MS Brainstem Lesions and Their Impact

An Entirely New Way to Think About Multiple Sclerosis?

MS Brainstem Lesions and Their Impact

Hi. I'm Dr Stephen Krieger, a neurologist at the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai Hospital in New York.

I'm here at the American Academy of Neurology meeting in Washington, DC, where I had the chance to present for the first time a new visualization of multiple sclerosis (MS) disease course that I call “The Topographical Model of MS,” so I thought I would show that to you and present it here.

We've had disease course categories in MS for 20 years: our relapsing-remitting, secondary progressive, and primary progressive types, but often those don't fully and neatly apply to individual patients.

So I've come up with a different model of MS disease course that looks at the mixture of relapsing disease and progressive disease as more of a continuum rather than having discrete categories of disease course. This is because our differences between categories may not always capture the clinical nuance that individual patients have and perhaps could have implications for how we think about our therapies and our goals of treatment.

So the topographical model of MS looks at a few key factors, things relapse rate, recovery, severity, and also what I'm calling the topographical distribution of lesions—really lesion localization, which is obviously so important in neurology and in MS particularly. And then there is the progression rate, and progression rate seems to be a really separate feature of the disease course in MS.

The main observation of this model is that progress in MS, when it occurs, seems to take the form of prior relapses.

For example, take a patient who had a bad relapse of right leg weakness that recovered and got back to normal—if she begins to progress some years later, that progression begins again with the same right-leg weakness that she experienced as part of her relapse.

That recapitulation of relapse symptoms permanently in the context of progression, I think, is an important feature in the MS clinical course, and that is what is shown in this model.

The model is principally a visual one and depicts the central nervous system as a pool with a shallow end and a deep end.

The shallow end and the deep end refer to different amounts of neurologic and functional reserve—the spinal cord and optic nerves have little reserve, and most relapses in MS happen in these areas. The brain stem has a bit more reserve and is in the middle—certainly some relapses can occur there.

Finally, the hemispheres have the most reserve, so most of our periventricular lesions that we think of as being so typical in MS rarely cross the clinical threshold to cause symptoms. That clinical threshold, I think, is really an important feature of the MS clinical course.

It's what defines whether a patient develops signs and symptoms or whether their lesions remain subclinical. So I show, through a series of 3D-rendered models, how the disease course unfold over time.

Here I'll show you some of a secondary progressive disease course, which begins with relapsing-remitting disease and proceeds through early progression. In the earliest stages of the disease course in MS, we have lesion formation shown here as these topographical peaks.

This is the radiologic isolated syndrome—nothing has crossed that clinical threshold. so there are no signs or symptoms. By year 5, a first attack occurs in the spinal cord, so this peak crosses the clinical threshold, causes a myelopathy, and then recovers below the threshold.

A couple of years later, we have more subthreshold lesions that emerge and are consistent with additional brain stem or hemisphere lesions. Then in year 7, the second attack occurs. In this case, it is a brain stem syndrome that recovers right to the threshold.

But you see that the threshold is declining, and so even as relapses and new lesions continue to occur, perhaps more significantly that threshold has declined as functional reserve is lost. The topographical peaks, the lesions, are now visible above the surface.

So even while there is continued disease activity, disability is really being driven here in years 11, 12, and 13 by the declining water level—that loss of reserve revealing a multifocal cord syndrome myelopathy (multifocal brain stem signs that are such cardinal manifestations of progressive MS). Here at year 17, we see a black hole that formed; it too crossed the threshold. Black holes are these more damaging lesions in MS, and so we see that here they're peaking above the threshold even in the cerebral hemispheres.

I think we can think of disease course in MS as having both effects from the floor—new lesions emerging—and also effects from the surface as the threshold declines as functional reserve is lost. This is a clinical manifestation framework. It's not making any new claims about mechanism of disease or the underlying biology.

But I think if we look at disease course through this lens, we could think about how better to model and predict the emergence of relapses—and also the transition into progression, which happens so gradually—and think about the goals of our disease-modifying therapies as preventing lesions from rising from the floor of the tank but also acting on the surface by affecting the decline of functional reserve that happens over the course of progression. These two things may be fundamentally different goals of our disease-modifying therapies, and this may have implications for how we think about MS, how we teach it to our patients, how they distinguish between new relapses and stability, or relapses and pseudoexacerbations, or Uhthoff's phenomenon. It may help patients better understand MS, and we may be able to model and study disease course over time.

