The Types and Stages of MS

SOURCE: Many websites

The course of Multiple Sclerosis (MS) results from the interplay of two clinical processes, relapses and progression.

Three main clinical forms may be identified as Relapsing/Remitting, Secondary/Progressive and Primary/Progressive.

The disease appears on average at the age of 30 and follows a Remitting or a Progressive course in 85% and 15% of the cases, respectively.

Initial symptoms are related to an isolated or combined disturbance(s) of the long tracts of the Central Nervous System, of the BrainStem, or of the Optic Nerve in 70%, 20% and 25% of the cases, respectively.

The relapse rate is one relapse on average every other year. After an Exacerbating/Remitting onset of MS, secondary progression appears after  19 years on average.

The median time to reach the landmarks of irreversible disability are 8 years regarding limitation of ambulation, 20 years for walking with a stick, and 30 years for wheel-chair dependency.

In fact, MS prognosis is highly variable depending on individuals. All the intermediate types do exist between malignant forms, possibly lethal, and Benign forms (circa 30% of the cases) that allow normal daily life.

The clinical and para clinical predictive factors identified so far have been acknowledged statistically. They provide little help however, if any, when an individual is concerned.

Recent research has showed that relapses have only a marginal effect, relatively to progression, on the accumulation of irreversible Neurological disability.

Furthermore, the age when reaching the landmarks of irreversible disability is essentially similar whatever the mode of onset of MS, be it Exacerbating/Remitting or Progressive.

In spite of the outstanding clinical polymorphism of MS, a unifying concept of the disease ("complexity vs. heterogeneity") can be put forward.

People with MS can typically experience one of four disease courses, each of which might be mild, moderate, or severe. 

No two people have exactly the same experience of MS, the disease course may look very different from one person to another. And, it may not always be clear to the physician—at least right away—which course a person is experiencing.  Read Just the Facts to find more information.

Devic's Syndrome

Devic's syndrome (also known as Devic's disease and Neuromyelitis Optica) is a rare, chronic, inflammation and demyelinating disease of the central nervous system (CNS) which resembles multiple sclerosis in several ways and is considered a special form of multiple sclerosis (MS) with a severe and rapid course.

Devic's disease is characterized by attacks of acute optic neuritis (ON), usually in both eyes (bilateral or on both sides of the body or head). At the same time or within a few days, weeks or occasionally months, the ON is followed by severe transverse myelopathy (TM) - acute inflammation of the spinal cord. However, in about 20% of cases, TM can precede the ON.

In Devic's syndrome, the fatty sheath that protects these nerves is lost. Individuals may experience vision impairment and various degrees of paralysis, as well as incontinence. The disorder is closely linked with MS and lupus, but usually appears before any symptoms of MS are noted. If an isolated disease episode affecting the spinal cord and optic nerve occurs after an infection or common cold, it is considered a post-infectious acute demyelinated encephalomyelitis (ADE) rather than Devic's syndrome.
 
Optic neuritis in Devic's is often retrobulbar (not visible on back of the eye through an opthalmoscope). Recovery from attacks of Devic's disease is typically poorer than remissions from relapsing-remitting multiple sclerosis but the relapses are usually less frequent than is typical in MS.
 

The symptoms of Devic's disease include marked loss of vision in both eyes (optic neuritis) followed by numbness, muscle weakness, spasticity, incoordination, ataxia, urinary, bowel, sexual and autonomic dysfunction in parts of the trunk and limbs served by nerves exiting the spine below the spinal lesions.

Neurologists argue as to whether Devic's syndrome is a completely different disease to MS or whether it a variant of it. Many authors consider Devic's syndrome to be a variant of post-viral Acute Disseminated Encephalomyelitis (ADEM) perhaps related to the varicella zoster virus.
Other believe that, like MS, Devic's disease is an autoimmune condition.
The most obvious difference between the two is that Devic's typically attacks the optic nerve chiasma, optic tract, and spinal cord - usually bilaterally - whereas MS lesions can be anywhere in the CNS white matter albeit with a preference for the optic nerve, brainstem, corpus callosum and periventricular regions.

