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Table of Contents
Year : 2019  |  Volume : 1  |  Issue : 1  |  Page : 16

Pediatric ocular myasthenia gravis: Case report and literature review

Department of Ophthalmology, Pediatric Ophthalmoilogy and Strabismus Sector, Fundación Universitária de Ciências de la Salud, Hospital de San José, Bogotá, Colombia

Date of Submission08-Jul-2019
Date of Acceptance22-Aug-2019
Date of Web Publication03-Dec-2019

Correspondence Address:
Dr. Adriana Solano
Calle 10 # 18.75, Bogota
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/PAJO.PAJO_11_19

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Objective: The objective was to describe a case of ocular myasthenia gravis (MG) in a pediatric patient.
Design: This is a descriptive, retrospective study and case report.
Methodology: For the purpose of the case report, we searched and analyzed the literature referring to the diagnosis and treatment of ocular MG (OMG) in children.
Description: A previously healthy 5-year-old girl presented to the emergency room because of sudden-onset ptosis of the right upper lid without other symptoms. Her examination demonstrated fluctuating ptosis and limitation to downgaze in the right eye. Because of the fluctuation of the ptosis, OMG was suggested, and the patient was tested with ice-pack test and neostigmine test with positive results. Treatment with pyridostigmine was initiated with a good response.
Discussion: OMG has a very low incidence in pediatric patients. It is a disorder characterized by impairing neurotransmission at the neuromuscular junction that generates extraocular muscle weakness. It is important that ophthalmologists have knowledge about this disease because it is a differential diagnosis when there is a patient who has ptosis, strabismus, or limitation of movements. There are no standard diagnostic criteria for this disease; the diagnosis is based on clinical presentation and pharmacologic, serologic, and electrophysiologic tests. The treatment is based on steroids and anticholinesterase drugs. Some patients will require plasmapheresis or immunomodulators.

Keywords: Childhood ocular myasthenia gravis, ocular myasthenia gravis, pediatric ocular myasthenia gravis

How to cite this article:
Solano A, Jimeno V, Montoya L, Espinosa N. Pediatric ocular myasthenia gravis: Case report and literature review. Pan Am J Ophthalmol 2019;1:16

How to cite this URL:
Solano A, Jimeno V, Montoya L, Espinosa N. Pediatric ocular myasthenia gravis: Case report and literature review. Pan Am J Ophthalmol [serial online] 2019 [cited 2023 Sep 29];1:16. Available from: https://www.thepajo.org/text.asp?2019/1/1/16/272218

  Introduction Top

Myasthenia gravis (MG) is a disease that affects the availability of acetylcholine (Ach) receptors in the neuromuscular junction. Ocular MG (OMG) is a disease subtype characterized by weakness of extraocular muscles, eyelid elevator, and orbicular muscle. It is characterized by having variable patterns over the involved muscles, and its initial sign in most adults and children is ptosis. MG is a rare disease in pediatric patients with an incidence of 3–9.1 cases per million per year, and of these, only 10%–15% have only ocular involvement.[1]

The case of a 5-year-old patient with ptosis and limitation for depression of the right has been presented and discussed.

  Case Report Top

A 5-year-old female patient, of mixed race, was taken by her parents to the Hospital of San José, Bogotá, Colombia, with a clinical history of a week of evolution of the right upper eyelid ptosis of sudden onset without other associated symptoms.

On physical examination, the patient was found with a compensating position of the head with chin elevation, visual acuity 20/20, normal pupillary response, ptosis of the right upper eyelid with 5-mm palpebral opening, and 8-mm elevator function [Figure 1]. In the cover test, it was found orthophoric; in primary position, the red filter test was negative for diplopia, and in ocular motility, a limitation was found for depression in the abduction of −2 in the right eye [Figure 2]. The rest of the eye movements were normal. Biomicroscopy was within normal limits, with normal intraocular pressure and dilated fundus without abnormalities. The patient left 15 min of the office, and when re-evaluating it, an increase in the eyelid ptosis was found [Figure 3].
Figure 1: Initial assessment of the patient by the ophthalmologist

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Figure 2: Limitation for depression in abduction

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Figure 3: Patient evaluation 15 min later

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Due to the clinical picture and the variation of palpebral ptosis, a diagnosis of MG ocular was made. In conjunction with a neuropediatrician, the ice-pack test was performed for 2 min in the right eye, resulting in a slight improvement of the ocular opening. Subsequently, a pharmacological analysis with 0.5-mg neostigmine was conducted in the pediatric intensive care unit due to the risk of adverse drug effects. With this dose, an inadequate ocular response was evidenced, so the second dose of 0.5 mg neostigmine was administered, which resulted in a marked improvement of the right palpebral ptosis and improvement in eye movements of the same eye [Figure 4]. After this pharmacological test, the patient presented an episode of emesis of food content, which is a common side effect of acetylcholinesterase inhibitors.
Figure 4: Post assessment of neostigmine test

