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Postvaccination Miller Fisher Syndrome FREE

Ashkan Shoamanesh, MD; Kristine Chapman, MD; Anthony Traboulsee, MD
[+] Author Affiliations

Author Affiliations: Department of Medicine and Neurology, University of British Columbia, Vancouver, Canada.


Arch Neurol. 2011;68(10):1327-1329. doi:10.1001/archneurol.2011.236.
Text Size: A A A
Published online

ABSTRACT

Background Although postvaccination Guillain-Barré syndrome is commonly reported, there have only been 2 previously reported cases of postvaccination Miller Fisher syndrome, and none in association with the novel influenza A(H1N1) vaccine.

Objective To describe a case of Miller Fisher syndrome following receipt of the seasonal influenza and novel influenza A(H1N1) vaccine.

Design Case report and literature review.

Setting Vancouver General Hospital.

Patient A 77-year-old Chinese woman.

Results The patient presented with ophthalmoplegia, ataxia, areflexia, and a sensory neuropathy within 2 weeks of immunization. Findings of parainfectious evaluation were unremarkable. Treatment with 2 courses of intravenous immunoglobulin led to clinical improvement. Her presentation and natural history of disease were similar to the 2 previously published cases.

Conclusions We present the third case of postvaccination Miller Fisher syndrome in the literature and the first associated with the novel influenza A(H1N1) vaccine.

The benefits of the development of vaccines and the ensuing modern immunization programs are overwhelmingly without question. Nevertheless, there is a growing public concern surrounding the potential for postvaccination adverse events, a sentiment that has dwelled since their nascence.1 In view of the recent novel influenza A(H1N1) pandemic and scramble toward developing new vaccines for mass worldwide immunization campaigns, a better understanding of these potential adverse events is vital. We present a case of Miller Fisher syndrome (MFS) following seasonal influenza and novel influenza A(H1N1) vaccination, as well as a review of the literature on postvaccination MFS.

METHODS

Published cases of MFS associated with the receipt of a vaccine were obtained via a Medline search, with no date limitations, using the broad search terms (vaccine, vaccination, immunization, post-vaccination or post-immunization and Miller Fisher syndrome, Fisher or Guillain-Barré syndrome). Review articles on postvaccination autoimmunity and postvaccination neurological complications were compiled. The references of the resulting articles were screened for relevant articles.

REPORT OF A CASE

A 77-year-old self-reported ethnic Chinese woman presented in January 2010 with a 6-day history of progressive ascending dysesthesia, unsteadiness, diplopia, and nausea that commenced 13 days after immunization with the seasonal influenza and novel influenza A(H1N1) vaccine. Pertinent findings on examination included complete external ophthalmoplegia, bilateral ptosis, anisocoria, appendicular and axial ataxia, areflexia, and a moderate symmetrical glove-and-stocking sensory deficit involving all 4 primary modalities. Her medical history was remarkable for hypertension and diabetes mellitus type II. Her medications were not contributory. She had no other recent illness or travel history in the preceding 24 months.

Findings of testing of initial cerebrospinal fluid collected 7 days after symptom onset were unremarkable. However, she later demonstrated cytoalbuminologic dissociation at 16 days, with a cerebrospinal fluid protein level of 595 mg/L and white blood cell count of 1/μL. Oligoclonal banding was negative. Findings of standard serum biochemistry screening including creatine kinase, thyroid stimulating hormone, cobalamin, and folate levels were unremarkable. Findings of parainfectious evaluation including cerebrospinal fluid herpes simplex virus and varicella-zoster virus as well as serology for human immunodeficiency virus, cytomegalovirus, syphilis, and Lyme disease were negative. Magnetic resonance imaging of the brain showed patchy periventricular and deep white matter T2 fluid-attenuated inversion recovery hyperintensities suggestive of chronic small-vessel ischemic disease. These were felt to be consistent with her ischemic risk factors and age. Furthermore, none of the lesions would account for her clinical presentation. Electrophysiology was consistent with a demyelinating sensory neuropathy, with sensory nerve conduction studies demonstrating prolonged distal latencies and conduction block. Results of testing for anti-GQ1b antibody in samples collected 14 days after symptom onset were negative.

