Anti-GQ1b Antibody Associated Syndrome under the Veil of Holmes-Adie Syndrome

(1)

Anti-GQ1b Antibody Associated Syndrome under the Veil of Holmes-Adie Syndrome

Jin-Woo Park, MD¹, Ye-Ji Kwon, MD¹, Jeong-Yoon Choi, MD²

1Department of Neurology, Korea University College of Medicine, Korea University Anam Hospital, Seoul; ²Department of Neurology, Seoul National University College Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

Holmes-Adie syndrome is a classic neurological disorder that comprises unilateral or bilateral mydriasis with cholinergic supersensitivity and areflexia or hyporeflexia in both lower extremities. Of interest, acute ophthalmoplegia without ataxia, a variant form of Miller-Fisher syndrome, can mimic Holmes-Adie syndrome by showing similar clinical findings. In this report, we described a patient with acute ophthalmoplegia without ataxia and discussed how IgG anti-GQ1b antibody related syndrome can be linked to Holmes-Adie syndrome.

Keywords: Miller-Fisher syndrome; Mydriasis; Internal ophthalmoplegia; Acute ophthalmoplegia without ataxia; Holmes-Adie syndrome;

Anti-GQ1B antibody

Introduction

Holmes-Adie syndrome comprises unilateral or bilateral mydriasis with cholinergic supersensitivity and areflexia or hyporeflexia in both lower extremities.¹ It was first linked to viral infections, and it has since been associated with diverse infectious, autoimmune, tumorous, and paraneoplastic conditions.² On the other hand, acute ophthalmoplegia without ataxia, a variant form of Miller-Fisher syndrome, was linked to IgG anti-GQ1b antibody. Diverse combinations of external and internal ophthalmoplegia have been introduced in acute ophthalmoplegia without ataxia, and some of cases were manifested as isolated internal ophthalmoplegia.^3-8 However, the association between Holmes-Adie syndrome and IgG anti-GQ1b antibody related isolated internal ophthalmoplegia has not been discussed. Herein, we report a patient initially diagnosed with Holmes-Adie syndrome based on clinical examination and whose serologic test revealed IgG anti-GQ1b antibody.

CASE REPORT

An 18-year-old female presented with headache and blurred vision that had started three days prior. She had self-remitted sticky diarrhea one week earlier. Her headache was electrical and stabbing and mostly occurred during eye motion along the territory of both frontal nerves.

She had no limitation in extraocular motility, but both pupils were sym- metrically dilated and fixed (R: 6 mm/ L: 6 mm) (Fig. 1A). Near target caused slow pupillary constriction, and dilation lag was also observed after removing near stimuli. Cholinergic supersensitivity with diluted (0.2%) pilocarpine was absent at initial examination (Fig. 1B). Other neurological signs and symptoms were normal, except for decreased deep tendon reflexes in both lower extremities. Three days later, diluted pilocarpine induced pupillary constriction (Fig. 1C). Brain MRIs including angiography were normal. She was diagnosed with Holmes-Adie syndrome based on clinical manifestations. The patient was given intrave- nous methylprednisolone 1 g daily for three days, which dramatically re-

Correspondence to: Jeong-Yoon Choi, MD

Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 13620, Korea Tel: +82-31-787-7562, E-mail: [email protected]

Received: June 1, 2017 / Accepted: June 27, 2017

CASE REPORT

ISSN: 2234-0971 대한안신경의학회지: 제7권 제1호

Clin Neuroophthalmol 7(1):20-22, June 2017

(2)

Anti-GQ1b Antibody Related Holmes-Adie Syndrome • Park JW, et al.

Clin Neuroophthalmol 7(1):20-22, June 2017 http://neuro-ophthalmology.co.kr 21

duced her headache. The further etiologic evaluations for autoimmune disorders such as Sjogren syndrome and system lupus erythematous were normal. However, a ganglioside antibody test conducted on the day of admission showed highly elevated anti-GQ1b antibody titers (>100

IU, ELASIA method with reference for normal value= 0-30). A nerve conduction test was normal including latency of F-wave. One month later, pupillary size and reactivity were recovered completely.