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Anti-ACh antibodies were requested, which were negative (<15% inhibition). Due to the positivity of the pharmacological test, the clinical diagnosis of OMG was confirmed, and management was started with pyridostigmine 0.5 mg/kg/dose every 6 h, with which the patient presented a significant improvement of the symptoms [Figure 5].
Figure 5: Assessment after 3 months of treatment

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  Discussion Top

MG is a neuromuscular disorder that affects striated muscles, especially extraocular muscles, secondary to an alteration in the neuromuscular junction due to the decrease in the number of available ACh receptors.[2]

It is characterized by weakness and fatigue of the voluntary muscles as a result of an impaired transmission in the neuromuscular junction. The neuromuscular junction is the site of chemical communication between nerve fibers and muscle, where the motor impulse is transmitted from the motor fiber to the muscle cell. The action potentially begins in the neuromuscular transmission. It results in the release of ACh molecules in the synaptic cleft. These molecules spread through the synaptic cleft by joining the receptors of the striated muscle, depolarizing the postsynaptic membrane and generating the muscle contraction.[3]

In more than 99% of patients with systemic myasthenia and 40%–70% of patients with OMG, antibodies against ACh receptors have been found. These antibodies decrease the availability of ACh receptors by blocking them directly or degrading them, which leads to reduced transmission in the neuromuscular junction and secondary muscle weakness.[3]

Extraocular muscles are more commonly affected because they have a faster and higher synaptic frequency than limb muscles; they also have a lower number of ACh receptors, which makes them more susceptible to fatigue. On the other hand, they are affected more frequently because the tonic muscle fibers are necessary to maintain a position of the gaze, and these fibers have a smaller amount of ACh receptors, which makes them more susceptible to the loss or damage of receptors.[3]]

MG in childhood can be classified as congenital MG (CMG), congenital transient MG (CTMG), and autoimmune MG (AMG). CTMG is given by the passage of anti-ACh antibodies from the mother through the placenta. As reported by Mullaney et al., 15% of these patients have systemic and ocular symptoms which resolve at approximately 2 months of life. Babies have generalized hypotonia, weak crying, respiratory distress, poor suction, and extraocular muscle weakness.[4]

Symptoms are usually self-limited, but respiratory support may be necessary. It responds well to treatment with neostigmine and plasma exchange. This pathology does not require long-term treatment once autoantibodies are no longer present.[5]

CMG is caused by pre- or postsynaptic structural or functional abnormalities in the neuromuscular junction, which will lead to abnormal ACh release or ACh receptor dysfunction. Symptoms usually begin around 2 years. Diagnosis is made with early symptoms of MG, a relative affected by the disease, and the absence of fluctuations in the course of the disease. CMG is not an autoimmune form of the disease; it requires supportive therapy but not immunosuppression. Treatment with anticholinesterase agents may be useful in some cases but may worsen symptoms in others.[3]

Finally, juvenile AMG is the most frequent (75% of cases). It is due to a blockade of ACh receptors. It has a later onset and affects children between 0 and 19 years old, but may coincide with CMG in the 1st or 2nd year of life and is more frequent between 2 and 5 years. Before the onset of symptoms, children have a healthy psychomotor development, and sometimes, it is preceded by an infection. This type of myasthenia is subdivided into OMG and systemic or generalized MG.[6]

OMG in children is a rare disease with an approximate incidence of 3–9.1 cases per million per year and occurs mostly in Asian children. In 90% of these cases, there are ocular alterations such as ptosis and ophthalmoplegia associated with systemic symptoms.[1],[7]

This pathology has a female-to-male ratio of 1.3:1; usually women and non-Caucasian patients are diagnosed earlier. So far, there is no evidence on whether these differences affect the prognosis, conversion to MG, or the response to treatment.[8],[9]

It is essential for ophthalmologists to know this pathology as 90% of children with MG will have ophthalmological symptoms, and 50% go first to ophthalmologist.[4] Ophthalmological symptoms can vary from ptosis, which is the first sign in the majority of patients with strabismus who can present with any pattern (some authors report that exotropia is more frequent) until ophthalmoplegia, Cogan's sign, and amblyopia.[2],[10]

Systemic MG can affect any skeletal muscle of the body and can be suspected by deficits in body hygiene (e.g. difficulty combing hair), or by a generalized weakness (problems with walking, running, climbing stairs, or getting up), and if it affects muscles related to breathing, it can lead to respiratory distress that could lead to death.[11]