Medscape Neurology © 2015  WebMD, LLC

Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: An Entirely New Way to Think About Multiple Sclerosis? – Medscape – May 14, 2015.


The Multiple Sclerosis Lesion Checklist

MS Brainstem Lesions and Their Impact

Paraphrasing W.B. Matthews about ‘dizziness,’ there can be few physicians so dedicated to their art that they do not experience a slight decline in spirits when they learn that a patient’s brain MRI shows nonspecific white matter T2-hyperintense lesions compatible with microvascular disease, demyelination, migraine, or other causes.

1 The situation is particularly vexing if the patient with multiple nonspecific brain lesions also has multiple nonspecific sensory, vestibular, cognitive, and affective symptoms.

Could this patient have multiple sclerosis (MS), a potentially crippling, neuroinflammatory disorder characterized by diverse symptomatology and multiplicity of white matter lesions?

The author argues that in a patient with no clinical history of MS- relapses and a normal neurologic examination—improbable MS—the absence of lesions typical for demyelination makes the diagnosis of MS untenable.

This contention is the premise that cerebral demyelination signs on MRI are sufficiently recognizable and characteristic to be considered a sine qua non of MS diagnosis.

2 A corollary is that presence of multiple white matter lesions does not increase lihood of MS as long as none, or very few, of the lesions are typical of MS. The key question, then, is whether a patient’s MRI shows MS- lesions.

To answer this all-important question, I propose a systematic, checklist-based approach to reviewing brain MRI and have developed The MS Lesion Checklist my clinical experience and extensive literature review. It is not yet validated.

The MS Lesion Checklist

The MS Lesion Checklist provides brief definitions for 10 types of lesions that are best appreciated on axial or sagittal T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) sequences. Typical examples are shown in Figures 1-8.

Only lesions that conform to a description in The MS Lesion Checklist should be regarded as distinctly MS-. For example, Dawson’s fingers (See Figure 6) must be firmly in contact with the ventricles, as originally described by Dawson.

3 Juxtacortical lesions, best seen on FLAIR sequences (See Figure 8) should be contiguous with cortex.4 MS brainstem lesions may be seen more clearly on T2W sequence than FLAIR and should only be considered distinctly MS- if they border the subarachnoid space or a ventricle (See Figures 1-4).

5 MS corpus callosum lesions should border callososeptal interface on sagittal FLAIR as in Figure 7.

Figure 1. Nerve root entry zone lesion. Arrow: Lesion along left trigeminal root; the trigeminal nerves are seen in the prepontine cisterns.

Figure 2. Cerebellar hemisphere lesions. Two small demyelinating lesions are seen in the right cerebellar hemisphere. Note there is also a typical peripheral brainstem lesion that appears to track along the left glossopharyngeal nerve root.

Figure 3. Middle cerebellar peduncle lesions. Bilateral middle cerebellar peduncle (MCP) lesions as well as lesions within basilar pons and cerebellar hemispheres.

Figure 4. Medial longitudinal fasciculus lesion. A vertical lesion in the central midbrain involves the medial longitudinal fasciculus near the dorsal edge and spreads all the way to the ventral surface giving an appearance of a split midbrain. The right temporal lobe subarachnoid cyst is an incidental finding.

Figure 5. Inferior temporal lobe lesion. An inverted J lesion is in the left inferior temporal lobe, and a subtler lesion is in the right temporal lobe. Note the peripheral brainstem lesion in the left midbrain and a lesion in the left temporal cortex.

Figure 6. Lesions adjacent to lateral ventricle (Dawson’s fingers). MRI from a patient with early MS shows a few Dawson’s fingers on sagittal fluid-attenuated inversion recovery (FLAIR) image (A). MRI from a patient with more advanced MS shows numerous Dawson’s fingers on axial FLAIR image (B).

Figure 7. Corpus callosum lesion. Corpus callosum lesion (arrow) is easy to appreciate on the midsagittal image to the left. The same colossal lesion can also be spotted on an axial T2 to the right.

Figure 8. Cortical, juxtacortical lesions, and U-fiber lesions. Arrows: multiple small juxtacortical and cortical lesions throughout cerebral hemispheres.

By definition, no white matter may interpose between a juxtacortical lesion and the cortex.

Note U-fiber lesions along arcuate fibers in middle left frontal lobe, highly characteristic of demyelination and not seen in normal aging or vascular disease.

