Miller Fisher Syndrome With Papilledema and Antecedent Helicobacter pylori Infection

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Gour Wang, MD Miller Fisher Syndrome With Papilledema and Antecedent Helicobacter pylori Infection Peter Wawrzusin, MD, Stella Chung, MD, Nicole Sakla, DO, Roger Turbin, MD, Larry Frohman, MD A 16-year-old girl from Guinea (in the United States one year) with a history of malaria treated as a child and mild anemia, developed symptoms of headache, meningismus, malaise, upper then lower extremity weakness, diarrhea, nausea, emesis, and polydipsia resulting in multiple outside emergency department visits beginning 3 weeks before presentation to our institution. One week before her presentation to us, she was noted to have altered mental status and was admitted to an outside hospital. A lumbar puncture provided temporary headache relief and yielded clear cerebrospinal fluid (CSF) with an opening pressure of 55 cm/H2O, with one white blood cell, 41 red blood cells, protein 23.4 mg/dL, and glucose 70 mg/dL. She was started on acetazolamide (dose 500–1000 mg daily). She developed syndrome of inappropriate antidiuretic hormone. She had a normal computed tomography of the head and MRI of the spine. MRI of the brain one day after admission revealed flattened posterior globes with bulging papillae and a partial empty sella. Headaches recurred and she complained of blurred vision. Papilledema was noted on ophthalmologic examination and repeat lumbar puncture showed an opening pressure of at least 35 cm/H20 (column max 35 cm/H20 in instrument used), with one white blood cell, protein 32.2 mg/dL, glucose 77 mg/dL, negative venereal disease research laboratory test, and negative Borrelia burgdorferi DNA. A ventriculoperitoneal shunt was placed with intraoperative opening pressure noted to be 50 cm/H2O. The CSF testing for Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus agalactiae, Streptococcus pneumoniae, Cytomegalovirus, Epstein–Barr virus, herpes simplex virus 1, 2, and 6, Parechovirus, Varicella zoster, Lyme’s western blot and Cryptococcus was normal. Interferon gamma release assay was negative. Serum testing for HIV, complement levels, antiproteinase 3 antibody, antimyeloperoxidase antibody, and antinuclear antibody were normal. Antidouble stranded DNA was weakly positive. One Department of Ophthalmology and Visual Science (PW, SC, RT, LF), Rutgers New Jersey School of Medicine, Newark, New Jersey; Department of Radiology (NS), Newark Beth Israel Medical Center, Newark, New Jersey; and Department of Neurology (LF), Rutgers New Jersey School of Medicine, Newark, New Jersey. The authors report no conflicts of interest. Address correspondence to Peter Wawrzusin, MD, Department of Ophthalmology and Visual Science, Rutgers New Jersey School of Medicine, 90 Bergen Street, Doctor’s Office Center Suite 6100, Newark, NJ 07103; E-mail: [e-mail] e346 day after shunt placement, she was transferred to our institution for neuro-ophthalmic management. At our initial evaluation, she endorsed improvement of vision after shunt placement, a severe headache that worsened on sitting up, nausea, right-sided pulsatile tinnitus, binocular horizontal diplopia, and diarrhea. She denied transient visual obscurations. Her vision was 20/25 in each eye with no relative afferent pupillary defect, and 10/11 Ishihara color plates were named correctly in each eye. She had bilateral ptosis (right more than left) and ocular rotations notable for a near total bilateral abduction deficit with 50% adduction in the right eye. Although her severe headache diminished the reliability of her visual fields, the initial threshold fields were suspicious for partial superior arcuate scotomata with a nasal step in each eye. Mild disc edema was seen in each eye with a high watermark in the right eye and a few peripapillary hemorrhages in the left eye. Optical coherence tomography confirmed mild bilateral disc edema. Her neurologic examination showed ataxia, bilateral finger to nose dysmetria, diffuse hyporeflexia, and upper greater than lower bilateral extremity weakness. Repeat MRI with contrast taken 10 days after shunt placement no longer demonstrated posterior globe flattening and showed diminution in compression of the pituitary gland. As she was felt to have cerebral hypotension from overshunting, acetazolamide was discontinued and the shunt was clamped. As ataxia, weakness, hyporeflexia, ophthalmoplegia, and a gastrointestinal prodrome led to suspicion of Miller Fisher Syndrome (MFS), Helicobacter pylori was tested; serum immunoglobulin G (IgG) and stool antigens were both abnormal. She was treated with amoxicillin, clarithromycin, and lansoprazole for a 14-day course. Her serum