Abstract
- Miller Fisher syndrome can present with various forms of ophthalmoplegia. This case report describes a 57-year-old woman who initially showed bilateral internuclear ophthalmoplegia (INO), with normal imaging and laboratory findings. Her neurologic symptoms progressed to include hyporeflexia and ataxia, leading to a diagnosis of Miller Fisher syndrome. Intravenous immunoglobulin treatment resulted in gradual improvement. This case report highlights the need to consider rare conditions like Miller Fisher syndrome in patients with INO-like features and unclear etiology.
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Keywords: Miller Fisher syndrome; Internuclear ophthalmoplegia; Ophthalmoplegia
INTRODUCTION
Internuclear ophthalmoplegia (INO) is an ocular movement disorder caused by a lesion of the medial longitudinal fasciculus (MLF), typically presenting with characteristic ophthalmoplegic features. These features include adduction limitation ipsilateral to the lesion and abduction nystagmus contralateral to the lesion [1]. Common etiologies of INO include stroke and multiple sclerosis, with lesions mainly involving the brainstem [2]. Additionally, several case reports of myasthenia gravis (MG) have described pseudo-INO, which exhibits ocular movement patterns similar to INO due to extraocular muscle weakness rather than a lesion of the MLF [3,4]. The patient reported here presented challenges in reaching a differential diagnosis based solely on the initial history and examination. We conducted several diagnostic tests, including magnetic resonance imaging (MRI), video-oculography (VOG), and nerve conduction studies (NCS), which could provide valuable insights into Miller Fisher syndrome (MFS) and pseudo-INO. However, the most crucial factor in diagnosing MFS or other forms of pseudo-INO was a careful neurologic examination and follow-up. Here, we report a rare case of a patient with MFS who initially presented with clinical features of bilateral INO.
CASE REPORT
A 57-year-old woman visited the emergency department with a two-day history of binocular diplopia. The patient had a history of hypertension, dyslipidemia, and noninvasive breast cancer (ductal carcinoma in situ), for which she was taking olmesartan, hydrochlorothiazide, atorvastatin, and tamoxifen. The symptom had been worsening since onset, with no fluctuation throughout the day. Aside from a cough lasting for approximately 1 month, she had no other history of infections or vaccinations.
On the first day in the emergency room, the neurological examination revealed bilateral medial rectus limitation and abducting nystagmus, which is often seen in patients with INO (Fig. 1A). Additionally, no spontaneous nystagmus, positional nystagmus, or ocular tilt reaction was observed. Convergence was impaired, and both pupils were isocoric with a prompt light reflex. No visual field deficits were observed and the patient did not report any visual symptoms other than diplopia. Additionally, there was no pain with extraocular movements. No other cranial nerve involvement was noted. Deep tendon reflexes were normal, and ataxia was not prominent. No additional focal neurological deficits were observed. Based on these initial findings, bilateral INO was suspected at the time. Imaging studies, including contrast-enhanced MRI with brainstem thin-sections, were conducted, which did not reveal any abnormalities including brain parenchyma, cranial nerves, and orbital area. Further evaluation included cerebrospinal fluid analysis, NCS, Jolly test, and laboratory tests including antibody assays, all of which produced normal results except slightly delayed H-reflex on the right. Additionally, otolith function tests, including cervical vestibular evoked myogenic potentials, ocular vestibular evoked myogenic potentials, and subjective visual vertical test (SVV) were conducted, and the results were normal. The VOG test provided more accurate results of the nystagmus pattern observed in the examination findings (Fig. 1C).
