This document provides an overview of multiple sclerosis (MS), including its causes, pathophysiology, clinical features, diagnosis, course, classifications, and the role of MR imaging. MS is a demyelinating disease of the central nervous system that typically affects people aged 20-40. It has an unknown cause but is thought to involve genetic, viral, autoimmune, and environmental factors. Clinically, it presents with sensory issues, optic neuritis, spasticity, and other symptoms. Diagnosis involves identifying neurological abnormalities via history, exam, and MRI findings. The disease course is highly variable but can be classified as relapsing-remitting, secondary-progressive, primary-progressive, or progressive-

1. MULTIPLE SCLEROSIS: Overview and role of MR imaging
Himadri Sikhor Das,MD
Multiple sclerosis (MS) is an idiopathic inflammatory and most common demyelinating
disease of the CNS. Most people with this disease are affected in their prime of their lives,
usually between 20 and 40 years of age though exceptions have been documented. Cause of
this disease remains unknown. Genetic, viral, autoimmune and environmental factors have
been implicated in the disease.
Pathologic hallmark of MS is multicentric and multiphasic CNS inflammation and remyelination
scattered over space and time. In MS, cells of the immune system invade the CNS and
destroys the myelin cover leading to demyelination of the axon and damage to the axon itself.
In response, other cells of the CNS produce a hard sclerotic lesion (“ the MS plaque”)
around the multiple demyelinated sites. Areas of axonal damage can be measured by
magnetic resonance spectroscopy (MRS) and is found to correlate with clinical disability. Few
lesions in non-eloquent areas do not produce clinical symptoms or neurological dysfunction.
Such lesions are referred to as “silent lesions”. Approximately 1 per 1000,000 people acquire
MS internationally. Throughout adulthood, the female to male ratio is 2:1.
Clinical features:
Sensory problems occur in 20%-50% of patients and are often the earliest symptoms. These
manifest as tingling, tight band feeling, crawling sensations etc are found in the extremities and
in the trunk and are referred to as paresthesias. Few patients may experience an electric like
sensation that goes down the back and legs with head or neck motion (Lhermitte’s sign).
Optic neuritis is the presenting symptom in 15%-20% of patients with MS and usually starts
with blurring of vision followed by loss of vision. May appear on one side followed by a later
appearance in the other. It rarely involves both eyes simultaneously.
Spasticity occurs due to cortico-spinal tract involvement . Occurs with the initial attack of MS
in 30%-40% of patients. It is present in 60% of patients with progressive disease. Usually legs
are involved more than the arms.
Other clinical features of MS includes gait and balance incoordination, bladder & bowel
dysfunction, fatigue (the single most complaint of people with MS), heat sensitivity, cognitive
and emotional dysfunctions etc.
Diagnosis of MS is based on a classic presentation (optic neuritis, transverse myelitis,
paresthesias etc) and on the identification of other neurological abnormalities, which is
indicated by the patients history and clinical examination. Typical findings in MRI greatly help
to establish diagnosis of MS. Patients with atypical presentations and /or a normal or atypical
MRI may require evoked potential studies to know about subclinical neurological abnormality.
CSF analysis is done to exclude treatable conditions and to document immunological activity in
the CNS. Oligoclonal bands are present in over 90% of definite MS, though these can be seen
in other inflammatory diseases and in 7% of
normal controls. An IgG index of >0.7 is seen in 86%-94% of MS patients and is usually the
first CSF abnormality in early MS. 25% patients show elevated protein levels. Presence of
myelin basic protein in CSF indicates demyelination though these also can be seen in other
neurological conditions like infections, infarct etc. However this protein can be found in the first
2 weeks after a substantial exacerbation in 50%-90% of patients.

