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Only five cases of optic nerve involvement in Miller Fisher syndrome (MFS) have been documented in the literature. This report further confirms that optic neuritis may be seen in anti-GQ1b positive MFS.
This 23 year old woman presented with acute blurry vision, diplopia, and pain with eye movement. Her visual acuity was 20/20 right eye and 20/200 left eye with a left relative afferent pupillary defect (RAPD). She had left red colour desaturation. Her visual field on tangent screen revealed an enlarged left blind spot and a left upper quadrant temporal peripheral field constriction. She had bilateral sixth nerve palsies, nystagmus in all gazes, and left optic disc oedema. After 1 week her visual acuity improved to 20/20 in both eyes, but her left disc remained oedematous. She then developed rapidly progressive gait ataxia to such a degree that she was unable to walk. Dysmmetria and dysdiadochokinesia were more marked in her left upper extremity. She had very mild distal lower extremity weakness, absent lower extremity deep tendon reflexes, and bilateral Babinski’s. She also had tingling in her hands and feet and decreased lower extremity vibratory sensation. Her mental status was normal throughout her illness. She was not taking any drugs. A magnetic resonance image (MRI) of the brain and entire spine and MR venogram were all normal. Her cerebrospinal fluid (CSF) opening pressure was 150 mm H2O. Her CSF protein was elevated at 70 mg/dl, but CSF glucose and cell count were normal; CSF VDRL, Gram stain, routine bacterial, viral, and fungal cultures were all negative. No oligoclonal bands were seen on CSF electrophoresis. Her visual evoked potential (VEP) revealed a delayed left P100 latency at 131 ms and her brainstem auditory evoked potential (BAEP) was normal. Electromyogram/nerve conduction study (EMG/NCV) study revealed mildly prolonged median and peroneal F-waves, normal distal motor latencies in her extremities and a reduced left median sensory nerve action potential (SNAP). Anti-GQ1b antibody (162 EIA U (normal = 100) Athena Diagnostics, Worcester, MA, USA) and anti-GM1 antibody (1035 EIA U (normal = 800) Athena Diagnostics, Worcester, MA, USA) were both positive at high titres. Syphilis and Borrelia serology was normal. Antibodies for acetylcholine receptor, hepatitis A, B, and C; Mycoplasma, Campylobacter jejuni, Lyme, Hu, MaTa, Yo, CV-2, and Ri were all negative. Sedimentation rate, ANA, and c-ANCA were all normal. Serum and urine toxicological screen were both negative. After 5 days of plasmapheresis, her anti-GQ1b and anti-GM1 antibodies were negative. Her optic disc oedema, ocular motor palsies, and nystagmus immediately resolved, but she continued to walk with assistance. Two months later she had fully recovered. Six months after her recovery she developed a similar recurrence of her neurological symptoms and signs with left optic disc oedema. Her visual acuity at that time was 20/20 right eye and 20/100 left eye. She had a left RAPD and enlarged left blind spot again, but no extraocular motility defects. Her VEP showed a delayed left P100 latency at 142 ms and her BAEP was normal. Single fibre EMG of her left frontalis muscle revealed no blocking suggestive of a neuromuscular transmission defect. HLA-DR2 allele was positive and HLA-Cw3 allele was negative. Her anti-GQ1b antibody (212 EIA U (normal = 100) Athena Diagnostics, Worcester, MA, USA) was elevated again. She underwent plasmapheresis with full recovery in about 6 months.
In addition to the classic triad of ophthalmoplegia, ataxia, and arreflexia,1 visual impairment presenting as optic neuritis may be a feature of anti-GQ1b positive recurrent MFS. Only five cases of optic nerve involvement in MFS have been documented in the literature.2–5 In the two previously reported cases of visual impairment in MFS, visual evoked potentials were either absent2 or suggestive of pre-chiasmal and post-chiasmal visual pathway dysfunction.3 Demyelinating optic neuropathies confirmed by VEP were reported in one patient with possible MFS.4 Two other cases of presumed optic neuritis were associated with anti-GQ1b positive MFS.5,6 In the patient presented here, her markedly decreased visual acuity, pain with eye movement, dyschromatopsia, and optic disc oedema that resulted in good visual recovery are all indicative of the diagnosis of optic neuritis. Since high concentrations of GQ1b gangliosides are known to be present in the human optic nerve and anti-GQ1b antibodies can cross the blood-brain barrier,7 the optic disc oedema in this patient could represent an anti-GQ1b IgM complement mediated inflammatory demyelination. Furthermore, her ipsilateral delayed P100 latency is consistent with a pre-chiasmal demyelinating optic neuropathy.
In addition to her optic neuritis, this patient concomitantly demonstrated the classic features of MFS which are the acute onset of external ophthalmoplegia, ataxia of the cerebellar type, and the loss of deep tendon reflexes.1 MFS is considered a variant of Guillain-Barré syndrome (GBS) because some patients who present with MFS progress to GBS.8 High titres of anti-GQ1b IgG antibodies are present in 80% to 100% of patients with MFS.8 MFS may be immunologically differentiated from GBS by the presence of anti-GQ1b and anti-GM1 antibodies. Although both anti-GD1a IgG and anti-GM1 IgG are associated with GBS,9 anti-GM1 IgG is present in patients with typical MFS who have limb weakness,9 as in this patient. As further evidence linking this antibody to MFS,8 the decrease in anti-GQ1b antibody levels after plasmapheresis correlated with the clinical recovery in this patient. Therefore, the elevated titres of anti-GQ1b and anti-GM1 antibodies, along with the clinical triad of ophthalmoplegia, arreflexia, and ataxia in this patient all support the diagnosis of MFS, and not GBS.
In rare cases, MFS has been known to recur. This patient presented with a relapse of similar clinical features 6 months after recovery from her initial episode. In the study done by Chida et al,10 patients with recurrent MFS appeared to have similar HLA typing characteristics as the non-recurring ones. Both types shared HLA-DR2 and Cw3 alleles, but the frequency of HLA-DR2 was slightly higher in the patients with recurrent MFS.10 Therefore, this patient’s HLA-DR2-positive status may have been a risk factor for her recurrence of MFS.
This case report emphasises that optic neuritis may be a central nervous system feature that should be recognised as part of the Miller Fisher syndrome. The presence of both anti-GQ1b IgG and anti-GM1 IgG in this patient provides immunological evidence supportive of typical MFS. The delayed P100 latency in her VEP also provides electrophysiological evidence that the optic nerve is affected in anti-GQ1b antibody positive MFS. Furthermore, this is the first documented case known to the author of optic neuritis in the recurrent subtype of MFS which is associated with a higher frequency of the HLA-DR2 allele.