On the third day of admission, the patient’s symptoms worsened, manifesting a nearly fixed horizontal gaze with vertical gaze limitation (Fig. 1B). The pupillary light reflex was prompt, and no worsening of visual symptoms other than binocular diplopia was observed. The follow-up VOG test also revealed a decrease in pursuit movement compared to previous findings, and although nystagmus was still detected, a worsening of gaze limitation was also observed (Fig. 1D). A follow-up MRI was conducted however no abnormal findings were noted. Additionally, generalized hyporeflexia and mild ataxia were noted on the fifth day. These clinical manifestations of ophthalmoplegia, hyporeflexia, and ataxia were consistent with MFS, and treatment with intravenous immunoglobulin (IVIG) was started. By the third day of IVIG treatment, there was a slight improvement in lateral rectus limitation. Following completion of the treatment course, deep tendon reflexes normalized, and the patient was discharged with improving symptoms. After discharge, the patient was followed up as an outpatient, and the ophthalmoplegia gradually improved, completely resolving after 6 months. During the follow-up, an H-reflex test was performed again in the third month, and it showed that the previously slightly delayed findings had normalized. Despite the result for anti-GQ1b antibodies found to be negative, the patient showed the classic triad of MFS, and MRI revealed no evidence of brain lesions. Additionally, symptom improvement was observed following IVIG administration. These findings strongly suggest MFS.
Written informed consent was obtained for publication of this case report and accompanying images.
DISCUSSION
This case presented a rare case of MFS initially manifesting with clinical features resembling INO. Initially, the patient did not present with clear features suggestive of MFS apart from ophthalmoplegia. However, as time progressed, the emergence of hyporeflexia, ataxia, and the absence of other signs such as limb weakness or hypersomnolence met the diagnostic criteria for MFS [5]. Despite the absence of supportive features from anti-GQ1b antibodies or NCS, the patient showed a prominent clinical triad and a characteristic clinical course, supporting the diagnosis. While several pseudo-INO cases have been reported in MG, case reports about MFS remain limited. There was a similar case report previously [6]; however, in this patient, an additional VOG test was performed during symptom presentation, providing more objective data (Fig. 1C, D). The nystagmus pattern observed in this VOG exhibited an exponentially decreasing form, which is known to be associated with gaze-evoked nystagmus or central lesions [7]. Although MFS is classified within the group of peripheral neuropathies, there is evidence suggesting concomitant central nervous system (CNS) involvement [8,9]. The nystagmus pattern shown in this VOG could be one finding that suggests concomitant CNS involvement in MFS. However, specific characteristics of nystagmus patterns and mechanisms of CNS involvement in MFS have not been well established. The nystagmus pattern observed in this patient is expected to be helpful for future discussions on this topic.
In addition to clinical presentation, diagnostic tests that could help in distinguishing pseudo-INO early on can be considered. Some studies suggest SVV measurements aid in distinguishing unilateral INO from MG, though differentiating bilateral INO remains challenging [10]. It can be expected that the previously mentioned VOG would be helpful in this regard.
The most significant implication is that MFS can present with various forms of ophthalmoplegia. In certain conditions, as demonstrated in this case report, it may manifest clinically as INO or bilateral INO. Therefore, when encountering patients showing clinical features similar to INO but with uncertain etiology or unusual characteristics, it is important to consider rare conditions like MFS. This case emphasizes the importance of suspecting MFS in cases with acute exacerbation of accompanying symptoms, along with various patterns of ophthalmoplegia, and highlights the need for follow-up on symptoms and examination.
ARTICLE INFORMATION
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Funding/Support
None.
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Conflicts of Interest
No potential conflict of interest relevant to this article was reported.
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Availability of Data and Materials
All data generated or analyzed during this study are included in this published article. For other data, these may be requested through the corresponding author.
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Authors’ Contributions
Conceptualization, Data curation, Methodology: Bae D; Formal analysis, Investigation: Kim S, Bae D; Writing–original draft: Kim S; Writing–review & editing: All authors.
All authors read and approved the final manuscript.
Fig. 1.(A) The initial 9-gaze photo shows bilateral medial rectus limitation. (B) Follow-up 9-gaze photo on the third day of admission shows a nearly fixed horizontal gaze with vertical gaze limitation. (C) The initial video-oculography (VOG) shows poor performance in horizontal pursuit and an exponentially decreasing form of nystagmus. (D) Follow-up VOG on the third day of admission shows worsened performance on horizontal and vertical pursuit.
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