It was felt that her clinical presentation was consistent with MFS. She was treated with 2 courses of intravenous immunoglobulin, separated by a 1-week interval. Dosing was 2 g/kg, administered over 2 to 3 days. She only improved with respect to her ataxia, with the remainder of her deficits persisting on transfer to a rehabilitation facility 4 weeks following presentation.

COMMENT

Miller Fisher syndrome is a variant of Guillain-Barré syndrome (GBS), accounting for 5% to 10% of cases, with higher incidences reported in Asian populations.2,3 It is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia4 and is strongly associated with anti-GQ1b antibodies, which are present in excess of 90% of cases.5 Our patient developed MFS 13 days after immunization to both seasonal influenza and novel influenza A(H1N1). Results of testing for anti-GQ1b antibody were negative; however, the sample was collected later into the course of her illness, which can decrease its sensitivity.5,6 We were able to find 2 other cases of MFS following vaccination in the literature (Table). One occurred in a 64-year-old man 5 days after seasonal influenza vaccination and the other in a 66-year-old woman 1 week after receipt of the seasonal influenza and the Pneumovax vaccine.7,8 All cases occurred within a 2-week interval from vaccination and showed improvement following intravenous immunoglobulin treatment. Recovery was incomplete in all cases; however, this finding may be confounded by short follow-up durations. In our case, it is uncertain which vaccine, if either, was the offending agent.

Table Graphic Jump LocationTable. Cases of Postvaccination Miller Fisher Syndrome

Although postvaccination MFS specifically is rarely reported, GBS after vaccination is reported more frequently, particularly in association with the influenza vaccine. During the US novel influenza A(H1N1) vaccination campaign of 1976, the 45 million adults immunized with the A/New Jersey/8/76 swine flu vaccine were found to have a statistically significant 4- to 8-fold higher incidence of GBS than the general public. Cases occurred within 6 weeks of vaccination (P < .05), with a peak in the second and third weeks.9,10

Initially, subsequent studies spanning from 1978 to 1988 looking at the risk of post–seasonal-influenza-vaccination GBS found relative risks of 1.1 to 1.4 that were not statistically significant.1113 However, a review of cases between 1992 and 1994 found a relative risk of 1.7 (confidence interval, 1.0-2.8; P < .04).14 Overall, influenza immunization is thought to cause approximately an additional 1 case of GBS per million vaccinations. Fifteen percent of these cases result in permanent disability and 4%, in death.15 With respect to the 2009-2010 novel influenza A(H1N1) vaccination campaign, there were 0.42 and 1.75 verified cases of GBS reported to the Vaccine Adverse Event Reporting System per million vaccinations for vaccine recipients younger than 25 years and those 25 years or older, respectively, from July 1, 2009, through January 31, 2010. Based on previous studies, these rates were deemed lower than the expected background rates of GBS. Specific background rates for the period studied were, however, not provided.16 Conversely, preliminary results from the Center for Disease Control and Prevention's Emerging Infections Program shows an age-adjusted rate ratio of 1.77 (confidence interval, 1.12-2.56) in comparing the incidence of GBS among patients hospitalized through March 31, 2010, who received the 2009 novel influenza A(H1N1) vaccine and those who did not. This would correspond to an attributable risk of 0.8 excess cases of GBS per million vaccinations.17

Guillain-Barré syndrome, including MFS, is thought to be an autoimmune disorder, with molecular mimicry serving as a potential mechanism. Influenza vaccination has been shown to increase autoantibodies in humans.18 More specifically, the injection of various influenza vaccines, including the 1976 novel influenza A(H1N1), induced experimental allergic neuritislike disease in rabbits.19 Similarly, Nachamkin et al20 have shown that the 1976 novel influenza A(H1N1) vaccine can induce anti-GM1 antibodies in mice in the absence of antibodies toward Campylobacterjejuni. This was also the case with seasonal influenza vaccines. The authors proposed that the individual immunogenic properties of various influenza vaccine strains could account for the variability in GBS incidence seen from one season to another. The immunogenic potential is likely a function of the influenza virus itself, rather than the preservatives or detergents used in the manufacturing process.21 The induction of anti-GQ1b antibodies by vaccines is unexplored and worthy of research.