anti-GQ1b returned positive at a titer of 1:800 (abnormal is above 1:100). After 3 days of intravenous immunoglobulin (IVIg) 1 mg/kg, the patient’s ophthalmoplegia, ataxia, dysmetria, and strength improved. Her papilledema resolved. Electromyogram and nerve conduction studies yielded normal findings, although these were performed after the treatment course of IVIg. One month postpresentation, the patient was 20/25 in each eye with improving ophthalmoplegia. Acetazolamide was restarted at 1 g daily for headache and trace bilateral papilledema that developed after the shunt had been clamped. Wawrzusin et al: J Neuro-Ophthalmol 2021; 41: e346-e347 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence The clinical triad of hyporeflexia, ataxia, and ophthalmoplegia with positive serology for anti-GQ1b antibodies supports the diagnosis of the MFS variant of Guillain–Barre Syndrome (GBS) in our patient. Her first spinal tap was 2 weeks into her clinical course; thus, a suspected transient elevation in spinal fluid protein may have been missed, consistent with reports noting a transitory elevation of CSF IgG that correlates with the degree of damage to the blood–brain barrier and therefore the clinical course of the disease (1). An elevation in spinal fluid protein leading to obstruction of the CSF arachnoid granulations serves as one theory for the etiology of papilledema in GBS (2). An alternative theory leans on elevated effective venous pressures at points of CSF outflow noted in hydrodynamic studies in a GBS patient; this is completely independent of the spinal fluid protein level (2). Idiopathic intracranial hypertension (IIH) and MFS were noted to occur coincidentally in one previous report (3); however, the lack of risk factors for IIH (body mass index of 19 kg/m2 and absence of use of exogenous agents known to cause elevated intracranial pressure) argues against the possibility that she had a co-occurrence of these 2 rare entities. The presentation of MFS with increased intracranial pressure has only rarely been reported and has yet to be reported in a case with H. pylori (2,3). The prodrome of diarrhea, nausea, and vomiting; the absence of remote episodes of antecedent gastrointestinal illness; and positive stool and serum studies for H. pylori suggest that it may have been the etiologic agent for MFS in this case. One meta-analysis found that the prevalence of H. pylori IgG was significantly more common in GBS patients in both the serum and CSF vs controls (4). Other data show an increase in CSF antibodies to the vacuolating cytotoxin epitope of H. pylori in patients with known MFS, possibly affecting the ion channels in the nodes of Ranvier (5). The leading Wawrzusin et al: J Neuro-Ophthalmol 2021; 41: e346-e347 theory behind H. pylori’s role in triggering MFS centers around molecular mimicry (4). H. pylori is a relatively common cause of gastroenteritis that requires antibiotic treatment. This case reinforces the importance of considering this bacterium, in addition to Campylobacter, as a potential etiology for MFS. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: P. Wawrzusin, R. Turbin, and L. Frohman; b. Acquisition of data: P. Wawrzusin, S. Chung, N. Sakla, R. Turbin, and L. Frohman; c. Analysis and interpretation of data: P. Wawrzusin, S. Chung, N. Sakla, R. Turbin, and L. Frohman. Category 2: a. Drafting the manuscript: P. Wawrzusin, S. Chung, N. Sakla, R. Turbin, and L. Frohman; b. Revising it for intellectual content; P. Wawrzusin, S. Chung, N. Sakla, R. Turbin, and L. Frohman. Category 3: a. Final approval of the completed manuscript: P. Wawrzusin, S. Chung, N. Sakla, R. Turbin, and L. Frohman. REFERENCES 1. Segurado OG, Krüger H, Mertens HG. Clinical significance of serum and CSF findings in the Guillain-Barré syndrome and related disorders. J Neurol. 1986;233:202–208. 2. Bruce CT, McClelland CM, Van Stavern GP. Papilledema in an otherwise clinically typical case of Miller Fisher syndrome. Can J Ophthalmol. 2015;50:e69–e71. 3. Yeak J, Zahari M, Singh S, Mohamad NF. Co-occurrence of acute ophthalmoplegia (without ataxia) and idiopathic intracranial hypertension. Eur J Ophthal. 2018;29:NP1–NP4. 4. Dardiotis E, Sokratous M, Tsouris Z, Siokas V, Mentis AA, Aloizou AM, Michalopoulou A, Bogdanos DP, Xiromerisiou G, Deretzi G, Kountouras J, Hadjigeorgiou GM. Association between Helicobacter pylori infection and Guillain-Barré Syndrome: a meta-analysis. Eur J Clin Invest. 2020;5:e13218. 5. Chiba S, Sugiyama T, Yonekura K, Tanaka S, Matsumoto H, Fujii N, Yokota S, Hirayama T. An antibody to VacA of Helicobacter pylori in the CSF of patients with Miller-Fisher syndrome. Neurology. 2004;63:2184–2186. e347 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.