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Anti-GQ1b-Negative Miller Fisher Syndrome After Campylobacter jejuni Enteritis
Pediatric Neurology 47 (2012) 213e215
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Case Report
Anti-GQ1b-Negative Miller Fisher Syndrome After Campylobacter jejuni Enteritis Kyung Yeon Lee MD * Department of Pediatrics, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea
article information
abstract
Article history: Received 9 March 2012 Accepted 30 April 2012
Miller Fisher syndrome is a clinical variant of Guillain-Barré syndrome, characterized by acute-onset ophthalmoplegia, ataxia, and areflexia. It results from an immune response to a cross-reactive antigen between GQ1b ganglioside in human neurons and lipooligosaccharides of certain bacteria, e.g., Campylobacter jejuni. Anti-GQ1b antibody is a powerful diagnostic marker for Miller Fisher syndrome. However, only a small number of anti-GQ1b-negative Miller Fisher syndrome cases are documented. A 13-year-old boy demonstrated typical clinical features of Miller Fisher syndrome 1 week after C. jejuni enteritis, but was anti-GQ1b and anti-GM1b antibody-negative. Ó 2012 Elsevier Inc. All rights reserved.
Introduction
Miller Fisher syndrome is a clinical variant of GuillainBarré syndrome, characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia [1]. The discovery of the GQ1b ganglioside antibody in patients with Miller Fisher syndrome has led to advances in understanding the pathogenesis of Miller Fisher syndrome [2]. Because of the molecular mimicry between GQ1b ganglioside in the neuronal cell surfaces of humans and lipo-oligosaccharides in the outer membranes of certain bacteria, such as Campylobacter jejuni, anti-GQ1b antibody generated in bacterially infected patients can cause Miller Fisher syndrome [3]. However, a small number of patients with Miller Fisher syndrome were also documented to manifest antibodies against isolated gangliosides other than GQ1b or ganglioside complexes [4,5]. In the present case, clinically typical Miller Fisher syndrome developed after C. jejuni enteritis, but the patient was negative for anti-GQ1b antibody. Case Report A 13-year-old boy was admitted to the emergency department of our hospital because of diplopia, left ptosis, and unsteadiness that began * Communications should be addressed to: Dr. Lee; Department of Pediatrics; Ulsan University Hospital; 290-3 Jeonha-Dong; Dong-Gu, Ulsan 682-714, Republic of Korea. E-mail address: [email protected]. 0887-8994/$ - see front matter Ó 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2012.04.024
abruptly on the previous day. He had manifested severe diarrhea 1 week earlier. At that time, he was diagnosed with acute enterocolitis, and was managed at a local clinic. The diarrhea resolved within 3 days, but the signs of diplopia, left ptosis, and unsteadiness appeared on the day before admission. He was previously healthy, and was fully vaccinated according to schedule. No history of medication or toxic substances and no history of head trauma were reported. On arrival at the emergency department, he could not stand nor walk steadily. On neurologic examination, he was fully alert, but his pupils were anisocoric (left, 5 mm; right, 3 mm), and the light reflex of his left eye was sluggish. He demonstrated ptosis of the left eyelid and a complete failure of left eye movements in all directions. His right eye movements were intact, and ptosis of the right eyelid was absent. Neither swallowing problems nor facial palsy was evident. He did not exhibit motor weakness in his four extremities. Pain and light touch sensations were intact. He was unable to perform the finger-to-nose test and rapid alternating movements well, in particular on his left side. Results of a heel-to-shin test and tandem gait findings were abnormal. Deep tendon reflexes, including both knee jerks, were absent. The Babinski sign on both sides was absent. A complete blood count, serum biochemistry, C-reactive protein analysis, routine urine analysis, and a chest radiograph produced results within normal limits. Cerebrospinal fluid analysis, which was performed on the second day, revealed a normal protein content (26 mg/dL) and cell count (leukocytes, 0/mm3; erythrocytes, 3/mm3). Blood, urine, stool, and cerebrospinal fluid cultures produced negative results. Cultures for C. jejuni in stool and cerebrospinal fluid specimens also revealed negative results. However, an enzyme-linked immunosorbent assay for the serum C. jejuni antibody produced positive results (1.72; positive, 1.1). AntiGQ1b immunoglobulin G/immunoglobulin M and anti-GM1b immunoglobulin G/immunoglobulin M levels, which were determined on the second day, were all negative. Mycoplasma antibody titers, which were performed twice on the second and thirteenth days, yielded results of