2. Course of disease: The natural course of MS is highly variable and it is impossible to predict
the nature, severity or timing of progression in a given patient. Patients with sensory problems
tends to have a better prognosis than those with spasticity or paralysis. Another factor that
influences prognosis is age of onset. Disease progression tends to be more rapid in patients
who experience their first symptoms after age 40. Other factors predictive of rapid progression
include male gender, frequent attacks and burden of disease as detected by MRI scans.
Classifications of MS :
Clinically definite MS is further categorized according to disease course. Relapsing-remitting
MS (RR-MS) is characterized by symptoms that develop over a period of a few hours to a few
days, followed by recovery and a stable course between relapses. Approximately 80% of
patients are initially dignosed with relapsing-remitting MS. Almost 50% of patients with
relapsing- remitting MS eventually develop secondary-progressive MS (SP-MS)
characterized by gradual neurological deterioration with or without superimposed acute
relapses. If there is continual disease progression from onset with only minor fluctuation the
classification becomes primary-progressive MS (PP-MS). PP-MS occurs in approximately 10
% of patients and mostly who are > 40 years of age. Progressive-relapsing MS (PR-MS), a
rare from of the disease, is characterized by gradual neurological deterioration from the onset
of symptoms to subsequent relapses.
MR IMAGING IN MS:
MR imaging is the modality of choice in patients with MS. Use of MRI in MS was first
described by Young et al in 1981. Previously spin echo (SE) sequences like T1, T2 and PD
weighted images are commonly used to screen patients with MS. Recently fast or turbo spin
echo (FSE & TSE) techniques with similar PD and T2 weighted lesion contrast has become
popular because this sequences utilize ¼ to 1/3rd
of acquisition time. Very small lesions can be
missed on FSE sequences because of edge blurring, but taking thinner slices compensates it.
Recent MR developments in imaging of white matter disease :
Nowadays FLAIR (fluid attenuated inversion recovery) sequences are widely used because
heavily T2 weighted images can be obtained with CSF suppression and enables greater lesion
conspicuity in the gray white interface areas. Another technique is EPI (echo planar imaging).
Use of EPI FLAIR is very useful in detecting early lesions that do not enhance such as
Demyelinating disease, acute infarcts and infection.
Diffusion weighted imaging (DWI) :
Normal white matter exhibit anisotropic diffusion with increased diffusion parallel to white
matter fibers and restricted diffusion present perpendicular to these fibers. Demylination results
in increase in extracellular space which in turn results in increase in water diffusion and
diffusion coefficient as compared to normal white matter. Hence in MS, both in acute and
chronic plaques there will be increase in diffusion coefficient. Acute plaques has higher
diffusion coefficient than chronic plaques probably due to gliosis in chronic plaques. Currently

3. modalities like DTI (diffusion tensor imaging) and FA (fractional anisotropy) are being utilized
for more research in MS.
Quantative magnetisation transfer (MT) technique :
Useful in MS patients on drug therapies to know the disease activity. In active plaques there is
little demyelination and their MT ratio is slightly reduced which indicates that lesions are most
likely to respond to methylprednisolone and more likely to disappear. In contrast chronic
plaques have more demyelination and very low MT ratio. These are unlikely to respond to any
drug therapy. This technique is now applied to other white matter disease also.
Magnetic resonance spectroscopy (MRS):
This technique does not produce images but graphs that display levels of metabolites as zones
of different colors or shades of gray known as spectroscopic images. In MS tissue metabolite
like NAA ( N - acetyl aspartate ) is decreased in chronic plaques and remains normal in active
plaques.
MR appearance of MS lesions:
Lesions are typically nodular or ovoid in appearance. Size varies from few mm to more than
1cm. Lesions have propensity to involve the large white matter tracts particularly corpus
callosum, medial longitudinal fasciculus and middle cerebellar peduncle. Lesions can also be
found in juxtacortical location involving the “U” fibres, along the perimedullary veins at the
calloso-septal interface and also in periventricular location giving rise to the classical
“Dawson’s fingers appearance”. MS lesions however can involve any portion of the white
matter. Recently presence of “ Subcallosal Striations”has been described using sagittal
FLAIR sequence. These are thin white lines radiating from the calloso-septal interface and
represents the earliest manifestation of MS in this location. Occasionally, MS lesions present
as large lesions with mass effect and vasogenic edema indistinguishable from brain tumor by
MR imaging (tumefactive MS plaque). Other nonspecific findings include thinning of the
corpus callosum, dirty white matter on T2 weighted images and deposition of non haem iron in
the basal ganglia with progression of the disease
Spinal MS : Spinal MS has a predilection for the cervical spinal cord ( 67 % of cases), with
preferential eccentric involvement of the dorsal and lateral areas of the spinal cord abutting the
subarachnoid space around the cord. About 55 to 75 % of patients with MS have spinal lesions
at some point of time during the course of the disease. As many as 20% of spinal MS lesions
are isolated. Spinal lesions enhance after contrast administration. Enhancement may last for 2
to 8 weeks. Steroids do not suppress enhancement of active plaques. Chronic plaques do not
enhance and often demonstrate focal cord atrophy. Lesions of other etiologies ( eg, viral
myelitis, ADEM ) may resemble MS plaques and must be considered along with the clinical
history and the patients sign and symptoms.
Typical MR morphology of MS lesion:
Initially MS lesions are isointense to mildly hypointense (black) on T1 weighted images. With
time, the hypointensity progresses to develop the so-called “T1 black hole”. Some lesions
show slight peripheral hyperintensity surrounding the lesion due to presence of free radicles in
the surrounding inflammatory tissues. On T2 and PD weighted images the lesions are usually
hyperintense (bright).

