Question Regarding Ocular Myasthenia Gravis

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3rdyrmdstdnt

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Hello,

I am new to this board and have a question regarding Ocular Myasthenia Gravis. I have noticed that patients with Ocular Myasthenia Gravis who are on Prednisone therapy and smoke, or drink more than 4 cups of coffee/soda per day require are larger dosage of steroid therapy(Insensitivity/Resistance?). Is there any relevance to this. I have searched PubMed and could not find anything. I also have tried to find the Link between Tobacco/Nicotine or Caffeine to Prednisone. For metabolism of caffeine/glucocorticoids CYP3A4 is implicated. I am having a harder time finding a link between tobacco/Nicotine and Prednisone. Smoking/Nicotine induce CYP1A2 and CYP2A1 respectively. I have also found that smokers have an Increased TNF-alpha/IL-4 which is thought to increase the number of glucocorticoid (beta) receptors and cause glucocorticoid resistance. I am a 3rd year med student who is interested in Ophthalmology and thought this might be a good research project and would appreciate any advice on this topic.

Thanks
Richard

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Here is a paper showing that steroid therapy helps in MG.

http://www.ncbi.nlm.nih.gov/sites/e...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005224. Links
Immunosuppressive agents for myasthenia gravis.Hart I, Sathasivam S, Sharshar T.
BACKGROUND: The benefits of different immunosuppressants for myasthenia gravis (MG) are unclear. OBJECTIVES: Assessment of immunosuppressant drug efficacy in MG. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register, MEDLINE (from January 1966 to July 2007), EMBASE (from January 1980 to July 2007), review and trial bibliographies and contacted trial authors. SELECTION CRITERIA: Types of studies: Randomised and quasi-randomised controlled trials.Types of participants: Any age, any type or severity of MG regardless of concomitant treatment.Types of interventions: Any immunosuppressive agent.Types of outcome measures:primary:(1) Improvement or not at six monthsSecondary:(1) Improvement or not at one year(2) Need for other treatment, for example corticosteroid dose, at six months(3) Number of exacerbations during the first year(4) Acetylcholine receptor antibody titre after at least six months(5) Occurrence of one or more adverse events at any time after the introduction of treatment. DATA COLLECTION AND ANALYSIS: One author extracted and two checked the data. MAIN RESULTS: Seven trials are included but few reported the outcomes selected for this review. A meta-analysis of ciclosporin versus placebo from two trials (59 participants) - one as monotherapy (20 participants) and the other with corticosteroids (39 participants) - showed that it resulted in improvement of participants in the ciclosporin group compared with those in the placebo group, with a relative rate of improvement of 2.44 (95% confidence interval (CI) 1.13 to 5.27). In addition the weighted mean difference in QMG score between the ciclosporin and placebo groups was -0.34 (95% CI -0.52 to -0.17). Azathioprine (plus prednisolone for first month) had no significant benefit over prednisolone alone (41 participants). The effects of azathioprine plus prednisolone versus prednisolone plus placebo were similar (34 participants). Cyclophosphamide was reported to be statistically more efficacious than placebo at 12 months in corticosteroid-dependent participants (23 participants), but no raw data were available. Trials of mycophenolate mofetil and tacrolimus did not provide relevant endpoint data for this review. All trials had low numbers of participants. Adverse event reporting was variable. Trial protocol heterogeneity prevented comparison of the different immunosuppressants. AUTHORS' CONCLUSIONS: In generalised MG, limited evidence from small RCTs suggests that ciclosporin, as monotherapy or with corticosteroids, or cyclophosphamide with corticosteroids, significantly improve MG.Limited evidence from RCTs shows no significant benefit from azathioprine (as monotherapy or with steroids), mycophenolate mofetil (as monotherapy or with either corticosteroids or ciclosporin) or tacrolimus (with corticosteroids or plasma exchange). Bigger, better-designed, longer trials are needed.

PMID: 17943844 [PubMed - in process]
 
I think the OP's question is whether smoking or excessive caffeine intake increases the steroid dose needed to control symptoms.
To the OP: how do you define a "higher" dose? Patients with OMG as a rule are a heterogeneous group and while it may be possible in some patients to control symptoms on a fairly low dose (e.g. 20 mg qd), there are others who need a robust dose of 60 mg qd. Most patients I have seen were nonsmokers; and I don't ask them about their caffeine intake so I can't comment. Speaking of which, how did you make this observation? How many patients are we talking about?
 