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K.Y. Lee / Pediatric Neurology 47 (2012) 213e215
1:160 and 1:80, respectively. Electromyography and a nerve conduction study indicated that the F-wave in both ulnar nerves and H-reflexes in the right gastrocnemius muscle were absent. A repetitive nerve stimulation test was not performed. Visual evoked potential, brainstem auditory evoked potential, and blink reflex were normal. Cranial and spinal magnetic resonance imaging, performed on the second and third days, respectively, did not reveal any abnormality. On the second day, the patient demonstrated ptosis of the right eyelid and a limitation of right eye movements in all directions as well as on the left side. On the third and fourth days, intravenous immunoglobulin (1 g/kg/day) was administered. On the seventh day, he was able to stand on his own and begin to walk. On the eleventh day, he was able to walk independently. The ptosis of both eyelids improved, predominantly on the right side. On the thirteenth day, he could walk up and down stairs without assistance. He was discharged on the fourteenth day. Two months later, he complained of intermittent diplopia and demonstrated minimal limitation in the nasal gaze of his left eye. Although he was able to perform well on the fingerto-nose test, rapid alternating movements, and heel-to-shin test, his tandem gait was abnormal. After 3 months, his diplopia continued to improve and he could perform the tandem gait exercise. Both knee jerks remained decreased at that time.
Discussion
Miller Fisher syndrome is a clinical variant of GuillainBarré syndrome, characterized by a clinical triad of acute-onset ophthalmoplegia, ataxia, and areflexia, with a relative sparing of strength in the extremities and trunk [1]. In 1956, Charles Miller Fisher reported on three patients with this disorder, and postulated that it represented a distinct clinical variant of Guillain-Barré syndrome with a good prognosis, because one of his patients had demonstrated cerebrospinal fluid albuminocytologic dissociation [1]. In 1992, the discovery of immunoglobulin G antibodies against GQ1b ganglioside in patients with Miller Fisher syndrome inaugurated a new era in research on the pathogenesis of Miller Fisher syndrome [2]. Subsequent study revealed that a monoclonal anti-GQ1b antibody immunostained the paranodal regions of the extramedullary portions of the human oculomotor, trochlear, and abducens nerves, and that the human oculomotor nerve contained a larger amount of GQ1b [6]. The detection rate of antiGQ1b antibodies in patients with Miller Fisher syndrome was estimated at between 83% and 100% [3]. These antibodies are now widely used as a diagnostic marker for Miller Fisher syndrome. Anti-GQ1b immunoglobulin G antibody titers peak at disease onset and then decrease with time, whereas cerebrospinal fluid albuminocytologic dissociation is present in only 25% of patients with Miller Fisher syndrome during the first week, but is present in 84% during the third week [3]. On the other hand, C. jejuni is the most frequently identified antecedent agent in Miller Fisher syndrome [7]. Monoclonal antibodies against the GQ1b ganglioside were demonstrated to react to lipo-oligosaccharide fractions from C. jejuni isolated in patients with Miller Fisher syndrome [3]. This case involved typical clinical Miller Fisher syndrome, including an acute onset of ophthalmoplegia, ataxia, and areflexia without limb muscle weakness, although bilateral ophthalmoplegia appeared one after another. However, the anti-GQ1b antibody-negative status of this patient was unexpected because of his typical manifestations of Miller Fisher syndrome after infection with C. jejuni, which is the representative bacterium related
