684

Case reports / Journal of Clinical Neuroscience 14 (2007) 684688

Osmotic demyelination syndromes: Central and

extrapontine myelinolysis
S. Huq
a

a,b,*

, M. Wong

c,d

, H. Chan

c,d

, D. Crimmins

c,d

Department of Neurology, Gosford District Hospital and Royal North Shore Hospitals, Pacic Highway, St Leonards, NSW 2065, Australia
b
Department of Medicine, University of Sydney, Camperdown, NSW, Australia
c
Department of Neurology, Gosford District Hospital, Gosford, NSW, Australia
d
Departments of Neurology and Medicine, University of Newcastle, Callaghan, NSW, Australia
Received 16 December 2005; accepted 21 February 2006

Abstract
Osmotic demyelination syndromes are often progressive disorders, with clinical features ranging from a mild tremor or dysarthria to a
progressive quadraparesis. Although rapid correction of serum sodium is known to be a potent causative factor, additional pathogenic
factors exist, which appear critical in predisposing pontine and extrapontine glia to osmotic stress. Interestingly, several cases of osmotic
demyelination have emerged where serum sodium was found to be within normal limits and minimal or no correction of a hypo or hypernatraemic state was implemented. We describe two cases one of extra pontine and another of central-pontine myelinolysis, both of
which have occurred in the context of relatively normal serum sodium. The rst case illustrates the association of extrapontine myelinolysis with the traditional risk factor of alcoholic cirrhosis and intravenous uid resuscitation, while the second, more unusual case,
describes a patient who developed central pontine myelinolysis possibly in association with alpha interferon therapy.
 2006 Elsevier Ltd. All rights reserved.
Keywords: Central Pontine Myelinolysis; Chronic Liver Disease; Hyponatraemia; Alpha Interferon

1. Introduction
Osmotic demyelination syndromes, which consist of
central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM), are rapidly progressing, often fatal focal
symmetric syndromes, with clinical features ranging from
a mild tremor or dysarthria to a progressive quadraparesis
and a locked-in syndrome. The aetiology of osmotic demyelination is not well understood. Although rapid correction
of serum sodium in the context of chronic hyponatraemia
has been implicated as a potent causative factor,1 it is clear
now that additional pathogenic factors exist, which are
critical in predisposing pontine and extrapontine glia to osmotic stress.2 Among these, the most prominent appear to
be signicant alcohol use and orthotopic liver transplantation.3,4 Interestingly, several cases of CPM and EPM have
been described in the literature where serum sodium was
found to be within normal limits.5 We describe two cases,
one of extra pontine and another of central-pontine myelinolysis, both of which have occurred in the presence of
chronic liver disease and normal serum sodium. The rst
case illustrates the association of extrapontine myelinolysis
with the traditional risk factor of alcoholic cirrhosis and
intravenous uid resuscitation. The second, more unusual

Corresponding author. Tel.: +612 9926 8656; fax: +612 9439 8418.
E-mail address: sohuq75@yahoo.com (S. Huq).

case describes a patient with chronic liver disease secondary

to viral hepatitis, who developed CPM with normal serum
sodium levels, no correction of electrolyte status, and the
possible additional risk factor of alpha interferon therapy.
1.1. Case 1
A 56-year-old man with known alcoholic liver disease
was brought into the emergency department. He was
unconscious on arrival and reported to have been drinking
heavily. Vital signs were normal, and he was afebrile. On
examination he was acutely delirious. Neurological examination revealed equal but sluggishly reactive pupils. He was
hypertonic in both limbs, and his reexes were brisk with
bilaterally upgoing plantar responses. Power, coordination
and sensation could not be formally assessed, but he was
moving all limbs and withdrawing from pain. The remaining systemic examination was unremarkable.
He was admitted to an intensive care unit (ICU) where
high ow oxygen and intravenous uids were administered.
To investigate his poor level of consciousness, a urine drug
screen and a septic work-up was performed, both of which
were negative. His blood alcohol level was 2 mmol/L (0
4.3 mmol/L). Blood glucose was measured at 5.1 mmol/L
(3.58.0 mmol/L). A full blood count, electrolytes, urea
and creatinine, calcium, magnesium and phosphate, thyroid function test and troponin were all within normal limits. Liver function tests were consistent with the history of

