Associate Professor Karl Ng has an interest in the diagnosis and management of patients with multiple sclerosis. Please contact SNNN on 02 82871900 to arrange an appointment with the help of your doctor.
FAQs & information
What is Multiple Sclerosis? | Statistics | Risk Factors | Progression of Multiple Sclerosis | Symptoms of Multiple Sclerosis | Clinical Examination of Multiple Sclerosis | How is it diagnosed? | Prognosis of Multiple Sclerosis | How is it treated? | References |
What is Multiple Sclerosis?
Multiple sclerosis (MS) is a disease of the central nervous system (brain and spinal cord). Nerves in the body are covered with a fatty sheath called myelin. Myelin considerably increases the speed that nerve signals (impulses) travel down the axons. A thin myelinated axon transmits impulses at anything from 5 to 30 meters per second, whereas an unmyelinated one transmits them at 0.5 to 2 meters per second. It does this by both insulating and containing the nerves.
In MS, there are multiple areas of damage to the myelin sheath (demyelination) within the brain and spinal cord. This causes conduction problems within the central nervous system. The peripheral nervous system is not usually involved but may be subtly. MS can manifest in different ways, including:
- Clinically isolated syndrome (CIS): In this type, there is a first episode of demyelination causing symptoms which must last at least 24 hours. It is characteristic of MS but does not yet meet criteria for a diagnosis. When there are multiple lesions in the brain, there may be a higher likelihood of proceeding to a diagnosis of MS. Sometimes, new radiological criteria in a revised consensus of MS diagnosis (2017) have allowed a diagnosis of MS to be made when there has only been an apparent case of CIS;
- Relapsing remitting (RRMS): This is the most common type of MS. Relapses are followed by partial or complete recovery with no apparent progression between attacks. There are variabl degrees of activity of the disease;
- Primary progressive (PPMS): Making up some 10-15% of patients, this is characterised by worsening neurologic function or disability from the outset. There may be periods after the initial progression when the disease may be more active or more stable;
- Secondary progressive (SPMS): This follows a relapsing remitting with progression over time. The disease may be active or less active at any point in time.
MS is one of the most common causes of chronic neurological disability in adults, and affects more than 2 million people worldwide. The disease usually starts in early adult life (20–45 years) and causes progressive disability over several decades. MS is more common in women, who outnumber males by a ratio of 2:1.
The prevalence of MS is directly proportional to distance from the equator. At 50–65 degrees latitude (north or south), the prevalence is 60–100 per 100,000 people. At the equator, MS is a rarity. The incidence, however, is very variable.
Approximately one in 3,000 Australians are affected by the disorder.
The exact cause of MS is not entirely understood, but it is thought to be due to a number of genetic, environmental and immune factors. It is hypothesised that individuals with a genetic predisposition who are infected with certain viruses induce an immune response that attacks their own nerve cells.
Risk factors for MS therefore include:
- Latitude: Latitude is more strongly related to MS than any other risk factor. Risk of MS increases when an individual lives further away from the equator. If you migrate to a high-risk area before the age of 15, you will have the same high risk as those who were born in the area. Therefore, your risk of MS reflects that of the area in which you spent your first 15 years.
- Sex: MS affects females more than males, but the reason for this difference is unknown.
- Family history: If you have a first degree relative with MS, you are 15 times more likely than the general population to suffer from MS (this is still a very low risk). Twins from the same egg (monozygotic) are more likely to have MS than those from separate eggs (dizygotic) if one twin is affected.
- Race: MS presents more often in populations of northern European ancestry.
- Vitamin D Status:Low levels of vitamin D exposure result in an increased risk of MS.
- Smoking: Smokers have an increased risk of developing MS
- Epstein-Barr Virus: Exposure to EBV increases the risk of MS
- Diet:It is thought that diets high in animal fats may increase the risk of MS, due to observations that MS is uncommon in coastal communities where large amounts of fish are consumed.
Progression of Multiple Sclerosis
Most patients have a relapsing/remitting disease, where they have discrete attacks of symptoms (such as loss of vision and limb sensations/weakness) that last weeks to months and then completely resolve. These attacks may not have a clear precipitant, and on average tend to occur once every two years. These attacks or relapses should be distinguished from minor exacerbations of previous symptoms which can occur with increases in body temperature. Later in the course of the disease, patients may not fully recover from attacks and experience progressive disability. This is the secondary progressive form of disease, which used to occur in up to 50% of patients after 15 years; this number is undoubtedly less with the advent of effective therapies these days (see later). The majority of MS cases will eventually evolve into the secondary progressive form if left untreated.
Some patients may have only one or two attacks and may fully recover from these attacks. In other patients, the disease will progress and produce severe disability, or even death.
Other patients have primary progressive disease, which shows a rapid decline in function without any acute attacks. This occurs in approximately 15% of patients and affects males and females equally. However, males with this disorder have the worst prognosis, as spinal cord involvement leads to early disability.
Symptoms of Multiple Sclerosis
As MS can affect virtually anywhere in the CNS, a wide variety of neurological manifestations are possible. However, some of the major patterns of symptoms aside from weakness and loss of sensation/pain include:
- Fatigue (the most common symptom);
- Blurred vision and mild pain of the eye due to damage to the optic nerve;
- Diplopia (double vision), vertigo, facial numbness and weakness or dysphagia due to brainstem demyelination;
- Ataxia (imbalance) and tremor;
- Spasticity (sometimes with spasms) with difficulty walking, urinary dysfunction, and sexual dysfunction;
- Mood alteration.