Using The MS Lesion Checklist, a clinician can score each of the 10 lesion types as present or absent and note how many of each are found on their patient’s T2W/FLAIR sequence.

If none or just one of the 10 types is present, and the patient does not have a history of MS- relapses, neurologic disease progression, or abnormalities on examination (eg, afferent pupillary defect, extraocular or sensory deficits, long-tract signs), diagnosis of demyelinating disease should not be made.

In a high-probability patient, even normal or near-normal cerebral MRI findings do not necessarily exclude a diagnosis of MS.

A patient may have predominantly spinal MS, in which case the brain may be largely spared of lesions, whereas spinal cord MRI contains peripherally placed, short-segment intramedullary lesions typical of demyelination.6 Another rare scenario is a patient with a history of a classic MS- relapse (eg, optic neuritis or brainstem syndrome) in whom a lesion may have resolved on subsequent MRIs.

One additional caveat concerns the scenario when, contrary to expectations, brain MRI, in a patient with improbable MS, shows findings suggestive of MS (ie, multiple lesions fit The MS Lesion Checklist criteria).

In this case, the possibility of preclinical or asymptomatic MS—radiologically isolated syndrome—should be entertained even in the absence of a clinical history consistent with MS.

In this case, a more comprehensive evaluation may be indicated, including MRI of the spinal cord, lumbar puncture and cerebrospinal fluid (CSF) analysis, ocular computerized tomography (OCT), and referral to a specialized MS center.

The MS Lesion Checklist Versus Barkhof Criteria

The MS Lesion Checklist differs from Barkhof criteria for MS (Box) in 2 key aspects.

7 First, Barkhof imaging criteria were “created to predict development of MS in a patient with clinically isolated syndrome (CIS) that suggest inflammatory demyelination, a clinical syndrome typical of MS.

8” Barkhof criteria were not designed to be applied to patients without suspicion of MS (eg, a case of chronic headache) in whom they are more ly to yield a false-positive than a true-positive result.

9 This disclaimer is often lost in translation, in part because radiologists are rarely informed of a patient’s probability for MS. The MS Lesion Checklist is a screening tool emphasizing sensitivity over specificity, designed to help exclude MS in a low-probability patient referred to MRI for headache, fatigue, dizziness, or some other nonlocalizing symptom.

Secondly, The MS Lesion Checklist focuses exclusively on findings that help differentiate MS from other etiologies, most importantly normal aging and vascular disease. For example, subcortical or basal ganglia lesions, despite the number, do not help separating MS from microvascular disease.

Discrete lesions in the inferior temporal lobe, on the other hand, are common in MS and rare in microvascular disease. Thus, inferior temporal lobe lesions are included, and subcortical and basal ganglia lesions, despite their ubiquity in MS, are not. Similarly, only brainstem lesions that border CSF space are included.

The more interiorly located brainstem lesions that do not border CSF space occur in MS but are omitted because they are less helpful for differentiating MS.

MRI Red Flags

To further discriminate MS from its mimics, findings that are atypical for MS are compiled as The MS Red Flag List. Screening for these involves review of both T2-weighted and non-T2-weighted sequences. The MS Red Flag Checklist is intended to alert the clinician that a search for an alternative diagnosis is in order and may point to a specific etiology.7,10,11

Limitations of the Checklist Approach

The MS Lesion Checklist reflects the author’s experience and literature review and is not yet validated. Developed by a clinician for clinicians, it is designed as a quick and practical tool for trying to determine whether MRI findings support a diagnosis of MS.

The MS Lesion Checklist is not intended to replace review by qualified neuroradiologists that takes into account a full range of features that may help discriminate MS from other causes (eg, lesional signal intensity on various sequences, shape, presence of gadolinium enhancement) and assesses for presence of a wide variety of pathologic processes.12-,13 A third limitation is availability and quality of relevant MRI images for review. If a patient’s scan parameters deviate materially from the recommended MRI protocol for MS,14 comprehensive evaluation for demyelinating lesions may not be possible.


Radiology reports can be nonspecific, leaving uncertainty as to whether MRI confirms or confutes MS diagnosis. Mention of demyelinating disease in patients with few or no radiographic characteristics of MS is the most common cause of MS misdiagnosis.

15 It is beneficial, perhaps even imperative, for clinicians who diagnose MS to acquire the skill set necessary to independently review brain MRI for evidence of demyelination. This article outlines a practical, checklist-based approach for the practicing clinician and neurology trainee.