Table 1. Clinical features of IgG anti-GQ1b antibody related isolated internal ophthalmoplegia from literature review Patient (Sex/Age) Mydriasis Cholinergic

supersensitivity LND DTR Preceding

infection Associated

symptoms & signs Prognosis

Criteria for Holmes-Adie

syndrome

1 (M/33)³ Bilateral Positive Present Normal Present Mild ataxia Fully recovered No

2 (M/36)⁴ Bilateral Positive Present Absent Present None Fully recovered Yes

3 (F/53)⁵ Bilateral Positive Absent Increased Absent Headache Fully recovered No

4 (F/22)⁶ Bilateral Positive Present Decreased Present Headache &

delayed diplopia

Fully recovered Yes

5 (F/37)⁷ Bilateral Not mentioned Not mentioned Absent Absent Dizziness Fully recovered No

6 (M/28)⁸ Bilateral Positive Absent Decreased Present None Fully recovered Yes

7 (M/29)⁸ Bilateral Positive Absent Normal Absent Mild ataxia Fully recovered Yes

8 (F/18) our case Bilateral Positive Present Decreased Present Headache Fully recovered Yes

LAD, light-near dissociation of pupillary response; DTR, deep tendon reflexes.

Fig. 1. Clinical findings of our patient. (A) There was no extraocular limitation for all cardinal gaze positions. (B) Dilated pupils did not respond to diluted (0.2%) pilocar- pine drops at presentation (three days after symptom onset). (C) Three days later, repeat diluted pilocarpine test demonstrated pupillary constriction in both eyes.

A

B

C

(3)

Park JW, et al. • Anti-GQ1b Antibody Related Holmes-Adie Syndrome

Clin Neuroophthalmol 7(1):20-22, June 2017 22 http://neuro-ophthalmology.co.kr

DISCUSSION

In our patient, Holmes-Adie syndrome is attributed to IgG anti-GQ1b antibody, considering the temporal relationship between the symptoms, serologic test, and preceding gastrointestinal illness. Of interest, the diluted pilocarpine test performed 3 days after onset of symptoms showed no specific pupillary response. However as shown in follow-up examination in our patient, tonic pupils that resulted from cholinergic denerva- tion super-sensitivity are known to occur 5 to 7 days after initial insults.⁹ Among the diverse clinical features of IgG anti-GQ1b antibody associated syndrome, isolated internal ophthalmoplegia is a unique manifestation that has been reported in only eight patients (including our patient) (Table 1).^3-8 Among them, five patients who had decreased or absent tendon reflexes fulfilled the diagnostic criteria for Holmes-Adie syndrome.^{4, 6-8} Because preceding flu-like or gastrointestinal infection are established features of both conditions, IgG anti-GQ1b antibody related isolated internal ophthalmoplegia and Holmes-Adie syndrome seem to share common clinical features. Therefore, we suggest that IgG anti-GQ1b antibody is one cause of Holmes-Adie syndrome.

Holmes-Adie syndrome should be carefully evaluated for underlying etiologies given that diverse benign or malignant conditions can result in

Holmes-Adie syndrome.² Though our suggestion should be evaluated in more patients, a test for IgG anti-GQ1b antibody may be also considered when identifying the cause of Holmes-Adie syndrome.

REFERENCES

1. Adie WJ. Tonic pupils and absent tendon reflexes - A benign disorder sui generis, its complete and incomplete forms. Brain 1932;55:98-113.

2. Dynes JB. Adie’s syndrome - Its recognition and importance. JAMA 1942;

119:1495-7.

3. Radziwill AJ, Steck AJ, Borruat FX, Bogousslavsky J. Isolated internal ophthalmoplegia associated with IgG anti-GQ1b antibody. Neurology 1998;50:307.

4. Yuki N, Koga M, Hirata K. Isolated internal ophthalmoplegia associated with immunoglobulin G anti-GQ1b antibody. Neurology 1998;51:1515-6.

5. Sugita A, Yanagisawa T, Kamo T, Takahashi Y, Yuki N. Internal ophthal- moplegia with anti-GQ1b IgG antibody. J Neurol 2002;249:1475-6.

6. Bae JS, Kim JK, Kim SH, Kim OK. Bilateral internal ophthalmoplegia as an initial sole manifestation of Miller Fisher syndrome. J Clin Neurosci 2009;16:963-4.

7. Fleury V, Aqallal A, Lagrange E, Besson G, Caudie C. Acute bilateral my- driasis associated with anti-GQ1b antibody. J Clin Neurosci 2010;17:514-5.

8. Sato H, Naito K, Hashimoto T. Acute isolated bilateral mydriasis: case re- ports and review of the literature. Case Rep Neurol 2014;6:74-7.

9. Biousse V, Newman NJ. Neuro-Ophthalmology Illustrated. Thieme Medi- cal Publishers, New York, NY, USA (2009).