Multiple Sclerosis (MS)

What is MS?

Multiple sclerosis or MS is a disease of unknown etiology but thought to be due to an autoimmune mechanism whereby the body's own immune system attacks the cells that normally line and protect the nerve fibers (the so called myelin sheath) in the brain and spinal cord. This process is associated with inflammation causing damage to this insulating myelin sheath leading to "demyelination" (thinning or loss of myelin), scarring and disruption of signals that normally propagates along these nerve fibers. Even though the myelin can be partially repaired in the early course of the disease, with repeated attacks the myelin is eventually lost leaving a nonfunctioning and permanently damaged nerve fiber.

MS tends to occur in female young adults (30-40's) with a prevalence of 2-150 per 100,000. In the older population (older than 50) the male to female ratio is less obvious. Through numerous epidemiological studies based on both population, familial and geographic data such as the disease being more common in northern Europeans and less so in certain ethnic groups and those residing along the equator and factors like sunlight and vitamin D intake, most believe that the cause of MS is likely the result of interplay of genetic and environmental influences including infectious agents such as viruses.

What are the symptoms, risk and subtypes of MS?

As both the nerve fibers in the brain and spinal cord can be affected MS may cause a whole myriad of neurological symptoms including loss of coordination and balance, numbness and tingling, muscle spasm and weakness, bowel and bladder dysfunction and Lhermitt's sign (described as a shock sensation radiating down the back when the neck is flexed). The disease can also affect the optic nerve leading to loss of visual acuity, double vision as well as causing slurred speech and swallowing difficulty. As MS progresses over time you may experience generalized fatigue, depression and other mental impairments.

These symptoms often occur in acute episodes during the course of the disease the so called "flare-ups" against a background component of progressive deterioration. Viral infections and stress have been cited as triggers for relapses and also seem to occur more often in the spring and summer months. Compared to the general population there is also a higher risk of acquiring MS for relatives of individuals with the disease while smoking in itself is also an independent risk factor.

The pattern of disease progression can be further divided into subtypes with prognostic implications.

  1. Relapsing-remitting is the most common (80%) initial course of MS represented by periodic relapses (usually < 1.5 episodes per year) with months to years of non-activity in between. Deficits during the flare ups may or may not completely resolve. This subtype also often started out with a clinically isolated syndrome (CIS) where a single suggestive episode takes place but does not satisfy the overall criteria for MS.
  2. About 65% of the initial relapsing-remitting group goes on to become secondary progressive subtype (average time 19 years from onset of disease) as this population develops progressive neurological deficit between acute episodes without any defined intervals of remission.
  3. Primary progressive subtype is characterized by those who almost never or at most experience occasional periods of remission from the beginning of their symptoms and constitute about 10-15% of MS patients. Age of onset in this group is about 40 years old.
  4. Progressive relapsing is the least common subtype that describes a clinical course with a steady decline from the onset but with additional distinct superimposed flare ups.

Others have also described some atypical MS variants such as Balo concentric sclerosis, Neuromyelitis Optica (NMO or Devic's disease), Marburg multiple sclerosis and Schilder's diffuse sclerosis where these diseases all share some features of MS but does not fit the overall clinical picture.

Who to go to and what needs to be done to diagnose MS?

  • For the work up and diagnosis of MS one needs to be seen by a neurologist as many of the symptoms can be similar to other disease entities and may be difficult to differentiate. A detailed history of timeline of the first and subsequent episodes and recovery time are helpful. The McDonald diagnostic criteria was established and updated most recently in 2010 to address and integrate clinical, neuroimaging and laboratory data of the evolution of MS lesions both in time and space in an attempt to standardize the diagnostic process. Neuroimaging thus becomes an integral part of both initial and subsequent work up of MS. Especially if you seek medical attention only after the first attack, imaging (such as MRI) of the brain and spinal cord, cerebral spinal fluid (CSF) analysis and visual and sensory evoked potentials are needed in addition to clinical information for definitive diagnosis. CSF is collected via a lumbar puncture (where a small needle is inserted into the spinal canal at the lower back) and analyzed for oligoclonal bands of immunoglobulin G (IgG) which indicates presence of inflammation related proteins (positive in 75-85% of MS patients) though can also be present in other diseases. Damage to eye and sensory nerve fibers cause them to react less strongly to stimulation resulting in decreased propagated electrical signals (evoked potentials).

What does MS look like on imaging and what should I know about MRI?

