and the World Association of Sarcoidosis.

Patrick J. Tchou, MD is a practicing Staff Physician in the Robert and Suzanne Tomsich Department of Cardiovascular Medicine at Cleveland Clinic concentrating on treatment of cardiac arrhythmias, especially those of complex origins. Dr. Tchou is board-certified in internal medicine and cardiovascular disease, with added qualification in clinical cardiac electrophysiology. His research interests include sudden cardiac death and percutaneous catheter ablation of cardiac arrhythmias.

Jinny Tavee, MD is a staff neurologist in the Neuromuscular Center at the Cleveland Clinic. Dr. Tavee’s clinical focus is on patients with neuromuscular disorders and neurosarcoidosis. However, she has a special interest in integrating holistic medical practices, such as nutrition therapy and meditation, with conventional medicine for the treatment of chronic neurological diseases.

Cleveland_Clinic_Host: To make an appointment, please call the Sarcoidosis Center of Excellence at 216.444.3613 or toll-free 866.783.3679.

You can also visit us online at http://my.clevelandclinic.org/lungs-breathing-allergy/default.aspx

Cleveland_Clinic_Host: Join us October 5th in Cleveland Ohio for the 2012 Sarcoidosis Patient Conference. This conference is presented by Cleveland Clinic in conjunction with the World Association of Sarcoidosis and Granulomatous Disorders (WASOG) North America meeting.

For more information go to www.ccfcme.org/Sarcoidosis12

Cleveland_Clinic_Host: Welcome to our Online Health Chat with Dr. Culver, Dr. Tavee and Dr. Tchou. We are thrilled to have them here today for this chat. Let’s begin with some of your questions.


Cardio and Neuro Sarcoidosis

char4681: What are common signs that there could be something wrong with your heart or nervous system with sarcoidosis?

Dr__Culver: There is an association between cardiac and neurologic sarcoidosis, so that people with neurologic disease are more likely than others to have cardiac involvement. The neurologic disease can manifest in a whole variety of ways--a common pattern is drooping of one side of the face (Bell's palsy). Optic neuritis, where there is inflammation of the optic nerve leading to loss of vision, is another common way that neurologic sarcoidosis can present. Since any part of the nervous system can be affected, there are a whole range of symptoms, including weakness, numbness, clumsiness, problems with balance, and a range of other ones. Cardiac sarcoidosis most typically presents with palpitations, dizzy episodes that result from electrical conduction difficulties (either heart block or dysrhythmias like ventricular tachycardia), or symptoms of heart failure like edema, shortness of breath, and fatigue. Chest pain is almost never due to sarcoidosis involvement of the heart.

LuAnne: Hi. I have small fiber neuropathy, and I was wondering about the possibility of this spreading into other parts of the nervous system or cardiac involvement?

Dr__Culver: We have seen several patients with simultaneous small fiber neuropathy and involvement of the nervous system or heart with classic sarcoidosis inflammation. However, the much more common scenario is that the cardiac and neurologic symptoms are related to small fiber symptoms, such as occur with dysautonomia. For example, palpitations and racing heart are very common with small fiber disease. We usually do a careful assessment for typical sarcoidosis organ involvement, and also for SFN with very different tests, in order to determine the cause of the symptoms.


Sarcoidosis Medications

mtnclimber: I am on 80mg bid of sotalol for my ventricular dysrhythmias presumably caused by cardiac sarcoidosis. It is making me very tired; is there another drug I can try?

Dr__Tchou: Sotalol is a beta blocker as well as an antiarrhythmic medication (type III). If sotalol at this low dose is causing too much tiredness, then it can be switched to another type III antiarrhythmic that does not have much beta blocker effect. Dofetilide (Tikosyn®) is currently the only other pure type III antiarrhythmic medication available that can be used. It works very much in the same manner as sotalol, but has NO beta blocker effect. Separate doses of beta blockers can be added as needed. Another alternative is amiodarone. But that medication may have much more organ toxicities when used as a long term therapy. Not all physicians use dofetilide, so you would need to consult with a specialist who is comfortable with using this drug.

albertcamus111: For cardiac sarcoidosis, which one of the steroid-sparing agents might be best, and does it have any primary benefit in and of itself?