Hopefully, publication of The MS Lesion Checklist will help reduce MRI-supported misdiagnosis of, with its attended psychologic, economic, and medicolegal costs, and stimulate research to improve MRI reporting in suspected MS.

Ilya Kister MD, FAAN

Director, NYU Multiple Sclerosis Fellowship Program,Associate Professor of Neurology, NYU School of MedicineNew York, NYThe author welcomes comments and feedback at


The author has served on scientific advisory boards for Biogen Idec and Genentech and received research support from Guthy-Jackson Charitable Foundation, National Multiple Sclerosis Society, Biogen-Idec, Serono, Genzyme, Genentech, and Novartis.


What Distinguishes MS From Its Mimics?

MS Brainstem Lesions and Their Impact

HILTON HEAD—Multiple sclerosis (MS) is the most common demyelinating disease, and its mimics are rare, according to an overview provided at the 39th Annual Contemporary Clinical Neurology Symposium.

Given that the treatments and outcomes for MS and its mimics are so different, neurologists should take care to establish a diagnosis early, said Sid Pawate, MD, Assistant Professor of Neurology at Vanderbilt University School of Medicine in Nashville.

Because of the varied clinical presentation of MS, a wide variety of conditions enter the differential diagnosis. Because of the central role that MRI plays in MS diagnosis, imaging mimics that cause white matter lesions also need to be considered, said Dr. Pawate.

Typically, the white matter lesions seen in MS are periventricular, juxtacortical, and callososeptal in location. Infratentorially, cerebellar peduncles are a common site. The lesions tend to be ovoid, are 3 mm to 5 mm or larger, and appear hyperintense on T2 and FLAIR sequences.

Acute lesions may show restricted diffusion or enhancement after the administration of gadolinium contrast.

Typical Presentations of MS

The three most common presentations of MS are transverse myelitis, optic neuritis, and brainstem–cerebellar dysfunction. Acute partial transverse myelitis is “the most classic” form of transverse myelitis among patients with MS, said Dr. Pawate.

Acute complete transverse myelitis, on the other hand, may be postinfectious or idiopathic, or seen as part of acute disseminated encephalomyelitis (ADEM).

Similarly, longitudinally extensive transverse myelitis is more suggestive of neuromyelitis optica spectrum disorders (NMOSD) than MS.

The most typical presentation of MS optic neuritis is unilateral and has acute or subacute onset. Patients often have retrobulbar, “gritty” pain when they move their eye. Complete blindness is unusual, and complete recovery occurs in nearly all patients.

Hyperacute onset suggests a vascular process rather than optic neuritis, said Dr. Pawate. Slow, insidious onset may indicate an infiltrative process such as neoplasm or sarcoidosis.

Painless vision loss may indicate ischemic optic neuropathy, and severe blindness without recovery may result from NMOSD.

The most pathognomonic brainstem dysfunction in MS is intranuclear ophthalmoplegia (INO), especially when it is bilateral. Other brainstem symptoms typical of MS include ataxia, painless diplopia, facial numbness, and trigeminal neuralgia in a young patient.

Hyperacute or insidious onset of brainstem symptoms is unly to indicate MS. Symptoms that localize to a vascular territory usually result from a stroke.

In addition, multiple cranial neuropathy is more suggestive of infections such as Lyme disease, sarcoidosis, or carcinomic ulcers.

Unusual Presentations of MS

Certain variants of MS do not present with the typical periventricular ovoid lesions. Tumefactive MS often presents with a large (ie, larger than 2 cm), solitary demyelinating lesion. These lesions usually are biopsied.

Treatment with steroids usually brings improvement. After this first manifestation, the patient’s course is typical of relapsing-remitting MS. “Rarely do patients have tumefactive lesions in the middle of their MS course,” said Dr.


Another unusual presentation is concentric rings of demyelination, sometimes with mass effect. This variant is called Balo’s concentric sclerosis, and the patient may have typical MS lesions in addition to the rings.

“Historically, Balo’s concentric sclerosis was thought to be a severe disease with a poor prognosis,” said Dr. Pawate.

“With the advent of MRI, we know that these [rings] are more common than we initially thought, and more benign—not much different from any other MS lesions.”

Patients also may present with multiple large lesions and aggressive disease onset. Such patients need early treatment.

“When I see something this, I treat aggressively using plasma exchange and IV steroids,” said Dr. Pawate. This treatment may be followed by natalizumab infusions, and the patients may make a good recovery.

