125 St. Marianna Med. J. Vol. 34, pp. 125῏128, 2006
Ataxic Form of Guillain-Barre ´Syndrome: Di#erential Diagnosis of Acute Cerebellar Ataxia Jun Ohshima and Shunji Yasaki ῌReceived for Publication: April 20, 2006῍ Abstract A 52-year-old man experienced fever, sore throat, and rhinorrhea for several days. Some days after resolution he developed dizziness, paresthesia on the hands, and unsteady gait. Ocular movement was not limited. His gait was ataxic and no limb weakness on Romberg sign was evident. Muscle stretch reﬂexes were absent. Acute cerebellar ataxia was suspected. Anti-GQ1b antibody, however, was detected in his serum during the acute phase of the illness. Ataxic form of Guillain-Barre ´ syndrome was diagnosed. Ataxic Guillain-Barre ´syndrome is one of the di#erential diagnoses for acute cerebellar ataxia. Key Words cerebellar ataxia, anti-GQ1b antibody, ganglioside, Guillain-Barre ´syndrome, Miller Fisher syndrome
able gait unsteadiness that prohibited walking and had sensations of ﬂoating, dizziness, and tingling in his hands. He did not experience double vision. His medical history was unremarkable except for having right peripheral facial palsy at 22 years of age. He consulted a physician at our hospital in late May 1999 for sensations of ﬂoating. He was treated for 7 days with peroral prednisolone ῌ30 mg῎day῍ but admitted 9 days later because of increased di$culty in walking. Upon admission, he had no fever and a general physical examination was normal. He was alert and his mental state and higher brain function were normal. The pupils were isocoric having a round shape. The light reﬂex was prompt and the convergence reﬂex was normal. External ocular movements were una#ected. Examination revealed a horizontal gaze-evoked nystagmus. The other cranial nerves were normal. He had no motor paralysis in the limbs and his sensory system was normal. Romberg sign was negative. Ataxic gait was recognized. The ﬁnger-to-nose test and ﬁnger-to-ﬁnger
Introduction Acute cerebellar ataxia, Miller-Fisher syndrome ῌMFS῍ and the ataxic form Guillain-Barre ´ syndrome ῌGBS῍ all present with symptoms of cerebellar ataxia after ﬂu-like illness. The ataxic form of GBS without ophthalmoplegia or a loss of proprioceptive sense is rarely reported1῍. We present herein a rare case of the ataxic form of GBS without ophthalmoplegia after a ﬂu-like illness. Initially we suspected a diagnosis of acute cerebellar ataxia, but serum anti-GQ1b IgG antibodies were detected during serological examinations. Here we describe how we conﬁrmed the di#erential diagnosis of the ataxic form of GBS and discuss the relevance to clinical practice. Case Report A 52-year-old man developed a ﬂu-like illness ῌlow grade fever, sore throat, and rhinorrhea῍ 10 days prior to the onset of neurologic symptoms. The day before admission, he developed remark-
Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine Yokohama City Seibu Hospital 67
Oshima J and Yasaki S
the increased protein level in the cerebrospinal ﬂuid and serum anti-GQ1b IgG antibody. However, the patient presented with an unusual type of MFS because he did not show progressive ocular movement dysfunction. During a literature search we found only one case similar to the one presented here. This case was reported by Mori et al.2῍ described a 35-year-old male patient presenting with ataxic gait and positive serum anti-GQ1b and antiGT1a IgG antibodies, without motor paralysis in the limbs or opthalmoplegia. Particular importance was attached to the ﬁnding of positive serum antiGQ1b IgG antibodies by Mori et al. and they proposed that acute cerebellar ataxia without opthalmoplegia is one clinical feature of anti-GQ1b IgG antibody syndorome2῍. In addition, Kusunoki et al. described 5 patients who had anti-GQ1b IgG antibodies and ataxia without profound weakness in the limbs3῍῍ In terms of acute ataxia without ophthalmoplegia, reports of the ataxic form of GBS in addition to the above are rare1῍. In this ataxic form of GBS, patients present with remarkable cerebellar ataxia which is unaccompanied by external ocular paralysis or proprioceptive loss at the onset of GBS and thus, it is considered to be a variant of GBS. On the other hand, MFS manifests typical symptoms of ocular movement dysfunction, ataxic gait, and areﬂexia clinically4῍, and often reveals positive serum anti-GQ1b IgG antibody5῍. Willison et al.6῍ reported one patient as having incomplete MFS from acute ataxic neuropathy and positive serum anti-GD1b and anti-GD3 antibodies. MFS, Bickersta#’s brainstem encephalitis, and GBS concomitant with ocular palsy generally show positive serum anti-GQ1b antibody. This antibody is localized in the paranodes of the human oculomotor nerve, trochlear nerve and abducent nerve7῍. The anti-GT1a antibody induces cross-reaction for the anti-GQ1b antibody in MFS7῍, but the mechanism remains unclear. One report describes a case of acute oropharyngeal palsy associated with the anti-GT1a antibody8῍. It is unclear why the present patient had positive serum anti-GQ1b and anti-GT1a antibodies despite having no ocular or pharyngeal palsy. When we compare the present case with that of Mori et al.2῍ῌ however, a change in the gangliosides of the cerebellum or sensory nerve is suggested by the presence of acute ataxia and dysesthesia. Generally acute cerebellar ataxia is a disease that a#ects infants, but
