Autonomic Dysfunction in Miller Fisher Syndrome: Paralytic Ileus and Isolated Internal Ophthalmoplegia

Abstract

We describe a rare case of Miller Fisher syndrome (MFS) in a 37-year-old woman characterized by paralytic ileus and isolated internal ophthalmoplegia without any external ophthalmoplegia. The patient initially presented with severe abdominal pain and photophobia. A physical examination revealed mydriasis, impaired pupillary light reflexes, ataxia, and areflexia; however, her extraocular movements were preserved. The serum test results were positive for anti-GQ1b IgG antibodies. Treatment with intravenous immunoglobulin led to a near-complete resolution of the symptoms. This case demonstrates that MFS can manifest as significant gastrointestinal autonomic dysfunction and isolated internal ophthalmoplegia, which may not fit the classic triad presentation. Clinicians should include MFS in the differential diagnosis of patients with unexplained autonomic symptoms even in the absence of external ophthalmoplegia, and a thorough pupillary examination is crucial.

Introduction

Miller Fisher syndrome (MFS) is a rare variant of Guillain-Barré syndrome (GBS) and it is characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia (1). MFS has an annual incidence of approximately 1-2 cases per million and accounts for 5% of GBS cases in Western countries (2,3). However, its prevalence is notably higher in East Asia, where it comprises 15-34% of GBS cases, with Japan reporting the highest rates (1,4).

While the classic triad is well-recognized, atypical and incomplete presentations, occurring in up to 30% of cases, pose significant diagnostic challenges, particularly for non-neurologists (3,5). The diagnosis is often supported by the detection of anti-GQ1b antibodies; however, their absence does not exclude MFS.

We herein report an unusual case of a 37-year-old woman who initially presented to the emergency department with abdominal pain and photophobia, and was subsequently found to have ataxia and areflexia on examination, despite the absence of external ophthalmoplegia. This case is noteworthy not only because of its atypical onset with gastrointestinal symptoms but also because of the unique presentation of ophthalmoplegia due to selective involvement of the internal ocular muscles, while sparing the extraocular function-a feature that makes the initial diagnosis more challenging.

Case Report

A 37-year-old woman presented to the emergency department with a three-day history of progressive abdominal pain, distension, severe photophobia, and exhaustion that made ambulation difficult. She reported a history of cough and rhinorrhea one week prior to the onset of symptoms. The patient had no relevant medical history.

Upon examination, her vital signs were stable. She exhibited mild abdominal distension and diffuse tenderness, with decreased bowel sounds. The initial evaluation revealed bilateral pupillary dilation with sluggish light reflexes, while the extraocular movements were intact. Abdominal radiography revealed colonic distension, and subsequent abdominal computed tomography (CT) confirmed diffuse colonic distension without evidence of obstruction, inflammation, or perforation, consistent with paralytic ileus (Figure). A subsequent neurological examination revealed ataxia and absent deep tendon reflexes in all four extremities, with preserved muscle strength and sensory function.

Figure.

Abdominal imaging demonstrating diffuse colonic dilatation consistent with paralytic ileus. (A) A supine abdominal radiograph showing marked gaseous distension of the colon and the small bowel. (B) Axial view of abdominal computed tomography without intravenous or oral contrast, confirming diffuse colonic dilatation without evidence of mechanical obstruction (no transition point), significant bowel wall thickening, or perforation (no free air).

Laboratory tests, including a complete blood count and basic metabolic panel, were within the normal limits. Brain and cervical spine magnetic resonance imaging (MRI) showed no significant abnormalities. A cerebrospinal fluid analysis revealed a total protein level of 53 mg/dL and a cell count of 3 cells/μL, consisting of one polymorphonuclear cell and two mononuclear cells. These findings are consistent with mild albuminocytologic dissociation. Initial nerve conduction studies, performed on Day 2 of hospitalization, were normal, except for reduced sensory nerve action potentials in the sural nerve. Based on the clinical presentation and investigative findings, MFS was suspected and thereafter was later confirmed by a positive serum anti-GQ1b IgG antibody test. Although the GM1 antibody test result was negative, nerve conduction studies also suggested the potential for MFS/GBS overlap.

The patient received intravenous immunoglobulin, 0.4 g/kg/day of five days. Over the subsequent weeks to months, the patient's symptoms gradually improved. The patient's abdominal pain, a primary presenting symptom, completely resolved within one week of treatment initiation. Two weeks post-treatment, her ataxia significantly improved, thus enabling ambulation with assistance. The severe photophobia associated with pupillary dilation persisted thereafter, but gradually diminished over a two-month period.

At the four-month follow-up, the patient reported an almost complete resolution of her symptoms. She described a normal motor function with a complete resolution of abdominal pain and photophobia. A neurological examination revealed a normal pupillary response and restored full-body coordination. Diminished deep tendon reflexes were the only residual finding. Repeat nerve conduction studies demonstrated an improvement in the sensory nerve action potential of the sural nerve. Throughout her clinical course, there was no external ophthalmoplegia or evidence of cardiovascular or urinary autonomic dysfunction.