Dr__Culver: There are no studies that really evaluate that question well. We think that the response to therapy in the heart is slower, and less reliable than in the lungs. Many physicians think that higher doses of steroids are needed as well, but there is one study from Japan (Yazaki) that suggests that using doses of more than 1/2 mg/kg of steroids did not confer additional benefit as opposed to more moderate doses.

We have used combinations of agents, including methotrexate, leflunomide, azathioprine and steroids. Cyclophosphamide was used more in the past, and might be useful for truly refractory cases. However, more recently we have started using some infliximab for cardiac sarcoidosis. This must be done with caution, as some trials in heart failure patients suggested that infliximab actually caused death more often than placebo. Therefore, there is a black box warning about the use of that class of medications in heart failure patients. However, in selected refractory cases, in consultation with a physician experienced with these issues, it can still be considered.

NE: I was on infliximab (Remicade®) for a year for my sarcoidosis but was taken off in March of 2010 because of stocking and glove neuropathy that my doctor felt might be a symptom of demyelinating disease. After spinal tap, nerve conduction testing, and brain MRI, I was told that there was white matter but did not appear to be demyelination, so I could resume the Remicade. I am reluctant to begin the Remicade again. My question is, “Is it wiser to live with the symptoms (joint pain, muscle pain, night sweats/temperature dysregulation, tremors, memory loss) or to resume the Remicade?”

Dr__Culver: The symptoms you describe sound more like manifestations of small fiber neuropathy than classic neurosarcoidosis. If they are very severe, you could consider resuming the infliximab. However, infliximab is often not very helpful for them. Other options could be considered, such as gabapentin for the nerve pain. Sometimes, in very severe cases, we have used immune globulin (IVIG) to treat small fiber disease.

walkerfreely: Is sarcoidosis of the nervous system treated with steroids also?

Dr__Tavee: Yes. It is actually sometimes the first line of treatment depending on where the problem is. For brain and spinal cord problems, I usually start with high dose IV steroids as patients tend to respond quickly. Steroids are also helpful for headaches. For small fiber neuropathy, however, steroids usually don't help as much. I tend to prefer IVIG.


Neuro Sarcoidosis

ASFL: What are some of the beginning signs that sarcoidosis is having a neurological effect?

Dr__Tavee: Just about any part of the nervous system can be affected by sarcoidosis. But the most common manifestations are facial weakness on one or both sides, visual changes due to optic nerve involvement, and headaches. Other symptoms include numbness and tingling in the feet/hands due to neuropathy or weakness which could be related to muscle or spinal cord disease.

ASFL: Are there specific tests or blood work a person with Sarcoidosis should inquire about undergoing with their doctor if they suspect signs of neurosarcoidosis?

Dr__Tavee: The tests ordered depend on what kind of symptoms you're having. With numbness and tingling of the limbs, an EMG and possibly a skin biopsy would be good to look at the nerves. Headache, cognitive changes, visual changes would be evaluated with an MRI brain scan. Changes in reflexes and leg and arm weakness with sensory problems can also point towards a brain or spinal cord lesion, so an MRI of both may be necessary. Bowel or bladder issues especially point towards a spinal cord lesion. A spinal tap may also be helpful. There are of course many other tests that you can order, but these are the most common. For blood work, an ACE points toward sarcoidosis but not necessarily neurosarcoidosis. Soluble IL 2 receptor level is another marker we're obtaining to help confirm active disease, but again this could be for systemic sarcoidosis rather than neurosarcoidosis.

rtournas10: Is uveitis that is caused by sarcoidosis considered neurosarcoidosis?

