Benign Intracranial
Hypertension:
Atypical Presentation
of Miller Fisher
Syndrome?
Leena D. Mewasingh, MD*,
Tayeb Se´khara, MD*, Bernard Dachy, MD
†,
Maurice C. Djeunang, MD*, and
Bernard Dan, MD*
Acute ocular paresis, nausea, vomiting, and headaches
associated with high intracranial pressure without
obvious intracranial pathology are typical features of
benign intracranial hypertension. We describe two
young children whose presentation, initially suggestive
of idiopathic or benign intracranial hypertension,
evolved to comprise ophthalmoplegia, ataxia, and
areflexia. This triad characterizes Miller Fisher
syn-drome, a clinical variant of Guillain-Barre´ syndrome
that occurs rarely among children. In both patients,
this diagnosis was supported by the clinical course and
neurophysiologic findings. Plasma serology was
posi-tive for
Campylobacter jejuni
and anti-GQ1b antibodies
in one patient and for antimyelin antibodies in the
other. This report of two children with Miller Fisher
syndrome presenting with intracranial hypertension
adds to the findings for a similar patient treated
previously, which raises the question concerning the
possible role or contribution of benign intracranial
hypertension in Miller Fisher syndrome.
© 2002 by
Elsevier Science Inc. All rights reserved.
Mewasingh LD, Se´khara T, Dachy B, Djeunang MC, Dan
B. Benign intracranial hypertension: Atypical presentation
of Miller Fisher syndrome? Pediatr Neurol 2002;26:
228-230.
Introduction
Miller Fisher syndrome is an acute demyelinating
con-dition of the peripheral nervous system primarily affecting
cranial nerves [1]. It is rare in children, with an incidence
estimated at 2-8 cases/10 million [2]. It is considered to be
a variant of Guillain-Barre´ syndrome, which typically
presents with acute ascending flaccid paralysis with little
or no sensory involvement [1]. In Miller Fisher syndrome
the immune-mediated process often involves anti-GQ1b
antiganglioside antibodies [3] with a specificity of 90%
[4]. Miller Fisher syndrome characteristically presents
with acute or subacute ophthalmoplegia affecting mostly
the sixth cranial nerve, ataxia, and areflexia. In two thirds
of cases, there is a preceding respiratory or gastrointestinal
infection [5],
Campylobacter jejuni
being a common
isolate in the latter [6]. The pathophysiology in such cases
involves molecular mimicry between certain bacterial
membrane lipopolysaccharides and myelin surface
gan-gliosides leading to autoantibody formation [7]. We
de-scribe two children whose presentation, initially typical of
raised intracranial pressure, evolved to Miller Fisher
syndrome over 48-72 hours.
Case Reports
Patient 1
A 9-year-old female presented with sudden-onset frontal headaches associated with nausea, diplopia, and a convergent strabismus. She had been well up to 2 weeks earlier when she developed an acute febrile episode of diarrhea. Clinically she had a left sixth nerve palsy. General and neurologic examination, including heart rate, blood pressure, fun-duscopy, muscle power, deep tendon reflexes, and coordination were normal. The results of a cerebral computed tomogram were also normal. Lumbar puncture revealed an opening pressure of 30 cm H2O, and 15 mL
of cerebrospinal fluid was withdrawn. Cerebrospinal fluid protein content (0.28 gm/L) and cell count were normal. Her headache and nausea improved over the following 24 hours. These symptoms then recurred in association with vomiting. Acetazolamide was begun (10 mg/kg/day), and her headache and nausea improved. Three days later she developed bilateral third and sixth nerve palsy and became ataxic. Deep tendon reflexes were absent. A diagnosis of Miller Fisher syndrome was made, and she received a 2-day course of intravenous immunoglobulin therapy (1 gm/kg/day). Sensory and motor nerve conduction velocities of the lower limbs and electromyography were normal (Table 1). H reflexes were absent. The results of cerebral magnetic resonance imaging were normal. Serology forCampylobacter jejuniwas positive in plasma (titers of 1 in 2,000 initially and of 1 in 5.21 2 weeks later) and negative in cerebrospinal fluid.Borrelia burgdorferiserology was negative in both. Serum anti-GQ1b antiganglioside antibodies were present. Ataxia im-proved within a week of intravenous immunoglobulin therapy. One
From the *Department of Neurology; Hoˆpital Universitaire des Enfants Reine Fabiola; 1020 Brussels, Belgium; and the†Department
of Clinical Neurophysiology; Hoˆpital Brugmann; 1020 Brussels, Belgium.
