|Year : 2020 | Volume
| Issue : 4 | Page : 249-252
Ocular myasthenia gravis: A case series
Sandra C Ganesh, Amrutha Sindhu, Jogitha
Department of Pediatric Ophthalmology and Strabismus, Aravind Eye Hospital, Coimbatore, Tamil Nadu, India
|Date of Submission||04-Jul-2020|
|Date of Decision||04-Aug-2020|
|Date of Acceptance||18-Aug-2020|
|Date of Web Publication||16-Dec-2020|
Dr. Sandra C Ganesh
C-2, Staff Quarters, Aravind Eye Hospital, Avinashi Road, Coimbatore - 641 014, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Aim: To report the clinical profile of patients with myasthenia gravis (MG) at a tertiary eye care center in Tamil Nadu. Material and Methods: This is a retrospective case series of patients in a single center between February 2019 and March 2020. Result: We present a series of five cases of ocular myasthenia in the pediatric age group (0–16 years), comprising three males and two females. The patients had varied presentations on the initial examination. Conclusion: It is important to differentiate MG from other diagnostic mimics such as neurological causes such as cranial nerve palsy, myopathies, ocular pathologies, and neuromuscular junction pathologies such as botulism and brainstem tumors. Diagnosis and treatment of myasthenia is done as a team effort of ophthalmologist and neurologist. This study is to reinforce a vigilant lookout for this great masquerader.
Keywords: Autoimmune disease, neuromuscular junction disorder, ocular myasthenia gravis, pediatric ophthalmology
|How to cite this article:|
Ganesh SC, Sindhu A, Jogitha. Ocular myasthenia gravis: A case series. TNOA J Ophthalmic Sci Res 2020;58:249-52
| Introduction|| |
Myasthenia gravis (MG) is an autoimmune disease, in which antibodies target the postsynaptic acetylcholine receptors or functionally related molecules in the postsynaptic membrane of skeletal muscles, resulting in a defect in neuromuscular transmission. MG mimics the ocular manifestations of various other ocular diseases such as myopathies, cranial nerve palsies, orbital pathologies, and central nervous system disorders. The clinical history and examination provide the most important clues for the diagnosis of myasthenia. The purpose of this article is to describe the various ocular manifestations and clinical outcomes in children with isolated ocular MG.
| Materials and Methods|| |
This is a hospital-based retrospective review of case records of children seen in our outpatient department between February 2019 and March 2020. All patients with a clinical diagnosis of ocular MG were included in the analysis. A detailed ocular and systemic history was taken. A complete ocular examination including best-corrected visual acuity and anterior segment examination were done with slit-lamp biomicroscopy, and posterior segment examination was done with + 90D and indirect ophthalmoscopy. Investigations done included magnetic resonance imaging (MRI), repetitive nerve stimulation (RNS), and acetylcholine antibody report. Neurologist opinion was taken for the confirmation of diagnosis and further management. Patients were started on tablet pyridostigmine/syrup dosed by weight. In refractory cases, other immunosuppressant drugs such as prednisolone and azathioprine were added as required.
| Results|| |
[Table 1] is a summary of the clinical presentation and treatment of the five children with ocular myasthenia seen in our hospital between February 2019 and March 2020. The mean age of presentation was 6.4 years (range: 0–16 years). Three patients were male and two patients were female. All patients had unilateral ocular findings on clinical presentation. Two of the five patients were initially diagnosed to have third cranial nerve palsy. MRI scan of two patients was normal and of one patient showed signs of chronic progressive external ophthalmoplegia. Fatigability test and ice pack test were positive in all patients. All children were seen by a neurologist and treated based on the concurrence of treatment plan.
|Table 1: Clinical presentation and treatment protocol of children with ocular motility restriction or ptosis|
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|Figure 1: (a) Photograph of 1-year-old baby who presented with variable ptosis for 10 days. (b) Improvement of ptosis is seen after sleep test|
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|Figure 2: Photograph of the above child taken during 3-month follow-up with complete remission of symptoms spontaneously without any treatment|
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| Case Series|| |
The clinical presentation and treatment protocols of five children who were diagnosed to have ocular myasthenia and their treatment protocols are tabulated as shown in [Table 1].
| Discussion|| |
MG is an autoimmune disease, in which antibodies target the postsynaptic acetylcholine receptors or to functionally related molecules in the postsynaptic membrane of skeletal muscles, leading to defective neuromuscular transmission. MG in children can be classified based on the disease pathogenesis and age at onset as transient MG, neonatal MG, congenital MG, and juvenile MG.
In transient and neonatal MG, there is a transfer of antibodies from mother to child. Serum acetylcholine receptor antibody titer of affected neonate follows the same pattern as their mother. Onset occurs within a few hours (in two-third) to the first 3 days after birth. Clinical symptoms last for 2–3 weeks (1 week to 2 months). A good response is seen on treatment with oral pyridostigmine bromide or parenteral anticholinesterase.
