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Ask the Doctor 2016 Number 1 (Jan/Feb/Mar)

Disclaimer: neither the BEBRF nor members of the BEBRF Medical Advisory Board has examined these patients and are not responsible for any treatment.

  1. QUESTION: I've been getting BOTOX® shots for 20 years (I am currently getting 100 units). They used to work quickly, and I would be able to see again. But lately after the injections, I just can't see at all. My eyes continue to spasm shut. This has been going on for the last four sets of injections. I also take Klonopin (1 tablet at night). I have been under a lot of stress this past year with several illnesses and deaths in my family and wondered if it could it be stress alone or if I am getting immune to the BOTOX®?

    ANSWER: Botulinum toxin injections, such as BOTOX®, are considered the treatment of choice for blepharospasm. I have been injecting some of my patients for over 25 years with continued benefit and virtually no side effects. Rarely, some patients lose their full benefit or stop responding altogether, but this is extremely rare. Since some patients who have been treated for long time had received the "old" BOTOX®, used before 1998, which contained a much high protein load than the "current" BOTOX®, it is possible that they have developed "blocking antibodies," which means that they stop responding because of immunoresistance. This used to occur in up to 10% of patients but is now extremely rare, particularly in blepharospasm patients who require a relatively low dose (e.g. 100 units). In such individuals, an alternative form of botulinum toxin, such as MYOBLOC®, may be helpful. Another reason why some patients lose their response to botulinum toxin is because they are taking certain antibiotics that may interfere with the action of the drug. Rarely, stress can also compromise the response to botulinum toxin, but the mechanism of this phenomenon is not well understood. Without knowing more about the exact circumstances, it is difficult to provide a specific answer to the question, but I hope the above explanation helps.

  2. QUESTION: I am 82 years old and have been getting BOTOX® injections for about 20 years. I am also taking Restasis for dry eye. I've had some tearing in the past after I got the injections, but it did not last very long. I got my last injections, and the tearing has been heavy and has lasted for 3 weeks. When I called the doctor about it, he says it is to be expected. I am wondering what caused it to be so bad this time and what I could do to alleviate it or avoid it happening again.

    ANSWER: The eye surface must be always lubricated for the eye to remain healthy and pain-free. To achieve this, tears are constantly made, sweep across the eye with each blink, bathe the eye, and then normally depart by either evaporation into the air or drainage down the tear drains into the back of the nose and throat. Now you understand, in large part, why when someone cries hard, making lots of tears, their nose runs and they may choke, as tears flow both down the throat and down the nose. This drainage of tears is not facilitated by just gravity alone. There is an actual "pump" mechanism powered by normally blinking eyes that pumps the tears down the tear drain system. In fact, some have argued (although there has been heavy debate over this issue) that the "dry eye" in blepharospasm is due in part to excessive, forceful blinking and the rapid clearance of tears from the eye surface. So, when you use botulinum toxin to decrease the ability of the eyes to squeeze closed (forcefully blink), you decrease the normal tear drainage pump, and the tear production exceeds the rate of tear evaporation, and tears pour down the face.

    If you take a twig and stick it in your eye (don't try this at home), your eyelids will squeeze shut (forceful blink) and then the eye produces copious tears to wash the foreign material out of the eye. The eye is not very smart. It will have this same kind of reaction to varying degrees whether you poke it with a finger, hit it with a softball, splash in vinegar, or allow it to dry out, all of which are irritating to the eye. When you get a botulinum toxin treatment, you decrease forceful blinking, and decrease the ability for the eyelids to spread the tears nicely across the eye. This allows the eye to dry out, and the eye's response is to make a huge quantity of tears, because the not-so-smart eye doesn't know whether it is trying to lubricate itself or wash out a twig. It turns out that the tears made in this situation are mostly water-tears, and not the complex, multi-component tears essential for keeping the eye surface healthy and safe.

    So now you know two reasons why your eyes might tear after botulinum toxin treatments. What's interesting to me is that the vast majority of my blepharospasm patients DON'T make excess tears when their eyes severely dry out. Somehow this response to eye irritation is interrupted. In my experience, it tends to be the people with more mild forms of blepharospasm that experience tearing. The trick to finding the right toxin dose and injection pattern (which again in my experience must be individualized for each person) is to disturb the forceful blink of blepharospasm, but leave enough "normal" blink to keep the eyes from burning or tearing. As another aside, if your eyes burn and tear EARLY AFTER your injections, you are getting a bit too much toxin effect and adjustment to dose or location of injections may be warranted, but balanced against not getting enough effect, a little too much is often preferable, since eye drops and ointments can help. If your eyes burn and tear shortly BEFORE your next injection, you may be getting too little toxin or not getting it frequently enough (see previous article in this Newsletter on FABS, Frontalis Antagonist Blink Syndrome - March/April 2012 BEBRF Newsletter - Page 9).

