Journal of the Neurological Sciences 276 (2009) 187–188

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Short communication

The co-occurrence of serologically proven myasthenia gravis and MillerFisher/Guillain Barré overlap syndrome — A case report

Kwok Kwong Lau a,⁎, Khean Jin Goh b, Han Chih Hencher Lee c, Yuk Tat Eric Chan d, Chong Tin Tan b

a Department of Medicine and Geriatrics, Princess Margaret Hospital, Kwai Chung, New Territories, Hong Kongb Division of Neurology, Department of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysiac Department of Pathology, Princess Margaret Hospital, Kwai Chung, New Territories, Hong Kongd Department of Immunology, Queen Mary Hospital, Hong Kong

⁎ Corresponding author. Tel.: +852 2990 1111; fax: +8E-mail address: dominickklau@hotmail.com (K.K. La

0022-510X/$ – see front matter © 2008 Elsevier B.V. Aldoi:10.1016/j.jns.2008.08.019

a b s t r a c t

a r t i c l e i n f o

Article history:

The co-occurrence of myast Received 11 July 2008Received in revised form 16 August 2008Accepted 19 August 2008Available online 19 September 2008

Keywords:Myasthenia gravisMiller Fisher/Guillain Barré overlap syndromeAnti-acetylcholine receptor antibodyAnti-GQ1b antibody

henia gravis (MG) and Guillain Barré syndrome (GBS) is uncommon with a fewreported cases in the literature. There is only one reported case of MG and Miller Fisher variant of GBS. Wedescribed an 84 year old Chinese woman with underlying seropositive myasthenia gravis (MG) whopresented with ophthalmoplegia, areflexia and acute neuromuscular weakness. She was proved to have co-occurrence of MG and GBS/Miller Fisher overlap syndrome with positive anti-GQ1b antibody. The unusualfinding in this patient raises an interesting question on their pathogenesis with the possibility that prioractivation of the immune system may predispose the development of autoantibodies against other antigenswithin the same set of muscles.

© 2008 Elsevier B.V. All rights reserved.

1. Introduction

Myasthenia gravis (MG) and the Guillain Barré syndrome (GBS) arewell described autoimmune disorders affecting the neuromuscularjunction and peripheral nerve respectively which are now recognizedto be heterogeneous with autoantibodies against several differentantigens [1–6]. The co-occurrence of MG and GBS is rare. To date therehas been only a few cases in the literature [7–12]. The association ofMG and the Miller Fisher syndrome, a variant of GBS, is even rarer,with one case reported [13]. Interestingly, both have remarkablysimilar clinical features at presentation and neuromuscular transmis-sion abnormalities have been recognized in Miller Fisher syndrome[14–17].

We report an elderly woman, known to have MG, presentingacutely with ophthalmoplegia and diplopia, bulbar, limb and respira-torymuscleweakness, proving tobe an acuteMiller Fisher/GBSoverlapsyndrome.

2. Case report

An 84 year old Chinese lady diagnosed to have ocular myastheniagravis six years ago and was on pyridostigmine. Five days prior toadmission, she developed upper respiratory tract infection followedby ptosis, diplopia, swallowing difficulty and slurring of speech. Her

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symptoms rapidly deteriorated, with severeweakness of all four limbsand respiratory distress. She was admitted into Intensive Care Unit(ICU) for mechanical ventilation. While on ventilator, she remainedconscious and alert. Clinically, she had bilateral ptosis, ophthalmo-plegia and horizontal nystagmus. There were no rotatory or verticalnystamus. Her upper limbs had power of MRC 2/5 bilaterally while herlower limbs had power of MRC 1/5 bilaterally. All tendon reflexes wereabsent except minimal response on left brachioradialis. Sensation tolight touch and pain were normal.

Lumbar puncture showed markedly elevated cerebrospinal fluid(CSF) protein of 188 mg/dL (normalb45 mg/dL), CSF white blood cellcount of 2/mm3 and negative gram stain and culture. Computerisedtomography (CT) brain was normal while CT thorax showed noevidence for thymoma. Edrophonium test on day 5 was negative. MRIof cervical spine showed an arterio-venous malformation (AVM)extending from C5 to T9 which was incidental and was not related toher symptoms.

Nerve conduction tests (NCT) showed demyelinating peripheralneuropathy with increased distal motor latency, low compoundmotoraction potential amplitude, prolonged F-wave response in 3 periph-eral nerves. The right tibial nerve F-wave was at 73.2 ms, the left tibialF-wave was at 59.3 ms and the right Median nerve F-wave was at32.1 ms (Table 1). These findings were NCT evidence for GBS. Inaddition, there were decremental responses on repetitive nervestimulation (RNS) over right facial and right trapezius muscles. Thedecremental response was NCT evidence for MG.

