Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Rubin reports he is a consultant for Merck Sharp & Dohme Corp.
SYNOPSIS: Other than the classic triad of neurological signs that define Miller Fisher syndrome, it also is common to see delayed facial palsy, loss of taste, and weakness of pharyngeal and cervical muscles.
SOURCE:Jung JH, Oh EH, Shin JH, et al. Atypical clinical manifestations of Miller Fisher syndrome. Neurol Sci 2019;40:67-73.
Ophthalmoplegia, ataxia, and areflexia comprise the classic triad of Miller Fisher syndrome (MFS), a rare variant of Guillain-Barré syndrome (GBS), with an annual incidence of less than one patient per million population, and accounting for 5% of adults and 1.6% of children with GBS. About one-quarter demonstrate limb weakness, and some develop fixed dilated pupils. GQ1b antibodies are found in 90%, and nerve conduction studies show reduced or absent sensory responses with normal velocities. What is the spectrum and frequency of atypical features that may occur in MFS that are important to recognize, since they may lead to delayed or misdiagnosis?
Between 2012 and 2017, 38 patients with the classic MFS triad (pure MFS) were recruited consecutively from Pusan National University Yangsan Hospital in Gyeongsangnam-do, South Korea. Those with only two classic features were termed incomplete MFS, and those with additional features were termed overlapping MFS. Investigators reviewed all records, including demographics, neurological examination, pattern of clinical evolution, laboratory investigations, treatment, and outcome.
All 38 patients demonstrated the clinical triad at initial presentation, of which 68% (n = 26) remained pure MFS while 32% (n = 12) had an overlapping syndrome, encompassing MFS plus the pharyngeal-cervical-brachial (PCB) variant of GBS in six, MFS plus GBS in four, and MFS plus Bickerstaff brainstem encephalitis (BBE) in two. Antecedent illness occurred in 89% (n = 34) prior to developing MFS, 68% (n = 26) were positive for anti-GQ1b antibodies, and five patients had additional anti-ganglioside antibodies, one each with anti-GM1 or anti-GM1/GD1b, and three with anti-GD1b.
Prior to initiation of intravenous immunoglobulin (IVIG) therapy, headache of moderate severity was present in 16% (n = 6) and tended not to respond to nonsteroidal anti-inflammatory agents, but resolved within two weeks. Delayed facial palsy developed in 8% (n = 3) within 10-16 days after disease onset, was unilateral in two and bilateral in one, and resolved fully in all three patients within two months. Only one patient with facial palsy had positive GQ1b antibodies. Divergence insufficiency without external ophthalmoplegia was seen in two, with esotropia at a distance. Within two months, these resolved with IVIG. Taste was lost over the entire tongue in two patients without facial weakness, but resolved within a month prior to ophthalmoplegia resolution. Overall, 30% of MFS patients have additional atypical features, awareness of which will avoid misdiagnosis and unnecessary investigations.
COMMENTARY
Acute ophthalmoparesis is the most common diagnosis among Korean children with anti-GQ1b antibody syndrome. In a retrospective study of 11 children, ages 5.4 to 18 years, with anti-GQ1b antibody syndrome, acute ophthalmoparesis occurred in six, classic MFS in two, and one each experienced acute ataxic neuropathy, MFS/GBS, or pharyngeal-cervical-brachial weakness. Variability of the clinical manifestations of anti-GQ1b antibody syndrome in children and adults is unclear, but may be related to differences in the specificity of anti-GQ1b antibodies and the different expression of gangliosides in the nervous system. Alternatively, variable accessibility of these antibodies to different parts of the nervous system also may result in varied clinical phenotype. Maturational change in GQ1b antigen expression and accessibility of anti-GQ1b antibodies are areas remaining to be explored.1
REFERENCE
- Yoon L, Kim BR, Kim HY, et al. Clinical characterization of anti-GQ1b antibody syndrome in Korean children. J Neuroimmunol 2019; Jan 8. pii: S0165-5728(19)30008-6. doi: 10.1016/j.jneuroim.2019.01.003. [Epub ahead of print].