Neuro-ophthalmological manifestations in three cases of Miller Fisher syndrome and a brief review of literature
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.170075
Source of Support: None, Conflict of Interest: None
Miller Fisher syndrome, a variant of Guillain–Barre syndrome (GBS), is characterized by acute onset of gait ataxia, ophthalmoplegia, and areflexia. The annual incidence of Miller Fisher syndrome (MFS) is approximately one patient per one million individuals. Autoimmune neuropathies such as the GBS and MFS are regarded as diseases of the peripheral nervous system. However, there are several reports of central nervous system (CNS) involvement in MFS, which includes optic neuritis and internal ophthalmoplegia. There can be involvement of the ocular motor nerves, the brainstem, or the cerebellum in some cases.
Disturbances of consciousness, oculomotor signs, electroencephalographic abnormalities, computed tomography findings and magnetic resonance imaging (MRI) findings have been reported as evidence for CNS involvement in MFS. The prognosis of MFS is good., Contrast enhancement of the nerve roots and MRI evidence of CNS involvement reported in a few cases support the hypothesis of an anti-GQ1b syndrome. Randomized trials for defining the specific management of MFS are lacking at present.
Three patients who attended the neurological services at a tertiary care university hospital in South India and fulfilling the criteria for MFS along with neuro-ophthalmological manifestations were studied prospectively from 2012 to 2014, and their clinical course, neurophysiology, radiological findings, and response to treatment are described. We report two cases of MFS with bilateral demyelinating optic neuropathy and one case of MFS with areflexic mydriasis.
A 55-year-old man presented with a history of bifacial weakness for 7 days, binocular vertical diplopia, drooping of the left eyelid, and difficulty in reading small newspaper prints for 3 days along with blurred vision without any limb weakness. There was antecedent history of fever with myalgia and joint pains. In the left eye, there was partial ptosis, restricted adduction, depression, and intortion. The left pupil was 5-mm dilated and not reacting to light. The right pupil was 4-mm dilated with sluggish reaction. Accommodation and convergence were impaired. Bilateral lower motor neuron-type facial paresis and flaccid dysarthria were observed. He had mild shoulder abductor and elbow extensor weakness. Sensory system was normal. Diffuse areflexia was observed.
With internal ophthalmoplegia (areflexic mydriasis), oculomotor and facial nerve palsy, mild motor weakness, areflexia, and ataxia, a possibility of MFS was considered. The cerebrospinal fluid (CSF) protein level was 139 mg%, with six cells. His brain MRI was normal. The nerve conduction study results were normal except for absent F wave in the right common peroneal nerve. Facial nerve was inexcitable. Blink reflex and H reflex were absent. He received a short course of parenteral steroids followed by oral steroids for a month.
After 5 days of treatment, the ptosis improved. Subsequently, his diplopia, external ophthalmoplegia, and ataxia improved. During the follow-up after 2 months, bifacial weakness had improved partially, and motor system appeared normal. Pupillary anisocoria persisted along with sluggish reaction.
A 19-year-old young woman presented with bilateral drooping of the eyelids, double vision with vertical separation of images, restriction of eye movements, headache, and blurring of vision for 7 days. A history of simultaneous onset of tingling and paresthesia of both hands and feet was present. She also had a history of swaying while walking, with requirement of one person's support to walk. The duration from onset to peak of the illness was 3 days and the course plateaued for 1 week. There was an antecedent history of fever for 3 days, 10 days ago.
On examination, visual acuity was finger counting at 0.5 meters, and concentric constriction of visual fields was present, as documented by perimetery. Bilateral ptosis was present. All extraocular movements were restricted. Pupils were bilaterally dilated with a sluggish reaction. Fundi were normal. Motor and sensory systems were normal with absent reflexes. Bilateral finger–nose and knee–heel incoordination were observed. Gait ataxia was also noted.
Her motor and sensory conductions were normal. The brain MRI was normal. Her visual evoked potential (VEP) scan showed prolongation of latencies bilaterally. Right P100 was 114.6 and left, 113.1 with a low amplitude. CSF protein level was 63 mg%, with three cells. The vasculitic workup and autoantibody profile were negative.
She was given a pulse therapy of methylprednisolone parenterally. After 6 days of treatment, the eye movements improved, but visual acuity deficit and ataxia persisted. Hence, she was started on three large-volume plasmapheresis exchanges. Gradually, visual acuity improved to 6/18 bilaterally, and eye movements, headache, ptosis, and ataxia also improved. On the 15th day, at discharge, the reflexes were elicitable. She was given a short course of tapering oral steroids for a month. During follow-up after 1 month, her condition had completely improved and she had no deficits.
