790

J Neurol Neurosurg Psychiatry 2000;68:790–791

LESSON OF THE MONTH

Cerebral infarction complicating intravenous
immunoglobulin therapy in a patient with Miller
Fisher syndrome
Benjamin Turner, Adrian J Wills

Abstract
Intravenous immunoglobulin (IVIg) therapy is being increasingly used in a wide
range of neurological conditions. However,
treatment is expensive and side eVects may
be severe. A patient with Miller Fisher syndrome who developed cortical blindness as
a consequence of occipital infarction precipitated by IVIg is reported on.
(J Neurol Neurosurg Psychiatry 2000;68:790–791)
Keywords: Miller Fisher syndrome; intravenous immunoglobulin; cerebral infarction

Division of Clinical
Neurology, University
Hospital, Queen’s
Medical Centre,
Nottingham NG7 2UH,
UK
B Turner
A J Wills
Correspondence to:
Dr B Turner
nnxbt@
nnn1.nottingham.ac.uk
Received 2 February 2000
Accepted 9 February 2000

Case report
A 60 year old woman presented with a 5 day
history of left sided ptosis, diplopia, paraesthesia of the hands and feet, and impaired manual
dexterity. One week previously she had had a
diarrhoeal illness lasting 24 hours.
On examination she was apyrexial and mildly
tachycardic. Her forced vital lung capacity was
1.45 l. Examination of the cranial nerves showed
a left sided ptosis with a total external ophthalmoplegia of the left eye and impaired abduction
of the right eye. The pupillary reflexes were normal to light and accommodation. She had a bulbar palsy causing dysarthria and mild dysphagia
with bilateral facial weakness. Examination of
the peripheral nervous system showed mild (4/5
MRC scale) weakness in the arms and legs associated with loss of deep tendon reflexes. There
was severe loss of proprioception and diminished vibration sense in the hands and feet with
associated limb ataxia yet pain and temperature
sensation was relatively preserved. She was
unable to walk.
It was considered that she had the Miller
Fisher variant of Guillain-Barré syndrome
complicating a campylobacter jejuni infection 1
week earlier. Subsequent investigations disclosed raised IgG antiganglioside antibodies to
GQ1b glycolipids (titre of 1/3000) and high
IgM (+1280) and IgA (+320) titres against
campylobacter jejuni. There was neurophysiological evidence of an axonal sensory neuropathy (sensory conduction in the left sural
and radial nerves was absent; left median
motor compound muscle action potential was
7.2 mV with a conduction velocity of 43.4
m/s). Electrolytes and brain CT performed at
the referring hospital were normal. A lumbar

puncture was performed on day 5 of the illness
and demonstrated normal CSF constituents
with a protein concentration of 0.1g/l. Intravenous immunoglobulin (IVIg) was given for 5
days at a dose of 0.4 g/kg/day starting 6 days
after the onset of neurological symptoms.
On the second day of IVIg treatment it was
noted that the plasma sodium had fallen to 128
mmol/l, with a urinary sodium of 205 mmol/l,
random cortisol of 510 nmol/l, and normal renal
function, fulfilling the criteria for the syndrome
of
inappropriate
antidiuretic
hormone
(SIADH). Five days later the plasma sodium
reached 124 mmol/l and a 1.5 l/day fluid restriction was instigated. Her neurological status
began to improve but after 3 days she became
acutely confused. Within a few hours her confusion had settled but she complained of visual
loss. Examination showed that she had perception of light only in both eyes with normal pupillary responses. Magnetic resonance imaging
showed bilateral occipital lobe infarcts (figure).
Plasma viscosity was measured at 1.85

Magnetic resonance image showing bilateral occipital
infarction (arrows).