Your doctor will take a detailed history of your symptoms and try to determine whether you fit a relapsing/remitting or progressive form of the disorder. The diagnosis of MS relies on the demonstration of symptoms that are separated in time and anatomical location, and are unexplained by another condition.
Clinical examination of Multiple Sclerosis
Your doctor will perform a complete neurological examination, including testing your gait (walking), sensation and vision. They will also use a device called an ophthalmoscope to look at the retina at the back of the eye. This can identify abnormalities of the optic disc caused by optic neuritis. Double vision, nystagmus (oscillating movements of the eyes) and loss of vision are other signs often found on examination.
How is it diagnosed?
MS can usually be diagnosed by careful history and examination as there are very few neurological conditions of young people that follow a similar relapsing and remitting course. However, some patients may not have the classical signs, or may be affected at a very young or older age. In these patients, further investigation may be needed to exclude other medical conditions, such as vasculitis, sarcoidosis, encephalitis, tuberculosis, brain tumours, Alzheimer’s disease and vitamin B12 deficiency.
The most common investigations for MS include:
- MRI: This is the first-line investigation. MRI may show plaques of demyelination in the brain and spinal cord.
- Lumbar puncture:: Analysis of spinal fluid by lumbar puncture may show raised numbers of cells during acute attacks. Between attacks, there may be local production of antibodies (known as oligoclonal bands).
- Electrophysiological testing (evoked potentials): This measures the nerve potentials in visual, auditory and somatosensory pathways, and can detect whether nerves have been damaged and conduction delayed.
- Blood tests: These are usually employed to see refute conditions that can look like MS, as a blood test usually cannot confirm MS. One related similar (but certainly not the same) disease is neuromyelitis optica (NMO) where there are specific antibodies to aquaporin -4, a water channel protein.
Prognosis of Multiple Sclerosis
There is no way to predict the course of MS in a patient. In some, the disease will not affect them much and they will be able to continue their normal lives, others may have considerable disability. Overall, patients with MS used to have a shortened life expectancy of some 7 years but nowadays with effective treatments, patients may approach normal longevity. Most deaths occur from complications of disability (such as recurrent infections in bedridden patients) rather than from acute attacks.
The following factors may be associated with a worse prognosis:
- Bowel and/or bladder symptoms at onset
- Short interval between first and second attacks
- Incomplete remission after first relapses
- Early disability
- High relapse rate in early years
- High lesion load detected by MRI during early years of illness
- Male sex, though this has been contradicted by more recent research
- Older age at onset, though this has been contradicted by more recent research.
How is it treated?
There are a number of different treatments available for MS to reduce the severity and frequency of exacerbations, and possibly to alter the progression of disability later on. However, to date, no drug has been found that can halt or reverse the progression of disease. This would require a drug that can perform the difficult task of remyelination of damaged nerves.
Your doctor will discuss the best treatment for you based on the severity and type of your condition. This may include some of the following treatments:
- Drugs that alter the natural course of the disease:
- Beta-interferon:(Betaferon, Avonex, Rebif): This drug is given by a subcutaneous injection and can reduce the rate of relapses by a third. This used to constitute first-line treatment for relapsing/remitting disease, but still has a place in patients with milder disease.
- Glatiramer acetate (Copaxone):This drug is another immunomodifier that also reduces the frequency and severity of attacks, and is regarded to be of a similar potency to beta-interferon.
- Oral immunomodulatory agents: Regarded as second tier, these have been recently developed and show promise in reducing the number of attacks by an even larger amount. These include dimethylfumarate, teriflunomide, fingolimod and siponimod, as well as infused agents like natalizumab (a monoclonal antibody).
- Immunosuppressant medications such as azothioprine have been used in some patients in the past to reduce relapses. Many rely on suppressing either cell mediated or antibody mediated processes and come in oral (cladribine) or infused forms which are usually monoclonal antibodies to different targets of the immune system (ocrelizumab, alemtuzumab).
- Chemotherapeutic agents like mitoxantrone and cyclophosphamide have also been used in the past, and research is looking into stem cell transplantation is still being conducted.
Many of the above agents have a more potential side-effects and complications the more powerful they are. Your doctor will help you decide the best treatment for your profile taking into account your disease activity, your background risk factors and any other special considerations such as family planning etc.
Drugs that are for symptoms:
- Corticosteroids: Methylprednisolone is the usual treatment given in acute attacks to reduce their severity. This is usually but not always given intravenously.
- Muscle relaxants (baclofen, dantrolene, benzodiazepines, injectable therapy):Can reduce the discomfort and pain of spasticity; occasionally, baclofen may have to be infused into the cerebrospinal fluid with the help of a pump and specialised medical supervision for severe cases. Medical cannibinoids have also been explored. Intramuscular botulinum toxin injections can also be used and relatively devoid of central side-effects.
- Oxybutinin, a bladder muscle antispasmodic, and intermittent urinary catheterisation (inserting a thin tube via the urethra to empty the bladder):May help urinary incontinence. Occasionally, intravesical (within the bladder with an endoscope) injections of botulinum toxin may also have a role.
Physiotherapy and occupational therapy: Have an very important role in managing spasticity.
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