Miller Fisher Syndrome : a case report and clinical review
Abstract
Introduction : Miller Fisher Syndrome is considered as a benign variant of Guillain-Barre syndrome (GBS) accounting for 1% to 5% of GBS cases which manifests with the clinical triad of ataxia, areflexia, and ophthalmoplegia. The annual incidence is around 1 patient per 1 million population.
Purpose : To describe a diagnostic approach and the management a rare case of Miller Fisher Syndrome.
Case Report : A 54 year old woman came to Cicendo Eye Hospital with a chief complaint of eye movement restriction in all direction 3 weeks ago that followed by drooping both eyelids. The patient also had history of chronic cough for 3 weeks before the onset. Patient noticed imbalance and tendency to fall on either side during walking. Neurological examinations findings showed ataxic gait when the patient performed tandem gait test. Deep tendon reflexes were absent in the arms and the legs. Patient was diagnosed as Miller Fisher Syndrome. She was given oral methylprednisolon 48 mg, ranitidin 150 mg and mecobalamin 500 mg.
The patient gradually improved in symptoms including ophthalmoplegia and ataxia at 4th and 6th week follow up.
Conclusion : Diagnosis of Miller Fisher syndrome in this patient is supported by the clinical findings of acute onset ophthalmoplegia, ataxia, and areflexia following an episode of upper respiratory tractus infection. Although analysis CSF and serological testing anti GQ1B antibodies was not performed, the electromyography finding of this patient supported the clinical diagnosis. The patient had shown gradual improvement in symptoms including power, ataxia, ophthalmoplegia at 4th and 6th week follow up.
I. INTRODUCTION
Miller Fisher Syndrome (MFS) is a multifocal neuropathy, classified as an acute, autoimmune, inflammatory demyelinating disease that primarily affects peripheral neurons. Miller Fisher syndrome is considered a benign variant of Guillain Barre Syndrome (GBS) accounting for 1% to 5% of GBS cases, which manifests with the clinical triad of ataxia, areflexia, and ophthalmoplegia.
Incidence of the syndrome is not known and can vary among geographic areas.
Various authors have reported an annual incidence is around 1 patient per 1 million population, showing that the disease affects patients between 13 and 78 years of age, being more common among patients in their 40s, and more prevalent in males than in females, at a ratio of 2:1.1,2,3
Studies show that approximately 70% of cases are preceded by respiratory or intestinal tract infection. Infectious agents are believed to contribute to the formation of anti-GQ1b IgG antibodies, which were first credited as determining factors in the pathogenesis of MFS.3,4,5
II. CASE REPORT
A 54-year-old woman came to Cicendo Eye Hospital with a chief complaint of eye movements restriction in all direction that was started 3 weeks ago. It was followed by drooping both eyelids that was not differ along the day.
Patient also noticed imbalance and tendency to fall on either side during walking.
She was hospitalized 1 month ago in another hospital with complaints of general weakness and paresthesia. The patient was diagnosed by the neurologist as suspected Guillan Barre Syndrome. The patient underwent brain CT-Scan and the result was within normal limit. She reported that 3 weeks before the onset of those symptoms, she has had cough for 3 weeks that was treated by general practitioner. She admitted a history of blurred vision especially in the left eye since she was young but she has never used any spectacles. She denied history of headaches, diplopia, periorbital pain, difficulty in swallowing, breathing, trauma, or any abnormality in bladder, bowel function, and other systemic disease.
General states were within normal limit. Ophthalmologic examination on the right eye showed visual acuity of the right eye 0,32 ph 0,4 and 1/60 ph 1/60 on the left eye. Best corrected visual acuity on the right eye was 0.63 with S-2,00 D C-1,50 x90 and the left eye was 0.2 with S-16.00 D C -5,00 x90. On primary position there was esotropia 150 in Hirschberg test. It was found complete restriction of ocular movement to all directions on the both eyes. The external examination revealed ptosis of both eyes. Interpalpebral fissure (IPF) width was 3 mm, margin reflex distance 1 was -2 mm and levator function was 11mm on the right eye and intrapalpebral fissure (IPF) width was -3 mm, margin reflex distance
1 was -2 mm and levator function was 11 mm on the left eye. Intraocular pressured within normal limit. Anterior segment examination on both eyes showed opacity of the lens and others within normal limit with no relative afferent
pupillary defect. Funduscopy examination on the right eye within normal limit and on the left eye showed myopic fundus with large peripapilar chorioretina atropy. Color vision, contrast sensitivity, amsler grid and confrontation visual field were within normal limit. Ice pack test result was negatif. Neurological examinations found that she had ataxic gait with difficulty walking heel-to-toe in tandem gait test. Deep tendon reflexes were absent in the arms and the legs.