Congenital MG presents in the 1st year of life (1–3 years). It constitutes a heterogeneous group of genetic disorders affecting neuromuscular junction (presynaptic/synaptic/postsynaptic level). Most cases are seronegative. There is a history of the decreased movement of fetus in utero. It is not immune-mediated and is caused by structural/functional alteration at the myoneural junction.
Juvenile MG presents before 19 years of age and is an autoimmune disease similar to adult myasthenia. It is more frequently familial, showing slower progression, characterized by more severe ophthalmoplegia, and having a higher rate of spontaneous remissions. It is exacerbated by illness, pregnancy, and medication. Postsynaptic neuromuscular junction is affected similar to adult variant. Drugs such as ampicillin and ciprofloxacin are associated with cause or precipitation of juvenile MG.
Ocular motor signs of MG include levator fatigability, Cogan Lid Twitch, quiver-like movements, slow saccades, intersaccadic fatigue, orbicularis weakness, lid retraction, increased contralateral ptosis with manual lid elevation, positive sleep test, and positive Winterkorn test.
Investigations done for diagnosis are positive ice pack test, sleep test, rest test, Tensilon test, and neostigmine methylsulfate test. In RNS test, a decremental response is found. Single-fiber electromyography test is more specific but difficult to perform. In clinical application, ice pack test is very useful with a sensitivity of around 70% and a specificity of over 90%.
Pyridostigmine is the first-line treatment for ocular MG. The standard dose of pyridostigmine is 1.0 mg/kg every 4–6 h with a maximum dose of 7 mg/kg/day in divided dosing. Prednisolone is the second-line treatment for ocular MG and acts as a long-term immunosuppressant. It is started with a high dose, 1–2 mg/kg/day, with a maximum of 60–80 mg, and the dose is then weaned to the lowest effective dose given on alternating days. Immunomodulators such as azathioprine, cyclosporine, mycophenolate mofetil, and tacrolimus can be used. Azathioprine acts on immunomodulation by interfering with T-cell function when metabolized to 6-mercaptopurine. Dosing is initiated at 0.5 mg/day and increased in increments of 0.5 mg weekly to a final dose of 1–2.5 mg/kg/day with the maximum benefit being seen between 3 and 12 months after initiation. Newer treatment includes intravenous immunoglobulin, plasmapheresis, rituximab, and eculizumab for refractory cases.,
Plasmapheresis is effective for improving strength within days in myasthenic crisis. The mechanism of plasmapheresis is to remove antibodies from circulation. Hence, for those patients who are known as acetylcholine receptor antibody positive, it is an effective form of rapid treatment. The benefit of therapy lasts for 4–10 weeks and may be beneficial as a continued therapy for those who are resistant to other immunomodulating treatments.
Surgical options include strabismus surgery in patients who have residual strabismus and amblyopia with ocular alignment and symptoms stable for at least 6 months. Ptosis surgery is done in patient's refractory to treatment and ptosis stable for at least 2 years. Prism glasses can be effective for patients with diplopia. Ptosis crutch/eyelid crutch is an inexpensive and noninvasive option for patients with persistent refractory ptosis. Thymectomy is done in adults, especially in those with severe disease.
Other clinical disorders can mimic with similar clinical signs and can be mistakenly labeled as MG. The probability of successful treatment for the patient depends on accurate diagnosis.
First-line treatment for ocular myasthenia gravis (OMG) is commonly pyridostigmine alone or in combination with oral steroids. For refractory patients, treatment is generally steroid-sparing immunosuppressant.
Ocular pseudomyasthenia is MG-like clinical symptoms due to cranial nerve palsies associated with intracranial lesions, usually tumors or aneurysms are described as. Some of these patients have had positive Tensilon tests, which leads to false diagnostic security. Brain MRI should be hence considered when there is doubt about the diagnosis of ocular myasthenia. Consideration of pseudomyasthenia is important in diagnosis of isolated ocular myasthenia.
Differential diagnosis of MG includes many conditions such as myopathies, dystrophies, chronic progressive external ophthalmoparesis, neuromuscular junction disorders such as botulism, cranial nerve palsies (III, IV, and VI), ptosis – congenital or acquired, orbital pseudotumor, orbital trauma, and central nervous system disorders, so accurate diagnosis is essential for further management.
| Conclusion|| |
In our study, children who were later diagnosed as MG were initially misdiagnosed as third nerve palsy or ptosis. So in children who present with acquired ptosis or ocluar movement restriction differential diagnosis of OMG should always be kept in mind. Pediatric OMG is difficult to diagnose and manage. Once correctly diagnosed, the outcomes are generally good with a higher rate of disease resolution. Stabilization of disease with medical management is more common in pediatric patients.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]