to anti-GQ1b antibody in the pathogenesis of Miller Fisher syndrome, as already mentioned. Anti-GQ1b antibody-negative cases in clinically typical Miller Fisher syndrome are rare. However, several individual case reports described anti-GQ1b-negative Miller Fisher syndrome, most of which involved atypical Miller Fisher syndrome, e.g., early infantile onset (in a 2-year-old patient), one-sided horizontal gaze palsy, overlapping features of Miller Fisher syndrome and Guillain-Barré syndrome, and the complication of Burkitt lymphoma, irrespective of coexisting anti-ganglioside antibodies [8-11]. Recently, however, antibodies against isolated gangliosides other than GQ1b, ganglioside complexes, or ganglioside-like lipo-oligosaccharides other than GQ1b-like lipo-oligosaccharides were identified in patients with Miller Fisher syndrome [4,5,12]. Kimoto et al. reported that 22 (16%) of 139 patients with C. jejuni-isolated neuropathy developed Miller Fisher syndrome, and two (9%) of these 22 patients were anti-GQ1b or anti-GT1a antibody-negative, whereas four (18%) were anti-GM1 or anti-GD1a antibody-positive [4]. The most recent investigation by Koga et al. revealed that the clinical features of anti-GQ1b-negative Miller Fisher syndrome were similar to those of anti-GQ1b-positive Miller Fisher syndrome, except for an extreme male predominance and a history of antecedent gastrointestinal illness [5]. In addition, immunoglobulin G antibodies against heterologous ganglioside complexes, as well as isolated GM1b, GD1c, and GalNAc-GM1b ganglioside, were revealed to be serologic markers of anti-GQ1b-negative Miller Fisher syndrome [5]. Among the 24 patients with anti-GQ1b-negative Miller Fisher syndrome, three with serologic evidence of recent C. jejuni infection tested positive for the immunoglobulin G antibody against GD1a and GalNAc-GD1a, GM1/GT1a and GM1/GQ1b, and several ganglioside-like lipo-oligosaccharides, respectively. The authors suggested that antibodies against gangliosides other than GQ1b play a pathogenic role in the development of Miller Fisher syndrome. The present case may also support the suggestion of Koga et al., although no antibody against gangliosides, including GQ1b, was detected. More efforts to identify antibodies against other gangliosides, as well as GQ1b, even when evaluating patients with typical Miller Fisher syndrome, appear necessary to elucidate the pathogenesis of Miller Fisher syndrome more clearly. Moreover, the need exists to determine why a small subset of patients with Miller Fisher syndrome tests positive for antibodies against gangliosides other than GQ1b. To the best of our knowledge, this case report is the first to describe typical clinical Miller Fisher syndrome developing after C. jejuni enteritis, but with negative test results for the anti-GQ1b antibody. This finding suggests that other mechanisms may be relevant in the development of Miller Fisher syndrome in addition to the presence of the antiGQ1b antibody, such as the presence of antibodies against gangliosides other than GQ1b. References [1] Fisher M. An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia). N Engl J Med 1956;255:57e65. [2] 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;31:677e9.
K.Y. Lee / Pediatric Neurology 47 (2012) 213e215 [3] Yuki N. Fisher syndrome and Bickerstaff brainstem encephalitis (Fisher-Bickerstaff syndrome). J Neuroimmunol 2009;215:1e9. [4] Kimoto K, Koga M, Odaka M, et al. Relationship of bacterial strains to clinical syndromes of Campylobacter-associated neuropathies. Neurology 2006;67:1837e43. [5] Koga M, Gilbert M, Takahashi M, et al. GQ1b-seronegative Fisher syndrome: Clinical features and new serological markers. J Neurol 2012;259:1366e74. [6] Chiba A, Kusunoki S, Obata H, Machinami R, Kanazawa I. Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barré syndrome: Clinical and immunohistochemical studies. Neurology 1993;43:1911e7. [7] Koga M, Gilbert M, Li J, et al. Antecedent infections in Fisher syndrome: A common pathogenesis of molecular mimicry. Neurology 2005;64:1605e11.
215
[8] Tan H, Caner I, Deniz O, Buyukavci M. Miller Fisher syndrome with negative anti-GQ1b immunoglobulin G antibodies. Pediatr Neurol 2003;29:349e50. [9] Akinci G, Oztura I, Hiz-Kurul S. Anti-GQ1b-negative Miller Fisher syndrome presented with one-sided horizontal gaze palsy. Turk J Pediatr 2010;52:317e20. [10] Hayashi Y, Koga M, Takahashi M, Uchida A, Yuki N. Anti-GQ1b IgG-negative case of overlapping Fisher’s and Gullain-Barré syndromes after Campylobacter jejuni (Pen 19) enteritis. Rinsho Shinkeigaku 2001;41:801e4. [11] Gentile S, Messina M, Rainero I, Lo Giudice R, De Martino P, Pinessi L. Miller Fisher syndrome associated with Burkitt’s lymphoma. Eur J Neurol 2006;13:430. [12] Mori M, Kuwabara S, Yuki N. Fisher syndrome: Clinical features, immunopathogenesis and management. Expert Rev Neurother 2012;12:39e51.