Case reports / Journal of Clinical Neuroscience 14 (2007) 684688

alcoholic cirrhosis, with an elevated bilirubin, alkaline

phosphotase and gamma-glutamyl transferase. Serum sodium was 140 mmol/L (135149 mmol/L) at presentation
and remained within normal limits through the entire
admission. Over the next 24 h, further management with
intravenous thiamine and vitamin supplementation was
implemented and his level of consciousness gradually improved. Ceftriaxone was started for possible sepsis, as well
as intravenous phenytoin for seizure prophylaxis. Formal
neurological testing subsequently revealed ataxia, dysdiadochokinesis, and poor coordination bilaterally. Given
persisting signs, further investigations were performed to
exclude a brainstem infarct, meningoencephalitis, subdural
haematoma or hypoxic brain injury. Cranial CT scanning
and a lumbar puncture were performed, both of which
were normal. Finally, an MRI of the brain revealed multiple foci of hyper-intense long TR signals in the cerebral
white matter, the corpus callosum and the cerebellar hemispheres bilaterally (Fig. 1a, b). However, there were no signal changes within the pons, and no loss of grey-white
dierentiation to suggest a hypoxic insult. These MRI ndings were consistent with extra pontine myelinolysis.
The patient had a uctuating course of illness over the
next 3 weeks and required high-level nursing care. By day
5 he was orientated to time and place, and speaking more
uently. His mental state gradually improved and he was
nally discharged to a rehabilitation hospital on day 21
of admission.
1.2. Case 2
A 51-year-old man presented for assessment with a
4-week history of gradual onset of dysarthria, ne-move-

685

ment incoordination and unsteadiness of gait. These symptoms deteriorated during the day and improved after rest.
His background history included hepatitis C infection
(genotype 3a), acquired 15 years previously through intravenous drug use, and complicated by cirrhosis. His other
medical history was signicant for type 2 diabetes mellitus
of 10 years duration, complicated by retinopathy and
nephropathy. Two weeks prior to admission, he had just
nished a 6-month course of alpha interferon treatment
for the viral hepatitis. He reported being completely abstinent from alcohol for at least two years prior to commencement of this treatment. On examination, the
patient was alert and orientated with normal vital signs.
Neurological examination revealed normal tone but brisk
reexes, especially in the lower limbs. The power of the left
leg was reduced to 4/5. Coordination was impaired on the
left side with past pointing in the left hand and dysdiadochokinesis in the left leg. Sensory and cranial nerve examinations were unremarkable. He also had peripheral
stigmata of chronic liver disease with ecchymoses, spider
naevi, and tender hepato-splenomegaly.
Given the above neurological ndings, the diagnostic
possibilities included a brainstem or cerebellar infarct or
neoplasm, cerebellitis, multiple sclerosis or a late-onset
hereditary ataxia. Laboratory tests showed a normal serum
sodium level of 139 mmol/L (135145 mmol/L). Serum
sodium, which was checked quarterly while on alphainterferon therapy, had always been within normal limits
prior to admission. Liver function tests revealed a transaminitis consistent with the history of chronic hepatitis.
Alpha-foetal protein levels were normal. Neurological
work-up including a lumbar puncture and cranial CT scan
were normal. Magnetic resonance imaging demonstrated

Fig. 1. T2 axial (A) and FLAIR (B) MRI of cerebellum and brainstem (case 1). In the cerebellar hemispheres bilaterally, there are hyperintense long TR
signal abnormalities (arrows) involving the white matter, fairly symmetrical and extending to the posterior margin of the middle cerebellar peduncles,
particularly on the right side, consistent with extrapontine myelinolysis.

