José L. Ruiz-Sandoval, Erwin Chiquete, Lucía E. Álvarez-Palazuelos, Miguel A. Andrade-Ramos & Luis R. Rodríguez- Rubio Osmotic demyelination syndrome (ODS) is the damage over the central nervous system caused by several electrolytes, metabolic and toxic disorders. We aimed to describe cases of unusual forms of ODS. In a 9-year period, 25 consecutive patients with ODS (15 men; mean age 42 years) were registered in our referral institution, among them, four (16 %) with atypical neuroimaging findings were abstracted for this communication. None of them presented cardiorespiratory arrest, head trauma, seizures, neuromyelitis optica spectrum or contact with toxic chemicals. Case 1 was a 33-year-old alcoholic man without hypertension or electrolyte imbalance, who presented a classic central pontine myelinolysis (CPM) and a hemorrhage within the pons. Case 2 was a 34-year-old alcoholic man with hypoglycemia and hyponatremia who presented CPM and diffuse bihemispheric extrapontine myelinolysis (EPM) after correction of serum sodium. Case 3 was a 52-year-old woman with mild hypokalemia and hyponatremia (inadequately corrected), who presented a peduncular and cerebellar EPM. Case 4 was a 67-year-old woman who had a suicidal attempt with antidepressants and carbamazepine without impaired consciousness, who complicated with mild hyponatremia associated with a classical CPM and a spinal cord EPM. Case 2 died and the rest remained with variable neurological impairments at last follow-up visit. With modern neuroimaging, the so-called atypical forms of ODS may not be as rare as previously thought; however, they could have a more adverse outcome than the classical ODS.

1. Atypical forms of the osmotic
demyelination syndrome
José L. Ruiz-Sandoval, Erwin Chiquete,
Lucía E. Álvarez-Palazuelos, Miguel
A. Andrade-Ramos & Luis R. RodríguezRubio
Acta Neurologica Belgica
ISSN 0300-9009
Acta Neurol Belg
DOI 10.1007/s13760-012-0110-5
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3. Author's personal copy
Acta Neurol Belg
DOI 10.1007/s13760-012-0110-5
ORIGINAL ARTICLE
Atypical forms of the osmotic demyelination syndrome
´
´
´
Jose L. Ruiz-Sandoval • Erwin Chiquete • Lucıa E. Alvarez-Palazuelos
• Luis R. Rodrıguez-Rubio
´
Miguel A. Andrade-Ramos
•
Received: 27 March 2012 / Accepted: 22 June 2012
Ó Belgian Neurological Society 2012
Abstract Osmotic demyelination syndrome (ODS) is the
damage over the central nervous system caused by several
electrolytes, metabolic and toxic disorders. We aimed to
describe cases of unusual forms of ODS. In a 9-year period,
25 consecutive patients with ODS (15 men; mean age
42 years) were registered in our referral institution, among
them, four (16 %) with atypical neuroimaging findings
were abstracted for this communication. None of them
presented cardiorespiratory arrest, head trauma, seizures,
neuromyelitis optica spectrum or contact with toxic
chemicals. Case 1 was a 33-year-old alcoholic man without
hypertension or electrolyte imbalance, who presented a
classic central pontine myelinolysis (CPM) and a hemorrhage within the pons. Case 2 was a 34-year-old alcoholic
man with hypoglycemia and hyponatremia who presented
CPM and diffuse bihemispheric extrapontine myelinolysis
(EPM) after correction of serum sodium. Case 3 was a
52-year-old woman with mild hypokalemia and hyponatremia (inadequately corrected), who presented a peduncular and cerebellar EPM. Case 4 was a 67-year-old
woman who had a suicidal attempt with antidepressants
and carbamazepine without impaired consciousness, who
complicated with mild hyponatremia associated with a
classical CPM and a spinal cord EPM. Case 2 died and the
rest remained with variable neurological impairments at
last follow-up visit. With modern neuroimaging, the
so-called atypical forms of ODS may not be as rare as
J. L. Ruiz-Sandoval (&) Á E. Chiquete Á
´
L. E. Alvarez-Palazuelos Á M. A. Andrade-Ramos Á
´
L. R. Rodrıguez-Rubio
´
´
Servicio de Neurologıa y Neurocirugıa, Hospital Civil de
Guadalajara ‘‘Fray Antonio Alcalde’’, Hospital 278, Guadalajara,
Jalisco 44280, Mexico
e-mail: jorulej-1nj@prodigy.net.mx
previously thought; however, they could have a more
adverse outcome than the classical ODS.
