CASE STUDY
www.nature.com/clinicalpractice/neuro

The role of spinal cord imaging in the diagnosis
of multiple sclerosis
Jessica M Nielsen*, Frederik Barkhof, Bob W van Oosten and Chris H Polman

S U M M A RY
Background A 29-year-old male presented with fluctuating but

progressive sensory disturbances comprising tingling and dysesthesia
in his right leg. MRI of the brain showed white matter lesions initially
thought to be caused by multiple sclerosis.
Investigations Neurological examination, cerebrospinal fluid
examination, laboratory blood testing, brain and spinal MRI scans.
Diagnosis Spinal cord schwannoma.
Management Surgical removal of the schwannoma. An algorithm is
provided that clarifies the appropriate MRI work-up for cases where the
clinical presentation is suggestive of multiple sclerosis.
KEYWORDS brain MRI, cerebrospinal fluid, diagnosis, multiple sclerosis,
spinal MRI

CME

JM Nielsen is a clinical research fellow, F Barkhof is Professor of Radiology,
BW van Oosten is a neurologist, and CH Polman is Professor of Neurology,
at the VU University Medical Center, Amsterdam, The Netherlands.
Correspondence:
*VU University Medical Center, Department of Neurology, De Boelelaan 1117, PO Box 7057,
1007 MB Amsterdam, The Netherlands
jm.nielsen@vumc.nl
Received 26 September 2005 Accepted 23 February 2006
www.nature.com/clinicalpractice
doi:10.1038/ncpneuro0169

MAY 2006 VOL 2 NO 5

This article offers the opportunity to earn one
Category 1 credit toward the AMA Physician’s
Recognition Award.
THE CASE

A 29-year-old man presented to the neurology
department of a local hospital with an 18-month
history of fluctuating sensory disturbances
consisting of tingling and dysesthesia in the
right leg. The symptoms had initially been limited
to the right foot, but approximately 1 year before
his presentation they had worsened and ascended
to the right knee and later to the entire right leg.
The patient also complained about a general
feeling of stiffness, slight balance problems and
a tendency to fall. He had noticed increased
fatigue, especially when walking long distances.
He had not noticed any muscle weakness, and his
bladder function was normal. His medical history
was unremarkable and revealed no other neurological problems. Neurological examination was
normal, apart from brisk muscle tendon reflexes
in all four extremities. Laboratory testing for
hematology, renal function, glucose, thyroid function and vitamin B12 was normal. Borrelia antibody and treponemal hemagglutination (TPHA)
testing was negative in the serum as well as in the
cerebrospinal fluid (CSF). CSF testing also showed
normal electrophoresis with no oligoclonal bands
and a normal IgG index, but a slightly increased
total protein level (0.67 g/l). An MRI scan of the
brain showed several white matter lesions, some
of which were located close to the cerebral ventricles (Figure 1). On the basis of these findings, the
patient was diagnosed with multiple sclerosis
(MS) and was referred to an MS clinic for a second
opinion, including a therapy consultation.
Approximately 2 months passed after the
diagnosis before the patient was seen at the MS
clinic. On presentation, his symptoms had
worsened—walking had become more problematic, and he reported an altered sensory function
while urinating, although his bladder control was
still normal. On neurological examination, no
major walking problems were observed. Detailed

NATURE CLINICAL PRACTICE NEUROLOGY 283
©2006 Nature Publishing Group

CASE STUDY
www.nature.com/clinicalpractice/neuro

GLOSSARY
DYSESTHESIA
An unpleasant abnormal
sensation, which can be
spontaneous or evoked
HYPOESTHESIA
A decreased tactile
sensitivity

Figure 1 T2-weighted transverse image of the
brain showing multiple high-signal lesions around
the ventricles (arrows).