A 60-year-old hypertensive woman presented with a history of headache for 2 days followed by acute onset of dizziness, nausea, binocular double vision, blurred vision, and swaying to the right while walking. She also had a history of transient difficulty in swallowing, which subsequently improved. Distal paresthesias of hands and soles were observed. The duration between onset to peak of the clinical manifestations was 3 days and course of the illness reached a plateau for 10 days. On examination, the blood pressure was 170/100 mm of Hg. She had bilateral ptosis, complete external ophthalmoplegia, and normal pupils. Visual fields were normal. Bilateral nuclear sclerosis grade I was present, and disc and macula were normal. She had hypopigmented areas at posterior pole in both eyes suggestive of retinal pigmentary epitheliopathy, which was unrelated to the present visual problem. Her visual acuity of the right eye was 3/60 and the left eye was 3/60 at admission. There was mild finger–nose and knee–heel incoordination along with gait ataxia. Motor sensory examination was normal, with reflexes being sluggish. The possibility of MFS versus vertebrobasilar insufficiency was considered.
The brain MRI and MR angiography results were normal. Echocardiography revealed hypertensive heart disease, and Doppler scan of the neck was normal. CSF examination revealed a protein level of 75 mg%, with no cells. Motor conduction was normal, and sensory nerve action potential was absent. H reflex was absent in bilateral lower limbs. The right eye VEP scan showed prolonged P100 of 122.7 with dispersed waveforms [Figure 1]; on the left, it was 107.7. This suggested a bilateral demyelinating optic neuropathy. Therefore, a diagnosis of MFS with optic neuropathy was considered. Five large-volume plasmapheresis exchanges resulted in the gradual improvement in visual acuity over the next 10 days to 6/24 bilaterally, and significant improvement in ataxia.
Antiganglioside estimation was not performed in our patients due to nonavailability of the antibody kits.
The most common presenting symptom of MFS is diplopia, which arises due to complete bilateral external ophthalmoplegia. Other ophthalmological abnormalities include partial ptosis; lid retraction; upper lid retraction on attempted up gaze and preserved Bell's phenomenon; upper lid jerks; internuclear ophthalmoplegia; chronic ophthalmoplegia; divergence paralysis; partial sparing of the levator palpebrae superioris; Parinaud's syndrome; defective vestibulo-ocular reflex; convergence spasm; convergence failure; isolated abducens nerve palsy; horizontal dissociated nystagmus; rotatory, retractory, and rebound nystagmus; and acute angle closure.,, Pupillary abnormalities can include mydriasis, anisocoria, and a sluggish direct response to light. Facial nerve involvement occurs in approximately 30% of patients and causes lagophthalmos.
We have described two MFS patients with demyelinating optic neuropathy similar to reports described by Colding-Jørgensen et al., (2001), Lolekha et al., (2008), Colding-Jørgensen et al., (2001), Toshniwal et al., (1987), and Carvalho et al., (2003).,,, High titers of anti-GQ1b IgG antibodies are present in 80–100% of patients with MFS, and this helps to differentiate it from GBS. Immunohistochemical studies have shown preferential location of GQ1b gangliosides in the oculomotor, trochlear, optic, and abducens nerves, in accordance with the ophthalmoplegia in MFS. The human optic nerve contains high levels of sulfated glucuronyl glycolipids and gangliosides, such as GD1b, GQ1b, and GT1b. The involvement of both peripheral and optic nerves in GBS may result from these shared pathogenic epitopes. Optic nerve involvement may be part of a spectrum of CNS involvement. Only five cases of optic nerve involvement in MFS have been documented in the literature.
Mydriasis is present in 35–50% of typical MFS. There are several reports of MFS presenting as acute bilateral mydriasis, either isolated or associated with external ophthalmoplegia with positive anti-GQ1b antibodies.,,,, Radziwill et al., demonstrated the presence of denervation supersensitivity of the pupillary sphincter muscles by testing with dilute pilocarpine (0.1%), which induced miosis. This may occur due to an immunopathological involvement of the ciliary ganglion by anti-GQ1b.
Odaka et al., introduced the term "anti-GQ1b antibody syndrome" to designate different illnesses in which anti-GQ1b antibodies are found, and suggested a common autoimmune mechanism. MFS, acute ophthalmoparesis (AO), Bickerstaff's brainstem encephalitis, and GBS form a continuous spectrum of this syndrome. Recognition of this syndrome is useful for understanding the etiological relationship among the various illnesses and for introducing the established treatments of GBS.
MFS can have various neuro-ophthalmological manifestations, including optic neuropathy and areflexic mydriasis. Prompt awareness is required to provide the available treatment protocols. Knowledge regarding anti-GQ1 autoantibodies is expanding the clinical spectrum of MFS.
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