Miller Fisher Syndrome: An eye opening case

Learning Objective 1: Recognize the symptoms and signs of the Miller Fisher variant of Guillain-Barre Syndrome (GBS)Learning Objective 2: Describe the role of GQ1b antibodies in Miller Fisher Syndrome (MFS)

Case: A 24-yo woman with a history of pseudotumor cerebri presented with numbness, tingling, and weakness throughout her body and diplopia for 1 day. Her prior symptoms of pseudotumor included lightheadedness, diplopia, and headache, but not numbness. She denied recent illness, fever, chills, rash, trauma, headache, blurry vision, and gait instability. Diamox was discontinued 4 months prior to presentation. Family history revealed only diabetes. She did not use recreational drugs. On exam, she was awake and alert. Vital signs 111/62-79-14-36.4. HEENT showed blurring of the left optic disc. Neurologic exam revealed impaired eye abduction bilaterally. DTRs were 1+ in the upper extremities and trace in the lower extremities. The remainder of the physical exam including a complete neurologic exam was otherwise normal. WBC 11, protein 8.5. The remainder of the CBC and CMP were normal. ESR 37, CRP 33.9. CT brain revealed an empty sella without change from the prior CT. MRI of the orbits and brain revealed changes suggestive of intracranial hypertension. LP opening pressure was 37. The CSF was normal. EMG was unremarkable. Acetazolamide was begun. She developed a change in speech quality and worsening ophthalmoplegia. These findings suggested MFS. She was begun on IVIG and her symptoms improved. Anti-GQ1b then returned positive.

Discussion: MFS, a variant of GBS, is a demyelinating condition characterized by ophthalmoplegia, ataxia and hyporeflexia. Patients may also develop dilated pupils, slurred speech, difficulty swallowing and weakness of the extremities. Like GBS, a viral illness may precede the development of MFS. Immunoglobulins that result from these viruses and share antigenic epitopes with them are thought to target gangliosides (including GM1, GD1a and GQ1b) in nodes of Ranvier, nerve roots and end organs (including the brainstem), causing their demyelination. GQ1b gangliosides, abundant in the motor nerves of the extraocular muscles, are the targets of the primary antibody that causes this syndrome. 85% of patients with MFS possess the GQ1b antibody, which is associated with oculomotor nerve involvement. Imaging of the brain and spinal cord is usually normal. Nerve conduction studies may demonstrate reduced sensory response without decreased sensory conduction velocity. LP may reveal elevated CSF protein. Like GBS, treatment for MFS is supportive care, IVIG and plasma exchange. Although most patients do well with recovery beginning 2-4 weeks after symptom onset, some develop respiratory compromise, so patients with MFS are typically hospitalized for observation. Patients most often recover in full within 3 months. Recurrence rates of MFS are low and are associated with increased anti-GQ1b antibody levels.