Keywords Central pontine myelinolysis Á Extrapontine
myelinolysis Á Neuroimaging Á Osmotic demyelination Á
Osmotic myelinolysis
Introduction
Osmotic demyelination syndrome (ODS) is the term that
better describes the damage that over the central nervous
system cause multiple electrolytes, metabolic and toxic
disorders. Since the original description in 1959 by Adams
et al. [1], and later in 1979 by Wright et al. [2], central
pontine (CPM) and extrapontine myelinolysis (EPM),
respectively, have been reported as the common forms of
ODS. Rapid correction of hyponatremia was the first recognized risk factor, but it is currently known that ODS can
occur even with an ‘‘adequate’’ correction of hyponatremia
[3] and in the absence of serum sodium imbalances [4, 5].
Histopathologically, CPM is an axonal-sparing noninflammatory degeneration of oligodendrocytes localized
in the basis pontis [5]. The lesions are typically symmetrical and can spread to other anatomical areas such as
cerebellum and supratentorial structures. This spread represents the main concept of EPM [4, 5].
ODS can be suspected on CT, but MRI is the technique
of choice that suggests a premortem diagnosis of myelinolysis; lesions with hypointense signals are seen on T1
and they are hyperintense on T2-weighted MRI. Since
ODS is not an inflammatory process, the lesions are classically non-enhancing after gadolinium administration [4, 6].
These neuroimaging characteristics correspond pretty well
with those observed in autopsy investigations [4]. Thus,
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Acta Neurol Belg
MRI has increased the recognition of atypical forms of this
entity in the context of known risk factors, typical neuroimaging as well as the clinical and radiological presentation.
Herein, we describe four patients with unusual radiological
presentations of ODS.
Methods
In a 9-year period, 25 consecutive patients with ODS
(15 men, mean age 42 years) were registered, of whom
four (16 %) with atypical neuroimaging findings were
abstracted for this analysis (Fig. 1). All patients were
assessed with 1.5 Tesla MRI. All patients were alert during
the initial clinical evaluation. We excluded cases associated with cardiorespiratory arrest, head trauma, seizures,
the neuromyelitis optica spectrum (i.e., positivity to NMOIgG/anti-AQP4) or contact with toxic chemicals, given
their neuroimaging appearance similar to that of ODS [6].
Results
Hemorrhagic CPM (Fig. 1a)
A 33-year-old alcoholic man, without history of hypertension, was admitted to our center due to acute bilateral
lower-limb paresis that evolved to quadriparesis in 48 h,
accompanied with vomiting, diplopia and dysphagia. At
hospital arrival the patient was alert, with dysarthric
speech, unable to abduct both eyes, with moderate bilateral
facial paresis, with dysphagia, with quadriparesis and
bilateral Babinski sign. No electrolyte, platelet count or
coagulation abnormalities were observed. A non-contrast
head CT scan showed an atypical patchy and confluent
hyperdensity within the tegmental pons without changes on
the contrast phase. All these findings were compatible with
a pontine hemorrhage. Six days later a brain T2-weighted
MRI showed a heterogeneous lesion with a diffuse
hyperintense signal and a central hypointensity suggestive
of hemosiderin deposits within the pons. An angiographic
study was negative for intracranial vascular malformations.
Medical support treatment and rehabilitation was offered.
At 2-year follow-up, the patient presents occasional dizziness and has brisk reflexes without paresis.