Pathologic reflexes were absent.
The patient was diagnosed as Miller Fisher Syndrome. The patient was managed with orally metylprednisolon 1 x 48 mg, ranitidin 2 x 150 mg, and mecobalamin 1 x 500 mg. She also consulted to neurological department and underwent electromyography (EMG) examinations. The EMG result showed a periphery neurogenic lesion sensoric nerve of medianus, axonal demyelinating sensoric nerve of ulnaris, axonal demyelinating motoric nerve of medianus, motoric axonal nerve of ulnaris. The EMG also showed an elongation velocity conductivity of medianus sensoric nerve and perineous and tibialis motoric nerve.
This results supported the diagnosis of mixed demyelinating (both motor &
sensory) polyneuropathy that related to Miller Fisher Syndrome.
The patient came 4 weeks and 6 weeks later and had shown gradual improvement in symptoms including power, ataxia, ophthalmoplegia. Ocular movements had improved in both eyes. The prognosis quo ad vitam and quo ad functionam in this patient were ad bonam.
Figure 2.1 A.Ptosis at initial examination, B.Ptosis improvement after at 6th week follow up B
A
Figure 2.2 Ocular Movement showed total restriction on the both eyes at initial examination
Figure 2.3. Brain CT scan showed no abnormality
Figure 2.4. Ocular movement improvement to all direction at 4th week follow up
Figure 2.5. Ocular movement significantly improved to all direction at 6th week follow up
III. DISCUSSION
Miller Fisher syndrome (MFS) is still descriptive depending on the presentation the triad of ophthalmoplegia, ataxia and areflexia. The features of MFS may also be present with signs and symptoms indicative of more widespread neuropathy. This suggests that a autoimmune mechanism similar to that of GBS is involved in the pathogenesis of MFS. 4,5,6,7,14
In this case, we diagnosed the patient as Miller Fisher Syndrome. History taking from the patient, it revealed that she had complaint restriction of eye movements in all directions. The patient also had droopy both of eyelids that started 3 weeks ago. Physical examination found ophthalmoplegia, ataxia and areflexia and ptosis at both of eyelids. According to the literature, other symptoms which may also develop include dysphagia, dysphonia, facial paralysis, and pupillary abnormalities. But there were not performed in this patient.2,3,4,9,11,12
Studies show that approximately 70% of cases are preceded (by 10 days, on average) by respiratory or intestinal tract infection. The patient also has history of chronic cough for 3 weeks before the onset of MFS which related to upper respiratory tract infection. It may induce immune-mediated reaction that could predispose the incidence of MFS. As an immune-mediated disorder, auto- antibodies may form in response to a variety of antigen stimuli, such as bacterial or viral infection. The infectious agents most commonly involved include
Haemophilus influenzae, Campylobacter jejuni, Mycoplasma pneumoniae, Epstein-Barr virus, and Cytomegalovirus and possibly others.1,5,8,9,10,13
This condition may contribute to the formation of anti-GQ1b IgG antibodies. Antecedent infectious event that initiates the process of molecular mimicry, whereby a humoral immunological attack occurs against both the infectious agent and similar host GQ1b gangliosides found on peripheral and cranial nerves that leading to myelin inflammation, conduction block, axonal degradation and loss of function of the nerve.2,5,7,8,10,14
Serological testing showed positive anti GQ1B antibodies in support of the diagnosis of MFS with a high level of sensitivity and specificity. Unfortunately, this patient was not tested for anti-GQ1b because it is not available in Indonesia.
Anti-GQ1b is usefull for determining factors in the pathogenesis of MFS which is found on both peripheral and cranial nerves and strongly expressed in the oculomotor, trochlear and abducens nerves that cause ophthalmoplegia in this patient. Ophthalmoplegia is often leading to diplopia, which is a frequent presenting symptom in patients with MFS, however because of the refractive status of this patient had anisometrop ambliopia, thus no diplopia was presented.