We present the third case of postvaccination MFS in the literature, and the first in association with the novel influenza A(H1N1) vaccine. In accordance with the World Health Organization's causality assessment criteria,22 it is “very likely” that, in our patient, disease was caused by the administration of vaccine. Postvaccination GBS, and MFS in particular, is a rare occurrence and should not deter at-risk populations from being vaccinated.

ARTICLE INFORMATION

Correspondence: Ashkan Shoamanesh, MD, Department of Medicine and Neurology, University of British Columbia, 1103-1068 W Broadway Ave, Vancouver, BC V6H 0A7, Canada (ashkan.sho@gmail.com).

Accepted for Publication: December 31, 2010.

Author Contributions:Study concept and design: Shoamanesh. Acquisition of data: Shoamanesh. Analysis and interpretation of data: Shoamanesh, Chapman, and Traboulsee. Drafting of the manuscript: Shoamanesh. Critical revision of the manuscript for important intellectual content: Chapman and Traboulsee. Administrative, technical, and material support: Shoamanesh and Traboulsee. Study supervision: Chapman and Traboulsee.

Financial Disclosure: None reported.

Additional Contributions: We would like to thank Jon Stoessl, MD, for his clinical expertise and guidance in the treatment of the patient.

REFERENCES

Brown PK. Early vaccination controversy with an original letter by Jenner.  Cal State J Med. 1914;12(5):172-177
PubMed
Willison HJ, Yuki N. Peripheral neuropathies and anti-glycolipid antibodies.  Brain. 2002;125(pt 12):2591-2625
PubMed   |  Link to Article
Mori M, Kuwabara S, Fukutake T, Yuki N, Hattori T. Clinical features and prognosis of Miller Fisher syndrome.  Neurology. 2001;56(8):1104-1106
PubMed   |  Link to Article
Fisher M. An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia).  N Engl J Med. 1956;255(2):57-65
PubMed   |  Link to Article
Chiba A, Kusunoki S, Shimizu T, Kanazawa I. Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome.  Ann Neurol. 1992;31(6):677-679
PubMed   |  Link to Article
Tan H, Caner I, Deniz O, Büyükavci M. Miller Fisher syndrome with negative anti-GQ1b immunoglobulin G antibodies.  Pediatr Neurol. 2003;29(4):349-350
PubMed   |  Link to Article
Blanco-Marchite CI, Buznego-Suárez L, Fagúndez-Vargas MA, Méndez-Llatas M, Pozo-Martos P. Miller Fisher syndrome, internal and external ophthalmoplegia after flu vaccination.  Arch Soc Esp Oftalmol. 2008;83(7):433-435
PubMed   |  Link to Article
Thaler A. Miller Fisher syndrome in a 66-year-old female after flu and pneumovax vaccinations.  J Am Med Dir Assoc. 2008;9(4):283-284
PubMed   |  Link to Article
Breman JG, Hayner NS. Guillain-Barré syndrome and its relationship to swine influenza vaccination in Michigan, 1976-1977.  Am J Epidemiol. 1984;119(6):880-889
PubMed
Schonberger LB, Bregman DJ, Sullivan-Bolyai JZ,  et al.  Guillain-Barre syndrome following vaccination in the National Influenza Immunization Program, United States, 1976-1977.  Am J Epidemiol. 1979;110(2):105-123
