Case Reports / Journal of Clinical Neuroscience 19 (2012) 1599–1601 1599

hence, the lesion was suspected to be responsible for the observed be responsible for central vestibular imbalance in the vertical
downbeat nystagmus. direction, suggesting that a PMT–flocculus–vestibular nucleus
PMT cell groups are important in gaze holding and in the main- pathway might be important in maintaining vestibular balance.
tenance of vestibular balance. Impaired PMT cells have been shown This patient is unusual in that downbeat nystagmus was caused
to induce downbeat nystagmus in an animal model.3 In the present by vestibular imbalance as a result of damage caused to PMT cells
patient, the medullary lesion was much lower than the location of by small brainstem infarctions.
PMT cells that control eye movement. In the animal model,3 as also
suggested by a previously reported human lesion,6 the PMT cells Disclosure
are supposed to be at the medullary–pontine junction. However,
the PMT cell groups spread from the pons to the lower medulla The authors report no conflicts of interest.
oblongata and project to the cerebellar flocculus.2 Furthermore,
the eye movement disorders seen in our patient resembled those Acknowledgments
observed in the floccular lesions.7 According to previous reports,
the cerebellar flocculus and paraflocculus are important in main- This study was funded by a Scientific Research Grant (C) (No.
taining gaze holding and vestibular balance, and the impairment 23590869) from the Ministry of Education, Culture, Sports, Science,
of these regions induces downbeat nystagmus.1,7 In the present pa- and Technology of Japan.
tient, the impairment of PMT cells might have induced a disorder
similar to those resulting from floccular lesions. This finding sug- References
gests that feedback from the brainstem might influence the control
of ocular movement in the cerebellum. 1. Pierrot-Deseilligny C, Milea D. Vertical nystagmus: clinical facts and hypotheses.
Fig. 3 presents a summary of the pathogenesis of downbeat nys- Brain 2005;128:1237–46.
2. Büttner-Ennever JA, Horn AK. Pathways from cell groups of the paramedian
tagmus caused by lesions in PMT cell groups.3 Lesions in PMT cells tracts to the floccular region. Ann N Y Acad Sci 1996;781:532–40.
attenuate the activity of floccular Purkinje cells, which, in turn, re- 3. Nakamagoe K, Iwamoto Y, Yoshida K. Evidence for brainstem structures
duce the inhibition of secondary vestibular nucleus neurons that participating in oculomotor integration. Science 2000;288:857–9.
4. de Jong JM, Cohen B, Matsuo V, et al. Midsagittal pontomedullary brain
receive input from the anterior semicircular canals. However, the stem section: effects on ocular adduction and nystagmus. Exp Neurol 1980;68:
neuronal activity of the posterior canal-related secondary vestibu- 420–42.
lar nucleus neurons remains unaffected because the neurons do 5. Yeow YK, Tjia TL. The localizing value of downbeat nystagmus. Singapore Med J
1989;30:273–6.
not receive inhibitory regulation from the flocculus.8 As a result,
6. Wagner J, Lehnen N, Glasauer S, et al. Downbeat nystagmus caused by a
only the anterior canal-related secondary vestibular nucleus neu- paramedian ponto-medullary lesion. J Neurol 2009;256:1572–4.
rons are activated, which induces upward eye movement that con- 7. Zee DS, Yamazaki A, Butler PH, et al. Effects of ablation of flocculus and
stitute the slow phase of nystagmus. This is then followed by paraflocculus on eye movements in primate. J Neurophysiol 1981;46:
878–99.
compensatory fast-phase downward beating, resulting in down- 8. Sato Y, Kawasaki T. Operational unit responsible for plane-specific control of eye
beat nystagmus. It is suspected that lesions in PMT cells might movement by cerebellar flocculus in cat. J Neurophysiol 1990;64:551–64.

doi:http://dx.doi.org/10.1016/j.jocn.2012.03.016

Abnormalities of neuromuscular transmission in patients

with Miller–Fisher syndrome
Parvathi Menon a,b, Neil Mahant a,b, Steve Vucic b,c,⇑
a
Department of Neurology, Westmead Hospital, Cnr Hawkesbury and Darcy Road, Westmead, New South Wales 2145, Australia
b
Sydney Medical School, Westmead, University of Sydney, Australia
c
Neuroscience Research Australia, Sydney, Australia

a r t i c l e i n f o a b s t r a c t

Article history: The mechanism of motor weakness in patients with Miller–Fisher syndrome (MFS) remains to be fully
Received 12 March 2012 elucidated. We performed stimulated single fibre electromyography (sSFEMG) in a clinically weak fron-
Accepted 17 March 2012 talis muscle in a patient with MFS. Stimulate single fiber EMG revealed increased jitter in over 50% of the
apparent single fibre action potentials from the frontalis muscle in addition to increased mean jitter. The
findings in the present study suggest dysfunction of neuromuscular transmission in patients with MFS.
Keywords:
Ó 2012 Elsevier Ltd. All rights reserved.
Miller–Fisher Syndrome
Neuromuscular transmission dysfunction
Single fibre EMG

