Multiple Sclerosis

Overview: Multiple Sclerosis


Multiple sclerosis (MS) is a demyelinating disorder, meaning that the outside myelin “sheath” of the nerve cell axons that help insulate them to allow signals to pass more effectively is broken down. It is presumed to be autoimmune in nature, although this is not yet well understood. MS involves the central nervous system and spares the peripheral nervous system.


MS is more common in women than men, and more common in Caucasians than other races. Symptom onset are typically between ages 20 to 40 years. MS can run in families, but if a person has MS the first degree relative has only a 2-4% chance of having MS. Vitamin D deficiency may play some role with risk of developing MS.


Scientific studies have suggested an autoimmune process in causing MS, including breakdown of the blood-brain barrier and an overactive immune system attacking the myelin sheaths. B cells, T cells, plasma cells, and antibodies have been implicated in various studies as playing roles in MS.


Features of MS symptoms


In general, the focal neurological symptoms of MS tend to develop progressively over a period of hours and then resolve or improve over a period of days or weeks.


MS symptoms may reemerge or worsened in severe heat, called the “Uhthoff phenomenon.” In fact, prior to advances in MRI, Neurologists would often have hot tubs in the office to examine the patient before and after exposure to significant heat. In the modern worse, some patients with MS even wear cooling vests when going in the heat.


The focal neurological symptoms are referred to as “relapses” and the recovery is referred to as “remission.” The degree of remission may be incomplete. Sometimes, there may be a persistent progressive component.


Classic presentations


There are multiple classic ways in which MS first presents.

  • Lhermitte’s sign

    • When a person flexes the neck, there is an electric-shock-like sensation traveling down the back. This is not unique to MS, but it is often found upon questioning.

  • Internuclear ophthalmoplegia (INO)

    • An INO occurs when an MS lesion affects the medial longitudinal fasciculus, a structure that helps coordinate eye movements between the two eyes. This makes it difficult to move one eye fully in towards the nose and the other eye will have nystagmus, or jerking movements. This results in double vision when both eyes are open. When this occurs in a younger patient, MS is high considered.

  • Optic neuritis

    • Optic neuritis is progressive vision loss, usually first affecting color vision, in one eye. It may be painful. This is due to demyelination of the optic nerve. While ON can occur by itself or in other conditions, it is quite common in MS. It is the first symptom of MS in up to 15-20% cases of MS and up to 50% of people with MS will have ON at some time.

  • Partial myelitis

    • Myelitis refers to an inflammatory condition in the spinal cord. In contrast with other causes of transverse myelitis where the entire cross-section of the cord is affected, MS tends to only affect a portion of the level of the spinal cord. This may result in numbness in the feet/legs, spasticity, bladder dysfunction, or erectile dysfunction.


Chronic manifestations


In addition to the acute or relatively sudden symptoms of MS, there can be common chronic or long-term symptoms in MS.

  • Spasticity

    • Spasticity is when the muscles in the area supplied by the portion of the nervous system that is affected with MS become stiffer and tighter. This can cause pain and decreased motor function. Medications, such as baclofen, can help with this. Botox injections can be considered to loosen the muscles. When spasticity is severe, some people will benefit from a surgically implanted baclofen pump to deliver the medication consistently directly to the central nervous system.

  • Difficulty walking

    • Difficulty or slow walking becomes common in MS. There are medications which have been shown to improve walking speed, such as Ampyra

  • Fatigue

    • Fatigue is common in patients who have MS. Notably, the degree of fatigue is often reported to be out of proportion to the person’s activities. Stimulating medications are occasionally used to help combat fatigue.

  • Cognitive dysfunction

    • MS may lead to difficulties with multitasking and short-term memory over time.




Since the first diagnostic criteria was laid out as the “Schumaker Criteria” in 1965, MS has been defined as being a demyelinating disorder that affects the central nervous system with multiple attacks separated in space (affecting multiple areas of the nervous system) and time (occurring multiple times). Since this time, there have been monumental advances in technology and testing, but this general definition remains unchanged. The Neurologist must use clinical history/exam and / or diagnostic testing to prove that there have been multiple attacks in multiple regions of the nervous system.


The current gold standard criteria for diagnosing MS are the McDonald Criteria, which were last updated in 2017.

In addition to including a clinical history / exam, these criteria implement diagnostic testing, considered ancillary testing. While not required in all cases, this testing may take the form of MRI of the brain, MRI of the spinal cord, CSF analysis, Visual Evoked Potentials, and Ocular Coherence Tomography.

  • MRI of the brain with and without contrast

    • MRI of the brain can reveal lesions on T2 sequences that tend to be avoid in appearance. They are most commonly periventricular (near the ventricles), juxtacortical (next to the cortex or surface), or infratentorial (in the bottom part of the brain). They often seem to extend from the ventricles in an ovoid pattern that appears like fingers pointing outward, leading to the term “Dawson’s fingers” that was described in 1916. When an MS flare is actively occurring, there may be contrast enhancement of the active lesion. MRIs of the brain can be compared over time to see if new lesions develop.

  • MRI of the spine with and without contrast

    • MRI of the spine can reveal T2 lesions due to MS involvement. These tend to occur at only one level of the cord and tend to be seen more at the peripheral portion of the cord. Similar to MRI brain, active lesions can have contrast enhancement and the imaging can repeated over time to see if new lesions develop.

