Multiple Sclerosis: What Do You Know? #illumedati


It’s Medicine Mondays again and so I wanted to talk about Multiple Sclerosis. My in-laws are here in Hawaii with us now and we were all at the local community swimming pool/playground when my father-in-law brought up that a friend of the family was recently diagnosed with Multiple Sclerosis. He wanted to know more about it, so I started to explain.

It was a lot more difficult to do than I thought… and I probably went into way more depth than was needed. So I’ve decided to turn this into a learning experience for me (and my readers), and try to break it up into different levels of depth:

multiple-sclerosis-wdyk

Stock Photo from: Pixabay

First, you must realize that there is a lot to be said about multiple sclerosis. I am sure many, many people much smarter than me can talk for hours on end about multiple sclerosis. However, this post will be about what I know, and what I think each sub-section of the general population would want to know.

For the sake of this post, Multiple Sclerosis will be referred to as “MS” a lot.

GENERAL POPULATION

What is Multiple Sclerosis?

Multiple sclerosis is thought to be an auto-immune disease (the body attacks itself). More specifically, it is a demyelinating disease, meaning it causes the loss of the myelin sheath surrounding the nerves of the central nervous system.

What is the cause?

Unfortunately, we don’t know what causes it. It is felt to be secondary to destruction by the immune system or failure of the cells that produce myelin. Currently, the hypothesis is that it could may be genetically or environmentally related (or both).

What is the treatment?

Unfortunately, there is no cure. Treatment is mostly based around improving function, coupled with Physical Therapy.

There is acute therapy (for acute episodes) and disease modifying therapy (continued usage).

There was a recent therapy in Europe called the “liberation procedure” designed to help Chronic cerebrospinal venous insufficiency (CCSVI), which was felt to be related to Multiple Sclerosis. Early work in this in Europe yielded exceptional results. Many people were very excited to try this procedure in the United States… however, these early stunning results have not been reproducible.

How is it diagnosed?

There is something called the McDonald Criteria, which was revised in 2010.

The most important part of this criteria is that the attacks must be separated in disseminated in both time and space. This can be either demonstrated clinically (a good history) or via MRI. The one exception is to diagnose the “primary progressive” version of MS which is more MRI dependent, requiring lesions disseminated in space in both the brain and spine, as well as + CSF (from Lumbar Puncture).

What are the symptoms?

The symptoms of MS are expansive. However, the most common symptoms are:

Sensory loss (ie, paresthesias) – Usually an early complaint
Spinal cord symptoms (motor) – Muscle cramping secondary to spasticity
Spinal cord symptoms (autonomic) – Bladder, bowel, and sexual dysfunction
Cerebellar symptoms – Charcot triad of dysarthria, ataxia, and tremor
Optic neuritis
Trigeminal neuralgia – Bilateral facial weakness or trigeminal neuralgia
Facial myokymia (irregular twitching of the facial muscles) – May also be a presenting symptom
Eye symptoms – Including diplopia on lateral gaze; these occur in 33% of patients

Heat intolerance
Constitutional symptoms – especially fatigue (which occurs in 70% of cases) and dizziness; fatigue must be differentiated from depression (which may, however, coexist), lack of sleep, and exertional exhaustion due to disability
Pain – Occurs in 30-50% of patients at some point in their illness
Subjective cognitive difficulties – With regard to attention span, concentration, memory, and judgment
Depression – A common symptom
Euphoria – Less common than depression
Bipolar disorder or frank dementia – May appear late in the disease course but is sometimes found at the time of initial diagnosis.
Symptoms associated with partial acute transverse myelitis

The most important part of all this is that these symptomatic episodes are separated in time and space. This means these episodes occur months or years apart and affect different anatomic locations (as discussed by McDonald’s criteria above).

It is also important to understand that when people say “MS” they are usually referring to the most common type of MS, which is the Relapsing Remitting Multiple Sclerosis (RRMS) which is 85% of MS. The other types are: Secondary progressive MS (SPMS), Primary progressive MS (PPMS), Progressive-relapsing MS (PRMS).

Additionally, MS favors women over men on a 2:1 basis, and generally presents between the ages of 20-40.

The “classic presentation” is:

A 33 year old white female with neurological complaints that have occurred “once in awhile” or “on and off”. A good clinical history may be able to tease out that one of these events included a loss of vision (or loss of color vision) or pain on movement of the eye (optic neuritis). Fatigue is also a very common symptom (75%). Cognitive dysfunction and pain are also relatively common presenting complaints. All of these “episodes” or “attacks” lasted longer than 24 hours, and then resolved slowly, over a few weeks.

Take home: Vision Loss, Fatigue, Pain, Cognitive Dysfunction “attacks” lasting > 24 hours, occurring multiple times. –> needs workup

What is the prognosis?

This is dependent on the type, but for the purposes of this post, the most common type is RRMS, so I will talk about its prognosis:

Multiple sclerosis (in its RRMS type) usually does not shorten lifespan very much. A reasonable estimate is 5-10 years.

The major concern is for disability. After about 15 years, about 50% of MS patients will require a walking aid (cane, wheelchair, scooter). Of course, that means the other 50% are able to walk without any aid. Up to 1/3 of MS patients may not have any persistent disability.

Depression is also very common. I would encourage people with friends or family members that have multiple sclerosis to be aware of this. Encourage them to seek out the help of a psychiatrist.

Depression is at its worst when it is surrounded by silence.


MEDICAL STUDENTS

For medical students, your depth of knowledge requirement is higher.