The conversion rate of ocular to systemic MGA is 50% in 2 years and 75% in 4 years.[9] However, most of those who will develop systemic pathology do so in the 1st year after the onset of the disease. Different protective factors for the resolution of the disease have been studied, such as age at onset, gender, strabismus at baseline, or positive neostigmine test, but none has shown a statistically significant difference.[12],[13]

The diagnosis of MGO can be made with an ice-pack test, in which ice is placed on the affected eye for 2 min if the patient has ptosis or for 5 min if the patient has ophthalmoplegia. The test is positive if there is evidence of an improvement in symptoms.[4]

Pharmacological tests such as the neostigmine test, the pyridostigmine test that is performed in children under 1 year of age, and the edrophonium test (Tensilon®), which is positive in 84% of patients, can also be performed. These drugs are anticholinesterase, competing with cholinesterase in the neuromuscular junction, which generates an increase in the concentration of ACh and facilitates its binding with the receptors. The difference between these tests is the effect onset time and its duration. With the first two, the effect onset time is longer than with edrophonium.[4]

Other tests that can be performed in patients with a suspicion of this pathology are electrophysiology such as single-fiber electromyography or repetitive nerve stimulation. The first is abnormal in 97% of patients, and the second is positive in 48% of patients.[1],[10],[11]

It is suggested to do repetitive nerve stimulation and single-fiber stimulation (which is the most sensitive test) to confirm the diagnosis, but in the pediatric population, it is difficult due to its complexity.[9]

In addition, there are immunological tests to make the diagnosis of OMG; although when they are negative, they do not exclude the diagnosis. Anti-ACh antibodies (AChR) are used to diagnose and evaluate the response to treatment. It has been found that in MGO, antibodies have lower sensitivity compared to systemic MG and are positive in 72% of patients with systemic MG and only in 41% of patients with MGO. In the same way, it is essential to know that of the patients with MG with negative AChR at the onset of the disease, 41% are positive after approximately 2 years.[14]

In patients with negative AChR antibodies, anti-MuSK antibodies should be made, which are positive in up to 40% of all patients with MG with negative AChR.[9] Pediatric patients with anti-MuSK antibodies tend to have more severe, acute and generalized symptoms. It is essential to highlight that there are negative patients for both AChR and MuSK antibodies, which are called “double seronegative,” and the diagnosis in them is purely clinical. On the other hand, there are antibodies such as Titin-Ab that are 80%–90% positive in patients with MG associated with thymoma.[10],[15],[16]

OMG is associated with other autoimmune pathologies such as autoimmune thyroiditis, pathophysiologically related to the dysfunction of T lymphocytes that direct response against membrane receptors; hence, antithyroid antibodies and thyroid function tests should be performed during the diagnosis of MGO.[10],[16]

The first differential diagnosis of OMG that should be considered is the paralysis of oculomotor nerves. Other differential diagnoses are brain neoplasms, trauma, and inflammatory or vascular causes.[2]

Once the diagnosis of OMG is made, the first line of treatment is pyridostigmine in children or neostigmine in neonates.[17] The next line of treatment is corticosteroids, such as prednisone. Sparing corticosteroid therapy, such as azathioprine, can be added. If there is no adequate response to this treatment, management with cyclosporine, methotrexate, or cyclophosphamide can be initiated, and there are even reports in literature on the efficacy of tacrolimus (FK 506) in ocular symptoms refractory to treatment and use of plasmapheresis and immunoglobulins in acute phases.[2] Thymectomy should be avoided in childhood by immunosuppression, especially in children with negative antibodies; it is a rare measure in the pediatric population due to the low frequency of thymomas.[16]

There is no established intervention to manage strabismus and blepharoptosis, although the variation of these symptoms during daytime is very high. Binocular vision is rarely affected because it usually develops before 18 months. The age of onset of OMG in children is generally higher. The constant strabismus generated by the disease can generate microscopic changes in the primary visual cortex that require treatment and prevention.[8] Occlusion treatment is generally effective for amblyopia, and ptosis is one of the signs that improve faster at the start of oral treatment.[18]

There are some factors suggested by different authors as protectors to develop generalized MG, such as the use of steroids and thymectomy; but so far, they do not have enough evidence.[2],[12],[19]

In conclusion, OMG is a rare disease in the pediatric population and should be considered as a differential diagnosis in cases of ptosis or various forms of strabismus. The treatment in children is similar to that of adults and depends on the clinic. Its prognosis is benign and may present remission after 2 years of treatment.[20],[21] We did not find an incidence of generalization of the disease in the pediatric population, and more evidence is required to define whether the treatment changes the prognosis of the disease.

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.

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Conflicts of interest

There are no conflicts of interest.

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Mullaney P, Vajsar J, Smith R, Buncic JR. The natural history and ophthalmic involvement in childhood myasthenia gravis at the hospital for sick children. Ophthalmology 2000;107:504-10.  Back to cited text no. 4
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