testing of motor function revealed a slight loss
of strength in the left leg. The patient’s abdominal reflexes were absent, and he had very brisk
reflexes in the legs and bilateral extensor plantar
reflexes. Pinprick discrimination was decreased
descending from thoracic level 10 (T10) and
vibration sense was abnormal in both legs. Testing
of the patient’s coordination revealed a minimal
intention tremor of the right hand. Otherwise,
examination of his upper extremities, cranial
nerves and cognitive function was normal.
Because the current presentation was one of
a slowly evolving spinal cord syndrome, MRI
scanning was repeated, this time to also include
the spinal cord (Figure 2). The scan revealed an
intraspinal hypointense lesion at the level of T4–5,
which enhanced after intravenous administration
of a contrast agent. The lesion was surrounded
by edema and had a compressing effect on the
cord tissue. A diagnosis of an intraspinal tumor
was made and the patient was referred for neurosurgical intervention. The tumor was surgically
removed and microscopic examination showed
it to be a schwannoma. The postoperative course
was uneventful and in the following months the
patient fully recovered, apart from a focal area
of hypOesthesia on his trunk that had most
probably resulted from the T5 nerve origin of
the tumor.
DISCUSSION OF DIAGNOSIS

MS is one of the most common causes of disability
in young adults in Western countries, with a

284 NATURE CLINICAL PRACTICE NEUROLOGY

disease prevalence of approximately 1 per 1,000
in the white population. Establishing a diagnosis
of MS, however, requires careful consideration.
Fluctuating sensory disturbances and discrete
motor abnormalities are a fairly common presentation of MS in a young patient. Ever since the
disease was first described, doctors have faced
difficulties in determining whether an individual with certain neurological signs and symptoms actually has MS, because there is no single
definitive diagnostic test available for the disease.
Traditionally, the diagnostic process has involved
obtaining evidence from the patient’s history,
clinical examination and a variety of laboratory
tests, all intended to gather data consistent with
a diagnosis of MS and to rule out other possible
causes of disease.1,2
MRI investigations have become important in
helping to confirm a diagnosis of MS, but it was
not until 2001 that an international panel for
the diagnosis of MS presented new diagnostic
criteria known as the McDonald criteria, which
focused specifically on the use of MRI as an aid
to diagnosis.3 Although the McDonald criteria
stipulate that the core of an MS diagnosis is
the demonstration at physical examination of
typical disease symptoms and signs disseminated
in time and space, they were the first to provide
a detailed description of how MRI can be used
to demonstrate abnormalities consistent with
MS, with respect to dissemination in both time
and space. Revisions to the McDonald criteria
were recommended in 2005, both to incorporate new research findings and to clarify issues
that could easily be misinterpreted.4 These revisions relate to the guidelines for the use of MRI
to demonstrate dissemination of disease in time,
the question of how spinal cord MRI findings
should be taken into account in this context,
and the criteria required to achieve a diagnosis
of primary progressive MS. Even though the
MRI criteria have been selected because they
have a relatively high specificity for MS, both
the original publication and the recent revision
stress the importance of eliminating alternative
conditions that might ‘mimic’ this disease.
The MRI criteria to demonstrate brain abnormality and dissemination in space are based on
the Tintoré adaptation of the criteria initially
provided by Barkhof et al.5,6 For these characteristics to be demonstrated, three out of the four
following criteria should be fulfilled on the brain
MRI: at least one gadolinium enhancing lesion
or nine hyperintense lesions on T2-weighted

NIELSEN ET AL. MAY 2006 VOL 2 NO 5
©2006 Nature Publishing Group

CASE STUDY
www.nature.com/clinicalpractice/neuro

A

B

C

Figure 2 Spinal cord MRI revealing an intradural hypointense (probably calcified) mass on T2-weighted
images. (A) Showing surrounding edema (high signal) in the compressed cord. After contrast administration,
the mass is enhanced and is better delineated on (B) sagittal and (C) axial T1-weighted images.