Cerebral infarction, immunoglobulin treatment, and Miller Fisher syndrome

centipoise (cp) and over the next 3 days rose to
2.01cp (normal range 1.5 –1.72). Subsequent
magnetic resonance angiography of the cerebral
blood vessels and transoesophageal echocardiography showed no evidence of an embolic
source. There was no evidence of previous
hypotension or any episodes of arrhythmia.
By the time of discharge the patients’ vision
had improved to 6/9 bilaterally. Her left eye
remained moderately paretic and her right eye
was normal. The left sided ptosis and facial
weakness had improved and bulbar function
was normal. She was able to walk unaided and
had normal power in her limbs but remained
arreflexic. Romberg’s test was negative and
joint position sense had normalised.
Discussion
Guillain-Barré syndrome is an acute monophasic peripheral neuropathy characterised by
generalised muscle weakness and has an
incidence of 1–2/100 000/year and a mortality
of 10%.1 In 1956 Fisher described three
patients with a syndrome consisting of ophthalmoplegia, ataxia, and areflexia. This is considered a variant of Guillain-Barré syndrome.
About 6% of patients with Guillain-Barré syndrome start as Miller Fisher syndrome, half of
which go on to develop marked weakness and
half remain pure Miller Fisher syndrome. In
Miller Fisher syndrome the external ophthalmoplegia usually begins symmetrically with
abduction aVected initially. Ptosis, bilateral but
asymmetric, is present in over half the patients
and facial and bulbar palsy does occur.2 The
ataxia may involve the limbs or gait equally
often with clumsiness of fine finger movements; however, loss of joint position sense is
not invariable. Most patients have a preceding
illness and this is often Campylobacter jejuni
enteritis.3 It is thought that these postinfectious
syndromes are caused by the production of
antibodies to gangliosides, which are substantial components of neuronal membranes and
have regulatory roles.4 These antibodies may
arise due to molecular mimicry between
Campylobacter jejuni lipopolysaccharides and
gangliosides.3 In 90% of patients with Miller
Fisher syndrome there are high titres of
antibodies to the GQ1b ganglioside.5
In clinical practice the aetiology of SIADH is
often unclear but it is recognised in association
with Guillain-Barré syndrome. The diagnosis

791

of SIADH requires hyponatraemia with low
plasma osmolality, increased urinary sodium
excretion, absence of volume depletion, and
normal renal, adrenal, and hepatic function.
Symptoms of hyponatraemia range from a mild
confusion, clouding of consciousness to coma,
and seizures.6 In our patient the acute onset of
loss of vision and short lived confusion are
more consistent with acute ischaemia of the
occipital lobe than “hyponatraemic encephalopathy”.
Intravenous immunoglobulin is being used
to treat an increasing number of neurological
illnesses including Guillain-Barré syndrome,
multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, myaesthenia gravis,
dermatomyositis, and multifocal motor neuropathy with conduction block. Immunoglobulin treatment has been quoted as having a
minor complication rate of 59% and 4.5% of
patients have serious complications including
neutropenia, congestive heart failure, and renal
failure.7 There have been three previously
reported cases of cerebral infarction after IVIg,
and cerebral vasospasm, cerebral vasculitis,
and serum hyperviscosity have been implicated
in the pathogenesis.8 In our patient cerebral
infarction may have arisen as a consequence of
IVIg related hyperviscosity exacerbated by
fluid restriction. All patients receiving IVIg
must have careful fluid balance management
and if SIADH occurs fluid restriction should
only be instigated when hyponatraemic symptoms are severe.6 In view of the risk of serious
adverse events in those patients receiving IVIg,
the treatment must be clearly justified.
1 Hughes RAC. Intravenous IgG in Guillain-Barré syndrome.
BMJ 1996;313:376–77.
2 Ropper AH. Miller Fisher syndrome and other acute
variants of Guillain-Barré syndrome. In: Mcleod JG, ed.
Inflammatory neuropathies. London: Baillière’s Clinical
Neurology 1994;95–106.
3 Yuki N, Taki T, Takahashi M, et al. Molecular mimicry
between GQ1b ganglioside and liposaccharides of Campylobacter jejuni isolated from patients with Fishers syndrome.
Ann Neurol 1994;36:791–3.
4 Ledeen RW, Wu G. Ganglioside function in the neuron.
Trends in Glycoscience and Glycotechnology 1992;4:174–87.
5 Plomp JJ, Molenaar PC, O’Hanlon GM, et al. Miller-Fisher
anti-GQ1b antibodies: á-latrotoxin-like eVects on motor
end plates. Ann Neurol 1999;45:189–99.
6 Gill G, Leese G. Hyponatraemia: biochemical and clinical
perspectives. Postgrad Med J 1998;74:516–23.
7 Wills AJ, Unsworth DJ. A practical approach to the use of
intravenous immunoglobulin in neurological disease. Eur
Neurol 1998;39:3–8.
8 Stangel M, Hartung HP, Marx P, et al. Intravenous
immunoglobulin treatment of neurological autoimmune
diseases. J Neurol Sci 1998;153:203–14.