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

hence, the lesion was suspected to be responsible for the observed
downbeat nystagmus.
PMT cell groups are important in gaze holding and in the main-
tenance of vestibular balance. Impaired PMT cells have been shown
to induce downbeat nystagmus in an animal model.3 In the present
patient, the medullary lesion was much lower than the location of
PMT cells that control eye movement. In the animal model,3 as also
suggested by a previously reported human lesion,6 the PMT cells
are supposed to be at the medullary–pontine junction. However,
the PMT cell groups spread from the pons to the lower medulla
oblongata and project to the cerebellar flocculus.2 Furthermore,
the eye movement disorders seen in our patient resembled those
observed in the floccular lesions.7 According to previous reports,
the cerebellar flocculus and paraflocculus are important in main-
taining gaze holding and vestibular balance, and the impairment
of these regions induces downbeat nystagmus.1,7 In the present pa-
tient, the impairment of PMT cells might have induced a disorder
similar to those resulting from floccular lesions. This finding sug-
gests that feedback from the brainstem might influence the control
of ocular movement in the cerebellum.
Fig. 3 presents a summary of the pathogenesis of downbeat nys-
tagmus caused by lesions in PMT cell groups.3 Lesions in PMT cells
attenuate the activity of floccular Purkinje cells, which, in turn, re-
duce the inhibition of secondary vestibular nucleus neurons that
receive input from the anterior semicircular canals. However, the
neuronal activity of the posterior canal-related secondary vestibu-
lar nucleus neurons remains unaffected because the neurons do
not receive inhibitory regulation from the flocculus.8 As a result,
only the anterior canal-related secondary vestibular nucleus neu-
rons are activated, which induces upward eye movement that con-
stitute the slow phase of nystagmus. This is then followed by
compensatory fast-phase downward beating, resulting in down-
beat nystagmus. It is suspected that lesions in PMT cells might
be responsible for central vestibular imbalance in the vertical
direction, suggesting that a PMT–flocculus–vestibular nucleus
pathway might be important in maintaining vestibular balance.
This patient is unusual in that downbeat nystagmus was caused
by vestibular imbalance as a result of damage caused to PMT cells
by small brainstem infarctions.
Disclosure
The authors report no conflicts of interest.
Acknowledgments
This study was funded by a Scientific Research Grant (C) (No.
23590869) from the Ministry of Education, Culture, Sports, Science,
and Technology of Japan.
References
1. Pierrot-Deseilligny C, Milea D. Vertical nystagmus: clinical facts and hypotheses.
Brain 2005;128:1237–46.
2. Büttner-Ennever JA, Horn AK. Pathways from cell groups of the paramedian
tracts to the floccular region. Ann N Y Acad Sci 1996;781:532–40.
3. Nakamagoe K, Iwamoto Y, Yoshida K. Evidence for brainstem structures
participating in oculomotor integration. Science 2000;288:857–9.
4. de Jong JM, Cohen B, Matsuo V, et al. Midsagittal pontomedullary brain
stem section: effects on ocular adduction and nystagmus. Exp Neurol 1980;68:
420–42.
5. Yeow YK, Tjia TL. The localizing value of downbeat nystagmus. Singapore Med J
1989;30:273–6.
6. Wagner J, Lehnen N, Glasauer S, et al. Downbeat nystagmus caused by a
paramedian ponto-medullary lesion. J Neurol 2009;256:1572–4.
7. Zee DS, Yamazaki A, Butler PH, et al. Effects of ablation of flocculus and
paraflocculus on eye movements in primate. J Neurophysiol 1981;46:
878–99.
8. Sato Y, Kawasaki T. Operational unit responsible for plane-specific control of eye
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: s.vucic@neura.edu.au (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)
13
2004 9 44
200513 1 0
200610 1 Late sero-conversion
20077 7 100
Present study 2011 1 0
*
Mean consecutive difference was increased in 44% of patients with clinical MFS and detectable GQ1b antibodies.
associated production of immunoglobulin G (IgG) antibodies against
GQ1b gangliosides.3,4 Anti-GQ1b antibodies interfere with neuro-
transmitter release, thereby resulting in muscle weakness. 5,6
However, the issue of whether neuromuscular transmission is
dysfunctional in MFS remains controversial. 7
Function of the neuromuscular junction (NMJ) can be assessed
by single fibre electromyography (SFEMG), whereby increased ‘‘jit-
ter’’ indicates dysfunction at the level of the NMJ. Evidence for dys-
function of neuromuscular transmission in MFS is not established
(Table 1). 7–10 The present study, involving SFEMG of a clinically af-
fected muscle, aimed to clarify whether dysfunction of neuromus-
cular transmission was a feature of MFS.
2. Methods
2.1. Case history
A 24-year-old male of Chinese descent presented with acute on-
set bilateral ptosis, diplopia, dysphagia, paraesthesia of distal
upper and lower extremities along with ataxia 1 week after an
acute upper respiratory infection. The patient had been previously
well and denied extrapyramidal symptoms or bowel and bladder
dysfunction. There was no family history of neuromuscular
diseases.