    The next part of your question is why did this happen, this time, more than ever before? This is the same as asking why is there sometimes variation in the effect of botulinum treatments? Unfortunately, MANY things can influence each treatment. Please understand the list below is a mixed bag of things that are well established to have a significant effect as well as those that are more speculative or controversial.

    1. Toxin Potency. The companies that make the toxins are now making such vast quantities in each batch, that there is no longer the huge variability (we think) in bottle to bottle potency. The toxins are also more stable now compared to decades ago, both before and after being reconstituted (solution added to the powder in which it is stored). However, the toxin seems to be quite sensitive to how it is reconstituted. If the vial is shaken vigorously, some of the toxin may be degraded. So if someone new is making up the toxin, it may make quite a difference. Alcohol applied in abundance immediately before an injection may get dragged into the injection site and can denature the toxin.
    2. Injection Precision. Although you may have an experienced injector, we are not machines, and we may not put in EXACTLY the same amount of toxin in EXACTLY the same place each time.
    3. Injection Spread. The depth of the injection (the tissue plane), the dilution of the toxin, the brand of toxin used (competing companies are constantly offering physicians special deals), and whether or not there is any bruising all may change how much the toxin spreads away from the site of injection.
    4. Host Influences. Diet may influence the toxin effect, especially zinc levels. Although "aminoglcyocide" antibiotics are frequently mentioned as influencing the effects of botulinum toxin type A, anecdotal experience with MANY patients is that other newly started antibiotics and other non-antibiotic medications may have an impact as well. We know that local anesthetics will impact toxin effect as will cold compresses applied immediately before or after treatment. Extreme outdoor temperatures (freezing cold or burning hot) may play a role if one goes outside immediately after injection, since the uptake of the toxin into the nerves is temperature dependent. Some data also supports forceful blinking within the first 30 minutes after injection, as this possibly increases toxin uptake into the nerves before it is degraded extracellularly.

    So, to answer your question more succinctly, your doctor was right. But instead of saying "it's to be expected," a better answer might be, "It's not surprising. It sometimes happens."

    Charles N. S. Soparkar, MD, PhD, Plastic Eye Surgery Associates, Houston, Texas

  3. QUESTION: Can one have both Blepharospasm and myasthenia gravis? I have been treated for the former but additional neurological symptoms are suggesting the lateral...however, I definitely have blurred/and doubled vision and drooping eyes related to eye fatigue/usage and other neurological issues (neurology appt pending) but had significant spasms at times in past-seen by ophthalmologists and treated with Botox for blepharospasm, and eyes are very light/wind/ computer screen sensitive and will drop to closing. I am just wondering if one can have both-or very unlikely. One doesn't want to treat myasthenia with Botox....but if one has both??

    ANSWER: Both blepharospasm and myasthenia gravis can cause closure of the eyelids, but through different mechanisms. Blepharospasm causes active involuntary contractions of the eyelids whereas myasthenia gravis causes weakness and droopiness of the eyelids (ptosis). Rarely, those two conditions can co-exist as we have reported in our 1987 paper (see below). This rare occurrence can lead to diagnostic confusion and may delay appropriate therapy. In contrast to blepharospasm, myasthenia gravis is an autoimmune disorder and to make things more complicated blepharospasm may be associated with autoimmune disorders as we have reported the same year (see below) and a variety of autoimmune disorders may be manifested by blepharospasm, as we have reported more recently (see below). It is critical that the two disorders, blepharospasm and autoimmune disorders, are evaluated and treated separately as both have unique characteristics and specific treatments. Although botulinum toxin is the treatment of choice for patients with blepharospasm, this treatment is relatively contraindicated in patients with myasthenia gravis. When blepharospasm is associated with myasthenia gravis the dosage of botulinum toxin must be substantially reduced in order to avoid complications, such as ptosis, or other treatments may need to be considered, such as clonazepam, trihexyphenidyl, apraclonidine, or eyelid crutches.
    1. Kurlan R, Jankovic J, Rubin A, Patten BM, Griggs R, Shoulson I. Coexistent Meige's syndrome and myasthenia gravis. Arch Neurol 1987;44:1057-1060.
    2. Jankovic J, Patten BM. Blepharospasm and autoimmune diseases. Mov Disord.1987;2(3):159-63.
    3. Baizabal-Carvallo JF, Bonnet C, Jankovic J. Movement disorders in systemic lupus erythematosus and the antiphospholipid syndrome. J Neural Transm 2013 Nov;120(11):1579-89.
    4. Baizabal-Carvallo JF, Jankovic J. Movement disorders in autoimmune diseases. Mov Disord. 2012 Jul;27(8):935-46.

    Joseph Jankovic, MD
    Professor of Neurology
    Distinguished Chair in Movement Disorders
    Director, Parkinson's Disease Center and Movement Disorders Clinic
    Baylor College of Medicine Department of Neurology

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