tests revealed slightly reduced coordination and the heal-to-knee test was poor bilaterally. He had upper and lower limb incoordination and dysmetria. Tendon reﬂexes were decreased in the arms and were absent in the lower limbs. No pathological reﬂex was noted. He had no sphincter disturbance or dysautonomic function. Routine urinalysis, blood biochemistry, and hematology were normal upon admission. The cerebrospinal ﬂuid examination revealed a normal cell count of 6 ῎mm3 but an increased protein level of 127 mg῎dl. Anti-ganglioside antibody levels showed IgG antibody titers to GQ1b and GT1a were abnormally elevated ῌ1 : 4,000 and 1 : 1,000, respectively῍. No antibodies were detected against GM1, GM2, GD1a, GD1b or GT1b. No abnormalities were detected in the serum of various virus antibody titers. The bacilli that would indicate a speciﬁc diagnosis, such as Campylobacter jejuni, were not detected in the pharynx or feces. Electrophysiological examination revealed normal motor and sensory conduction velocities in the median, ulnar, posterior tibial, and deep peroneal nerves. F wave latencies, however, stimulated on the popliteal fossa were remarkably delayed to 42.5῏42.7 msec in the posterior tibial and deep peroneal nerves. A brain CT scans and MRI showed no abnormalities in any areas. On the day of admission, the dose of prednisolone was increased to 60 mg῎day. On the 13th hospital day, the horizontal gaze-evoked nystagmus disappeared, followed by the disappearance of ataxic gait 2 days later. He was discharged on the 42nd hospital day. On the hospital 76th day, numbness disappeared. The titers of serum anit-GQ1b IgG antibody and anti-GT1a IgG antibody were both 1 : 250 on the 137th day after the admission day. He has experienced no recurrent ataxia since then. Discussion A diagnosis of acute cerebellar ataxia was originally suspected in the present case because of the symptoms of remarkably acute ataxic gait and nystagmus after ﬂu-like illness. Acute cerebellar ataxia, however, does not manifest numbness in the hands. Richer1῍ proposed an ataxic variant of GBS for patients presenting with acute cerebellar ataxia without external ocular movements or loss of proprioceptive sense. The present case was regarded as a rare case of the ataxic form of GBS. In addition, MFS secondary to ataxic GBS was diagnosed from 68
Ataxic form of Guillain-Barre ´syndrome
onset in adulthood has been reported in recent years9῍. Epstein-Barr virus or other viral infections have been reported to cause acute cerebellar ataxia in adults9῍ 10῍, but viral infection was not conﬁrmed in the present case. When we consider our case and that of Mori et al.2῎, we postulate that there may be some association or common pathological mechanism between MFS and acute cerebellar ataxia, which are considered to be di#erent diseases currently. Moreover, we believe that the existence of the anti-ganglioside antibody is one of the important associations, since symptoms of acute cerebellar ataxia suggests that an unknown ganglioside antibody may be present. In addtion, Yuki et al.11῍ have reported that MFS and the ataxic form of GBS form a continuous spectrum clinically and serologically. The present case is regarded as a rare example of the ataxic form of GBS. Given out ﬁndings in the present case, we suggest that clinicians be cognizant of the ataxic form of GBS and incomplete MFS when di#erentially diagnosing acute cerebellar ataxia. Further research should determine the role of anti-ganglioside antibodies in these diseases.
Acknowledgements We wish to express our gratitude to the technical support of measurements of anti-gangliside antibody titers given by Dr. Keiichiro Susuki and Dr. Nobuhiro Yuki, Department of Neurology, Dokkyo University School of Medicine.
1῎ Richter RB. The ataxic form of polyradiculoneuritis ῌLandry-Guillain-Barre ´ syndrome῍. Clinical and pathologic observations. J Neuropathol Exp Neurol 1962; 21: 171῏184. 2῎ Mori M, Kuwabara S, Koga M, Asahina M, Ogawara K, Hattori T, and Yuki N. IgG antiGQ1b positive acute ataxia without ophthal-
moplegia. J Neurol Neurosurg Psychiatry 1999; 67: 668῏670. Kusunoki S, Chiba A, and Kanazawa I. AntiGQ1b IgG antibody is associated with ataxia as well as ophthalmoplegia. Muscle Nerve 1999; 22: 1071῏1074. Fisher M. An unusual variant of acute idiopathic polyneuritis ῌsyndrome of ophthalmoplegia, ataxia and areﬂexia῍ῌ N Engl J Med 1956; 255: 57῏65. Chiba A, Kusunoki S, Shimizu T, and Kanazawa I. Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome. Ann Neurol 1992; 31: 677῏679. Willison HJ, Almemar A, Veitch J, and Thrush D. Acute ataxic neuropathy with cross-reactive antibodies to GD1b and GD3 gangliosides. Neurology 1994; 44: 2395῏2397. Chiba A, Kusunoki S, Obata H, Machinami R, and Kanazawa I. Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barre ´ syndrome: clinical and immunohistochemical studies. Neurology 1993; 43: 1911῏1917. O’Leary CP, Veitch J, Durward WF, Thomas AM, Rees JH, and Willison HJ. Acute oropharyngeal palsy is associated with antibodies to GQ1b and GT1a gangliosides. J Neurol Neurosurg Psychiatry 1996; 61: 649῏651. Yasaki S. Acute cerebellar ataxia in adults. Nippon-rinsho, Supplement; Series of categorical syndromes 26: medical syndromes of neurological diseases I 1999; 724῏726 ῌin Japanese῍ῌ Fukuoka N. Acute cerebellar ataxia in adults. Neurol Med ῌTokyo῍ 1987; 27: 6῏10 ῌin Japanese῍. Yuki N, Susuki K, and Hirata K. Ataxic Guillain-Barre ´syndrome with anti-GQ1b antibody: relation to Miller Fisher syndrome. Neurology 2000; 54: 1851῏1853.
Oshima J and Yasaki S
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