  • CSF analysis

    • Cerebrospinal fluid can be obtained when the diagnostic criteria are not fully met by clinical history or imaging. In this case, oligoclonal bands or elevated IgG testing can show active inflammation in the nervous system, which can support the diagnosis of MS.

  • Visual Evoked Potentials (VEP)

    • VEP can confirm demyelination of the optic nerve, which is the nerve that receives input from the eye and carries it to the brain to allow for vision.

  • Ocular Coherence Tomography (OCT)

    • OCT utilizes advanced ultrasound technology to evaluate the optic nerve in the back of the eye to check for thinning or damage that could suggest MS. This can also be followed over time to see if a person’s MS is worsening or is stable.

  • Tests to rule out mimics of MS

    • The Neurologist may suggest blood tests to rule out other conditions that can mimic MS. Including conditions such as Lyme disease and lupus, this list is extensive and tailored to the individual.


Subtypes of MS


Some patients with MS tend to have flares and then recover, while other patients tend to have a steady progression over time.


There have been several efforts to define subtypes of MS to better communicate a particular person’s course, but the most common system was defined by the US National Multiple Sclerosis Society:

  • Relapsing-Remitting (RR)

    • RR is the classic pattern whereby a person has relapses – or “attacks” – of symptoms due to MS, and then the symptoms slowly improve.

  • Secondary Progressive (SP)

    • SP is a subtype of MS where the course starts out as RR but then transitions to having progressive worsening without recovery.

  • Primary Progressive (PP)

    • PP is a subtype of MS where there is steady progressive worsening of symptoms without any recovery.

  • Progressive-Relapsing (PR)

    • PR is a subtype of MS where there is progressive worsening of symptoms with intermittent sudden flares of symptoms.


A more recently named phenomenon of those that only have one episode of symptoms from demyelination of the nervous system without meeting full criteria for MS is “clinically isolated syndrome.” Typically, disease modifying treatment is not started at this time.


Similarly, with increase in MRI use in the general population there has emerged a subgroup of people who have imaging that may meet criteria for MS but no clinical symptoms to correlate, which has been termed “radiographically isolated syndrome.” In certain circumstances where the radiographic changes are significant and worsening, a

Neurologist may consider starting disease modifying treatment even if there are no symptoms, so as to attempt to prevent future disability.


MS relapse versus pseudo-relapse

  • An MS relapse is a new neurological symptom that lasts more than a day due to MS disease activity, in the absence of fever or infection. The treatment of MS relapse is discussed below.

  • An infection (such as pneumonia or urinary tract infection) or other medical illness can cause a pseudo-relapse, which is worsening or re-emergence of previous neurological symptom. In this situation, there is no clear new MS lesion. With pseudo-relapse, the treatment is to address the underlying infection or systemic illness. Steroids are often not given, as high dose steroids can impair the immune system, which could lead to worsening of an underlying infectious process.

  • MRI of the brain and spine may be used to help differentiate between an MS relapse and a pseudo-relapse, looking for new or contrast-enhancing lesions which would suggest a true MS relapse.


Acute MS flare / relapse treatments

  • Steroids

    • Steroids are the most common treatment for acute MS relapses. The steroids have been shown to speed up the recovery – or remission – process. Often a high-dose IV steroid called methylprednisolone is used for 3 to 5 days, although occasionally oral prednisone may be used. IV steroids are occasionally given at the hospital, but often these can be arranged in an outpatient infusion center or to be given in the person’s home.

  • Plasma Exchange (PLEX)

    • In rare cases where MS symptoms worsen despite high dose steroids, PLEX may be considered. This involves removing a person’s plasma from the blood and replacing it with other plasma. This requires a surgically placed special catheter and often requires hospitalization.


Disease modifying therapies

While there is no cure, there are currently many medications that can be used to reduce the number of relapses in MS to minimize disability. The medications vary widely in the route of the medication, the possible side effects, the safety profile, and the dosing frequency. The Neurologist have a detailed discussion with the person with MS in selecting a disease modifying treatment for MS.

  • Self-injectable: There are several medications when a person can inject at home either subcutaneously or intramuscularly. These include Betaseron, Avonex, Rebif, and Copaxone.

  • Oral therapies: There are pills that are used for MS through various mechanisms of action. These have variable dosing frequency and possible side effects. These include Tecfidera, Aubagio, and Gilenya.

  • Infusions: Tysabri is an infusion monoclonal antibody that is given every 28 days. It is considered to be one of the strongest medications against preventing MS relapses, but its immunosuppressant properties do require being vigilant for opportunistic infectious conditions. Lemtrada is an infusion monoclonal antibody that is given once per year, but the team needs to watch closely for any infusion reactions. Ocrevus is another monoclonal antibody infusion, and this is the only medication with an FDA indication for treating progressive forms of MS.


Neuromyelitis Optica Spectrum Disorder

Neuromyelitis Optica Spectrum Disorder (NMOSD) is another central nervous system demyelinating disorder that is distinct from MS. This condition involves antibodies against Aquaporin-4 receptors or MOG antibodies. While it can involve Optic Neuritis like MS, NMOSD spinal cord lesions tend to be more complete and extend 3 or more levels.


NMOSD tends to respond less well to steroids than MS, often requiring PLEX and consideration for stronger systemic immunosuppressant medications such as rituximab or azathioprine.


Further resources

Symptoms & Causes of MS 

What is MS

Treating MS 

Resources by National MS Society

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