4. Role of contrast administration in MS :
In MS contrast enhanced MRI plays an important role depending on the clinical context.
Contrast enhancement in general indicates the presence of active inflammatory process. Non
enhancing lesions are thought to be chronic lesions. Presence of enhancing and non-
enhancing lesions is strong evidence to indicate that these multiple lesions are separated in
time supporting diagnosis of MS. Presence of ring enhancement suggest reactivation of an old
lesion, the central nonenhancing portion representing the “burnt out” portion of the lesion. An
incomplete or open ring enhancement is more indicative of an MS lesion.
MR imaging criteria for clinical progression to MS in patients with clinically isolated
syndromes (CIS). MS typically presents as an acute reversible episode of neurologic
dysfunction.
Paty et al ( 1988 ) : 4 lesions ( Paty A)
: 3 or more lesions, including 1 periventricular lesion (Paty B)
Sensitivity 86 %, Specificity 54 %
Fazekas et al (1988): 3 lesions with 2 of the following properties.
: 5 or > 5 mm diameter of lesion.
: Infratentorial or periventricular location.
: Sensitivity 86 %, Specificity 54 %
Barkhof et al ( 19 97 ) : 4 lesions criteria
: 1 or > 1 Juxtacortical lesion.
: 1 or > 1 enhancing lesion or > 9 nonenhancing lesion.
: 1 or > 1 infratentorial lesion.
: 3 or > 3 periventricular lesions. (Sensitivity and specificity 73%)
Proposed new diagnostic category: MR imaging supported definite multiple sclerosis
(MRISDMS)
1. Age – Not older than 45 yrs.
2. At least one MS –like clinical episode with appropriate clinical findings, remission not
necessary.
3. Abnormal MR image findings (strongly suggestive of MS).
a. Four or more white matter lesions ( > 3 mm diameter ).
b. 3 lesions with at least one located in periventricular location.
4. One or more of the following specific features.
a. Involvement of corpus callosum.
b. Infratentorial location.
c. Oval shape.
d. > 6 mm in diameter.
e. Some but not all enhancing.

5. Variants of MS –
Balo’s concentric sclerosis: - Rare, affects young adults, last for few months, concentric
bands of intact myelin and demyelinated zones, responds to steroid.
Devic’s disease: - (neuromyelitis optica) Spinal cord and optic nerves affected.
Brain spared. Brain MRI normal. MRI spine shows striking lesions.
Marburg’s disease: - Acute form of MS. Fulminant and progressive.
Schilder’s disease: - Rare, affect children, visual problems and cortical blindness,
Seizures, headache, vomiting, large bilateral hemispheres demyelination.
Monophasic syndromes: - Optic neuritis, acute transverse myelitis, ADEM, acute
inflammatory brainstem syndrome.