Communications should be addressed to:
Prof. Dan; Department of Neurology; Hoˆpital Universitaire des Enfants Reine Fabiola; 15 Avenue JJ Crocq; 1020 Brussels, Belgium. Received June 7, 2001; accepted September 4, 2001.
month later, reflexes had reappeared and her ophthalmoplegia had largely recovered except for residual incomplete abduction of the right eye. Three months after initial presentation she had normal eye movements.
Patient 2
A previously well 2-year-old female presented with a 2-week history of increasingly frequent falls, vomiting, and a convergent strabismus. There was no preceding infection. Clinical examination revealed bilateral sixth nerve palsy and ataxia. The results of an examination was otherwise normal, including funduscopy, muscle power, and deep tendon reflexes. The cerebral computed tomography scan finding was normal. Forty-eight hours later, her vomiting and ataxia worsened. She became dysarthric and had swallowing difficulties. Clinically she had a persistent left sixth nerve palsy, generalized areflexia, and an ataxic gait. The results of funduscopy and repeated computed tomography scans remained normal. Lumbar puncture revealed cerebrospinal fluid with an opening pressure of 20 cmH2O, a protein content of 0.2 gm/L, and normal cell count.
Plasma serology was negative forC. jejuni,B. burgdorferi,Mycoplasma pneumoniae, Epstein-Barr virus, coxsackieviruses, influenza A and B, enteroviruses, and adenovirus. Antimyelin antibodies were present in plasma but not in cerebrospinal fluid. With the technique used (immu-nofluorescence on rodent sciatic nerve section), specific reactivity to myelin-associated glycoprotein or glycosphingolipids cannot be identi-fied. No anti-GQ1b or anti-GM1 antibodies were detected. Motor nerve conduction studies revealed decreased amplitude and delayed latencies of compound muscle action potentials in upper and lower limbs (Table 1). Sensory nerve conduction studies of the median nerve demonstrated loss of amplitude and decreased velocity. F waves from median nerve stimulation at the wrist were delayed. Electromyography of the upper and lower limbs revealed widespread fibrillation. Given the diagnosis of Miller Fisher syndrome, the patient received intravenous immunoglobu-lin therapy (2 gm/kg over 24 hours) followed by corticosteroids (meth-ylprednisolone 2 mg/kg/day for 5 days). Four weeks later she could talk and swallow without any difficulties and required minimal assistance to walk.
Discussion
Idiopathic intracranial hypertension, often referred to as
benign intracranial hypertension
or
pseudotumor cerebri
,
was initially described in 1937 by Dandy [8]. This
syndrome is characterized by signs of raised intracranial
pressure occurring in the absence of obvious cerebral
pathology. The cerebrospinal fluid is of normal
composi-tion with a raised opening pressure (more than 20 cm H
2O
above 5 years of age, more than 13.5 below 5 years of age,
and more than 7.5 below 2 years of age) [9,10]. Absence
of papilledema does not exclude the diagnosis [11].
Therapeutic measures include lumbar puncture to
with-draw cerebrospinal fluid and the use of acetazolamide or
corticosteroids [10].
The initial clinical picture in these two patients is
compatible with benign intracranial hypertension, given
the association of sudden-onset headaches, normal
menta-tion, and cerebral computed tomography imaging with
elevated cerebrospinal fluid opening pressure with a
nor-mal cellular and chemical profile. The pathophysiology in
benign intracranial hypertension remains unclear. Various
hypotheses have been proposed, based on neuroradiologic
and cerebrospinal fluid hydrodynamic studies. These
in-clude increased venous sinus pressure, decreased spinal
fluid absorption, overproduction of cerebrospinal fluid by
the choroid plexus [12], increased blood volume, and
diffuse cerebral edema [13]. Denny-Brown suggested that
cerebrospinal fluid protein increase impedes cerebrospinal
fluid resorption by arachnoid villi, resulting in intracranial
hypertension and papilledema [14]. However, this would
not account for increased cerebrospinal fluid pressure
when cerebrospinal fluid protein level is not raised, as in
our patients.