PubMed
Hurwitz ES, Schonberger LB, Nelson DB, Holman RC. Guillain-Barré syndrome and the 1978-1979 influenza vaccine.  N Engl J Med. 1981;304(26):1557-1561
PubMed   |  Link to Article
Kaplan JE, Schonberger LB, Hurwitz ES, Katona P. Guillain-Barré syndrome in the United States, 1978-1981: additional observations from the national surveillance system.  Neurology. 1983;33(5):633-637
PubMed   |  Link to Article
Roscelli JD, Bass JW, Pang L. Guillain-Barré syndrome and influenza vaccination in the US Army, 1980-1988.  Am J Epidemiol. 1991;133(9):952-955
PubMed
Lasky T, Terracciano GJ, Magder L,  et al.  The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 influenza vaccines.  N Engl J Med. 1998;339(25):1797-1802
PubMed   |  Link to Article
Souayah N, Nasar A, Suri MF, Qureshi AI. Guillain-Barré syndrome after vaccination in United States: data from the Centers for Disease Control and Prevention/Food and Drug Administration Vaccine Adverse Event Reporting System (1990-2005).  J Clin Neuromuscul Dis. 2009;11(1):1-6
PubMed   |  Link to Article
Vellozzi C, Broder KR, Haber P,  et al.  Adverse events following influenza A (H1N1) 2009 monovalent vaccines reported to the Vaccine Adverse Event Reporting System, United States, October 1, 2009-January 31, 2010.  Vaccine. 2010;28(45):7248-7255
PubMed   |  Link to Article
Centers for Disease Control and Prevention (CDC).  Preliminary results: surveillance for Guillain-Barré syndrome after receipt of influenza A (H1N1) 2009 monovalent vaccine - United States, 2009-2010.  MMWR Morb Mortal Wkly Rep. 2010;59(21):657-661
PubMed
Toplak N, Kveder T, Trampus-Bakija A, Subelj V, Cucnik S, Avcin T. Autoimmune response following annual influenza vaccination in 92 apparently healthy adults.  Autoimmun Rev. 2008;8(2):134-138
PubMed   |  Link to Article
Ziegler DW, Gardner JJ, Warfield DT, Walls HH. Experimental allergic neuritis-like disease in rabbits after injection with influenza vaccines mixed with gangliosides and adjuvants.  Infect Immun. 1983;42(2):824-830
PubMed
Nachamkin I, Shadomy SV, Moran AP,  et al.  Anti-ganglioside antibody induction by swine (A/NJ/1976/H1N1) and other influenza vaccines: insights into vaccine-associated Guillain-Barré syndrome.  J Infect Dis. 2008;198(2):226-233
PubMed   |  Link to Article
Hjorth RN, Bonde GM, Piner E, Hartzell RW, Rorke LB, Rubin BA. Experimental neuritis induced by a mixture of neural antigens and influenza vaccines: a possible model for Guillain-Barré syndrome.  J Neuroimmunol. 1984;6(1):1-8
PubMed   |  Link to Article
Collet JP, MacDonald N, Cashman N, Pless R.Advisory Committee on Causality Assessment.  Monitoring signals for vaccine safety: the assessment of individual adverse event reports by an expert advisory committee.  Bull World Health Organ. 2000;78(2):178-185
PubMed

Figures

Tables

Table Graphic Jump LocationTable. Cases of Postvaccination Miller Fisher Syndrome