Acetylcholine receptor (ACh-R) antibodies were screened by anELISA test. The result was raised at 10.57 nmol/L (reference for normal

Table 1F-wave during acute stage and after recovery

Name of nerve F-wave (before IVIG) F-wave (after IVIG) F-wave (normal)

R tibial 73.2 ms 52.4 ms 45.4–48.0L tibial 59.3 ms 45.6 ms 45.4–48.0R median 32.1 ms 26.2 ms 26.5–27.0

188 K.K. Lau et al. / Journal of the Neurological Sciences 276 (2009) 187–188

range: b0.45 nmol/L). Three Ach-R autoantibodies whichwere specificfor MG were demonstrated by radioimmunoassay: the ACh-Rmodulating, binding and blocking autoantibodies. The results wereall positive (Ach-R modulating autoantibodies 44% (reference range:b20% negative; 20–40% indeterminate; N40% positive), ACh-R bindingautoantibodies 1.6 nmol/L (reference range: b0.25 nmol/L negative;0.25–0.4 nmol/L equivocal; N0.4 nmol/L positive) and Ach-R blockingautoantibodies 48% (reference for normal range: b15%).

Autoantibodies ganglioside GQ1b autoantibody was positive at108% (reference for normal range: b20%). The external ophthalmople-gia, limb weakness, areflexia plus the positive anti-GQ1b autoanti-bodies was suggestive of Miller Fisher/GBS overlap syndrome [3–6].

A course of IVIG at 0.4 g/kg/day was given for 5 days. IVIG can begiven in both situations, either GBS or MG [18]. The patient improvedgradually and her motor power was normal after 15 days. A secondedrophonium test was performed on day 22 of illness. The result wasagain negative. Patient did not require pyridostigmine.

RepeatNCTafter IVIG showednodecremental response on repetitivenerve stimulation studies and improvement of the nerve conductionparameters viz. right tibial F-wave latency, 52.4 ms, left tibial F-wavelatency, 45.6 ms and right median F-wave latency 26.2 ms (Table 1).

She was discharged with no medications and was seen 4 weekslater in OPD. TheMGwas believed to have occurred in the past and shedid not require continuous pyridostigmine.

3. Discussion

The history and clinical presentation suggested an exacerbation ofmyasthenia gravis. This diagnosis of MG was supported by repetitivenerve stimulation testswhich showed significant decremental responseandpositiveACh-Rantibody. Thediagnosis ofMGwas further confirmedwith three Ach-R autoantibodies; namely the ACh-R modulating,binding and blocking autoantibodies.

However, the edrophonium tests performed was negative. Fur-thermore the NCT had evidence for acute demyelinating peripheralneuropathy with increased distal motor latency. Anti-GQ1b antibodyis seen in all acute GBS syndromes associated with ophthalmoplegiaincluding Miller Fisher syndrome, Miller Fisher syndrome/GBS over-lap syndromes and some acute ophthalmoparesis syndromes withoutataxia [6]. Together with the clinical ophthalmoplegia, areflexia,demyelinating NCT and positive anti-GQ1b antibody, a co-occurrenceof MG and Miller Fisher variant of GBS was established.

The association of MG with other autoimmune diseases e.g. auto-immune thyroiditis and system lupus erythematosus has been welldescribed. However, its association with GBS is rare. Hitherto, therehave been seven patients described in the literature [7–12]. Theassociation of MG and Miller Fisher syndrome is even rarer with onlyone previously reported case [13]. Although they may have clinicallysimilar features, clinical differentiation could be made on the basis ofataxia and areflexia [13]. Our patient on the other hand presentedwith

the co-occurrence of MG and Miller Fisher/GBS overlap syndrome,which mimicked an acute myasthenic crisis. In this instance, a highindex of suspicion clinically as well as relevant clinical investigationse.g. nerve conduction studies allowed the distinction to be made.

Neuromuscular junction abnormalities have been recognized inMiller Fisher syndrome and GBS with electrophysiological evidence ofdecremental response on repetitive nerve stimulation test in patients[14] and the demonstration of neuromuscular transmission blockadewith autoantibodies from Miller Fisher and GBS patients [15–17,19].While this can be an explanation for cases inwhich MG develops afteran episode of acute GBS, this was not the case in our patient whereMGpreceded Miller Fisher/GBS overlap syndrome. In our patient, priorchronic autoimmune activation at the neuromuscular junction of theextraocular muscles may have predisposed to the development ofanti-GQ1b autoantibodies in the presence of specific triggers. Theunusual patient raises an interesting question on the possibility thatprior activation of the immune system may predispose the develop-ment of autoantibodies against other antigens within the same set ofmuscles. This association may warrant further investigations.

