MS: What is it and how is it diagnosed?

What is Multiple Sclerosis?

Multiple sclerosis is a demyelinating disease of the central nervous system. The nervous system is made up of the central and peripheral nervous system. The central nervous system (CNS) consists of the brain, spinal cord and optic nerve. The optic nerve is a large nerve that runs from the back of your eye into your brain. The peripheral nervous system refers to other nerves that leave and enter the spinal cord and travel to and from the skin, muscles, joints and organs in your body. The central nervous system is made up of different types of brain cells called neurons, oligodendrocytes, and astrocytes. A neuron is a cell that conducts electrical signals in the brain. Each neuron has a cell body and a long tail called an axon. The axon conducts electric signals from one neuron to another. Many axons are covered by a fatty sheath made of myelin which is produced by oligodendrocytes. The myelin sheath speeds up electrical conduction along the axon. similar to insulation on an electric wire.

The three major structural components of the brain are called the grey matter, white matter, and fluid filled spaces. The grey matter contains the cell bodies of neurons and lies on the surface of the brain and deep within the brain. The white matter lies underneath the grey matter on the surface of the brain and contains the axons of the neurons which travel from one area of grey matter to other areas. Myelin covering these axons has a whitish appearance causing the regions where many myelin covered axons travel to appear white. These regions are thus called white matter.

Inflammation is part of your body’s response to harmful stimuli which involves immune cells, blood vessels, and chemical mediators (htt8). Inflammation in the central nervous system associated with multiple sclerosis destroys the myelin sheath on some axons. This destruction is called demyelination and hence multiple sclerosis is referred to as a demyelinating disease of the central nervous system.

MS appears to have two components. The first is an early inflammatory phase when episodes of inflammation in the CNS cause different types of neurological symptoms. Episodes of inflammation are called attacks, exacerbations, or relapses and usually are associated with new typical lesions on MRI scans. Sometimes inflammation is asymptomatic but still can be seen on MRI scans of the CNS. The second component of MS is a degenerative phase where inflammation has slowed or stopped but continued central nervous system damage occurs. These processes, working either separately or together, ultimately produce permanent damage to the brain, spinal cord, and/or optic nerve. This damage generally results in progressive disability. Disability is defined as a physical or mental condition that limit a person’s movement, senses, or activities.

What is a magnetic resonance image (MRI)?

Imaging of the central nervous system is important in the diagnosis and follow-up of MS. The term magnetic resonance imaging (MRI) refers to an imaging technique which is uses a magnetic field and radio waves to take pictures of your brain, spinal cord, and optic nerve. When you lie or sit in an MRI machine, you are inside of a big magnet. The magnet causes water molecules in your body to move slightly to align themselves in a certain direction. Next, your body is exposed to radio waves which move the water molecules a little more. When radio waves are turned off, the water molecules spring back to their original position. The energy they release when they spring back is emitted in the form of new radio waves which are sensed by the MRI machine and used to construct images of parts of your body.

Different types of images can be constructed from the returning radio waves which help to identify normal structures and abnormal lesions in the central nervous system. There are three main types of images used to diagnose and follow MS. These are called T1 weighted images, T2 weighted images and FLAIR images. On T1 weighted images, the gray matter and white matter appear grey and the fluid filled spaces are black. On T2 weighted images the grey matter appears a light grey, the white matter a darker grey, and the fluid filled spaces appear white. On FLAIR images, the grey matter appears a light grey and the white matter a darker grey, but the fluid filled spaces appear white.

T1 weighted images are best to look at the overall structures of the brain. Old inflammatory lesions caused by MS are best seen on T2 weighted images and FLAIR images. When active inflammation occurs, the blood vessels in the inflamed area of the brain leak. Gadolinium is a compound which appears white on T1 weighted MRI images and can be infused into a vein in your arm when you have an MRI scan. In an area of active brain inflammation, Gadolinium leaks out of blood vessels into the inflamed area making it appear white on T1 weighted images.

MRI abnormalities seen in MS are markers of disease and if worsening indicate that MS is active. These abnormalities include the presence of new or enlarging T2 lesions, gadolinium enhancing lesions, T1 black holes, and brain shrinkage which is called brain atrophy. The number of new or enlarging T2 lesions, gadolinium enhancing lesions, or black holes can be counted and the volume of T2 weighted lesions measured.

MRI is used in MS both as a diagnostic tool and as an outcome measure. As a diagnostic tool, certain guidelines, referred to as the 2017 McDonald Criteria, are used to help confirm the diagnosis of MS. Repeated MRIs after your initial diagnosis help you and your neurologist see how you are doing on treatment.

What are the different types of Multiple Sclerosis?

Multiple sclerosis is characterized by how it initially presents. There are five major presentations of multiple sclerosis: relapsing-remitting MS (RRMS), primary progressive multiple sclerosis (PPMS), secondary progressive multiple sclerosis (SPMS), clinically isolated syndrome (CIS), and, radiologically isolated syndrome (RIS).