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I dont know if its allowed to post personal questions in here, but any replies would be greatly appreciated.

My 70 yr old grandmother complains of diplopia and ptosis that worsens at night. Neurological examination was unremarkable. Brain CT and MRI haven't revealed any serious lesion except some senile changes. The Neurologist prescribed Mestonin (Pyridostigmine) with no improvement! Then he wanted us to do some tests (Anti-Ach receptor and EMG) .

Besides an ophthalmologist has found different ocular muscles affected everytime she sees him, made her 3 different glasses and she still sees double though!!


1. How come didn't she get any better on Mestonin if she really has Myasthenia? Isn't it the only treatment? with cyslosporine?

2. What should we be doing now? Do the tests? Or is it going to be worthless?


Thanks a lot.
 
I dont know if its allowed to post personal questions in here, but any replies would be greatly appreciated.

My 70 yr old grandmother complains of diplopia and ptosis that worsens at night. Neurological examination was unremarkable. Brain CT and MRI haven't revealed any serious lesion except some senile changes. The Neurologist prescribed Mestonin (Pyridostigmine) with no improvement! Then he wanted us to do some tests (Anti-Ach receptor and EMG) .

Besides an ophthalmologist has found different ocular muscles affected everytime she sees him, made her 3 different glasses and she still sees double though!!


1. How come didn't she get any better on Mestonin if she really has Myasthenia? Isn't it the only treatment? with cyslosporine?

2. What should we be doing now? Do the tests? Or is it going to be worthless?


Thanks a lot.

Some myesthenics require higher doses and longer trials to see an effect.
Some respond to Prednisone with relief of symptoms. Long-term dosing is problematic, however. Did she have a Tensilon test prior to her Mestinon trial?

Some patients are successfully treated with plasmapheresis, which is involved and expensive.
 
Some myesthenics require higher doses and longer trials to see an effect.
Some respond to Prednisone with relief of symptoms. Long-term dosing is problematic, however. Did she have a Tensilon test prior to her Mestinon trial?

Some patients are successfully treated with plasmapheresis, which is involved and expensive.

She didnt have the Tensilon test, nor any other tests for Myasthenia. But I was just thinking that we dont have to go for anything further because of failure of Mestinon trial treatment, but I guess that is not true?

And does Myasthenia explain the alteration of ocular muscles affection?
 
She didnt have the Tensilon test, nor any other tests for Myasthenia. But I was just thinking that we dont have to go for anything further because of failure of Mestinon trial treatment, but I guess that is not true?

And does Myasthenia explain the alteration of ocular muscles affection?

Tensilon test is only useful if it's positive. The false negative rate is so high that I don't even bother doing it any more (especially in elderly patients with cardiac comorbidities).
While Mestinon works well for ptosis, it doesn't work as well for diplopia. I would have tried her on prednisone. But not before I investigated her further with Ach receptor antibodies and single fiber EMG.
And yes, in general when patients have a different pattern of extraocular muscle weakness each time you see them, that's highly suspicious for myasthenia. Has she seen a neuro-ophthalmologist? If not, she should.
 
Tensilon test is only useful if it's positive. The false negative rate is so high that I don't even bother doing it any more (especially in elderly patients with cardiac comorbidities).
While Mestinon works well for ptosis, it doesn't work as well for diplopia. I would have tried her on prednisone. But not before I investigated her further with Ach receptor antibodies and single fiber EMG.
And yes, in general when patients have a different pattern of extraocular muscle weakness each time you see them, that's highly suspicious for myasthenia. Has she seen a neuro-ophthalmologist? If not, she should.


Unfortunately there are few sensitive tests for ocular myaesthenia. (At least one small study reported normals responding to Tensilon--go figure.)

I haven't done Tensilon testing in awhile, mostly because of the risks and the fact that I needed a rescue kit available in case of a testing -related cardiac event (never had one, thankfully). The informed consent process became necessarily burdensome and, while I was using Enlon-Plus mixture in my tests, there was understandably a reluctance to consent. If I had cardiac disease I doubt I would consent either. Unfortunately the alternatives aren't much better: anti ACH AB has a high false negative rate in ocular myaesthenia and unless you have an electrophysiology lab, single-fiber EMG is pretty much out. So that leaves Mestinon and Prednisone trials.

I have a few patients who stopped Mestinon due to intolerable side effects, despite it's successful resolution of the myaesthenia signs.

On the whole, it can be a difficult disease to diagnose and treat.
 
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