Multiple sclerosis (MS) is a complex disease. Symptoms can be subtle, especially early in the disease, and vary significantly among patients, which may complicate the process of making an accurate diagnosis. Disease course can also be different in every patient making it important to adjust treatment according to individual response.

Although patients with MS are often knowledgeable about the disease, it is frequent to find those who are not clear on their disease type, stage, or what defines an exacerbation and when or why they should report it to the treating physician. In order to clarify some of these issues and help patients understand disease types and whether they may have progressive MS, it is necessary to first review some basic information.

Disease Types

There are several major types of MS: Relapsing-Remitting (RR), Primary Progressive (PP), and Progressing Relapsing (PR). It is worth noting, that what is often referred to as Secondary Progressive MS, is really the late phase of relapsing-remitting disease. Due to progression of symptoms seen it appears similar to PPMS.

Relapsing-remitting is the most common type of MS, affecting approximately 85 percent of patients. It is characterized by relapses (also called ‘exacerbations’ or ‘attacks’) during which patients experience acute neurological dysfunction either with new symptoms or old symptoms becoming more severe. Relapses are followed by remissions, which are periods without obvious disease activity. A relapse is defined as new or recurrent neurological symptoms present constantly for 24 to 48 hours without improvement. Relapses usually last days to weeks before reaching a maximum and complete or incomplete recovery may occur. Duration and recovery depend on the severity of the attack, how soon is treated, and the stage of the disease. Recovery is typically most rapid and most complete early in the disease (Perkins & Wolinsky, 2006). Relapses should be reported to the treating physician as soon as identified, as appropriate medical treatment of relapses may reduce irreversible damage and accumulation of neurological disability.

Exacerbations should not be confused with Uhthoff’s phenomenon, also called “pseudo exacerbations,” which can be described as recurrence of previously experienced neurological symptoms after a temporary increase in body temperature from either an outside source (weather) or inside source (exercise, fever). An increase in body temperature decreases nerve conduction velocity in the brain and spinal cord, making old symptoms reappear. In general the symptoms resolve within hours after cooling down and resting. A good example is a patient who likes to work in the garden on sunny days: after a period as short as 30 minutes she/he may begin to experience tingling sensations in the hands and feet, which gradually resolve after going inside and drinking ice water. It is also important to remember that neurological symptoms may worsen due to fatigue and stress levels, physical activity, and with presence of infections.

Although not always easy, it is important for patients to learn to differentiate a relapse from normal fluctuations of the disease. This helps the physician make the diagnosis, clarify disease type, and evaluate disease activity, and treatment response. Magnetic resonance imaging (MRI) of the brain serves as an important additional tool to be used in conjunction with disease behavior for diagnostic and management purposes.

Progressive-relapsing is the least common disease type affecting only about 5 percent of patients. It is characterized by an initial course that simulates primary progressive disease, but with one or more superimposed attacks that appear after the progressive disease is well established (Perkins & Wolinsky, 2006).

Primary progressive disease affects about 15 percent of patients with MS. This type is characterized by slow accumulation of neurological disability without acute attacks of neurological dysfunction. The most common symptoms are leg weakness, leg stiffness and difficulty walking––slowly worsening over 1 to 2 years. These symptoms are often accompanied by urinary symptoms such as frequent urination and inability to hold urine for long periods of time. These symptoms are often caused by involvement of the spinal cord and a search for other similar conditions should be performed by the physician. An example would be a 60-year-old male, who over the last 18 months has noticed worsening difficulty lifting his left leg during walking. He also notices loss of flexibility of both legs and clumsiness of his hands; his feet feel numb to touch (Perkins & Wolinsky, 2006). Patients may also experience typical MS symptoms like fatigue, memory problems, visual abnormalities, and depression among others.

