Professor Tissa Wijeratne looks at the causes, epidemiology, diagnosis, management and prognosis of this debilitating condition
Multiple sclerosis (MS) is a disorder affecting the central nervous system. It has multifactorial causes encompassing genetic predisposition to environmental factors.
The condition is characterised by inflammation as well as loss of myelin in the central nervous system.1
CAUSES AND ‘WHY ME’?
Whenever a patient of mine is given the diagnosis of MS, the questions the patient usually asks are: what caused this? and why me?
Genetic factors play a role in some patients (e.g. HLA-DR 15 serotype confers a higher risk of early MS). Multifactorial environmental factors (infections, lifestyle factors such as smoking, the role of sunlight and vitamin D) in genetically susceptible individuals with a double-hit hypothesis probably is the answer to these questions, but more research is needed to give precise answers.2, 3
The epidemiology of MS varies from state to state. Published studies show MS varies with latitude. The condition is at its highest in Tasmania, with a reported prevalence of 100 patients per 100,000 and incidence of four per 100,000, and becomes less common as one moves further north from Tasmania.4
MS is more common among young women (just over two thirds of MS patients in Australia are female) with a diagnosis at mean age of the mid 30s.4
There are approximately 25,000 people with MS currently in Australia.
WHEN TO SUSPECT
Despite popular belief, there is no specific diagnostic test for MS. It remains a clinical diagnosis, often with a differential diagnosis, as one needs to rule out other neurological conditions that might produce similar signs and symptoms.
Common presentations of MS include neurological symptoms such as pain behind one eye or both eyes, diplopia, paresthesia in the face, arm or legs with a sub-acute onset over a few days. Diplopia is always with an acute onset.
The distribution of sensory symptoms varies from one side of the face to one arm, one leg or both legs, suggesting a partial transverse myelitis or complete transverse myelitis with weakness of both legs and urinary retention.
Some patients may complain of electric shock-like sensation travelling through their spines, especially at the hair dresser. This could well be the effect of a demyelination plaque in the cervical spine causing Lhermitte’s sign. 5, 6
One of the most common presentation of MS is following a relapse. These are patients with a diagnosis of MS, often presenting with a second or third episode of relapse with a subacute onset of symptoms.
WHEN TO REFER
It is important to refer patients to a neurology service as a matter of priority. Whether you suspect a new diagnosis or a relapse, close communication with a neurologist/neurology team is needed as a matter of urgency.
The neurology outpatient clinics and emergency room assessments are full of people with a clinical history of episodic neurological symptoms. Sensory symptoms are particularly common in both settings of in-patient and outpatient assessments.
The decision to refer a patient to an emergency room assessment or outpatient assessment will depend on a case-by-case basis. Since some of the acute symptoms of MS can also occur in ischaemic events, it depends on the clinical case at hand to whether a GP refers the patient to ED or to a neurology outpatient clinic. Speaking to the neurologist on call in a tertiary hospital can often help with triaging patients.
INVESTIGATIONS
It is critically important to perform a thorough medical history and examination.
There are five main groups of investigations that are available to help support the diagnosis of MS.
1. Blood tests
2. Magnetic resonance imaging (MRI)
3. Evoked potential studies
4. Cerebrospinal fluid examination
5. Vision-based assessments
Blood tests
Blood tests are helpful to rule out other diseases that may produce symptoms similar to MS. These tests are useful in the case of confirmed MS diagnosis as there are a variety of new, complex, powerful treatment options for MS with the need for ongoing monitoring with blood tests at times.
Some complex treatment options will need detailed blood tests as part of the work up to ensure the potential adverse effects are well managed and well prepared for.
MRI
MRI brain, as well as spinal cord, and sometimes optic nerves (neurologists may request these depending on the specific symptoms and signs of the patient) investigations reveal areas of MS-related lesions very well.
Demyelination protocol-based MRI may reveal fresh, active MS lesions in these areas with enhancing response to the contrast material injected. MRI is sufficiently sensitive to demonstrate old MS lesions as well as the changes of axonal degeneration that occur in MS.