1. Introduction

MFS is clinically characterised as a syndrome of ataxia, areflexia,

and ophthalmoplegia 1 but the phenotype may be varied and include
⇑ Corresponding author. Tel.: +61 2 9845 6097; fax: +61 2 9635 6684. facial and bulbar weakness. 2 MFS is typically associated with an
E-mail address: [email protected] (S. Vucic). antecedent infection, particularly with Campylobacter jejuni, and
1600 Case Reports / Journal of Clinical Neuroscience 19 (2012) 1599–1601

Table 1
Studies using single fiber electromyography in patients with Miller–Fisher syndrome (MFS)

Author (Year) No. of patients GQ1B antibodies (% positive) Muscle tested (clinically affected) Mean consecutive difference (ls)
13
2004 9 44 Orb icularis oculi (no) Increased*
200513 1 0 Frontalis (no) Increased
200610 1 Late sero-conversion Extensor digitorum communis (no) Increased
20077 7 100 Extensor digitorum communis (no) Normal
Present study 2011 1 0 Frontalis (yes) Increased
*
Mean consecutive difference was increased in 44% of patients with clinical MFS and detectable GQ1b antibodies.

associated production of immunoglobulin G (IgG) antibodies against (30% persistence) and ulnar (60% persistence) nerve F-wave re-
GQ1b gangliosides.3,4 Anti-GQ1b antibodies interfere with neuro- sponses despite manoeuvres for enhancement. Facial NCS revealed
transmitter release, thereby resulting in muscle weakness. 5,6 absent motor responses on both sides. The remainder of the NCS
However, the issue of whether neuromuscular transmission is was unremarkable. In particular, there was no neurophysiological
dysfunctional in MFS remains controversial. 7 evidence of demyelination. Needle EMG of the left orbicularis oculi
Function of the neuromuscular junction (NMJ) can be assessed and orbicularis oris muscles revealed absence of voluntary recruit-
by single fibre electromyography (SFEMG), whereby increased ‘‘jit- ment and an absence of ongoing changes (fibrillation potentials
ter’’ indicates dysfunction at the level of the NMJ. Evidence for dys- and positive sharp waves).
function of neuromuscular transmission in MFS is not established The patient was treated with intravenous immunoglobulin
(Table 1). 7–10 The present study, involving SFEMG of a clinically af- (IVIg, 2 mg/kg body weight). The clinical features of ataxia, facial
fected muscle, aimed to clarify whether dysfunction of neuromus- weakness and diplopia improved 3 weeks after IVIg therapy. Re-
cular transmission was a feature of MFS. peat NCS and electromyography (EMG) of the orbicularis oculi,
orbicularis oris and frontalis muscles on the left side, 5 weeks after
symptom onset, remained unchanged. In particular, the facial
2. Methods
nerve innervated muscles had no voluntary recruitment and
showed no evidence of ongoing changes (fibrillation potentials
2.1. Case history
and positive sharp waves).
A 24-year-old male of Chinese descent presented with acute on-
set bilateral ptosis, diplopia, dysphagia, paraesthesia of distal 2.4. Stimulated single fibre EMG
upper and lower extremities along with ataxia 1 week after an
acute upper respiratory infection. The patient had been previously Stimulated single fiber EMG was performed on the left frontalis
well and denied extrapyramidal symptoms or bowel and bladder muscle using the Synergy EMG machine, 6 weeks after symptom
dysfunction. There was no family history of neuromuscular onset. At testing, the left frontalis muscle was clinically weak. A
diseases. monopolar needle (Viasys Teca 50 mm; Carefusion, San Diego,
Neurological examination of the cranial nerves disclosed bilat- CA, USA) was used as the cathode, and the apparent single fibre ac-
eral. partial ptosis, marked external opthalmoparesis with vertical tion potentials (ASFAP) were recorded using a concentric needle
and horizontal separation diplopia. Pupillary reflexes were normal. EMG (Alpine Biomed, Fountain Valley, CA, USA). Filter settings
There was bilateral facial, bulbar and neck flexion weakness with were set between 2 KHz and 10 KHz. ASFAP with a rise time
preserved tone and strength in all other muscle groups. Deep ten- <300 ls and amplitude >100 lV were selected for analysis. In total,
don reflexes were absent throughout. Plantar responses were flex- 20 different ASFAP were collected, with 100 units collected within
or. Sensory examination was normal. The patient exhibited an each run. The mean consecutive difference (MCD) was increased in
ataxic gait with inability to tandem walk. Romberg test was 50% of ASFAP (Fig. 1). In addition, the MCD for 20 ASFAP was in-
positive. creased (MCD 29 ± 3.9 ls; laboratory reference, normal <23 ls).
There was no definite evidence of impulse blocking.
2.2. Laboratory investigations
3. Discussion
Laboratory testing revealed albuminocytologic dissociation
with a protein concentration of 47.7 mg/L on cerebrospinal fluid The present study established abnormalities of NMJ transmis-
(CSF) analysis. Antibodies to the membrane GQ1b and GM1 gan- sion in a clinically weak muscle in a patient with MFS using the
gliosides were not detected in the acute phase or convalescent ser- sSFEMG technique. The diagnosis of MFS was supported by clinical
um. Haematology, biochemistry and an autoimmune screen were findings of ataxia, ophthalmoplegia and areflexia, as well as recov-
normal. Serology for hepatitis B, hepatitis C, human immunodefi- ery with IVIg therapy.
ciency virus and herpes simplex virus infection was negative. Stool Failure of NMJ transmission, mediated largely by antiGQ1b anti-
culture was negative for Campylobacter jejuni. An MRI of the brain body-dependant mechanisms has been reported in MFS.11 Dys-
and orbits was normal. function of neuromuscular transmission, in the current patient,
in the absence of antiGQ 1b antibody, is possible as evidenced by
2.3. Neurophysiological testing the finding that serum from patients with antiganglioside anti-
body-negative Guillain-Barré syndrome impaired NMJ transmis-
A nerve conduction study (NCS) was performed on the Synergy sion to the same extent as sera from antibody-positive patients.12
EMG machine (Oxford Instruments, Surrey, UK). The temperature In the current study, the use of sSFEMG revealed increased
of the extremities was maintained at 32 °C. The nerve conduction mean and individual jitter in a clinically weak right frontalis mus-
study, performed 5 days after symptom onset, disclosed absent tib- cle, thereby confirming neuromuscular transmission dysfunction,
ial nerve H-reflexes, along with reduced persistence of median which concurs with some previous studies.9,10,13 Increased jitter
 Case Reports / Journal of Clinical Neuroscience 19 (2012) 1599–1601 1601

