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• Re:Letter to Practical Neurology: comment on MG: ABN's management guidelines (Sussman et al. Practical Neurology 2015 )
  Dr. Jon Sussman
  Published on: 14 April 2016
• Letter to Practical Neurology: comment on MG: ABN's management guidelines (Sussman et al. Practical Neurology 2015 )
  Sui Hsien Wong
  Published on: 14 April 2016

• Published on: 14 April 2016

  Re:Letter to Practical Neurology: comment on MG: ABN's management guidelines (Sussman et al. Practical Neurology 2015 )

  • Dr. Jon Sussman

  I am grateful to Drs Wong and Plant for their invaluable comments, based on their enormous experience of patients presenting with suspected ocular myasthenia. The Guidelines are intended to offer non-specialists an approach to management that will work, safely, in the majority of patients. Within them, we stressed repeatedly the need to seek specialist opinion when in any doubt, and their letter emphasises the benefit of...

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  I am grateful to Drs Wong and Plant for their invaluable comments, based on their enormous experience of patients presenting with suspected ocular myasthenia. The Guidelines are intended to offer non-specialists an approach to management that will work, safely, in the majority of patients. Within them, we stressed repeatedly the need to seek specialist opinion when in any doubt, and their letter emphasises the benefit of seeking such help. Their views, by and large, don't contradict our basic approach, except with respect to the timing of the introduction of azathioprine. With respect to the specific issues that they raise: Thyroid function should be assessed in all patients. We agree that if the diagnosis of myasthenia is not secure, then it is appropriate to look for evidence of thyroid ophthalmopathy, which would include antibody testing and imaging studies. Some patients seronegative for acetylcholine receptor antibodies may be seropositive using other techniques, as they describe. However, if the clinical diagnosis is of purely ocular myasthenia then the result will not affect the immediate management as proposed in the Guidelines We are not enthusiasts for the Tensilon? test and don't mourn its non- availability! We have seen numerous patients incorrectly diagnosed as having myasthenia on the basis of a test performed by somebody without appropriate experience. We agree that other forms of anti-cholinesterase testing may occasionally be helpful, and are grateful for their detailed proposals. However, we have doubts about these being undertaken by non- specialists. We agree that physical treatments (e.g. eye patches and prisms) have their place both acutely and in some patients with persisting diplopia despite optimal drug treatment, but of course they become unnecessary inn the majority of patients who respond extremely well to drug therapy. We also agree that the evidence base for using alternate-days steroids, in terms of reducing long-term side-effects, is minimal. At very high doses, as may be needed in generalised myasthenia, steroid-induced myopathy may be difficult to differentiate from myasthenic weakness. We have never seen steroid-induced myopathy on an alternate day regime. In patients with marked symptomatic fluctuation between steroid and non-steroid days, and those with diabetes, we would often have a preference for a daily steroid regime. In the past, thymectomy has not been used widely for non-thymomatous ocular myasthenia, perhaps largely because sternotomy represents major surgery, with unacceptable cosmetic consequences, particularly for the dominant young-female population. However, if the less invasive technique of video-assisted thymectomy reduced the risk of generalisation, and for some negated the need for immunosuppressant drug therapy, then it would potentially be very valuable. Unfortunately, the International Thymectomy Trial will not address these issues, and a further trial, at least in the foreseeable future, seems unlikely. We think it is an option that is appropriate to discuss with the patient. Although azathioprine is often considered a relatively safe drug, and its steroid-sparing effect potentially valuable to the patient, our experience suggests that many patients have their myasthenia controlled on a modest dose of prednisolone and that azathioprine is unnecessary. We are concerned by long-term side-effects, particularly cutaneous malignancies, increased risk of infection (including shingles) and the occasional case of late-myelosuppression. The points raised by Drs Wong and Plant emphasise the lack of data concerning the treatment of MG and should encourage us to design studies to help answer the really important questions in MG, such as whether it is possible to determine initial optimal treatment requirements from clinical or immunological features.

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• Published on: 14 April 2016

  Letter to Practical Neurology: comment on MG: ABN's management guidelines (Sussman et al. Practical Neurology 2015 )

  • Sui Hsien Wong
  • Other Contributors:
    • Dr. G T Plant

  Dear Sirs, Myasthenia gravis: Association of British Neurologists' management guidelines We read with interest the ABN's management guidelines on Myasthenia Gravis[1] and commend the authors for putting toget her guidelines for this condition where the evidence base is limited. The comments here reflect our experience of managing a large number of patients with ocular myasthenia gravis (OMG). Moor fields Eye Hospital is th...

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  Dear Sirs, Myasthenia gravis: Association of British Neurologists' management guidelines We read with interest the ABN's management guidelines on Myasthenia Gravis[1] and commend the authors for putting toget her guidelines for this condition where the evidence base is limited. The comments here reflect our experience of managing a large number of patients with ocular myasthenia gravis (OMG). Moor fields Eye Hospital is thelargest and only 24-hour eye casualty in London and as such patients with OMG often present early to us.