Typical sites of MS lesions in an MRI include periventricular white matter (when these lesions are at right angle to the corpus callosum, the MRI appearances are referred to as “Dawsen fingers”), corpus callosum, juxta cortical white matters, optic nerve, areas of the brain inferior to the tentorium ( infra-tentontirial structures, namely pons, cerebellum, cerebellar peduncles) and the spinal cord.
Evoked potential tests
Evoked potential tests record the electrical signals produced by different pathways of the nervous system in response to stimuli.
Optic nerve involvement is very common in MS. Assessment of the visual system is useful in diagnosis as well as monitoring MS. The patient watches a moving pattern and the connected electrodes measure how quickly the information travels along the visual pathway to the back of the brain. This test is known as a visual evoked potential (VEP).
Motor and sensory systems, other than the visual system, can also be tested in the same way. Delay in response is indicative of loss of myelin in the affected pathway.
Vision tests
The eye provides us with a unique opportunity to visualise the brain matter (optic nerve head) directly. This is the only place in the body where doctors can directly visualise live blood vessels, both arterioles and venules.
Optical coherence tomography (OCT) is a valuable tool to detect damage that occurs to the optic nerve. OCT is a scan of the optic nerves that is performed with a small machine with no pain or discomfort to the patient. OCT findings can mirror MS-related changes that occur in the brain.7, 8
Visual fields with Melbourne rapid field can objectively record the field defects and scotomas that may occur in MS.9, 10
DIAGNOSIS
Most patients with a relapsing-remitting form of MS can be easily diagnosed based on the patterns of symptoms and the results of investigations such as MRI, vision-based tests, blood tests and spinal-fluid test results.
Diagnosing MS in a clinically isolated syndrome and progressive form can be difficult. A neurologist may proceed with additional neuroimaging as well as spinal fluid tests.
TREATMENT
At present, there is no curative treatment for MS. But there are exceptionally good treatment options available to control disease activity and to prevent disease-disability in Australia.
These therapeutic options focus on speedy recovery of acute relapsing attacks of MS and to slow the progression of the disease, thus controlling the symptoms.
It is important that as an adjunct to pharmacological treatments, the patient’s mental health should be considered with regards to the stress of managing the diagnosis and its symptoms.
Smokers should be encouraged to quit the habit and adopt regular exercise and a healthy diet to help with their overall wellbeing.
ACUTE ATTACKS
When patients with MS present with acute attacks of relapses, high-dose steroids, such as intravenous methylprednisolone and oral prednisolone, are prescribed to reduce the inflammation and speed up the recovery process.
This decision should be taken up by the neurologist or the neurology team as patients with mild symptoms may not need these therapies.
Occasionally, a viral infection or urinary tract infection may cause these patients to have a pseudo relapse which does not need acute-attack treatment.
DELAYING PROGRESSION AND DISABILITY
Recent advances in MS therapeutics have revolutionised the progression of the disease and its associated disability, specifically for the relapsing type of MS.11-13 These medications are also known as disease-modifying therapies in MS.
The treatment options for relapsing remitting forms of MS include beta interferons and glatiramer acetate, which are intermittent subcutaneous or intramuscular injections.
There are oral tablets, such as dimethyl fumarate, fingolimod and teriflunomide with different mechanisms of actions on different components of the immune system.
There are variety of infusion treatments with different intervals of infusions in dedicated hospital-based centers with different mechanisms of actions and different profiles of adverse effects. This includes a monthly infusion treatment of natalizumab, that is considered as a first-line treatment for a severe relapsing form of MS by many neurologists. Alemtuzumab involves five consecutive days of drug infusions, followed by another three days of infusions after 12 months.
These are highly sophisticated medications with a mandatory drug safety monitoring program for the patients.
Ocrelizumab is another IV therapy that can be used to treat both the relapsing form of MS as well as the progressive form. Carefully selected patients with severe forms of MS can be treated with bone-marrow transplant therapy performed in highly specialised centers in Australia.