MRI if there is no gadolinium enhancing lesion;
at least one infratentorial or spinal cord lesion; at
least one juxtacortical lesion; and at least three
periventricular lesions. One spinal cord lesion
can substitute for one brain lesion.
The presenting symptoms of the patient
in this case were mild, abnormal findings at
neurological examination. These findings were
not recognized as representing a spinal cord
syndrome, and a spinal cord MRI was therefore
not performed at the initial stage. Not only was
the neuroanatomical interpretation of symptoms and signs at that time inappropriate, but
so was the interpretation of the time course of
the symptoms. A first episode of MS in a young
adult typically presents as a so-called ‘clinically
isolated syndrome’ of neurological dysfunction
of the type commonly seen in MS (e.g. optic
neuritis, incomplete spinal cord syndrome),
with a relatively sudden onset (within days), a
plateau phase, and at least partial recovery over
weeks to months. The patient described here
presented with fluctuating but slowly progressive abnormalities, rather than with a discrete
episode (deterioration–plateau–recovery).
Certainly, a so-called ‘primary progressive’
disease course does occur in a percentage of MS
patients (5–10%), but patients with this disease
subtype are typically in their forties or fifties.
Moreover, spinal cord MRI is of great diagnostic
relevance—particularly in cases of primary
progressive MS—and it is a requirement that
this be undertaken in patients presenting with
a spinal cord syndrome, irrespective of the
suspected underlying disease.
The diagnosis of MS in the present patient was
based heavily on the interpretation of the results

of his MRI brain scan. On critical review of the
scan, there were approximately 10 small lesions
distributed throughout the brain white matter, 3
of which were in a periventricular location. In the
absence of juxtacortical or infratentorial lesions,
only two out of the four Tintoré/Barkhof criteria
were fulfilled—insufficient to prove dissemination in space according to the McDonald criteria.
In addition, the results of the CSF examination
should have provided an alert—not only were
signs of intrathecal IgG synthesis lacking (the
IgG index was normal and oligoclonal bands
were absent), but there was also an elevated total
protein concentration, which is atypical of MS.
A spinal cord MRI scan enabled the correct
diagnosis to be achieved in the present case.
In addition to providing either proof of or
evidence to rule out an alternative diagnosis,
spinal cord MRI scans often provide positive
evidence of MS. Dual-echo spin-echo MRI is
most sensitive for the detection of spinal cord
abnormalities, which range from focal lesions to
signal intensity with greater diffusion, the latter
being more frequently observed in (primary)
progressive MS.7 In a diagnostic setting, spinal
cord imaging is valuable for two reasons. First,
the presence of asymptomatic spinal lesions can
help to confirm a diagnosis of MS in cases where
there are few brain lesions present,8 although it
should be noted that in patients with very few
or only one lesion—as is seen for example in a
number of patients with optic neuritis—there
is no extra value in performing a spinal cord
MRI scan because the presence of an additional typical spinal cord lesion would still not
fulfill the McDonald criteria. Second, because
asymptomatic spinal cord lesions are rare

MAY 2006 VOL 2 NO 5 NIELSEN ET AL.

NATURE CLINICAL PRACTICE NEUROLOGY 285
©2006 Nature Publishing Group

CASE STUDY
www.nature.com/clinicalpractice/neuro

Table 1 Algorithm for an MRI work-up in cases where the clinical presentation is suggestive of multiple sclerosis, either as a first
episode or as a slow progression.
Presentation

Recommended
procedure

Reasons for procedure

Next steps

Spinal cord
presentation

Spinal cord MRI

■ To exclude alternative lesions
such as spinal cord compression
■ To demonstrate multiplesclerosis-like abnormalities

■ Brain MRI recommended if multiple sclerosis is suspected,
to demonstrate (further) dissemination in space
■ Consider follow-up brain MRI at 3 months, 12 months, or both
to demonstrate dissemination in time

Non-spinal-cord
presentation
(i.e. brain or
optic nerve
presentation)

Brain MRI

■ To demonstrate multiplesclerosis-like dissemination
in space
■ To exclude an alternative
diagnosis

■ Spinal cord MRI recommended if multiple sclerosis is
suspected, (only) if brain MRI is inconclusive (e.g. multiple
white matter lesions in a hypertensive patient) or if criteria for
dissemination in space are not met on brain MRI
■ Consider follow-up brain MRI at 3 months, 12 months, or both
to demonstrate dissemination in time

Acknowledgments
The MS Centre of the VU
Medical Centre is partially
funded by a program
grant from the Dutch MS
Research Foundation.