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Case reports / Journal of Clinical Neuroscience 14 (2007) 684688

Fig. 2. T2 axial (A), and diusion weighted (B) MRI of the cerebrum and pons (case 2). Symmetrically within the central pons there are hyperintense long
TR signals sparing the periphery, without mass eect (arrows), consistent with central pontine myelinolysis.

hyperintense long TR signals within the central pons sparing the periphery (Fig. 2a, b). These MRI features were
consistent with central pontine myelinolysis.
No particular treatment apart from supportive measures
was initiated. The patient was reviewed regularly on a clinical basis as an outpatient. He remains well at 1-month follow-up, although the majority of his neurological ndings
persist.
2. Discussion
Advances in neuroimaging, especially MRI, have allowed earlier detection of the characteristic lesions of
CPM and EPM. The prevalence of this condition, once
thought to be rare, is highlighted by a number of large series, with one demonstrating an incidence of 3/1000 in an
unselected urban hospital population group.6 Evidence
from clinical and laboratory data implicate hyponatraemia
as a potent risk factor predisposing to CPM,79 and rapid
sodium replacement has been implicated as one of the principal pathogenic stimuli to glial damage.10 The precise
mechanism by which cellular injury occurs in CPM/EPM
is speculative and the prevailing hypothesis implicates reduced adaptive capacity of neuroglia to large shifts in serum osmolarity.11,12 Critical discrepancies to this hypothesis
are that most patients receiving even rapid sodium correction do not develop CPM.2 Conversely, mildly hyponatraemic patients whose rate of replacement never exceeded
11 mmol/24 h can develop CPM.13,14 A background predisposition thus appears to be central to the development
of this clearly heterogeneous condition. Two conditions appear to be particular risk factors for the development of
CPM/EPM. These include chronic alcohol abuse and

orthotopic liver transplantation.3,4 The latter group is particularly predisposed to CPM by virtue of operative
and post-operative uid resuscitation, co-existent renal disease and electrolyte derangement, and the use of cyclosporin A.4
Pathologically, CPM/EPM has been characterised by
dissolution of the myelin sheaths and sparing of nerve axons within the central aspect of the basis pontis or extrapontine regions. Surprisingly, given the extent of glial cell
death, there is a conspicuous absence of scavenger cells
or inammatory response, leading to the suggestion that
cell death is mediated largely by apoptosis.15 Glial cells,
the vulnerable cells in CPM, play a critical role in regulating extracellular osmolality and electrolyte balance in support of the neurones they envelop. In the face of an osmotic
challenge, neuroglia activate energy-dependant cell surface
pumps (eg. Na-K ATPase) to rapidly counteract the
electrolyte derangement.2 In patients with liver failure, it
is postulated that glia may inherently lack a plentiful supply of glucose or glycogen, hence relatively minor osmotic
derangements lead to rapid depletion of cellular energy
supply and cell death.2 This certainly appears to be the case
with the two cases we describe, where despite a relatively
normal serum sodium, both patients developed extensive
demyelination.
The second case is particularly interesting in this respect,
as the patient developed CPM in the outpatient setting, in
the absence of uid resuscitation and relatively normal serum sodium. An increasing number of risk factors are being
recognised for the development of osmotic demyelination,
including adrenal insuciency, malnutrition, chronic renal
failure and haemodialysis, sepsis, and malignancy.2 As
such, with more than one predisposing factor, CPM may

Case reports / Journal of Clinical Neuroscience 14 (2007) 684688

indeed develop in the absence of serum sodium uctations.