Dr__Culver: Uveitis refers to inflammation of the structures of the eye. Sometimes, vision is affected when the optic nerve, the nerve leading from the eye to the brain, is inflamed. That would technically not be termed uveitis, but could present with similar symptoms of blurry vision. Optic nerve involvement is probably the second most common manifestation of neurosarcoidosis.

nicnelson56: With respect to the upcoming neurosarcoidosis chat, I understand that ACE levels are of questionable use when determining whether a patient has neurosarcoidosis because many people with neurosarcoidosis don't have high levels. But, in my case, I am still searching for a diagnosis to explain my multifocal neurological problems, and a recent test showed high ACE levels. In your opinion, does a high ACE result in someone with neurological impairment suggest a need for further investigation into possible neurosarcoidosis? Similarly, in my case, I had an "indeterminate" level of neuron-specific enolase (15). Is NSE implicated at all in neurosarcoidosis? Thanks for considering my question(s)!

Dr__Tavee: Although ACE is indeed a nonspecific marker of inflammation, in my patients with confirmed neurological disease (via EMG, MRI, or skin bx) and an elevated ACE, I do proceed with further evaluation to look for systemic sarcoidosis. CXR and CT scan are good places to start usually. As for the NSE, this is more for brain death prognostication and neurodegenerative diseases. They're not routinely used in sarcoidosis.

LibbyJ: I have had some symptoms that I think may be related to my sarcoidosis. I am not sure if I could have neurosarcoidosis. A year and half ago I had long thoracic nerve palsy (which caused winging of my right shoulder), and recently my right index finger has become paralyzed at the top joint. The finger has been paralyzed since December. I also have numbness in my fingers and toes, hand tremors, and sometimes numbness on my face (mostly along the left cheek bone). A few months ago I had a weird arm seizure for about 10 seconds where my arm just kept jerking back and forth, and I had no control over it. I also have balance issues, and my memory is getting worse, mostly in terms of names of people and places or things. I will forget the name of something that is part of my everyday vocabulary. It is very scary and embarrassing. I am only 28 yrs old.

Dr__Culver: All these symptoms could be related to sarcoidosis involving the neurologic system, although long thoracic nerve palsy is much more often related to an injury to the nerve. However, these symptoms are very non-specific, and so if there is not a pre-existing diagnosis of sarcoidosis elsewhere, then they are very unlikely to be related to sarcoidosis. The best way to approach them would be an evaluation by a neurologist. If there is suspicion of sarcoidosis as a cause, then a chest CT and possibly a bronchoscopy are often useful to obtain a diagnosis.

Dr__Tavee: Sorry to hear about your symptoms. It is very possible that this could represent neurological complications of the sarcoidosis. I would recommend a formal evaluation with a neurologist, especially if you are having involuntary arm jerking. As you mention, this could represent seizures. An MRI brain and EEG (brain wave test) would be important for evaluation of this, as well as the balance and memory issues. As for the numbness, an EMG (nerve and muscle test) may be helpful. Finally, we usually recommend neuropsychiatric testing for cognitive issues. It's a 3- to 4-hour-long test that evaluates memory, reading comprehension, mood, etc. Good luck!

mlrm290: I was diagnosed with neurosarcoidosis of the spinal cord, affecting my lower body, and I also have small fiber neuropathy. Weather seems to have a huge effect on my nerves. Do you know if this is true, and why it reacts this way? Is there anything I can do to prevent feeling so terrible?

Dr__Tavee: Sorry to hear you have both the cord and the small fiber nerves involved. Unfortunately, temperature extremes will definitely affect how you feel. Increased heat as with hot tubs or a humid day slows down the signal transmission through your spinal cord, making everything you have worse. But cold affects nerve transmission in the small (or large) fibers, resulting in increased pain. My best advice would be to keep cool on a warm day by keeping an ice cold spritzer bottle near you and spraying your face/neck if you're out on the beach or outside. Avoid hot tubs and humid climates if possible. For cold, keep your feet as warm as possible. I recommend diabetic socks. Good luck!