Competing interests
The authors declared
they have no competing
interests.

in disorders other than MS, in a patient with
equivocal brain findings, such as an elderly
patient with ischemic vascular lesions and a
prolonged disease duration, a normal spinal cord
MRI scan can help to rule out MS.9
Table 1 presents an algorithm for the appropriate MRI diagnostic work-up in cases where
the clinical presentation is suggestive of MS; this
algorithm is proposed to support, rather than
replace, clinical decision making. On the basis of
the algorithm, the patient presented in this case
should have undergone spinal cord MRI, irrespective of whether the clinical presentation was
interpreted as being a spinal cord syndrome.
DIFFERENTIAL DIAGNOSIS

Brain white matter lesions are most frequently seen
in normal aging and in cerebrovascular disease, but
they are also prevalent in up to 10% of asymptomatic younger adults.10 In addition to normal
aging and cerebrovascular disease, the differential
diagnosis for brain white matter lesions includes
systemic inflammatory disease (for example
lupus erythematosus or sarcoidosis), brain infection such as neuroborreliosis, and migraine.10
In some patients, it is not possible to identify a
specific cause for the lesions, even after extensive
diagnostic investigation. In such cases, the lesions
are more likely to be of a vascular nature than to
be caused by MS. It is advisable, therefore, to apply
stringent—rather than lenient—MRI criteria for
MS, particularly in an atypical clinical setting.
CONCLUSION

The patient in the present case was initially
misdiagnosed with MS, thereby inducing a
therapeutic delay of several months that could
have been prevented if adequate imaging had

286 NATURE CLINICAL PRACTICE NEUROLOGY

been carried out after his initial presentation.
This case illustrates that, in order to achieve a
correct diagnosis in patients presenting with
symptoms similar to those seen in this patient,
a careful interpretation of medical history and
signs at the time of physical examination is essential. The proposed MRI algorithm ensures that
appropriate imaging procedures are undertaken.
White matter lesions—even when consistent
with a diagnosis of MS—should be interpreted
with care, and appropriate application of the
McDonald criteria can help to distinguish MS
from other conditions.
References
1 Poser CM et al. (1983) New diagnostic criteria for
multiple sclerosis: guidelines for research protocols.
Ann Neurol 13: 227–231
2 Schumacher GA et al. (1965) Problems of experimental
trials of therapy in multiple sclerosis. Ann NY Acad Sci
122: 552–568
3 McDonald WI et al. (2001) Recommended diagnostic
criteria for multiple sclerosis: guidelines from the
International Panel on the diagnosis of multiple
sclerosis. Ann Neurol 50: 121–127
4 Polman CH et al. (2005) Diagnostic criteria for multiple
sclerosis: 2005 revisions to the “McDonald Criteria”.
Ann Neurol 58: 840–846
5 Barkhof F et al. (1997) Comparison of MRI criteria at
first presentation to predict conversion to clinically
definite multiple sclerosis. Brain 120: 2059–2069
6 Tintoré M et al. (2000) Isolated demyelinating
syndromes: comparison of different MR imaging criteria
to predict conversion to clinically definite multiple
sclerosis. AJNR Am J Neuroradiol 21: 702–706
7 Lycklama G et al. (2003) Spinal-cord MRI in multiple
sclerosis. Lancet Neurol 2: 555–562
8 Bot JC et al. (2004) Spinal cord abnormalities in
recently diagnosed MS patients: added value of spinal
MRI examination. Neurology 62: 226–233
9 Bot JC et al. (2002) Differentiation of multiple sclerosis
from other inflammatory disorders and cerebrovascular
disease: value of spinal MR imaging. Radiology 223: 46–56
10 Fazekas F (1989) Magnetic resonance signal
abnormalities in asymptomatic individuals: their
incidence and functional correlates. Eur Neurol 29:
164–168

NIELSEN ET AL. MAY 2006 VOL 2 NO 5
©2006 Nature Publishing Group