Fig. 1. Mean consecutive difference (MCD) of 20 apparent single fibre action potentials from the clinically weak frontalis muscle.

in the present study could result from axonal loss in the studied 4. Jacobs BC, Endtz HP, van der Meche FG, et al. Humoral immune response
against Campylobacter jejuni lipopolysaccharides in Guillain-Barre and Miller
muscle which seems unlikely in the current patient, given the ab-
Fisher syndrome. J Neuroimmunol 1997;79:62–8.
sence of positive sharp waves and fibrillation potentials on needle 5. Halstead SK, O’Hanlon GM, Humphreys PD, et al. Anti-disialoside antibodies kill
EMG testing 5 weeks after symptom onset. Further, increased perisynaptic Schwann cells and damage motor nerve terminals via membrane
‘‘jitter’’ on sSFEMG recording may result from submaximal stimu- attack complex in a murine model of neuropathy. Brain 2004;127:2109.
6. Plomp JJ, Molenaar PC, O’Hanlon GM, et al. Miller Fisher anti-GQ1b antibodies:
lation of terminal axons,14 which was avoided by ensuring maxi- alpha-latrotoxin-like effects on motor end plates. Ann Neurol 1999;45:189–99.
mal stimulation of all the recorded units. In addition, the use to 7. Kuwabara S, Misawa S, Takahashi H, et al. Anti-GQ1b antibody does not affect
concentric needle recording is likely to underestimate jitter, the neuromuscular transmission in human limb muscle. J Neuroimmunol
2007;189:158.
opposite to that observed in the current study. 8. Lo YL. Clinical and immunological spectrum of the Miller Fisher syndrome.
In conclusion, the present study suggests that dysfunction of Muscle Nerve 2007;36:615–27.
NMJ transmission, at either the distal axon terminal or NMJ level, 9. Sartucci F, Cafforio G, Borghetti D, et al. Electrophysiological evidence by single
fibre electromyography of neuromuscular transmission impairment in a case of
may be a pathophysiological feature in MFS, and may result from Miller Fisher syndrome. Neurol Sci 2005;26:125–8.
antibodies directed against ganglioside epitopes other than 10. Lange D, DeAngelis T, Sivak MA. Single fiber electromyography shows terminal
GQ1b, located at or near the NMJ. axon dysfunction in Miller Fisher syndrome: A case report. Muscle Nerve
2006;34:232–4.
11. Buchwald B, Bufler J, Carpo M, et al. Combined pre-and postsynaptic action of
IgG antibodies in Miller Fisher syndrome. Neurology 2001;56:67.
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doi:http://dx.doi.org/10.1016/j.jocn.2012.03.016