Anti-GD1b-Positive Miller Fisher syndrome Presenting as Total Ophthalmoplegia

Abstract

Miller Fisher syndrome (MFS) is a variant of Guillain-Barre syndrome (GBS) characterized by ataxia, areflexia, and ophthalmoplegia. It is often linked to cross-reacting antibodies to the GQ1b ganglioside found in cranial nerve myelin [1]. The presence of GQ1b at significantly higher levels in the oculomotor, trochlear, and abducens nerve myelin is often cited as an explanation for ophthalmoplegia [1]. Anti-GQ1b immunoglobulin G (IgG) antibodies are detected in more than 90% of patients with MFS [2]. However, we observed a case of MFS with severe ophthalmoplegia presenting as frozen eyes, in which anti-GQ1b IgG was negative, while anti-GD1b IgG was positive. An 11-year-old boy presented to the outpatient clinic with headache, dizziness, vomiting, diplopia, ataxia, and a tingling sensation in the fingers for 3 days. He could not stand or walk without support. There was no fever at the time of presentation; however, 3 weeks ago he had experienced a high fever with loose stool for 2 days. His mental status was alert and his vital signs were within the normal range. His muscle strength was grade V in both the upper and lower extremities. The cranial nerve test was intact except for bilateral total ophthalmoplegia (Fig. 1). There was no nystagmus. Deep tendon reflex testing showed areflexia of both knees. On admission, brain magnetic resonance imaging (MRI) and whole-spine MRI were normal. Nerve conduction studies of both upper and lower extremities suggested acute inflammatory demyelinating polyneuropathy because both H-reflexes were absent. No electrophysiological abnormalities were observed in the left and right blink reflex pathways. On a blood test, the white blood cell count was 10,290/mm with 66.4% of segment neutrophils. The C-reactive protein level was 0.1 mg/dL. The thyroid function test was normal. Cerebrospinal fluid (CSF) examinations showed a white blood cell count of 2/mm, a protein level of 25.5 mg/dL, and a glucose level of 62 mg/dL. Bacterial culture, herpes simplex virus polymerase chain reaction (PCR), and acid-fast bacillus stain of CSF were all negative. In a stool PCR examination, Campylobacter species were identified. Serum anti-GM1 IgG and anti-GQ1b IgG were negative, but anti-GD1b IgG was positive. We administered intravenous immunoglobulin (0.5 g/kg/day) for 4 days upon admission under the diagnosis of MFS. The patient’s ataxia and headache immediately improved after treatment. However, only adduction of the left eye was possible immediately after the treatment. The tingling sensation of the fingers improved after 2 weeks. Ophthalmoplegia slowly improved. Two months later, bilateral total ophthalmoplegia had completely improved. Total bilateral ophthalmoplegia is very rare.