Sometimes when a careful history is taken, a patient with progressive symptoms may recall an isolated episode of acute neurological symptoms, such as vision loss in one eye, that may have preceded the development of progressive neurological disability by one or two decades. Often, these patients have not sought medical attention for the original symptoms or a definite diagnosis was never reached. This scenario is more consistent with secondary progressive MS and is seen in up to 60 percent of patients who were originally diagnosed with RRMS. While young women tend to present with the relapsing form of the disease, men and older women are more likely to present with progressive disease from the onset. Patients with progressive disease often have difficulty determining if they are worsening on a day-to- day, week-to-week, or even month-to-month basis. They are usually able to determine worsening in relationship to major milestones such as one year’s holiday to the next. Things that they can no longer accomplish eventually become evident; progression is usually slow, but constant. The disease course may have intervals in which the patient appears quite stable, experience some improvement for no clear reason or show a rapid deterioration of function overall. Eventually, in both primary progressive and secondary progressive disease a consistent pattern is seen with an increase in the level of disability. However, how fast the disease worsens cannot be clearly established, since it usually varies among patients and data from research studies vary considerably (Perkins & Wolinsky, 2006).

Pathology

MS is considered a chronic, autoimmune disorder that attacks the brain and spinal cord creating localized areas of inflammation called “plaques”. Acute (also called ‘active’) plaques are usually new, but old plaques can become active again. The difference between an acute (new) and a chronic (old) plaque is the degree of inflammation present. This can be detected by MRI using intravenous contrast and is called plaque “enhancement”. Chronic plaques are scars left in the brain or spinal cord tissue after the inflammation in the acute plaque resolves. They do not “enhance” on an MRI. Acute plaques may or may not cause symptoms. When they do, patients will experience an exacerbation, but a lot of them are silent. The degree of irreversible damage a new plaque may cause determines the degree of recovery from the relapse. Almost all new plaques turn into chronic ones and they accumulate throughout the duration of the disease. Although the number of plaques does not correlate well with the number of relapses, it does so with accumulation of disability. Acute or active plaques are not as common in primary or secondary progressive disease as in relapsing-remitting (Kutzelnigg & Lassmann, 2005)

Diagnosis

The diagnosis of PPMS can be a true challenge. It involves incorporating the history of the patient’s symptoms and the way they evolved over time with the findings of a careful neurological exam. Engaging both the patient and close family members in this process is essential for obtaining the best possible historical information. The diagnosis should also be supported by typical lesions on brain and spinal cord MRI and often requires further testing, such as a spinal tap or visual performance testing. Other conditions that may mimic PPMS also need to be evaluated and only if and when all the pieces of the puzzle create the right picture can a definite diagnosis be made. In 2001, a group of MS experts from around the world defined the newest criteria for an accurate diagnosis of MS. In 2005, they reunited and revised their previous recommendations making improvements especially in the area of PPMS diagnosis (Polman et al., 2005). According to the McDonald criteria PPMS is defined by at least 1 year of progression of neurological symptoms without acute attacks and at least two of the following:

1) A brain MRI with lesions typical for MS

2) A spinal cord MRI with lesions typical for MS

3) A positive spinal tap

People with PPMS tend to have fewer brain lesions (plaques) than people with RRMS and tend to have more lesions in the spinal cord than the brain. They also have fewer “active” plaques, meaning less evidence of inflammation. Together the differences between these two types of MS make PP more challenging to diagnose and treat than RR. Fortunately, there are many strategies available to help patients manage their symptoms so they can remain active and productive (Goodman, 2009).

By Flavia Nelson, MD; Assistant Professor of Neurology, Associate Director MRI Analysis Center––Multiple Sclerosis Research Group, University of Texas Medical School at Houston

References

Goodman, A. D. (2009). Talking About Primary Progressive MS. National Multiple Sclerosis Society. Available at: www.nationalMSsociety.org/PRC.

Kutzelnigg, A., & Lassmann, H. (2005). Cortical lesions and brain atrophy in MS. Journal of the Neurological Sciences, 233(1-2), 55-59.

Perkin, G. D., & Wolinsky, J. S. (2006). Fast Facts: Multiple Sclerosis (2nd edition).

Polman, C. H., Reingold, S. C., Edan, G., Filippi, M., Hartung, H.-P., Kappos, L., et al. (2005). Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria.” Annals of Neurology, 58, 840-846.

Wolinsky, J. S., Narayana, P. A., O’Connor, P., Coyle, P. K., Ford, C., Johnson, K., Miller, A., Pardo, L., Kadosh, S., Ladkani, D.; PROMiSe Trial Study Group (2007).

Please Note: This article was previously published in United Spinal Association’s Multiple Sclerosis Quarterly Report

spinalcord.org, March 2012