CPM and diffuse bihemispheric EPM (Fig. 1b)
A 34-year-old alcoholic man was admitted to the Emergency Department with altered mental status, hypoglycemia (58 mg/dl, normal 70–100 mg/dl) and hyponatremia
(122 mmol/l, normal 135–146 mmol/l), which was inadequately corrected in the following hours (4 mmol/l/h). An
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initial head CT scan showed collapsed ventricles and sulcal
effacement. No cardiorespiratory arrest or hypoxia events
were identified at any moment of the pre-hospital history or
during the hospital stay. However, due to worsening of the
neurological status (stupor), a second CT scan was performed 72 h after hospital presentation. The new imaging
showed hypodense basal ganglia and a diffuse hyperdense
laminar image at the cortical-subcortical junction in the
non-contrast CT phase and after contrast administration.
A T2-FLAIR brain MRI demonstrated diffuse brainstem
and bihemispheric abnormalities consistent with a dramatic
global myelinolysis. No gadolinium enhancement was
observed. The patient was discharged in vegetative state
and died at home 2 weeks later.
Cerebellar peduncular EPM (Fig. 1c)
A 52-year-old woman with a history of diabetes, hypertension and chronic antidepressants use was admitted to
our institution with a 5-day history of generalized mild
weakness, vomiting and difficult speech. On admission,
hyponatremia (119 mmol/l) and hypokalemia (2.9 mmol/l,
normal 3.5–5.0 mmol/l) were detected and inadequately
corrected (6 mmol/l/h). On the following 48 h, the neurological status worsened and mechanical ventilation was
installed. A brain T2-weighted MRI evidenced diffuse
peduncular hyperintense signals involving the cerebellum,
consisting with the rare cerebellar ODS. The patient was
discharged 3 weeks later after receiving gastrostomy and
feeding tube placement, with severe dysphagia, dysarthric
speech, gait disturbance, postural instability, moderate
ataxia of the four limbs and mild tremor and dysdiadochokinesis in the upper limbs.
CPM and spinal EPM (Fig. 1d)
A 67-year-old woman with history of diabetes, diabetic
neuropathy and depression was managed in another
hospital for a suicidal attempt (with antidepressants and
carbamazepine) complicating with a mild hyponatremia
(130 mmol/l), for which no information on management
could be obtained. After 1 week of hospital stay she was
discharged with somnolence, dysarthria, dysphagia and
quadriparesis. Asking for a second opinion she was
admitted to our hospital with pseudobulbar affect, horizontal nistagmus, dysarthria, spastic quadriparesis, bilateral
Babinski sign and urinary incontinence, without a sensory
level. A cranio-spinal T2-weighted MRI showed a typical
pontine hyperintensity compatible with a classic central
myelinolysis and a longitudinal lesion from C2 to T7 spinal
cord segments, suggesting a common etiology. CSF laboratory tests showed a non-inflammatory fluid (proteins

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Acta Neurol Belg
Fig. 1 Brain imaging studies in
the four cases presented.
a Hemorrhagic central pontine
myelinolysis. b Central pontine
and diffuse hemispheric
extrapontine myelinolysis.
c Peduncular and cerebellar
myelinolysis. d Pontine and
spinal myelinolysis
37 mg/dl, glucose 48 mg/dl, leukocytes 0) and the serum
was negative for NMO-IgG/anti-AQP4, antinuclear, SSA
or SSB antibodies. Routine CSF stains and cultures were
negative for microbial growth and no viral genome was
amplified by polymerase chain reaction. The patient was
discharged with mild quadriparesis, dysarthric speech and
dysphagia. She was lost to follow-up after 6 months
without any clinical recurrence.
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Discussion
ODS was first described as a distinct pathological entity
identified by autopsy; however, a reliable premortem
diagnosis is now possible on the basis of MRI techniques
[7, 8]. Here, we report four patients with infrequent
radiological forms of ODS who presented well-known risk
factors. Indeed, several toxic, infectious and inflammatory
disturbances can present similar neuroimaging findings to
those described in this case series. Nevertheless, we
excluded other causes of the clinical and radiological
characteristics of our patients. In our opinion, no other
common risk factors, blood tests, CSF analyses or brain
and spine MRI/CT scanning could demonstrate alternative
etiologies.