Relapsing-remitting MS which is sometimes referred to as just relapsing MS (RMS) is the most common type of MS and affects 85-95% of patients. It typically affects young adults with an average age at onset of 30 years. Females are affected more than males. There are 3 females for every male affected. Relapsing-remitting MS is characterized by relapses which are episodes of neurological symptoms lasting at least 24 hours in the absence of fever or infection. A relapse represents one or more new or enlarging areas of inflammation in the central nervous system. When a relapse will occur is unpredictable. Relapses are followed by remissions which are an improvement in neurological function corresponding to an improvement in CNS inflammation. Patients with relapsing-remitting MS may have periods of months to years without new symptoms or signs of disease activity. Nevertheless, the MRI may show asymptomatic inflammatory activity between clinical relapses. (Brownlee et al 2017)

Primary progressive multiple sclerosis (or progressive MS – PMS) affects 10-15% of patients. It usually begins at an older age than relapsing-remitting MS with the average age at onset of 40 years. Men and woman are equally affected. It typically presents with the insidious onset of weakness in one or both legs and slowly causes a progressive increase of neurological disability usually without relapses. Some primary progressive MS patients may have intermittent clinical relapses associated with new MRI lesions. These patients are termed as having active progressive disease

The term secondary progressive multiple sclerosis describes people who are initially diagnosed with relapsing-remitting MS but then develop a progressive course of neurological worsening. 50% of people who begin with relapsing-remitting MS will develop secondary progressive MS within 10 years and 90% within 25 years. The average age of onset of secondary progression is around 40 years of age. The median time between disease onset and conversion from relapsing-remitting to secondary progressive MS is about 19 years. (Brownlee et al 2017). The term median, which refers to the middle value in a list of numbers is used instead of the mean or average value when there is a lot of variation in an outcome for MS. [i] Secondary progressive MS may occur with or without relapses. Secondary progressive MS patients with relapses are termed active secondary progressive MS. Patients may have relapses, evidence of new lesions on MRI without relapses, or may just worsen without clinical relapses. Patients may also have plateaus when their neurological symptoms remain stable for various lengths of time.

The clinically isolated syndrome is a first episode of neurological dysfunction related to demyelinating disease of the optic nerve, and/or central nervous system. which is often but not always the first attack of MS. Patients with clinically isolated syndrome do not have a history of prior neurologic complaints. Clinically isolated syndromes frequently present with unilateral visual loss called optic neuritis, weakness and / or numbness, or a combination of symptoms. 30 to 70% of persons experiencing a clinically isolated syndrome later develop MS. In patients with clinically isolated syndrome an abnormal MRI predicts a 60-80% likelihood of developing MS; a normal MRI aside from the lesion causing the symptom predicts a 20% likelihood. (Brownlee et al 2017)

The radiologically isolated syndrome refers to people who do not have symptoms associated with MS but get an MRI scan for other reasons such as headache and are found to have MRI abnormalities similar to those seen in MS. 1/3 of people with RIS will develop MS in the next 5 years. Repeat MRIs may show no change or there may be radiological progression, with or without symptoms, over time in the form of new or enlarging T2 lesions or new gadolinium enhancing lesions.

How is Multiple Sclerosis diagnosed?

The diagnosis of relapsing-remitting MS is based on signs and symptoms of inflammation in the central nervous system (brain, spinal cord and/ or optic nerve) that have occurred at more than one time and in more than one place. This means that to be diagnosed with MS, you need to have had symptoms of a neurological problem involving your brain, spinal cord or vision in the past which you may or may not have been aware of and now have new symptoms. Many new patients with MS recall prior symptoms such as episodes of blurred vision or numbness in an arm or leg which improved on its own.

If you have had only a single episode of neurological symptoms, an MRI of your brain and/or spinal cord can be used to see if you have more than one area of the central nervous system involved which is called dissemination in space or prior episodes of brain or spinal cord inflammation that you may or may not have been aware of which is called dissemination in time. For the diagnosis of relapsing-remitting MS or a clinically isolated syndrome evidence for dissemination in space requires at least one lesion in at least two of 4 sites where lesions are usually seen in MS[ii] . Evidence for dissemination in time requires one gadolinium enhancing lesion and non-enhancing lesion in the same scan or a new lesion on another scan done more 30 days later.

The criteria for primary progressive MS are: two or more lesions in sites where lesions are usually seen in MS; two or more spinal cord lesions; a lumbar puncture which shows abnormalities in the cerebrospinal fluid that are consistent with MS; and, evidence of progressive worsening over 12 months.

When your neurologist sees you, he or she will take your medical history which involves asking you questions about your current and prior symptoms and do a neurological examination to look for evidence of dysfunction in different parts of the brain, spinal cord, or optic nerve. The neurologist will order an MRI of your brain and possibly your spinal cord to confirm the diagnosis and should order certain laboratory tests to rule out other diseases that mimic multiple sclerosis.

If there is any doubt about your diagnosis after the above testing, or you are diagnosed with primary progressive MS, your neurologist may order a spinal tap to allow examination of your cerebrospinal fluid which is the fluid which surrounds your brain and spinal cord. Two abnormalities in your cerebrospinal fluid which are associated with a diagnosis of MS are the finding of oligoclonal bands and an elevated IgG Index. (More about this in a later post) Finally, if your neurologist remains unsure of your diagnosis, he/she may request a second opinion from another neurologist who specializes in MS.

References

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