Test Your Knowledge: Ten Questions about Multiple Sclerosis

How much do you know about the epidemiology and treatment of MS? Test your knowledge by taking our online quiz.


Question 3. Which of the following is true about the epidemiology of MS?
There is a gradient of increasing prevalence with increasing latitude There is a gradient of increasing prevalence with decreasing latitude There is a gradient of increasing prevalence with increasing longitude There is a gradient of increasing prevalence with decreasing longitude Question 4. Based on clinical trial evidence, which of the following treatments is most effective for an acute relapse?
Corticosteroids Plasma exchange Interferon beta Question 5. Which of the following best refl ects the evidence on using corticosteroids for treating an acute relapse of MS?
The optimal dose, duration of treatment, and route of administration are unclear There is good evidence that 15 days of treatment is more effective than fi ve days There is good evidence that giving corticosteroids for an acute relapse can help prevent further relapses Question 6. Which of the following best refl ects the evidence on interferon beta for treating MS?
There is good evidence that it prevents disease progression in people with secondary progressive MS There is no value in giving it after a fi rst demyelinating event There is some evidence that interferon beta can reduce exacerbations and disease progression in people with relapsing, remitting disease Question 7. Which of the following treatments for fatigue in MS is well supported by high-quality evidence?
Exercise Behavior modifi cation Pemoline None of the above Question 8. Which of the following best refl ects our current knowledge of the relationship between stressful life events and acute exacerbations of MS?
A meta-analysis found a consistent association between stressful life events and subsequent exacerbations Although some individual studies have suggested an association between the two, a meta-analysis of all of these studies found no consistent association While some studies have suggested an association between the two, they were retrospective case-control studies, and the association has not been shown in a prospective study

Test Your Knowledge: Ten Questions about Multiple Sclerosis
This quiz is related to a Perspective in the February issue of PLoS Medicine (DOI: 10.1371/journal.pmed.0020033).
Question 9. Which of the following best refl ects the evidence on physiotherapy (physical therapy) as a treatment for spasticity in MS?
There is good evidence that physiotherapy improves mobility and activities of daily living in people with progressive MS There is good evidence that physiotherapy improves mobility and activities of daily living in people with relapsing, remitting MS Although physiotherapy is a very common treatment for spasticity in MS, there is insuffi cient evidence from RCTs to be sure of its effectiveness

Question 10. Which of the following interventions for MS is best supported by clinical trial evidence?
Hyperbaric oxygen to slow the progress of the disease Intravenous immunoglobulins to reduce the relapse rate and disease progression in relapsing, remitting disease Amantadine to reduce the fatigue of MS

Answer 1: Relapsing, remitting
In 90% of people, early disease is relapsing, remitting, characterized by episodes of neurological dysfunction interspersed with periods of stability. The other 10% have primary progressive disease, in which progressive neurological disability occurs from the outset. Most people with relapsing, remitting MS at presentation will go on to develop secondary progressive disease, usually about 6-10 years after onset [1].
In one study of the natural history of primary progressive MS (216 patients), the mean age of onset was 38.5 years, and the female:male ratio was 1.3:1 [2]. Relapsing, remitting MS typically begins in the second or third decade of life, and the female:male ratio is about 2:1 [3].

Answer 2: One in 800
The prevalence of MS in Europe and North America is one in 800 people, with an annual incidence of two to ten cases per 100,000 people, making MS the most common cause of neurological disability in young adults [1,2]. Regions with the highest prevalence of MS are Europe, Israel, Canada, northern United States, southeastern Australia, New Zealand, and easternmost Russia [3]. Medium frequency areas include southern United States, most of Australia, South Africa, the southern Mediterranean basin, Russia into Siberia, the Ukraine, and parts of Latin America. Prevalence rates under fi ve per 100,000 are found in the rest of Asia, Africa, and northern South America. Answer 3: There is a gradient of increasing prevalence with increasing latitude One of the most striking epidemiological features of MS is a gradient of increasing prevalence with increasing latitude [1]. For example, in Australia, the risk of developing MS in temperate Tasmania is 5-fold that in subtropical Queensland [2]. A recent case-control study found that higher levels of sun exposure during childhood and early adolescence, and greater actinic damage (skin damage from sun exposure), are associated with a reduced risk of MS; this association persisted after adjustment for fair skin and exposure after onset of disease [3]. These fi ndings suggest that ultraviolet radiation may be benefi cial against MS, possibly through increasing vitamin D levels [3].