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Case Report
Anti-GQ1b-Negative Miller Fisher Syndrome After Campylobacter jejuni Enteritis Kyung Yeon Lee MD * Department of Pediatrics, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea
article information
abstract
Article history: Received 9 March 2012 Accepted 30 April 2012
Miller Fisher syndrome is a clinical variant of Guillain-Barré syndrome, characterized by acute-onset ophthalmoplegia, ataxia, and areflexia. It results from an immune response to a cross-reactive antigen between GQ1b ganglioside in human neurons and lipooligosaccharides of certain bacteria, e.g., Campylobacter jejuni. Anti-GQ1b antibody is a powerful diagnostic marker for Miller Fisher syndrome. However, only a small number of anti-GQ1b-negative Miller Fisher syndrome cases are documented. A 13-year-old boy demonstrated typical clinical features of Miller Fisher syndrome 1 week after C. jejuni enteritis, but was anti-GQ1b and anti-GM1b antibody-negative. Ó 2012 Elsevier Inc. All rights reserved.
Introduction
Miller Fisher syndrome is a clinical variant of GuillainBarré syndrome, characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia [1]. The discovery of the GQ1b ganglioside antibody in patients with Miller Fisher syndrome has led to advances in understanding the pathogenesis of Miller Fisher syndrome [2]. Because of the molecular mimicry between GQ1b ganglioside in the neuronal cell surfaces of humans and lipo-oligosaccharides in the outer membranes of certain bacteria, such as Campylobacter jejuni, anti-GQ1b antibody generated in bacterially infected patients can cause Miller Fisher syndrome [3]. However, a small number of patients with Miller Fisher syndrome were also documented to manifest antibodies against isolated gangliosides other than GQ1b or ganglioside complexes [4,5]. In the present case, clinically typical Miller Fisher syndrome developed after C. jejuni enteritis, but the patient was negative for anti-GQ1b antibody. Case Report A 13-year-old boy was admitted to the emergency department of our hospital because of diplopia, left ptosis, and unsteadiness that began * Communications should be addressed to: Dr. Lee; Department of Pediatrics; Ulsan University Hospital; 290-3 Jeonha-Dong; Dong-Gu, Ulsan 682-714, Republic of Korea. E-mail address: [email protected]. 0887-8994/$ - see front matter Ó 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2012.04.024
abruptly on the previous day. He had manifested severe diarrhea 1 week earlier. At that time, he was diagnosed with acute enterocolitis, and was managed at a local clinic. The diarrhea resolved within 3 days, but the signs of diplopia, left ptosis, and unsteadiness appeared on the day before admission. He was previously healthy, and was fully vaccinated according to schedule. No history of medication or toxic substances and no history of head trauma were reported. On arrival at the emergency department, he could not stand nor walk steadily. On neurologic examination, he was fully alert, but his pupils were anisocoric (left, 5 mm; right, 3 mm), and the light reflex of his left eye was sluggish. He demonstrated ptosis of the left eyelid and a complete failure of left eye movements in all directions. His right eye movements were intact, and ptosis of the right eyelid was absent. Neither swallowing problems nor facial palsy was evident. He did not exhibit motor weakness in his four extremities. Pain and light touch sensations were intact. He was unable to perform the finger-to-nose test and rapid alternating movements well, in particular on his left side. Results of a heel-to-shin test and tandem gait findings were abnormal. Deep tendon reflexes, including both knee jerks, were absent. The Babinski sign on both sides was absent. A complete blood count, serum biochemistry, C-reactive protein analysis, routine urine analysis, and a chest radiograph produced results within normal limits. Cerebrospinal fluid analysis, which was performed on the second day, revealed a normal protein content (26 mg/dL) and cell count (leukocytes, 0/mm3; erythrocytes, 3/mm3). Blood, urine, stool, and cerebrospinal fluid cultures produced negative results. Cultures for C. jejuni in stool and cerebrospinal fluid specimens also revealed negative results. However, an enzyme-linked immunosorbent assay for the serum C. jejuni antibody produced positive results (1.72; positive, 1.1). AntiGQ1b immunoglobulin G/immunoglobulin M and anti-GM1b immunoglobulin G/immunoglobulin M levels, which were determined on the second day, were all negative. Mycoplasma antibody titers, which were performed twice on the second and thirteenth days, yielded results of