Ophthalmoplegia in this patient resolving after 4 and 6 week follow up.7,10,11,12, 13
Cerebrospinal Fluid (CSF) findings are also important in the diagnosis of MFS. The CSF is characterized by cytoalbuminologic dissociation, with protein elevation but no increase of white blood cell count. In a small percentage of cases, however, particularly if CSF is obtained early in the course of illness, CSF protein may be normal. Regrettably, our patient was not tested for analysis of CSF.1,7,9,10,14
Electromyography result of this patient showed mixed demyelinating in sensory and motory conduction parameters responses were consistent with a diagnosis of MFS. Electrodiagnostic studies (nerve conduction studies and Electromyography), which play a large role in confirming the diagnosis MFS.
Motor damage in the cranial nerves axonal neuropathy with predominant sensory nerve changes in the limbs was found in typical MFS.5,6,7,11,12,14
MFS is not typically associated with any abnormalities on brain imaging.
Many patients with MFS do undergo brain imaging, particularly if the triad of symptoms is not fully present, and the vast majority have normal brain MRI studies. Unfortunetly, this patient had not undergo MRI, however CT scan of the brain was normal. 3,7,8,11,14
Corticosteroid medications, such as cortisone and prednisone, were first used to treat GBS in the early 1950s. Initial reports indicated that they were effective. Otherwise various report explained that steroid resulting in the delay of recovery in GBS and their effect is difficult to judge. Madhavan demonstrated significant responsed using intravenous methyl prednisolone 1 gram once daily for 3 days by their patient. This patient was given orally metylprednisolon and mecobalamin that intend to induce remyelinitation and the patient gradually improved in symptoms including ophthalmoplegia and ataxia at 4th and 6th week follow up. 8,15,16,17,18
Being a rare disease, no randomized controlled trials have been performed in MFS, thus treatments used for GBS are usually applied to manipulation of the immune system with immunotherapy. There are two forms of immunotherapy such as intravenous immunoglobulin-G (IVIG) and plasmapheresis for GBS that have been shown to accelerate recovery. Although treatment with them has been proposed, no clinical trials have been performed to confirm a beneficial effect.
Numerous case series of patients with MFS treated with immunotherapy generally plasmapheresis, intravenous immunoglobulin-G (IVIG) or a combination including one of these have been reported, though their effectiveness is arguable.
Retrospective analyses of the largest MFS, the outcome was similar between treated and untreated subjects.4,11,13,16,17,18
MFS is a benign condition and has a good prognosis which is self-limiting.
MFS progresses for 1 to 2 weeks, but occasionally for as long as 4 weeks, then stabilizes and steadily improves. Rarely, the disease evolves to a stage that requires intensive care or mechanical ventilation, which is more common in Guillain-Barré syndrome.2,4,5,6,10,16,18
Ptosis in this patients initially suspected because of interference at the neuromuscular junction. However, an ice pack test showed a no improvement in her ptosis which was not felt to support the diagnosis of Myasthenia Gravis.
Ptosis of this patient showed spontan improvement after 6 weeks followed up.
Ptosis occurs in most patients of MFS, but associated pupillary paralysis has been reported in minority MFS by itself is a rare entity, which is a variant of GBS.2,4,9,15,16
Ataxia in this patients also have improved after 6 weeks follow-up. Ataxia, similar to ophthalmoplegia, is associated with antibodies to GQ1b ganglioside.
The pathogenesis of ataxia has yet to be determined and fully understood. Central and peripheral mechanism might be involved, comprising a proprioceptive or cerebellar component. The ataxia in MFS is due to peripheral mismatch between proprioceptive input from muscle spindles and kinesthetic information for joint receptors. Proprioception is severely impaired, and muscle spindle afferent fibers appear to be particularly involved.2,6,7,8,12,14,16
The prognosis quo ad vitam and quo ad functionam in this patient are dubia ad bonam because there were no sign of systemic deterioration along 6 weeks observations and most people fully recover and are back to normal within 2 to 3 months, although some have mild residual ataxia for longer. Diplopia and ptosis almost always completely resolve. Most patients will fully recover from ataxia and ophthalmoplegia, as well as areflexia, within 6 months after the neurological onset, with only a small percentage having residual neurological deficits.4,9,14,16,17,18
IV. CONCLUSION
Diagnosis of Miller Fisher syndrome in this patient is supported by the clinical findings of acute onset ophthalmoplegia, ataxia, and areflexia following an episode of upper respiratory tractus infection. Although analysis CSF and serological testing anti GQ1B antibodies was not performed, but electromyography finding of this patient supported our clinical diagnosis. Miller Fisher Syndrome has a good prognosis as in this patient. The patient had shown
gradual improvement in symptoms including power, ataxia, ophthalmoplegia at 4th and 6th week follow up.
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