Is there any treatment?

What is the prognosis?

What research is being done?

More stats:

Benign MS - approx 20%

Benign Multiple Sclerosis is a highly misleading term since it implies that the course and severity of Multiple Sclerosis will be slight. While this may initially be true, over time this form of the disease can often be as disabling as any other; indeed of the 20% of patients who are initially diagnosed with Benign Multiple Sclerosis, only around 5% actually fall into this category.

It is not possible to diagnose someone initially as having this form of MS, as it is only by looking at the disease ten or fifteen years after its onset that the pattern is visible. Benign multiple sclerosis has little impact on daily living. Individuals may experience a few mild attacks or relapses, but no ongoing disability.

The definition of benign MS has been heavily weighted towards physical disability and in particular ambulation. However, patients who are fully ambulatory may still be heavily disabled by non-motor symptoms like fatigue, pain, depression and cognitive dysfunction and short-term memory problems and upon MRI examination, may also show clear clinical evidence of brain or spinal cord atrophy.. These non-motor symptoms should be considered when defining benign MS.

After one or two attacks with complete recovery and without any disability, this form or stage of MS does not worsen with time and there is no permanent disability or disease progression. 

Benign Multiple Sclerosis tends to follow, non-visible Sensory Symptoms (ie. Dysesthesia, Optic Neuritis, paraesthesia, Paroxysmal) at onset; not Motor Symptoms (ie. Diplopia, InCoordination, Tremor), with a totally complete recovery and no disability.

However, some in this category will eventually experience disease progression; their course of disease will change and evolve into the Progressive stages of MS, within 10 - 15 years of its official onset. 

Benign MS can only be positively identified, after there is minimal disability (EDSS < 3.0), 10 to 15 years following its official onset. Initially, it would have been categorized as R/R MS

The Four Courses of MS

People with MS can typically experience one of four disease courses, each of which might be mild, moderate, or severe.

Relapsing Remitting Multiple Sclerosis (RRMS) - approx 25%

Relapsing remitting multiple sclerosis (RRMS) is the most common form of the disease. The title can also be misleading.
 

In this form or stage of MS there are sporadic attacks (exacerbations, relapses), during which new symptoms appear and/or existing ones become more severe. They can last for varying periods (days or months) and are followed by partial or total recovery and remission.

MS may be clinically inactive (SubClinical), for months or years, between any number of intermittent attacks. However, the disease process is ongoing and damage continues, with or without clinical attacks; microscopic lesions and diffuse damage (Axonal loss) silently proceed.

It is characterized by clearly defined acute attacks with full recovery (a) or with residual deficit upon recovery (b). Periods between disease relapses are characterized by a lack of disease progression. Approximately 85% of people with MS begin with a relapsing-remitting course.

Figure a

Figure b

This is where the title, relapsing remitting multiple sclerosis (rrms), can prove misleading.

Patients often assume that the remission stage of the disease will mean 100% recovery. While this can be true, particularly during the early stages of the disease, often the remission will only be a partial one, particularly as the disease progresses, thus leaving the patient with residual, usually permanent, symptoms.

This is the most common beginning phase of MS. However, 50% of cases will have progression within 10 - 15 years, and an additional 40% within 25 years of onset; as the disease evolves, into the Secondary/Progressive phase. The clinical signs of progression are:

Secondary-Progressive MS (SPMS) - approx 40%

Secondary Progressive Multiple Sclerosis (SPMS) begins with relapsing remitting multiple sclerosis (RRMS) a progression of disability (a) that may include occasional relapses and minor remissions and plateaus (b).

Figure a

Figure b

Individuals who initially had Relapsing MS (clear-cut attacks and remissions), over time (10 - 15 yrs) the disease pattern changes, evolving into the Progressive stage.