HECTOR: Dr. Tavee, I have white matter lesions—multiple in the brain and brain stem, and one in the cervical spine. I responded well to IV Medrol® and long-term oral prednisone. There is no biopsy-proven sarcoidosis found anywhere else. I have residual ataxia and pain and numbness in joints and muscles. I am down to 2.5 mg. prednisone/day. What are signs that I am in a flare-up of neurosarcoidosis. Would you recommend a PET scan? What other tests would run on a routine basis besides an MRI and a neurological exam every 3 months? Thank you.

Dr__Tavee: Hi, Hector. Glad that you have responded to the steroids. It's interesting that you have neurosarcoidosis in the absence of systemic sarcoidosis, which is rather rare. Unless it is biopsy-proven, then I would make sure you don't actually have another condition such as multiple sclerosis. Further work-up may be needed. However, if it is indeed biopsy-proven and you are otherwise stable, then serial monitoring with the MRI and neurological exams would probably be enough with respect to testing from a neurological standpoint. A PET may be useful to look for other mimics of sarcoidosis (if not biopsy-proven) or systemic involvement of the sarcoidosis if it is biopsy-proven. As for signs of recurrence: worsening of your current symptoms, vision changes, hearing loss, increased HA, more numbness and tingling, bladder/bowel problems or cognitive changes could indicate something new. Good luck


Cardiac Sarcoidosis

mmerkel: Is treatment always necessary when you have asymptomatic cardiac sarcoidosis (have ICD just in case), and if so, is it for a lifetime if PET scan shows activity still?

Dr__Culver: If the PET FDG scan shows active inflammation, I would recommend suppressive therapy. Active inflammation is probably what leads to scarring, which can then lead to ventricular arrhythmias. It is good that you have an ICD for a safety net just in case you develop serious ventricular arrhythmias. But it is much better to prevent ventricular arrhythmias if possible. The question of the duration of therapy is difficult. At present, PET FDG is probably the only decent way of assessing the activity of inflammation. So, after a few years of therapy, one can retest and see if the inflammation has subsided and then consider tapering off the medications.

The ICD that you had placed is like a safety net. It is great to have it there but you don't want to have to use it much. If you end up receiving a lot of therapies from it, it can be very traumatic. We usually try to suppress the need for therapies, using a combination of immunosuppressive, anti-arrhythmic medications, and sometimes ablation of irritable foci of the heart.

pfehrman: When my lymph nodes were biopsied around my aorta, it showed sarcoidosis. Does that automatically mean the heart is affected?

Dr__Culver: No, lymph node involvement, even near the heart, does not imply in any way that the heart is involved. In fact, even when the lining of the heart (the pericardium) is inflamed from sarcoidosis, that does not necessarily mean that heart muscle or electrical system is affected.

Sunpokebill: How does sarcoidosis invade the heart--through the neurological pathways or the muscle fibers? Can sarcoidosis be the only contributing factor that creates atrial fibrillation or does sarcoidosis show up as an opportunistic affliction only? I am curious as to its predominant mechanism once detected in or around the heart. Thank you for your reply. Perhaps there is a publication I should read instead of asking here; if so, can you direct me?

Dr__Tchou: Atrial fibrillation (AF) is such a common arrhythmia that it is difficult to attribute it to sarcoidosis. However, it is a possibility that sarcoidosis can influence AF in someone who has that propensity anyway. We don't think it traffics through nerves or muscle. Possibly it gets around via the lymphatic system, but we don't have any positive evidence.

LibbyJ: I was diagnosed with pulmonary sarcoidosis via VATS biopsy in November 2011. I have some cardiac issues and was wondering if you think this could be caused from cardiac sarcoidosis? My issues/symptoms include: shortness of breath, dizziness, close to blackout upon standing, chest pain (sharp pain and tightness when lying down), pain in left breast (could be from VATS), vascular problems (Reynaud’s & livedo reticularis), and a slight heart murmur. I have had a TTE w/ Doppler that showed an ejection fraction of 55%, minimal sclerosis of the aortic valve, mitral LDI lateral wall index low at 4. Also, my EKG was normal. Heart disease does run in my family (starting at a young age).