214
K.Y. Lee / Pediatric Neurology 47 (2012) 213e215
1:160 and 1:80, respectively. Electromyography and a nerve conduction study indicated that the F-wave in both ulnar nerves and H-reflexes in the right gastrocnemius muscle were absent. A repetitive nerve stimulation test was not performed. Visual evoked potential, brainstem auditory evoked potential, and blink reflex were normal. Cranial and spinal magnetic resonance imaging, performed on the second and third days, respectively, did not reveal any abnormality. On the second day, the patient demonstrated ptosis of the right eyelid and a limitation of right eye movements in all directions as well as on the left side. On the third and fourth days, intravenous immunoglobulin (1 g/kg/day) was administered. On the seventh day, he was able to stand on his own and begin to walk. On the eleventh day, he was able to walk independently. The ptosis of both eyelids improved, predominantly on the right side. On the thirteenth day, he could walk up and down stairs without assistance. He was discharged on the fourteenth day. Two months later, he complained of intermittent diplopia and demonstrated minimal limitation in the nasal gaze of his left eye. Although he was able to perform well on the fingerto-nose test, rapid alternating movements, and heel-to-shin test, his tandem gait was abnormal. After 3 months, his diplopia continued to improve and he could perform the tandem gait exercise. Both knee jerks remained decreased at that time.
Discussion
Miller Fisher syndrome is a clinical variant of GuillainBarré syndrome, characterized by a clinical triad of acute-onset ophthalmoplegia, ataxia, and areflexia, with a relative sparing of strength in the extremities and trunk [1]. In 1956, Charles Miller Fisher reported on three patients with this disorder, and postulated that it represented a distinct clinical variant of Guillain-Barré syndrome with a good prognosis, because one of his patients had demonstrated cerebrospinal fluid albuminocytologic dissociation [1]. In 1992, the discovery of immunoglobulin G antibodies against GQ1b ganglioside in patients with Miller Fisher syndrome inaugurated a new era in research on the pathogenesis of Miller Fisher syndrome [2]. Subsequent study revealed that a monoclonal anti-GQ1b antibody immunostained the paranodal regions of the extramedullary portions of the human oculomotor, trochlear, and abducens nerves, and that the human oculomotor nerve contained a larger amount of GQ1b [6]. The detection rate of antiGQ1b antibodies in patients with Miller Fisher syndrome was estimated at between 83% and 100% [3]. These antibodies are now widely used as a diagnostic marker for Miller Fisher syndrome. Anti-GQ1b immunoglobulin G antibody titers peak at disease onset and then decrease with time, whereas cerebrospinal fluid albuminocytologic dissociation is present in only 25% of patients with Miller Fisher syndrome during the first week, but is present in 84% during the third week [3]. On the other hand, C. jejuni is the most frequently identified antecedent agent in Miller Fisher syndrome [7]. Monoclonal antibodies against the GQ1b ganglioside were demonstrated to react to lipo-oligosaccharide fractions from C. jejuni isolated in patients with Miller Fisher syndrome [3]. This case involved typical clinical Miller Fisher syndrome, including an acute onset of ophthalmoplegia, ataxia, and areflexia without limb muscle weakness, although bilateral ophthalmoplegia appeared one after another. However, the anti-GQ1b antibody-negative status of this patient was unexpected because of his typical manifestations of Miller Fisher syndrome after infection with C. jejuni, which is the representative bacterium related