Discussion

This case highlights two unusual features of MFS: prominent gastrointestinal autonomic dysfunction presenting as paralytic ileus, and isolated internal ophthalmoplegia. These findings challenge the traditional diagnostic framework of MFS and underscore the need for greater clinical awareness of atypical presentations.

Although autonomic dysfunction is recognized in GBS (6), its prevalence and clinical significance in MFS are unclear. Although a comprehensive review specifically addressing autonomic dysfunction in MFS is lacking, the existing literature provides some insights. Mori et al. (7) analyzed symptoms in 50 patients with MFS and found that pupillary abnormalities occurred in 42% and urinary disturbance in 16%. Furthermore, Lyu et al. (8) observed a high frequency (83%) of cardiovascular autonomic dysfunction in patients with MFS using quantitative testing. These observations suggest that pupillary, urinary, and cardiovascular autonomic involvement may be relatively common in patients with MFS. In contrast, severe gastrointestinal dysmotility presenting as paralytic ileus, as in this case, is rare in MFS, with only one other reported case (9). This difference in frequency highlights the unusual nature of the patient's presentation. Although the mechanisms underlying autonomic dysfunction in MFS are still not fully understood, research on GBS indicates a potential association between anti-GQ1b antibodies and autonomic involvement. Kusunoki (10) found that GBS patients with GQ1b antibodies had a higher incidence of autonomic dysfunction than those with GM1 antibodies, thus suggesting a possible role of anti-GQ1b antibodies in this process.

However, given the marked predominance of severe gastrointestinal symptoms over other autonomic features in our case, localized or multifocal thoracolumbar radiculoneuropathy or ganglionitis-mechanisms that are particularly relevant in light of the potential GBS/MFS overlap in this specific context-could have contributed to these findings by causing radicular pain and impairing the patient's gut motility. This hypothesis is plausible within the spectrum of GBS and its variants, as radiculoneuropathy is a recognized feature that may be present in localized or multifocal distributions (11). Indirect support for this possibility comes from reports of severe abdominal pain resulting from thoracolumbar radiculopathy due to other causes (12) as well as from observations linking disruption of spinal nerve pathways at these levels with paralytic ileus (13). Although definitive evidence, such as the characteristic findings on gadolinium-enhanced spinal MRI, which was not performed in this case, is lacking, this potential mechanism involving localized nerve root or ganglion involvement offers an additional perspective on the pathophysiology underlying the specific clinical presentation observed in our patient.

Isolated internal ophthalmoplegia was also a noteworthy feature of this case. The mechanism of external ophthalmoplegia in MFS is well established, involving GQ1b ganglioside distribution at the paranodal myelin of relevant cranial nerves (14) and neuromuscular junctions (15). Internal ophthalmoplegia is linked to dysfunction of the ciliary ganglion or short ciliary nerves in the parasympathetic oculomotor pathway, with supporting evidence from cholinergic hypersensitivity reports (16). However, the precise cause of isolated internal ophthalmoplegia in MFS remains unclear. One possibility is that this specific ocular finding is caused by known anti-GQ1b antibody complexes, such as GQ1b/GM1 or GQ1b/GD1a, or by unidentified anti-GQ1b antibody complexes. Studies have shown a correlation between anti-GQ1b antibody complexes and the clinical features of MFS (17). Furthermore, Murakami et al. (18) found that all patients with MFS with isolated internal ophthalmoplegia who underwent testing for anti-ganglioside antibodies were positive for anti-GQ1b antibodies, suggesting a strong association between these antibodies and this specific clinical presentation. This finding raises the possibility that anti-GQ1b antibodies, either alone or in complex with other gangliosides, may have varying affinities for different neural structures, potentially contributing to the selective involvement of the internal ocular muscles. Another possibility is that isolated internal ophthalmoplegia arises from unidentified anti-ganglioside antibodies or complexes or even from mechanisms unrelated to anti-ganglioside antibody responses. Supporting this possibility, Koga et al. (19) described internal ophthalmoplegia in a patient with MFS who tested negative for known antiganglioside and antiganglioside complex antibodies. However, direct evidence supporting these hypotheses is lacking and this possibility thus remains speculative. Additional studies are needed to confirm these potential mechanisms and clarify the pathophysiology of this unusual presentation of MFS.

In conclusion, this case emphasizes the importance of considering MFS in patients presenting with unexplained autonomic symptoms, particularly gastrointestinal dysmotility (such as paralytic ileus) or pupillary abnormalities (such as isolated internal ophthalmoplegia), even if the classic triad of ophthalmoplegia, ataxia, and areflexia is not completely present. Early recognition of these atypical presentations is crucial for both timely management and an improved patient outcome. Further research is needed to better understand the prevalence, mechanisms, and optimal treatment strategies for autonomic dysfunction in MFS, particularly gastrointestinal dysmotility, presenting as paralytic ileus and isolated internal ophthalmoplegia.

The authors state that they have no Conflict of Interest (COI).