Dr__Culver: This question gets to the issue of diagnosing cardiac sarcoidosis. Most patients with cardiac symptoms and sarcoidosis actually have another cause for their symptoms, but if other causes for the cardiac symptoms have been evaluated carefully, and there are either electrical or imaging features consistent with sarcoidosis, then we generally attribute the symptoms to cardiac involvement. Chest pain is common in sarcoidosis but is almost never from cardiac involvement. It should be evaluated by a cardiologist.

char4681: When should your doctor be concerned if your heart is involved in sarcoidosis?

Dr__Tchou: If you have known sarcoidosis elsewhere and you have abnormalities in your cardiac electrical system, then you should be evaluated for the possibility that the sarcoidosis involves your heart as well. Abnormalities of atrioventricular conduction, high amounts of ventricular arrhythmias, or more seriously ventricular tachycardia should all raise the issue of cardiac involvement.

Winston: My 23-year-old daughter was just diagnosed with cardiac sarcoidosis—only in the heart that we know of. How common is it to just present itself in the heart? She has a biventricular pacemaker/defibrillator. How likely is cardiac sarcoidosis to reoccur after her prednisone treatments which, so far, have helped her EF jump from 25% to 50%? She has many more years to deal with it than most others because she is so young. Has cardiac sarcoidosis every resolved itself completely and not come back?

Dr__Culver: Isolated cardiac sarcoidosis is uncommon but can occur. I am not aware of any literature that gives a reliable frequency, probably because making the diagnosis is difficult. I would not be convinced about the diagnosis unless there is a biopsy showing granulomas in some part of the body. Notwithstanding that, the response to steroids is quite dramatic. I would favor long-term therapy, and very gradual cautious attempts to withdraw it. There are certainly a substantial number of patients for whom the disease seems to quiet down over time, but with that severe of an effect, I would be very cautious about withdrawing therapy anytime in the next few years.

Dr__Tchou: It is very encouraging that her ejection fraction has improved to the normal range. I suspect that the benefit is likely due to the biV pacing. You did not mention the scenario where she received the biV device. Given this response, I suspect that the biV pacing may have either compensated for left bundle branch block or for complete heart block with a standard pacemaker in the right ventricle. It is quite possible that the heart block or even the left bundle branch block could be due to sarcoidosis, but that is not the only possible explanation. If sarcoidosis is a confirmed diagnosis, then longer term immunosuppressive therapy should be pursued.

kimviola: Is a positive gadolinium MRI an indication of active cardiac sarcoidosis, or does it just indicate that there has been sarcoidosis involvement in the past?

Dr__Culver: Late enhancement on gadolinium MRI is the most common finding in cardiac sarcoidosis, but it can indicate either scar or active inflammation. When there is T2 prolongation on MRI, this is a sign of edema and is more suggestive of active disease. We often find PET to be a better tool for assessment of disease activity.

DonnaN: I have diagnosed with SVT, and my cardiologist says it isn't sarcoidosis related. I'm not so sure. Do you think it may be cardiac sarcoidosis related?

Dr__Culver: SVT or supraventricular tachycardia generally refers to a rapid heart rhythm that involves the upper chambers of the heart. These are generally not associated with other structural heart diseases. So, it is highly unlikely that SVTs are related to sarcoidosis. Although not totally impossible, it is quite unlikely that SVTs are related to sarcoidosis.


Additional Questions

intarsiablue: A sarcoidosis doctor has said I most likely have sarcoidosis. The needle biopsies of lymph nodes done on each side of my chest have left me with knots, predominantly over my heart area. It becomes inflamed if I try to work out. Can I work out and push through the pain without doing more damage? Sometimes inflammation is good. Can this spread the disease?

Dr__Culver: Sarcoidosis in the skin likes to involve areas of prior trauma, such as scars, tattoos, and prior injuries. So, it is possible that the lumps you have are from sarcoidosis involvement of the needle tract. However, the pain could be unrelated to sarcoidosis, or the lumps could be related to keloid formation. If you are having exertional chest discomfort, you should be evaluated for coronary artery disease (CAD). If there is no CAD, then I think it is fine to push through the pain during your work-out.

chhlaw: I was diagnosed with sarcoidosis 27 years ago. About 9 months ago, I began experiencing numbness in my lower extremities--from the upper abdomen down. Is this some form of neuropathy?