MS lesions or plaques are mostly located along nerve fiber tracts (white matter) that transmit signals between neurons (grey matter) where all the important information processing is performed. On magnetic resonance imaging (MRI) these lesions have a preference for areas next to the ventricles (CSF chambers in the brain) with a characteristic orientation along the small veins (venules), cerebellum (lower and back part of the brain), brain stem, optic nerve (eye) and spinal cord. MRI is the best imaging modality to detect these lesions as they are often small and numerous. MRI also consists of many different imaging techniques that can help differentiate MS from other disease such as strokes that clinically may mimic MS. Not only is MRI more sensitive than computerized tomography (CT/CAT scan) in picking up MS lesions it also does not involve radiation exposure as the images are generated by magnetic fields and radio waves. As metallic material is contraindicated in the magnet you will be asked to wear comfortable clothing without metal (such as belt buckle and wire straps) and all jewelry, watches, electronic devices and shoes are to be removed. You will lie on your back on a narrow platform and moved slowly into a tunnel within the machine. An intercom allows you to communicate with the operator.

The limitations of MRI include the need to remain motionless during the scanning (usually 30 to 40 minutes on the average) which can be problematic for MS due to uncontrolled tremors, claustrophobia due to the small space within the machine and loudness of the magnets when they are turned on and off. Certain internal and external medical devices such as pacemakers, heart valves, stents, aneurysm clips, medicine delivery pumps, ear implants, bullet fragments or other metallic material may prevent you from undergoing an MRI and consultation with your physician is imperative to avoid causing bodily injury (they can move and/or heat up), damaging the device or obtaining poor quality images. Ear plugs or head sets with piped in music are supplied to counteract noise sensation. To address claustrophobia an oral sedative may be needed prior to the exam which may preclude you from driving afterwards.

Often in the case of MS a contrast agent needs to be delivered via injection into a vein (IV) that helps to determine if any of the MS plaques are active (or enhance on imaging) so as to guide disease course and therapy. Contrast agents may not be used if you have intrinsic kidney problems or due to other diseases.

What is the role of a neuroradiologist?

  • The neuroradiologist who is a trained physician specializing in all imaging related to brain and spinal cord plans and interprets these tests (including CT and MRI) at every step to select the optimal technique to use to obtain the necessary information for best patient care. In essence as part of the treatment team, neuroradiologist serves as consultant to both you and your referring physician. Knowledge of your clinical symptoms as well as information on previous imaging is necessary to ensure that the most appropriate techniques and comprehensive interpretation are performed. It is therefore important to note that there are different types of magnets of different strengths and vendors and especially for MS where periodic imaging is performed over the course of the disease it is advantageous to have the exams done at the appropriate magnets in the same way whenever possible. This facilitates better interpretation of the study as more accurate comparisons can be made. The results of the MRI are then conveyed by the neuroradiologist to the referring physician (usually the neurologist) who will then discuss the findings with you amidst the overall context of the clinical picture as well as laboratory data.

What are the treatment options?

    During the acute episodes or flare ups, intravenous steroid is often the first line of therapy with plasmapheresis (filtering out and returning your own blood after removing the offending inflammatory protein) reserved for those not responding to steroids. As of fall 2012, seven approved medications are available for treatment of MS including interferons, monoclonal antibodies, immunosuppressant and two oral agents. Apart from one being an anticancer agent, all the others work on specific parts of the immune pathway to block or decrease the offending inflammatory cells from reaching the myelin sheaths in the brain. Almost all of these have some effectiveness for relapsing and remitting MS (decreasing relapse rate and slowing disability) though often the more effective ones are limited by stronger side effects. For CIS, treating with interferons may decrease the chance to develop full blown MS. The secondary progressive and progressive relapsing subtypes are more difficult to treat while none of these existing drugs have any proven impact on primary progressive MS.

Prognosis and latest controversy of CCVI

Even though MS is a disease of unknown etiology with suboptimal treatment options, life expectancy in some cases can approach near normal. Being female with early age and optic neuritis or sensory symptoms at onset, infrequent flare-ups during the initial years and of the relapsing-remitting subtype all confer a better course of disease. As physicians and different establishments continue to search for various causes and treatments for MS there has been many theories and "potential cures" over the years. The most recent is the chronic cerebrospinal venous insufficiency (CCVI) theory where in 2008 an Italian vascular surgeon reported data suggesting MS may be due to narrowing of veins that drain the brain and spinal cord. He then claimed that after performing surgical or other interventional procedures to open up these veins led to improvement in 73% of his patients with some even in complete remission. As other researchers were not able to duplicate his results and that his original research design was somewhat flawed, the official medical and scientific communities are not recommending these procedures at this time until the data is confirmed with better conducted controlled studies.