“Historically, this aggressive MS onset was called Marburg variant and was fatal,” said Dr. Pawate.

MS Mimics

ADEM is more common in children than in adults, and imaging can distinguish it from MS. One distinguishing feature of ADEM is that the patient has many lesions that appear to be of the same age.

Lesions may appear on the basal ganglia and the thalamus, which is atypical for MS. Spinal cord lesions tend to be longer in ADEM, compared with those in MS. ADEM tends to have a monophasic course, and patients usually present with encephalopathy, headaches, and vomiting.

Patients often have a history of preceding vaccination or infection.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) also can mimic MS on MRI. What distinguishes it from MS are lacunar infarcts, involvement in sites the thalamus and basal ganglia, and gray matter involvement. CADASIL affects middle-aged adults and leads to disability and dementia.

If a patient referred for suspected MS has bilaterally symmetric confluent lesions, “think more in terms of leukodystrophies,” said Dr. Pawate. The absence of gadolinium enhancement is typical in leukodystrophies. The disorders may involve the U-fibers, the brainstem, or the cerebellum, and patients may present with cognitive decline.

Susac’s syndrome is a triad of branch retinal artery occlusion, sensorineural hearing loss, and encephalopathy.

The syndrome is associated with a characteristic MRI that includes “spokes” (ie, linear lesions) and “snowballs” (ie, globular lesions) in the corpus callosum, as well as a “string of pearls” (ie, microinfarcts) in the internal capsule.

In the eye, the most pathognomonic finding is hyperfluorescence of the arterial wall on fluorescein angiogram. Early treatment can produce good outcomes, but missing the diagnosis may quickly result in dementia, vision loss, and hearing loss.

Lupus can cause CNS manifestations, including cerebritis, vasculitis, and myelitis.

“Primary CNS vasculitis can mimic MS on MRI sometimes, but the red flags are that the patient may have headache and infarcts on MRI, which are not seen in MS,” said Dr. Pawate.

The white matter lesions in neurosarcoidosis can be similar to those in MS, but neurosarcoidosis also causes leptomeningeal enhancement and cranial nerve enhancement, which are not seen in MS.

—Erik Greb


Activities of daily living and lesion position among multiple sclerosis patients by Bayes network

MS Brainstem Lesions and Their Impact

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MS Composite

MS Brainstem Lesions and Their Impact

Multiple Sclerosis (MS): Flair axial MRI images at the level of the medulla/cerebellum (left), and cerebral hemispheres (middle and right). Note the numerous lesions (MS plaques) in the white matter bilaterally.

If you look closely at the right lateral medulla, you will see the lesion that resulted in the patient's right facial numbness.

MS is a common neurological disorder, and one of the leading causes of disability in young adults.

It is characterized by recurrent neurological episodes separated by time and space, resulting in multiple demyelinating lesions in the central nervous system. Because MS affects different areas of the brain, brainstem, cerebellum and spinal cord, a variety of neurological symptoms and signs can be seen.

The most common temporal course in MS is a relapsing/remitting pattern. Patients with this temporal course experience intermittent neurological attacks that last days to weeks. Patients often recover to their baseline, whereas others may have some residual deficit following an attack. A minority of patients have a chronic progressive course.

Many patients with a relapsing/remitting course will evolve into a chronic progressive course years into their disease. Similar to many other autoimmune disorders, MS is more common in women than in men. MS most commonly presents in young adults, although any age can be affected.

MS affects the myelin in the CNS, with relative preservation of the axons. The etiology is unknown, but many observations point to an autoimmune pathogenesis. MS plaques usually develop in a perivenular distribution, and are characteristically seen in the periventricular white matter, brainstem, and spinal cord. The active lesions contain T lymphocytes and macrophages.

A variety of neurological symptoms and signs are seen in patients with MS. These may include cognitive, visual, cranial nerve, corticospinal, sensory, cerebellar, bladder and/or sexual impairment. Certain clinical syndromes are highly suggestive of MS, especially in the appropriate age group. These include:

� Optic neuritis – Optic neuritis presents as an acute unilateral loss of vision (mainly central vision), often accompanied by pain in the eye, that worsens with eye movement. On examination, an afferent pupillary defect is usually present.