References

[1] Romi F, Gilhus NE, Aarli JA. Myasthenia gravis: clinical, immunological andtherapeutic advances. Acta Neurol Scand 2005;111:134–41.

[2] Vincent A, Newsom-Davis J. Acetylcholine receptor antibody as a diagnostic testfor myasthenia gravis: result in 153 validated cases and 2967 diagnostic assays.J Neurol Neurosurg Psychiatry 1985;48:1246–52.

[3] Hayashi Y, Koga M, Takahashi M, Uchida A, Yuki N. Anti-GQIb IgG-negative case ofoverlapping Fisher's and Guillain–Barre syndrome after Campylobacter jejuni (PEN19) enteritis. Clin Neurol 2001;41:801–4.

[4] Ang CW, Laman JD, Willison HJ, Wagner ER, Endtz HP, De Klerk MA, et al. Structureof Campylobacter jejuni lipopolysaccharides determines anti-ganglioside specifi-city and clinical features Guillain–Barre and Miller Fisher patients. Infect Immun2002;70:1202–8.

[5] Hahn AF. Guillain–Barre syndrome. Lancet 1998;352:635–41.[6] Odaka M, Yuki N, Hirata K. Anti-GQ1b IgG antibody syndrome: clinical and

immunological range. J Neurol Neurosurg Psychiatry 2001;70(1):50–5.[7] Bourouresques G, Delpuech F, Giudicelli R, Poncet M, Kleibauer JP, Daniel F, et al.

Polyradiculoneuritis and myasthenia gravis. Nouv Presse Med 1981;10:253–4.[8] Regev I, Bornstein N, Carasso R, Vardi Y. Acute polyneuropathy combined with

myasthenia gravis. Acta Neurol Scand 1982;65:681–2.[9] Carlander B, Touchon J, Georgesco M, Cadilhac J. Myasthenia gravis and recurrent

Guillain–Barre syndrome. Neurology 1991;41:1848.[10] Farah R, Farah R, Simri W. Acute motor sensory Guillain–Barre syndrome and

myasthenia gravis. Eur J Intern Med 2005;16:134–5.[11] Kraus J, Teismann I, Kellinghaus C, Duning T, Ringelstein EB, Nabavi DG, et al.

Temporal coincidence between AMAN type of Guillain Barre syndrome andmyasthenia gravis. J Neurol 2007;254:264–5.

[12] Kizilay F, Ryan HF, Oh SJ. Myasthenia gravis and Guillain–Barre syndromeoccurring simultaneously in the same patient. Muscle Nerve 2008:544–6.

[13] Mak W, Chan KH, Ho SL. A case of ocular myasthenia gravis and Miller–Fishersyndrome. Hosp Med 2005;66(2):116–7.

[14] Silverstein MP, Zimnowodzki S, Rucker JC. Neuromuscular junction dysfunction inMiller Fisher syndrome. Semin Ophthalmol 2008;23(3):211–3.

[15] Roberts M, Willison H, Vincent A, Newsom-Davis J. Serum factor in Miller–Fishervariant of Guillain–Barré syndrome and neurotransmitter release. Lancet Feb 191994;343(8895):454–5.

[16] Buchwald B, Weishaupt A, Toyka KV, Dudel J. Pre- and postsynaptic blockade ofneuromuscular transmission by Miller–Fisher syndrome IgG at mouse motornerve terminals. Eur J Neurosci Jan 1998;10(1):281–90.

[17] Plomp JJ, Molenaar PC, O'Hanlon GM, Jacobs BC, Veitch J, Daha MR, et al. MillerFisher anti-GQ1b antibodies: alpha-latrotoxin-like effects on motor end plates.Ann Neurol 1999;45(2):189–99.

[18] Wiles C, Brown P, Chapel H, et al. Intravenous immunoglobulin in neurologicaldisease: a specialist review. J Neurol Neurosurg Psychiatry 2002;72:440–8.

[19] Krampfl K, Mohammadi B, Buchwald B, Jahn K, Dengler R, Toyka KV, et al. IgG frompatients with Guillain–Barre syndrome interact with nicotinic acetylcholinereceptor channels. Muscle Nerve 2003;27:435–41.