Dr__Tavee: It is possible that this may be a neuropathy, although usually the symptoms start in the feet and come up. The other consideration would be a spinal cord lesion in the thoracic or even cervical region, especially if you're having bowel/bladder issues, or increased reflexes in the legs. It is also possible that it could be something completely unrelated to the sarcoidosis given the big time differential between when you had the sarcoidosis and these current symptoms. I would recommend seeing a neurologist for further evaluation. Good luck!

Kimbre: I have sarcoidosis, and I was just diagnosed with small nerve fiber neuropathy. What is this exactly?

Dr__Tavee: Small nerve fibers mediate pain (burning, tingling) and the autonomic system, which affects parts of the body that are not under voluntary control like sweating, pupillary dilation, heart rate, and blood pressure. Patients with small fiber neuropathy typically have burning, tingling sensations in their limbs/face/chest, but do not have weakness or loss of position sense. The exam is usually normal, and routine tests such as the EMG will be normal. To diagnose it, you have to do specialized testing which includes skin biopsy and autonomic tests that look at how much you sweat. Treatment for sarcoidosis small fiber neuropathy is with IVIG, steroids, and treatment of the underlying sarcoidosis with other immunosuppressants. Pain medications such as gabapentin, Lidoderm® patches, or Elavil® can be helpful as well. Good luck!

jcnc: If a person has chronic multi-systemic sarcoidosis including bones, lungs, liver, spleen, and skin, is on treatment with infliximab, methotrexate, and hydroxychloroquine (plus a few other medications), and develops a small (1.7cm by 11 mm) brain cyst which is probably an arachnoid (described as atypical in appearance) cyst, what type of follow-up would you recommend? Two MRIs done 10 weeks apart found this cyst. Should other testing be considered to rule out neuro-sarcoidosis?

Dr__Tavee: In most cases, an arachnoid cyst in the brain is usually incidental, meaning it's clinically silent and not harming you. Depending on where it is and if you're having any symptoms from it (large lesions can sometimes press on the surround brain causing seizures), other testing to consider includes an EEG. However, if you're having neurological problems unrelated to the cyst, then a spinal tap may be of use. Otherwise follow-up imaging in 3 months would probably be adequate. Good luck.

ladybug70791: Recently I have been experiencing memory loss and feelings in my brain that doctors feel are seizures in the brain. Could this be related to my sarcoidosis? I have it in the nasal passage. I have had 6 growths removed, from both arms and back of neck, and it is also in my bones.

Dr__Tavee: It's possible. Further evaluation should include MRI of the brain and EEG and, of course, a neurological examination if not already done. A formal neuropsychiatric test which objectively evaluates memory and cognitive function as well as mood would be helpful as well. Good luck.

Vinman1950_1: What publications can my family read so we can better understand sarcoidosis and how it impacts the life of our loved one?

Dr__Culver: You can refer to our website more information about sarcoidosis at clevelandclinic.org/sarcoidosis


Closing

Cleveland_Clinic_Host: I'm sorry to say that our time with Dr. Culver, Dr. Tavee and Dr. is now over. Thank you again, doctors, for taking the time to answer questions about “Cardiac and Neuro Sarcoidosis.”


More Information

Cleveland_Clinic_Host: To make an appointment, please call the Sarcoidosis Center of Excellence at 216.444.3613 or toll-free 866.783.3679. You can also visit us online at http://my.clevelandclinic.org/lungs-breathing-allergy/default.aspx

Cleveland_Clinic_Host: Join us October 5th in Cleveland Ohio for the 2012 Sarcoidosis Patient Conference. This conference is presented by Cleveland Clinic in conjunction with the World Association of Sarcoidosis and Granulomatous Disorders (WASOG) North America meeting.

For more information go to www.ccfcme.org/Sarcoidosis12

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