PROGNOSIS
MS is a heterogenous neurological disorder. No two patients with MS behave the same way. Less than 5% of patients with MS will have severe disability within the first five years of onset of MS and 10 to 20% of patients remain unimpaired without treatment over two decades.14
Patients with MS can have impairments on processing speed, memory and executive skills, affecting their employability. Cognitive changes and impairment are noted in all stages of MS across the board.
CONCLUSION
Most of the patients with MS are diagnosed during their early adult years.
The diagnosis of MS can be very difficult, not just in terms of the possible neurological impairments in the future, but because it is a chronic condition with no known cure.
It is important to consider the toll this diagnosis and its treatment can take on the mental health of the patient and their families.
It is necessary to build a high level of empathy and rapport to support them during this process and establish a positive mindset to control the disease and get on with life.
It is important to remind the patient that his or her life is larger than MS, And that it is a small component of their life despite the load of information they receive at the time of diagnosis and beyond.
I always tell my patients with MS: “Just because they have been given a diagnosis of MS does not mean that they should let MS have them.”
Professor Tissa Wijeratne, MD, FRACP, FRSM, FAAN, FAHA, FRCP (Edin) FRCP (London), is the Chair, Department of Neurology at Western Health, Melbourne, Australia
References:
1. Weiner HL. A shift from adaptive to innate immunity: a potential mechanism of disease progression in multiple sclerosis. J Neurol. 2008;255 Suppl 1:3-11.
2. Bannon M. Aetiology of multiple sclerosis. Qjm. 2011;104(5):381-2.
3. van der Mei IA, Ponsonby AL, Dwyer T, Blizzard L, Taylor BV, Kilpatrick T, et al. Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia. J Neurol. 2007;254(5):581-90.
4. Simpson S, Jr., Pittas F, van der Mei I, Blizzard L, Ponsonby AL, Taylor B. Trends in the epidemiology of multiple sclerosis in Greater Hobart, Tasmania: 1951 to 2009. J Neurol Neurosurg Psychiatry. 2011;82(2):180-7.
5. Brody IA, Wilkins RH. Lhermitte’s sign. Archives of neurology. 1969;21(3):338-40.
6. Zaki SA, Dadge D, Shanbag P. Lhermitte’s sign as a presenting symptom of spinal demyelination. Indian J Pediatr. 2009;76(3):336-7.
7. Balk LJ, Cruz-Herranz A, Albrecht P, Arnow S, Gelfand JM, Tewarie P, et al. Timing of retinal neuronal and axonal loss in MS: a longitudinal OCT study. J Neurol. 2016;263(7):1323-31.
8. Balk LJ, Tewarie P, Killestein J, Polman CH, Uitdehaag B, Petzold A. Disease course heterogeneity and OCT in multiple sclerosis. Mult Scler. 2014;20(9):1198-206.
9. Kong YX, He M, Crowston JG, Vingrys AJ. A Comparison of Perimetric Results from a Tablet Perimeter and Humphrey Field Analyzer in Glaucoma Patients. Transl Vis Sci Technol. 2016;5(6):2.
10. Nesaratnam N, Thomas PBM, Kirollos R, Vingrys AJ, Kong GYX, Martin KR. Tablets at the bedside – iPad-based visual field test used in the diagnosis of Intrasellar Haemangiopericytoma: a case report. BMC Ophthalmol. 2017;17(1):53.
11. Freedman MS, Rush CA. Severe, Highly Active, or Aggressive Multiple Sclerosis. Continuum (Minneapolis, Minn). 2016;22(3):761-84.
12. Jones DE. Early Relapsing Multiple Sclerosis. Continuum (Minneapolis, Minn). 2016;22(3):744-60.
13. Krieger SC. New Approaches to the Diagnosis, Clinical Course, and Goals of Therapy in Multiple Sclerosis and Related Disorders. Continuum (Minneapolis, Minn). 2016;22(3):723-9.
14. Scalfari A, Neuhaus A, Degenhardt A, Rice GP, Muraro PA, Daumer M, et al. The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability. Brain. 2010;133(Pt 7):1914-29.