� Internuclear Ophthalmoplegia (INO) – This characteristic horizontal eye movement abnormality results from a lesion in the medial longitudinal fasciculus (MLF) which runs through the pons and midbrain. In a patient with an INO, when the patient looks to one side, the abducting eye moves correctly, but the adducting eye is restricted.

Often, the abducting eye movement is accompanied by nystagmus. However, with a convergence maneuver, both eyes move correctly, denoting that the medial rectus and cranial nerve III are intact. Unilateral and bilateral INOs are most commonly seen in patients with MS. In a younger patient, the presence of an INO is almost always due to MS.

In older individuals, an INO can be see in a brainstem stroke (typically due to basilar ischemia).

� Uhthoff's phenomenon – This refers to a worsening of neurological symptoms with an increase in body temperature (e.g., following exercise, a hot bath, or fever). This phenomenon occurs because transmission through demyelinated segments of nerve fails at higher temperatures.

� Lhermitte's phenomenon – Lhermitte's phenomenon refers to a transient “electric shock” or “buzzing” sensation that runs down the spine or into the limbs when the neck in flexed (note: this sign can also be seen in structural lesions compressing the spinal cord, e.g., spondylosis, tumor, etc.).

Diagnostic Evaluation of a Patient with Suspected MS

Until the advent of MRI, MS was often difficult to diagnose with certainty. Brain CT is unable to visualize the demyelinating plaques, and thus usually normal in a patient with MS.

In the past, the diagnosis was a clinical course of a relapsing and remitting neurological disease (two or more deficits separated in time and space) in the appropriate age group, and in the absence of another explanation.

The diagnosis was often supported by:

� CSF Abnormalities – The protein is often elevated with a mild lymphocytosis. In addition, signs of myelin breakdown and an ongoing immune response may be seen, especially during an attack (e.g., elevated myelin basic protein, the presence of oligoclonal bands, elevated IgG synthesis rate).

� Demonstration of “Silent” Lesions – Evoked potentials (EPs) were often used to confirm the presence of additional subclinical lesions.

These tests are done by stimulating an afferent pathway (visual, auditory or sensory) and recording their resultant potentials over the brain using scalp electrodes, similar to those used during EEG.

Visual evoked potentials are useful in detecting subclinical lesions of the optic nerves and visual pathways; auditory evoked potentials are able to detect lesions in the brainstem (thus, they are also known as brainstem evoked potentials); and somatosensory evoked potentials assess the posterior columns and rostral sensory pathways.

Although CSF studies and EPs were often used in patients with suspected MS, many times the results were normal or equivocal. In addition, these studies are not specific to MS; thus, false positives can occur.

� Magnetic Resonance Imaging – MRI has markedly improved the ability to diagnose MS correctly.

Not only is MRI able to exclude conditions that may mimic MS clinically, but it is also able to show the characteristic demyelinating plaques in over 90% of patients.

These plaques are typically located in the deep white matter, especially in a periventricular pattern. They are also seen in the brainstem, cerebellum and spinal cord.

Management and Treatment of MS

The treatment of MS involves both symptomatic and disease modifying therapy. Symptomatic therapy is available for spasticity, tremor, fatigue, bladder dysfunction, depression, and cognitive impairment.

Intravenous methylprednisolone (Solu-Medrol) is used during acute attacks to promote a quicker recovery. It is most commonly used in optic neuritis. It is also used for any attack wherein the symptoms are serious enough to interfere with daily functioning.

However, this treatment ly does not change the natural history of the disease.

Several disease-modifying drugs are now approved by the FDA in patients with relapsing/remitting MS. These include:

Interferon �-1b (Betaseron)

Interferon �-1a (Avonex and Rebif)

Glatiramer acetate/copolymer 1 (Copaxone)

Each of these agents have been shown to significantly reduce the relapse rate and the burden of lesions on MRI. Each is given as an injection, either by a subcutaneous or intramuscular route.

They vary in how often they are given: once a week for Avonex, three times a week for Rebif, and daily for Betaseron and Copaxone.

As a general rule, all patients with relapsing forms of MS should receive one of these agents indefinitely.

Treatment of the chronic progressive form of MS is more problematic. A variety of immunosuppressive regimens have been tried, including total lymphoid radiation, methotrexate, cyclophosphamide, mitoxantrone, and azathioprine.

Each of these are nonspecific immunosuppressive agents. While they may halt a rapidly progressive course, they are problematic when used indefinitely as they can be associated with significant toxicity and risks.

The risk-benefit ratio must be assessed on a case by case basis.