Miller Fisher Syndrome · What Is It, Causes, Signs, and More

Miller Fisher syndrome is caused by immune-mediated destruction of peripheral nerves. After being exposed to an inciting antigen (i.e., foreign substance), the immune system mounts an autoimmune response through molecular mimicry. Most often, this molecular mimicry occurs after an immune-mediated reaction to a virus. As antibodies against the virus are produced, they mistakenly attack the nerve, misidentifying it as the viral antigen due to structural similarities between the peripheral nerve and the foreign antigen. Ultimately, this causes the immune system to target components of the peripheral nerve, thereby causing demyelination. 

Signs and symptoms are related to demyelination of affected neurons and most commonly affect the oculomotor, trochlear, and trigeminal nerves (i.e., third, fourth, and fifth cranial nerves, respectively). Typically, signs and symptoms of MFS include a triad of ataxia (i.e., difficulty with balance and walking), areflexia (i.e. dysfunctional reflexes), and ophthalmoplegia (i.e., dysfunctional eye movements). Other symptoms of MFS can include diplopia (i.e., double vision), blurred vision, dysarthria (i.e., difficulty speaking), or dizziness. It can also cause facial paresis, bulbar weakness, muscle weakness, peripheral neuropathy (i.e., weakness, numbness, tingling in the periphery), hyporeflexia, and loss of vibratory sensation. 

Diagnosis of Miller Fisher syndrome is done with a thorough medical examination, physical assessment, laboratory and diagnostic testing, and meeting the Brighton criteria. A medical history may reveal a time course of 12 to 28 days between symptom onset and nadir (i.e. most severe symptomatic phase), as well as a recent infection. A physical exam with a thorough neurologic exam can be done, including assessment of reflexes, cranial nerve responses, sensation, and vital signs. Laboratory testing may include a cerebrospinal fluid (CSF) analysis through lumbar puncture, which may show normal cell counts but elevated protein levels (i.e. albuminocytologic dissociation); this is suggestive of GBS, raising suspicion for MFS. Diagnostic tests may include an electromyography (EMG) that shows findings consistent with GBS and its variants (i.e., abnormal nerve conduction).

The Brighton criteria can be used in the diagnosis of variants of GBS, like MFS, and considers findings from the history, physical exam, and laboratory and diagnostic tests. It includes criteria of bilateral limb weakness, diminished deep tendon reflexes, the associated time course, EMG results, and lack of an alternative diagnosis. 

Further, serology showing IgG anti-GQ1b ganglioside antibodies can indicate MFS and imaging, such as a CT or MRI, may show thickening of the spinal nerve roots and cauda equina.