Hemorrhagic CPM
Hyperdense lesions on CT have been identified within
hypodensities compatible with ODS. Calakos et al. [7]
reported a case of cortical–subcortical EPM, with lesions
described as ‘‘multifocal punctate hemorrhages’’. In classic
non-hemorrhagic CPM, hyperdense images on CT can be
seen only after contrast administration, suggesting a blood–
brain barrier disruption or myelin degradation with modification of the lipid/protein ratio [8]. Rouanet et al. reported
a patient with CPM who showed a hypointense signal
in T2-weighted MRI over the classical hyperintensity
consistent with pontine demyelination. They did not considered this finding as a pontine hemorrhage, since a noncontrast head CT did not show a hyperdense lesion [8]. In
our case, the hyperdensity was evident in the non-contrast
CT, a finding clearly compatible with a parenchymal
hematoma. We hypothesize that the same osmotic injury
that causes the myelinolytic process can also generate an
endothelial damage that could lead to vascular disruption
and hemorrhage, either as primary or collateral osmotic
injury, in a susceptible patient [9].
Diffuse supratentorial CPM/EPM
Although EPM in the basal ganglia, periventricular white
matter and cortico-subcortical junction have been described
as forms of ODS since 1988, these locations are unusual and
scarcely reported [2, 7, 10–12]. Cortical laminar lesions
have been described in ODS with variable pathological
findings that include cortical laminar necrosis [10–13],
laminar demyelination with gliosis, or both [2, 7]. In our
patient, the burden of chronic alcoholism, other inherent
nutritional deficiencies and the metabolic and electrolyte
disturbances documented at hospital admittance could
explain the diffuse demyelination. We completely excluded
in this patient a state of hypoperfusion or hypoxia, which
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may present similar neuroimaging findings compared with
those seen after the osmotic injury. Evidence exists on a
down-regulation of genes involved in myelin synthesis and
maintenance, associated with predisposition to alcohol
abuse [14]. Thus, it appears that alcoholism is a vulnerable
state that predisposes to ODS.
Cerebellar EPM
ODS presenting with ataxia is very rare [5], and cerebellar
myelinolysis with or without CPM has been reported
scarcely in the scientific literature [15, 16]. Cerebellar
syndrome is usually omitted from the list of clinical manifestations that announce osmotic brain injury; and on the
other hand, EPM is not included in the differential diagnosis of the cerebellar syndromes. Therefore, this rare form
of EPM may be overlooked in clinical practice. Given the
present evidence, clinicians should be aware of this diagnosis in a patient presenting with cerebellar deficit after
electrolyte imbalances [16].
Spinal CPM/EPM
Osmotic demyelination affecting the spinal cord remains
almost anecdotic, with the first reference dating back to
1985, reported by Zwick et al. [17], who described four
autopsy cases with spinal findings compatible with the
osmotic injury seen in the classic supratentorial CPM [17].
These patients, all alcoholic individuals, were considered
as affected by spinal myelinolysis with predominant
lesions in the posterior columns of the cervical spinal cord
segments [17]. In our patient, as in all Zwick’s cases, the
typical presentation of an injury confined to the spinal cord
was absent, which is incompatible with other etiologies that
may resemble the neuroimaging findings described in our
patient. Also, a non-inflammatory CSF and negativity to
NMO-IgG/anti-AQP4 exclude the neuromyelitis optica
spectrum [18, 19]. In 1998, Pneumatikos et al. [20]
reported a quadriplegic patient with cervical spinal EPM
confirmed by MRI, associated with hypernatremia. Moreover, neither Zwick et al. nor Pneumatikos et al. reported
that their patients had simultaneous CMP. In our patient,
the concomitant CPM and spinal EPM strongly suggest
ODS diagnosis. To our knowledge, this is the first case
reported with this particular characteristic.
In conclusion, clinicians should be aware of atypical
clinical and radiological findings in the context of known
risk factors for osmotic demyelination. Our observations
may help to expand the list of clinical syndromes associated with osmotic central nervous system injury.
Conflict of interest
None.

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