  Diagnostic tests In addition to thyroid function, we also routinely test for thyroid antibodies, as thyroid eye disease (TED) may coexist with OMG. Thyroid function may benormal in such circumstances, and the presence of TED may affect the response to treatment. There are two reasons for this. Firstly the presence of thyroidantibodies is circumstantial evidence for an autoimmune phenotype. Secondly patients with thyroid antibodies may be euthyroid and still have dysthyroid eyedisease. The coexistence of TED and OMG is important to recognize as the two conditions are managed differently. Approximately 50% of OMG patients are seronegative to anti-AChR antibodies[2]. In addition to anti-MuSK antibodies (MuSK+ MG can present as OMG only[3]), newer tests using the cell-based assays can be helpful, and willlikely become more widely available, which include:clustered anti-AChRantibodies (positive in up to 50% of seronegative OMG[2]) and LRP4 antibodies(which is part of the MuSK complex) [3]. At the time of writing, edrophonium (Tensilon) test is no longer available. Alternative methods of performing an anti-cholinest erase test may includeneostigmine or pyridostigmine: Neostigmine adminis tered intramuscularly has a long duration of action that allows pre- and post -test comparison and careful documentation of ocular motility; a trial of oral pyridostigmine can also be useful as a diagnostic test. We tend to perform the pyrid ostigmine challenge in the following manner: For in-patients, we start with a single oral dose of 30mg pyridostigmine and examine the patient one hour later. A sequential increase by30mg is administered every 4 hours, i.e. up to a single dose of 120mg. With the four hour interval between each dose, the test may therefore take two days to complete. This method also allows observation of any dose-related adverse effects e.g. diarrhoea. For the out-patient setting, pyridostigmine challenge is performed over 8-12 weeks, with 2-3 cycles of two-weeks on, two-weeks off pyridostgmine. The patient keeps a careful diary comparing their symptoms during the two weeks on pyridostigmine, and the two weeks off pyridostigmine. We prescribe a dose of 30mg three times daily, which is increased over days to 120mg three times daily, and continue the pyridosti gmine challenge on 120mg three times daily if tolerated by the patient.

  Treatment of ocular myasthenia gravis In addition to symptomatic treatment with pyridostigmine, other symptomatic treatments potentially useful include monocular occlusion (use of an eye patch, or frosting of one lens on the spectacles) and prisms (usually more useful if the deficits become more fixed after long term OMG). We prefer a daily dose of corticosteroid compared to alternate day dosing, as is the preference or recommendations by other MG experts[4]. The evidence for a better risk profile for alternate day dosing is limited. The literature on this seems to come predominantly from renal transplant in children, with regards to growth, although the evidence for this is mixed[5,6 ]. In our experience, dailydosing can help with medication compliance At present, we do not routinely refer our patients with OMG for thymectomy, unless imaging suggests that a thymoma may be present. This is an area that has unresolved questions. Some recent retrospective studies suggest that early thymectomy in non-thymomatous OMG could potentially improve outcome, but this question remains to be addressed in a randomised controlled trial [3]. The MGTX trial studied the effect of thymectomy in MG, is due to be reported in January 2016, but excluded patients with OMG[7].

  It is also our practice to start azathioprine early (i.e. approximately 1-2 months) in patients who have response to corticosteroids. In our experience, patients often relapse below 15-20mg prednisolone, and there fore find the relatively early introduction of azathioprine may help weaning off prednisolone earlier. One argument against starting azathioprine early is that some patients will be able to come off prednisolone and remain in remission. In our experience this is an unusual eventuality. After our patients have been in remission, we then start to consider weaning off the corticosteroid-sparing agent such as azathioprine if they have been on this alone for approximately two years. The ABN guidelines by Sussman et al are a useful resource for practicing neurologists, and we hope that our experience in the management of large numbers of patients with OMG described above could also be of value.

  References 1 Sussman J, Farrugia ME, Maddison P, et al.Myasthenia gravis: Association of British Neurologists' management guidelines. Practical Neurology2015;15 :199-206. doi:10.1136/practneurol-2015-001126 2 Jacob S, Viegas S, Leite MI, et al.Presence and pathogenic relevance of antibodies to clustered acetylcholine receptor in o cular and generalized myasthenia gravis. Arch Neurol 2012;69:994-1001.doi:10.1001/archneurol.2012.437 3 Wong SH, Huda S, Vincent A, et al. Ocular myasthenia gravis: controversies and updates.Curr Neurol Neurosci Rep 2014;14:421. doi:10.1007/s11910-013-0421-9 4 Kumar V, Kaminski HJ. Treatment of myasthenia gravis.Curr Neurol Neurosci Rep 2011;11:89-96. doi:10.1007/s11910-010-0151-1 5 Feldhoff C, Goldman AI, Najarian JS, et al. A comparison of alternate day and daily ster oid therapy in children following renal transplantation. Int J Pediatr Nephrol 1984;5:11-4. 6 Diethelm AG, Sterling WA, Hartley MW, et al. Alternate-day prednisone therapy in recipients of renalallografts. Risk and benefits. Arch Surg 1976;111:867-70. 7 Aban IB, Wolfe GI, Cutter GR, et al.The MGTX experience: challenges in planning and executing an international, multicenter clinical trial. J Neuroimmunol 2008;201-202:80- 4. doi:10.1016/j.jneuroim.2008.05.031

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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