Case 2 clearly demonstrates this, where the patient had
both liver disease and diabetic nephropathy. Furthermore,
he underwent treatment with alpha-interferon. Alphainterferon has been associated with a number of adverse
neuropsychiatric eects, including paraesthesia,16 seizure
activity,16 depression, neuralgic amyotrophy and polyradiculopathy,17 and severe neuropathy.18 Given the above,
we hypothesise that this patient may well have developed
CPM as a result of a combination of events, where chronic
liver disease and renal insuciency acted as predisposing
factors and the addition of a biological modulator lead
to glial injury. To our knowledge, the association of interferon treatment with osmotic demyelinating syndromes has
not been previously described. It is interesting to note that
the patient developed CPM several months after commencement of interferon therapy. With the extensive use
of alpha-interferon, adverse eects are increasingly being
recognised as early-onset (within 3 months of therapy) such
as depression and inuenza-like symptoms, and lateonset (after 3 months), such as anterior ischaemic optic
neuropathy and myasthenia gravis and sarcoidosis.19
Indeed, Finsterer et al.20 reported a case of multifocal
leukoencephalopathy and sensory-motor polyneuropathy
16 years after the commencement of alpha-interferon therapy. We hypothesise that CPM might be a late-onset adverse event of alpha-interferon therapy, hence the
development of symptoms several months after initiation
of therapy.
Prognostically, the osmotic demyelinating syndromes
are highly heterogenous with complete recovery and
reversal of MRI ndings reported in some cases to progression and death in others. No specic treatment has
been shown to convincingly halt the progress or reverse
CPM/EPM. Although isolated case reports suggest that
steroids21 or thyrotropin releasing hormone22 may be
helpful, no randomised trials exist. A number of guidelines outlining the appropriate rate of sodium replacement
in a hyponatraemic patient have been published;23,24 however, there is a distinct paucity of recommendations relating to the management of individuals with normal serum
sodium at presentation. To date, prevention of osmotic
demyelination remains the mainstay of treatment. The
predominant view (arising largely from case studies)25 is
that in individuals with one or more risk factors (severe
systemic illness, alcoholism, liver transplantation, or malnutrition) should undergo frequent neurological assessment coupled with appropriate imaging (MRI vs. CT)
to make the diagnosis. CPM/EPM needs to be particularly considered in individuals who fail to recover as expected after severe illness or in patients manifesting new
psychiatric symptoms after severe illness.25 It is recommended that high-risk individuals, once identied, should
receive prompt treatment with nutritional supplements,
with exacerbating factors such as drugs and salt-losing
nephropathies corrected.2 Finally, a multi-disciplinary
neuro-rehabilitation program combined with symptomatic

687

treatment of any movement disorders (which sometimes

accompany EPM) should be implemented to promote a
complete functional recovery.

References
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2. Ashraan H, Davey P. A review of the causes of central pontine
myelinosis: yet another apoptotic illness? Eur J Neurol 2001;8:
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myelinolysis after liver transplantation. World J Gastroenterol
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5. Mast H, Gordon PH, Mohr JP, et al. Central pontine myelinolysis:
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doi:10.1016/j.jocn.2006.02.015

Terminal syringomyelia communicating with a spinal dermal sinus

Natarajan Muthukumar

Department of Neurosurgery, Madurai Medical College, Madurai, India

Received 25 November 2005; accepted 22 February 2006

Abstract
Terminal syringomyelia occurs in approximately 25% of patients with occult spinal dysraphism. Congenital spinal dermal sinus is an
uncommon form of occult spinal dysraphism. This case report highlights the rare association of terminal syringomyelia communicating
with a spinal dermal sinus, resulting in an unique clinical presentation. The clinical, radiological and surgical ndings of this unusual case
are reported.
 2006 Elsevier Ltd. All rights reserved.
Keywords: Occult spinal dysraphism; Spinal dermal sinus; Terminal syringomyelia; Tight lum terminale

Terminal syringomyelia is a cystic dilatation of the lower

third of the spinal cord.1 The reported incidence of terminal syringomyelia in occult spinal dysraphism varies from
24% to 27%.1,2 The common forms of occult spinal dysraphism that are associated with terminal syringomyelia are:
tight lum terminale in the presence of an anorectal anomaly, meningocele manque and diastematomyelia, and is
infrequently associated with other anomalies.1 The treatment of terminal syringomyelia associated with occult
spinal dysraphism is controversial.1,2 Recent reports have
documented progression of the terminal syrinx even after
untethering of the cord.3,4 Spinal dermal sinus tracts are
an uncommon form of occult spinal dysraphism often presenting in childhood with cutaneous ndings, neurological
decits or infection.5 The true incidence of spinal dermal sinus tracts is not known and they are believed to be uncommon.6 The present case report highlights a rare association
of a terminal syrinx in a patient with tethered cord that
communicated with a spinal dermal sinus, resulting in epi-

*
Present address: Muruganagam, 138, Anna Nagar, Madurai, Tamil
Nadu 625020, India. Tel.: +91 452 2534 638/2534 551; fax: +91 452 2531
056.
E-mail addresses: prasan86@eth.net, drnmuthukumar@yahoo.com.

Fig. 1. Clinical photograph showing the skin tag in the lumbar region.