Typically, secondary-progressive disease is characterized by: less recovery following attacks, persistently worsening functioning during and between attacks, and/or fewer and fewer attacks (or none at all) accompanied by progressive disability. According to some natural history studies, of the 85% who start with relapsing-remitting disease, more than 50% will develop SPMS within 10 years; 90% within 25 years. More recent natural history studies (perhaps because of the use of MRI to assist in the diagnosis) suggest a more benign outlook that these numbers suggest. Nevertheless, many patients with RRMS do develop SPMS ultimately.  Recovery from attacks become less and less complete, deficits increase and disability grows.

Secondary progressive multiple sclerosis is a second-stage, chronic, progressive form of the disease where, unlike the relapsing remitting (RRMS) stage, there are no real periods of remission, only breaks in attack duration with no real recovery from symptoms although there may be minor relief from some.  Clinical attacks become less pronounced and remissions tend to disappear; but more CNS tissue has now been destroyed and disability becomes more visible - no remaining unused redundancy.

This cumulative damage is seen on MRI, as enlarged Ventricles, which is a definitive progression marker for increased Atrophy of the Corpus Callosum, and MidLine Centers.

SPMS has two sub-categories

1. Those continuing to have exacerbations and remissions, retain a R/R MS disease pattern (Inflammatory attacks), and the ImmunoModulatory drugs continue to be effective MS treatments.

2. Those who no longer have clinical attacks and remissions, become closer to a P/P MS disease course (Non-Inflammatory Axonal loss) and increasing permanent disability.

Primary-Progressive MS (PPMS) - approx 12%
 

Primary Progressive Multiple Sclerosis (PPMS) is most commonly found in men.

This form of MS is characterized by a slow steady onset, usually beginning with walking difficulties; steadily worsening motor dysfunctions and increased disability, but with a total lack of distinct inflammatory attacks.

Fewer and smaller Cerebral lesions, diffuse Spinal Cord damage, and Axonal loss are the hallmarks of this form of MS. There is continuous progression of deficits and disabilities, which may quickly level off, or continue over many months and years.

PPMS is characterized by progression of disability from onset, without plateaus or remissions (a) or with occasional plateaus and temporary minor improvements (b).  A person with PPMS, by definition, does not experience acute attacks.  There may be temporary periods where the disease appears to plateau, or level out, and this may include some partial, yet minor, relief from some symptoms, however the course of the disease is one of continual decline from the outset.  Of people with MS are diagnosed, only 10% have PPMS.  In addition, the diagnostic criteria for PPMS are less secure than those for RRMS so that often the diagnosis is only made long after the onset of neurological symptoms and at a time when the person is already living with significant disability.

Figure a

Figure b

Progressive-Relapsing MS (PRMS) - approx 3%

Progressive Relapsing Multiple Sclerosis (PRMS), which is the least common disease course, is a rarer form of multiple sclerosis where the disease takes a progressive form from the outset with acute attacks throughout and no relief from accumulated symptoms.  PPMS shows progression of disability from onset but with clear acute relapses, with (a) or without (b) full recovery. Approximately 5% of people with MS appear to have PRMS at diagnosis. Not infrequently a patient may be initially diagnosed as having PPMS and then will experience an acute attack, thereby establishing the diagnosis of PRMS.

Figure a

Figure b

Unlike Primary Progressive Multiple Sclerosis, Progressive Relapsing MS does not 'plateau'.

This subtype of Progressive MS is more complex; although its overall course mirrors P/P MS in terms of Disability, it differs. It includes periods of acute exacerbations that look like Relapsing MS (having Gd-enhancing T₁ lesions), either early on or after many years have elapsed, but lost functions never return.

Progressive/Relapsing is the most dreaded MS form, it was known as Marburg MS and demonstrates the need for protracted Steroid therapy, with a high mortality rate.