to anti-GQ1b antibody in the pathogenesis of Miller Fisher syndrome, as already mentioned. Anti-GQ1b antibody-negative cases in clinically typical Miller Fisher syndrome are rare. However, several individual case reports described anti-GQ1b-negative Miller Fisher syndrome, most of which involved atypical Miller Fisher syndrome, e.g., early infantile onset (in a 2-year-old patient), one-sided horizontal gaze palsy, overlapping features of Miller Fisher syndrome and Guillain-Barré syndrome, and the complication of Burkitt lymphoma, irrespective of coexisting anti-ganglioside antibodies [8-11]. Recently, however, antibodies against isolated gangliosides other than GQ1b, ganglioside complexes, or ganglioside-like lipo-oligosaccharides other than GQ1b-like lipo-oligosaccharides were identified in patients with Miller Fisher syndrome [4,5,12]. Kimoto et al. reported that 22 (16%) of 139 patients with C. jejuni-isolated neuropathy developed Miller Fisher syndrome, and two (9%) of these 22 patients were anti-GQ1b or anti-GT1a antibody-negative, whereas four (18%) were anti-GM1 or anti-GD1a antibody-positive [4]. The most recent investigation by Koga et al. revealed that the clinical features of anti-GQ1b-negative Miller Fisher syndrome were similar to those of anti-GQ1b-positive Miller Fisher syndrome, except for an extreme male predominance and a history of antecedent gastrointestinal illness [5]. In addition, immunoglobulin G antibodies against heterologous ganglioside complexes, as well as isolated GM1b, GD1c, and GalNAc-GM1b ganglioside, were revealed to be serologic markers of anti-GQ1b-negative Miller Fisher syndrome [5]. Among the 24 patients with anti-GQ1b-negative Miller Fisher syndrome, three with serologic evidence of recent C. jejuni infection tested positive for the immunoglobulin G antibody against GD1a and GalNAc-GD1a, GM1/GT1a and GM1/GQ1b, and several ganglioside-like lipo-oligosaccharides, respectively. The authors suggested that antibodies against gangliosides other than GQ1b play a pathogenic role in the development of Miller Fisher syndrome. The present case may also support the suggestion of Koga et al., although no antibody against gangliosides, including GQ1b, was detected. More efforts to identify antibodies against other gangliosides, as well as GQ1b, even when evaluating patients with typical Miller Fisher syndrome, appear necessary to elucidate the pathogenesis of Miller Fisher syndrome more clearly. Moreover, the need exists to determine why a small subset of patients with Miller Fisher syndrome tests positive for antibodies against gangliosides other than GQ1b. To the best of our knowledge, this case report is the first to describe typical clinical Miller Fisher syndrome developing after C. jejuni enteritis, but with negative test results for the anti-GQ1b antibody. This finding suggests that other mechanisms may be relevant in the development of Miller Fisher syndrome in addition to the presence of the antiGQ1b antibody, such as the presence of antibodies against gangliosides other than GQ1b. References [1] Fisher M. An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia). N Engl J Med 1956;255:57e65. [2] 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;31:677e9.
K.Y. Lee / Pediatric Neurology 47 (2012) 213e215 [3] Yuki N. Fisher syndrome and Bickerstaff brainstem encephalitis (Fisher-Bickerstaff syndrome). J Neuroimmunol 2009;215:1e9. [4] Kimoto K, Koga M, Odaka M, et al. Relationship of bacterial strains to clinical syndromes of Campylobacter-associated neuropathies. Neurology 2006;67:1837e43. [5] Koga M, Gilbert M, Takahashi M, et al. GQ1b-seronegative Fisher syndrome: Clinical features and new serological markers. J Neurol 2012;259:1366e74. [6] Chiba A, Kusunoki S, Obata H, Machinami R, Kanazawa I. Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barré syndrome: Clinical and immunohistochemical studies. Neurology 1993;43:1911e7. [7] Koga M, Gilbert M, Li J, et al. Antecedent infections in Fisher syndrome: A common pathogenesis of molecular mimicry. Neurology 2005;64:1605e11.
215
[8] Tan H, Caner I, Deniz O, Buyukavci M. Miller Fisher syndrome with negative anti-GQ1b immunoglobulin G antibodies. Pediatr Neurol 2003;29:349e50. [9] Akinci G, Oztura I, Hiz-Kurul S. Anti-GQ1b-negative Miller Fisher syndrome presented with one-sided horizontal gaze palsy. Turk J Pediatr 2010;52:317e20. [10] Hayashi Y, Koga M, Takahashi M, Uchida A, Yuki N. Anti-GQ1b IgG-negative case of overlapping Fisher’s and Gullain-Barré syndromes after Campylobacter jejuni (Pen 19) enteritis. Rinsho Shinkeigaku 2001;41:801e4. [11] Gentile S, Messina M, Rainero I, Lo Giudice R, De Martino P, Pinessi L. Miller Fisher syndrome associated with Burkitt’s lymphoma. Eur J Neurol 2006;13:430. [12] Mori M, Kuwabara S, Yuki N. Fisher syndrome: Clinical features, immunopathogenesis and management. Expert Rev Neurother 2012;12:39e51.