Neurological examination of the cranial nerves disclosed bilat-
eral. partial ptosis, marked external opthalmoparesis with vertical
and horizontal separation diplopia. Pupillary reflexes were normal.
There was bilateral facial, bulbar and neck flexion weakness with
preserved tone and strength in all other muscle groups. Deep ten-
don reflexes were absent throughout. Plantar responses were flex-
or. Sensory examination was normal. The patient exhibited an
ataxic gait with inability to tandem walk. Romberg test was
positive.
2.2. Laboratory investigations
Laboratory testing revealed albuminocytologic dissociation
with a protein concentration of 47.7 mg/L on cerebrospinal fluid
(CSF) analysis. Antibodies to the membrane GQ1b and GM1 gan-
gliosides were not detected in the acute phase or convalescent ser-
um. Haematology, biochemistry and an autoimmune screen were
normal. Serology for hepatitis B, hepatitis C, human immunodefi-
ciency virus and herpes simplex virus infection was negative. Stool
culture was negative for Campylobacter jejuni. An MRI of the brain
and orbits was normal.
2.3. Neurophysiological testing
A nerve conduction study (NCS) was performed on the Synergy
EMG machine (Oxford Instruments, Surrey, UK). The temperature
of the extremities was maintained at 32 °C. The nerve conduction
study, performed 5 days after symptom onset, disclosed absent tib-
ial nerve H-reflexes, along with reduced persistence of median
Muscle tested (clinically affected) Mean consecutive difference (ls)
Orb icularis oculi (no) Increased*
Frontalis (no) Increased
Extensor digitorum communis (no) Increased
Extensor digitorum communis (no) Normal
Frontalis (yes) Increased
(30% persistence) and ulnar (60% persistence) nerve F-wave re-
sponses despite manoeuvres for enhancement. Facial NCS revealed
absent motor responses on both sides. The remainder of the NCS
was unremarkable. In particular, there was no neurophysiological
evidence of demyelination. Needle EMG of the left orbicularis oculi
and orbicularis oris muscles revealed absence of voluntary recruit-
ment and an absence of ongoing changes (fibrillation potentials
and positive sharp waves).
The patient was treated with intravenous immunoglobulin
(IVIg, 2 mg/kg body weight). The clinical features of ataxia, facial
weakness and diplopia improved 3 weeks after IVIg therapy. Re-
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
nerve innervated muscles had no voluntary recruitment and
showed no evidence of ongoing changes (fibrillation potentials
and positive sharp waves).
2.4. Stimulated single fibre EMG
Stimulated single fiber EMG was performed on the left frontalis
muscle using the Synergy EMG machine, 6 weeks after symptom
onset. At testing, the left frontalis muscle was clinically weak. A
monopolar needle (Viasys Teca 50 mm; Carefusion, San Diego,
CA, USA) was used as the cathode, and the apparent single fibre ac-
tion potentials (ASFAP) were recorded using a concentric needle
EMG (Alpine Biomed, Fountain Valley, CA, USA). Filter settings
were set between 2 KHz and 10 KHz. ASFAP with a rise time
<300 ls and amplitude >100 lV were selected for analysis. In total,
20 different ASFAP were collected, with 100 units collected within
each run. The mean consecutive difference (MCD) was increased in
50% of ASFAP (Fig. 1). In addition, the MCD for 20 ASFAP was in-
creased (MCD 29 ± 3.9 ls; laboratory reference, normal <23 ls).
There was no definite evidence of impulse blocking.
3. Discussion
The present study established abnormalities of NMJ transmis-
sion in a clinically weak muscle in a patient with MFS using the
sSFEMG technique. The diagnosis of MFS was supported by clinical
findings of ataxia, ophthalmoplegia and areflexia, as well as recov-
ery with IVIg therapy.
Failure of NMJ transmission, mediated largely by antiGQ1b anti-
body-dependant mechanisms has been reported in MFS.11 Dys-
function of neuromuscular transmission, in the current patient,
in the absence of antiGQ 1b antibody, is possible as evidenced by
the finding that serum from patients with antiganglioside anti-
body-negative Guillain-Barré syndrome impaired NMJ transmis-
sion to the same extent as sera from antibody-positive patients.12
In the current study, the use of sSFEMG revealed increased
mean and individual jitter in a clinically weak right frontalis mus-
cle, thereby confirming neuromuscular transmission dysfunction,
which concurs with some previous studies.9,10,13 Increased jitter
 Case Reports / Journal of Clinical Neuroscience 19 (2012) 1599–1601
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
muscle which seems unlikely in the current patient, given the ab-
sence of positive sharp waves and fibrillation potentials on needle
EMG testing 5 weeks after symptom onset. Further, increased
‘‘jitter’’ on sSFEMG recording may result from submaximal stimu-
lation of terminal axons,14 which was avoided by ensuring maxi-
mal stimulation of all the recorded units. In addition, the use to
concentric needle recording is likely to underestimate jitter, the
opposite to that observed in the current study.
In conclusion, the present study suggests that dysfunction of
NMJ transmission, at either the distal axon terminal or NMJ level,
may be a pathophysiological feature in MFS, and may result from
antibodies directed against ganglioside epitopes other than
GQ1b, located at or near the NMJ.
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