In addition to the RRMS type, you will need to know the other types:

Secondary-progressive MS (SPMS): This happens after the more common RRMS course, then advancing progressively, punctuated by acute attacks. 50% of RRMS will progressive to SPMS in 10 years, and up to 90% in 25 years.

Primary-progressive MS (PPMS): For this one, patients demonstrate gradual worsening of symptoms instead of acute exacerbations. Uncommon, 10-15%

Progressive-relapsing MS (PRMS): This one has both gradual progression of disease as well as acute exacerbations. Relatively rare, 5-10%

Understand its treatments options:

Acute Therapy: Corticosteroids – intravenous methylprednisolone (Solumedrol) 1 gram daily for three to five days +/- tapering dose of oral steroids.

Disease Modifying Therapy (DMT): There are 14 DMT approved by the FDA for the RRMS type, which also includes the secondary progressive form that occurs after RRMS. The exact reason as to how these DMT help is not clear. However, for Interferon B (IFB-B) heals the blood-brain-barrier. Copaxone changes harmful inflammatory cells into non-inflammatory cells. Tysabri blocks passage of inflammatory cells from entering the brain and spinal cord.

Imaging features/lab values associated:

MRI:

MRI findings by themselves are not specific. However, T2/FLAIR hyperintensities in the periventricular white matter which has a perpendicular configuration to the the lateral ventricles (Dawson’s fingers) is a suggestive imaging characteristic. T2/FLAIR hyperintensities in the spinal cord are also demonstrated. You can also see optic neuritis on an orbital MRI as well. If these lesions demonstrate enhancement on post contrast imaging or restricted diffusion on DWI/ADC, then this is most compatible with active demyelination. I think MR Spectroscopy is probably outside your scope.

Lab Values:

Bloodwork is usually normal in MS patients.  Bloodwork is to exclude other possibilties, such as:

Collagen vascular disease and other rheumatologic conditions
Infections (ie, Lyme disease, syphilis)
Endocrine abnormalities (eg, thyroid disease)
Vitamin B 12 deficiency
Sarcoidosis
Vasculitis

Neuromyelitis optica (NMO, or Devic disease) can be confirmed by the presence of serum antibodies against aquaporin 4, a water channel expressed at major fluid-tissue barriers across the CNS. This gets special mention because it can mimic MS. Neurologists and Neuroradiologists like stuff like this. If you want to be a star, NMO is kind of like MS without the brain involvement (just optic nerve and spine). However, its pathophysiology and treatment are different, so it is not MS.


You should also have at least heard of the borderline forms of MS (separate entity versus variant of MS):

Marburg’s variant of multiple sclerosis: (also known as acute fulminant multiple sclerosis) Usually affects younger patients and is characterized by extensive and fulminant acute demyelination, often resulting in death within one year after the onset of clinical signs. Imaging wise, lesions are “tumefactive” with incomplete ring enhancement.

Balo concentric sclerosis: considered to be a variant of MS with a characteristic pattern of alternating hypotense and hypertense layers.

Schilder’s disease: (also known as Diffuse myelinoclastic sclerosis) considered a borderline form of MS. Affects children 5-14 years old.


NEUROLOGY/RADIOLOGY RESIDENTS

You need to know all of the above and:

Open Ring Sign:

A circular area of incomplete enhancement. This is an imaging finding is suggestive of demyelination and is seen in ADEM and MS (but not NMO).

Tumefactive Multiple Sclerosis:

This is an imaging variant of multiple sclerosis, which has a distinct name to describe how “tumor-like” it looks. These lesions are greater than 2 cm in size and cause mass effect, which is very atypical for demyelinating disease. So this moniker serves to remind neurologists/radiologists that not all “tumor-like” lesions are tumors, and tumefactive MS may be in the DDX in the appropriate clinical setting (patient with known MS, or has symptoms of MS). A helpful hint here is the Open Ring Sign, discussed above. This kind of enhancement would be uncommon in a primary or secondary brain neoplasm like GBM or mets. It would also be uncommon for a cerebral abscess as well.

Acute Disseminated Encephalomyelitis (ADEM):

Unlike MS, ADEM occurs usually in children and is marked with rapid fever, although adolescents and adults can get the disease too. ADEM consists of a single flare-up whereas MS is marked with several flare-ups over a long period of time.

Imaging wise: ADEM looks very similar to MS, but is MONOPHASIC. For this reason, you may see both in a differential if there is no prior history of a neurological event. ie. It is difficult to separate a first episode of MS versus ADEM, aside from age.

Neuromyelitis Optic (NMO, or Devic Disease):

This was discussed above, but residents require further detail:

Bilateral optic nerve involvement and chiasmal involvement is particularly suggestive of NMO.

Spinal cord involvement is extensive, with high T2 signal spanning at least three vertebral segments. 

*NMO tends to involve central part of the cord, whereas MS tends to involve the peripheral white matter tracts.

MR Spectroscopy:

NAA peaks may be reduced within plaques

What else could it be (DDX)?

Lyme Disease, ADEM (brain)

Transverse Myelitis, NMO (spine)

Sarcoidosis (either)


NEUROLOGISTS/NEURORADIOLOGISTS

Know all the other things in the brain (including orbits) and spine that aren’t MS, and be able to explain why or why not.


Wow, this post was wayyyyyyyyyy to long. However, I just kept thinking I had more to say… and kept typing.

TL;DR

Multiple sclerosis is a complex disease, even more so for those not in the medical field.

Be able to to explain it based on who you are talking to so they can get the most important/relevant information.

 

-Sensei

Agree? Disagree? Questions, Comments and Suggestions are welcome.

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