References

Brown PK. Early vaccination controversy with an original letter by Jenner.  Cal State J Med. 1914;12(5):172-177
PubMed
Willison HJ, Yuki N. Peripheral neuropathies and anti-glycolipid antibodies.  Brain. 2002;125(pt 12):2591-2625
PubMed   |  Link to Article
Mori M, Kuwabara S, Fukutake T, Yuki N, Hattori T. Clinical features and prognosis of Miller Fisher syndrome.  Neurology. 2001;56(8):1104-1106
PubMed   |  Link to Article
Fisher M. An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia).  N Engl J Med. 1956;255(2):57-65
PubMed   |  Link to Article
Chiba A, Kusunoki S, Shimizu T, Kanazawa I. Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome.  Ann Neurol. 1992;31(6):677-679
PubMed   |  Link to Article
Tan H, Caner I, Deniz O, Büyükavci M. Miller Fisher syndrome with negative anti-GQ1b immunoglobulin G antibodies.  Pediatr Neurol. 2003;29(4):349-350
PubMed   |  Link to Article
Blanco-Marchite CI, Buznego-Suárez L, Fagúndez-Vargas MA, Méndez-Llatas M, Pozo-Martos P. Miller Fisher syndrome, internal and external ophthalmoplegia after flu vaccination.  Arch Soc Esp Oftalmol. 2008;83(7):433-435
PubMed   |  Link to Article
Thaler A. Miller Fisher syndrome in a 66-year-old female after flu and pneumovax vaccinations.  J Am Med Dir Assoc. 2008;9(4):283-284
PubMed   |  Link to Article
Breman JG, Hayner NS. Guillain-Barré syndrome and its relationship to swine influenza vaccination in Michigan, 1976-1977.  Am J Epidemiol. 1984;119(6):880-889
PubMed
Schonberger LB, Bregman DJ, Sullivan-Bolyai JZ,  et al.  Guillain-Barre syndrome following vaccination in the National Influenza Immunization Program, United States, 1976-1977.  Am J Epidemiol. 1979;110(2):105-123
PubMed
Hurwitz ES, Schonberger LB, Nelson DB, Holman RC. Guillain-Barré syndrome and the 1978-1979 influenza vaccine.  N Engl J Med. 1981;304(26):1557-1561
PubMed   |  Link to Article
Kaplan JE, Schonberger LB, Hurwitz ES, Katona P. Guillain-Barré syndrome in the United States, 1978-1981: additional observations from the national surveillance system.  Neurology. 1983;33(5):633-637
PubMed   |  Link to Article
Roscelli JD, Bass JW, Pang L. Guillain-Barré syndrome and influenza vaccination in the US Army, 1980-1988.  Am J Epidemiol. 1991;133(9):952-955
PubMed
Lasky T, Terracciano GJ, Magder L,  et al.  The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 influenza vaccines.  N Engl J Med. 1998;339(25):1797-1802
PubMed   |  Link to Article
Souayah N, Nasar A, Suri MF, Qureshi AI. Guillain-Barré syndrome after vaccination in United States: data from the Centers for Disease Control and Prevention/Food and Drug Administration Vaccine Adverse Event Reporting System (1990-2005).  J Clin Neuromuscul Dis. 2009;11(1):1-6
PubMed   |  Link to Article
Vellozzi C, Broder KR, Haber P,  et al.  Adverse events following influenza A (H1N1) 2009 monovalent vaccines reported to the Vaccine Adverse Event Reporting System, United States, October 1, 2009-January 31, 2010.  Vaccine. 2010;28(45):7248-7255
PubMed   |  Link to Article
Centers for Disease Control and Prevention (CDC).  Preliminary results: surveillance for Guillain-Barré syndrome after receipt of influenza A (H1N1) 2009 monovalent vaccine - United States, 2009-2010.  MMWR Morb Mortal Wkly Rep. 2010;59(21):657-661
PubMed
Toplak N, Kveder T, Trampus-Bakija A, Subelj V, Cucnik S, Avcin T. Autoimmune response following annual influenza vaccination in 92 apparently healthy adults.  Autoimmun Rev. 2008;8(2):134-138
PubMed   |  Link to Article
Ziegler DW, Gardner JJ, Warfield DT, Walls HH. Experimental allergic neuritis-like disease in rabbits after injection with influenza vaccines mixed with gangliosides and adjuvants.  Infect Immun. 1983;42(2):824-830
PubMed
Nachamkin I, Shadomy SV, Moran AP,  et al.  Anti-ganglioside antibody induction by swine (A/NJ/1976/H1N1) and other influenza vaccines: insights into vaccine-associated Guillain-Barré syndrome.  J Infect Dis. 2008;198(2):226-233
PubMed   |  Link to Article
Hjorth RN, Bonde GM, Piner E, Hartzell RW, Rorke LB, Rubin BA. Experimental neuritis induced by a mixture of neural antigens and influenza vaccines: a possible model for Guillain-Barré syndrome.  J Neuroimmunol. 1984;6(1):1-8
PubMed   |  Link to Article
Collet JP, MacDonald N, Cashman N, Pless R.Advisory Committee on Causality Assessment.  Monitoring signals for vaccine safety: the assessment of individual adverse event reports by an expert advisory committee.  Bull World Health Organ. 2000;78(2):178-185
PubMed

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