Answer 4: Corticosteroids
One systematic review identifi ed four randomized, controlled trials (RCTs) of methylprednisolone against placebo, and two of corticotrophin against placebo, in people with an acute exacerbation of MS (377 patients in total) [1]. Corticosteroids improved symptoms compared with placebo within the fi rst fi ve weeks of treatment. One small, double-blind crossover RCT (22 people) provided insuffi cient evidence to assess the effects of plasma exchange in people with acute relapses of MS [2].
Interferon beta is used to prevent relapses and disability, not as a treatment for an acute relapse.
Answer 5: The optimal dose, duration of treatment, and route of administration are unclear While a systematic review did show that corticosteroids are effective at reducing symptoms of an acute relapse [1], there was insuffi cient evidence from the trials to determine the optimal dose, duration, and route of administration [1,2]. A small subgroup analysis using an indirect comparison suggested no difference between fi ve days and 15 days of treatment with methylprednisolone. One of the RCTs included in the systematic review [1] found no signifi cant difference between oral methylprednisolone and placebo in the prevention of new relapses after one year. Answer 6: There is some evidence that interferon beta can reduce exacerbations and disease progression in people with relapsing, remitting disease One systematic review identifi ed seven RCTs comparing interferon beta with placebo in people with active relapsing, remitting MS (two relapses in the previous two or three years) [1]. The review found that, over two years, interferon signifi cantly reduced the risk of exacerbations and disease progression compared with placebo. Two RCTs found that interferon beta given to patients after a fi rst demyelinating event signifi cantly reduced the risk of a second clinical event and, therefore, of conversion to a defi nite diagnosis of MS [2,3]. Three RCTs provided insuffi cient evidence to assess the effects of interferon beta on disease progression in people with secondary progressive MS [4,5,6].

Answer 8: A meta-analysis found a consistent association between stressful life events and subsequent exacerbations
A recent meta-analysis, which included 14 individual studies, showed a signifi cant increase in risk of exacerbation of MS after stressful life events [1]. Seven of the studies in the metaanalysis were prospective longitudinal studies.
Answer 10: Intravenous immunoglobulins to reduce the relapse rate and disease progression in relapsing, remitting disease In a Cochrane systematic review of RCTs of intravenous immunoglobulins for the secondary prevention of relapses and disease progression in MS, two trials met the inclusion criteria (involving a total of 168 patients) [1]. These found a reduction in relapse rate and increased time to fi rst relapse during treatment with intravenous immunoglobulins. Another Cochrane systematic review included nine RCTs of hyperbaric oxygen versus a sham therapy in patients with MS [2]. Two trials produced generally positive results, but the remaining seven reported generally no evidence of a treatment effect. The reviewers concluded, "We found no consistent evidence to confi rm a benefi cial effect of hyperbaric oxygen therapy for the treatment of multiple sclerosis and do not believe routine use is justifi ed." A third Cochrane systematic review included four RCTs of amantadine in patients with MS-related fatigue [3]. The reviewers concluded that the quality of the studies was poor and that all trials were open to bias. All of the studies reported small and inconsistent improvements in fatigue, but the clinical relevance of these fi ndings and the impact on patients' functioning and health-related quality of life remained undetermined. The reviewers concluded, "Amantadine treatment is generally well tolerated, however its effi cacy in reducing fatigue in people with MS is poorly documented."