[image:2.596.50.286.55.228.2]Co-occurrence of benign intracranial hypertension and
Guillain-Barre´ syndrome has been described [15]. A
survey of pediatric Guillain-Barre´ syndrome documented
the presence of papilledema in approximately 4% of
affected children [16]. This finding suggests the possible
coexistence of benign intracranial hypertension in a small
cohort of patients with Guillain-Barre´ syndrome.
How-ever, because papilledema is not an invariable feature of
benign intracranial hypertension [11], it is possible that
this association is underrecognized. This situation further
underpins the difficulties in diagnosing acute
inflamma-tory demyelinating polyneuropathies. Aside from the
clin-ical heterogeneity, there is also marked variability in
electrophysiologic findings as illustrated by our patients.
In the first patient the only significant finding was an
absent H reflex, which indicates impaired nerve
conduc-tion in proximal fibers. Such involvement is typical of
early acute inflammatory demyelinating polyneuropathy,
which could be missed if neurophysiologic investigations
are limited to conventional nerve conduction studies. In
the second patient, in addition to electrophysiologic
evi-dence of widespread demyelination (reduced motor and
sensory nerve conduction velocities, conduction blocks, and
Table 1. Electrophysiologic findingsPatient 1 Patient 2
Electromyography Normal† Fibrillations and positive sharp
waves at rest†
Motor units of normal morphology†
Motor nerve conduction studies
Normal‡§¶ 2CMAP amplitude (0.1–0.8
mV)*द
Reduced velocities (9–17 m/s)*‡§¶
Conduction blocks (up to 81%)द
Sensory nerve conduction studies
Normal§ 2SNAP amplitude (1.4
V)*‡
Reduced velocity (41 m/s)*‡
F waves Normal latencies¶
Delayed latencies (up to 78 ms)*‡
H reflex (soleus muscle)
Absent Not performed (no reliable M response)
* More than 2 standard deviations below reference values.
†Deltoid, biceps brachii, vastus lateralis, gastrocnemius medialis,
tibialis anterior muscles.
‡Median nerve. §Peroneal nerve. ¶Tibial nerve.
Abbreviations:
CMAP ⫽ Compound muscle action potential
SNAP ⫽ Sensory nerve action potential
increased F wave latencies), signs of acute axonal
neurop-athy were also present.
To our knowledge, only one previous case of Miller
Fisher syndrome presenting with benign intracranial
hy-pertension has been documented [17]. This case was a
5-year-old male with benign intracranial hypertension who
developed radicular pain, ataxia, and multiple cranial
nerve involvement and became hyporeflexic. He had
bilateral papilledema at presentation and a cerebrospinal
fluid opening pressure of 51 cm H
2O with 0.23 mg/dL of
protein. Blood and cerebrospinal fluid serology yielded no
positive results, although no search for
C. jejuni
or
anti-GQ1b antibodies was reported. The patient improved
over a 2-week period. These three patients and the finding
of papilledema in a comprehensive survey of pediatric
Guillain-Barre´ syndrome suggest that raised intracranial
pressure with or without papilledema may be an initial
feature of Guillain-Barre´ syndrome or its clinical variants,
such as Miller Fisher syndrome. This association raises
questions pertaining to both its epidemiology and clinical
significance. It also has therapeutic implications given the
possibility of symptomatic management of intracranial
hypertension. Because the evaluation of patients with
possible Guillain-Barre´ syndrome/Miller Fisher syndrome
includes a lumbar puncture, we propose that cerebrospinal
fluid opening pressure be monitored systematically. This
would help define the extent of benign intracranial
hyper-tension in this group of patients.
We would like to acknowledge the support of Dr. Catherine Christophe, Dr. Lofti Bassime, and Professor Anne Putteman in the management of Patient 1.
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