Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS)1. It is estimated that approximately two million people live with MS worldwide, making the disease the most common non-traumatic cause of neurological disability in young adults1,2,3. MS is twice more common in females than males and presents a considerable variation in prevalence from one region of the world to another3. Clinical features of MS were first described in the 19th century by Jean-Martin Charcot. Since then, our knowledge and understanding of the disease has dramatically increased as a result of the work of many researchers in the field4.
MS is often characterized by multiple lesions of CNS white matter that cause demyelination. In addition, gray matter can also be affected, and axonal damage can be observed1. While the exact cause of MS is not known, it is suggested that its pathogenesis is immune-mediated3,5.
It is thought that a complex combination of genetic and environmental factors contributes to the onset of MS1,6. Close relatives of patients with MS such as identical twins, children, parents, or siblings have an increased risk of developing the disease1,6. Plenty of potential culprit genes have been suggested, but it is highly likely that the cumulative effects of hundreds—if not thousands—of risk alleles throughout the genome lead to a kind of genetic susceptibility to MS7. A great number of environmental factors have been studied in relation to MS, for many of which available studies are not conclusive; however, available evidence is highly supportive of the roles of Epstein-Barr virus, vitamin D, and smoking in the causation of MS8.
Four disease courses are identified in patients with MS. The majority of patients (approximately 85%) initially present with a type of MS called relapsing-remitting, which is characterized by acute attacks followed by full or partial recovery and periods of remission in between attacks9. In contrast, about 10% of patients present with primary-progressive disease, in which the characteristic acute attacks do not occur; rather, there is a progression of disability from the onset with no improvement or occasional minor improvements. Many patients with initial relapsing-remitting disease will eventually develop secondary-progressive MS. These patients experience progressive neurological decline with occasional relapses and less recovery after attacks. The least common type of MS is progressive relapsing. Patients with progressive-relapsing MS have a steady accumulation of disability from the onset but also experience clear superimposed attacks9.
MS patients present a wide variety of neurological signs and symptoms, the majority of which are not specific to the disease. Common signs and symptoms include numbness, motor weakness, visual disturbances, gait and coordination problems, bowel and bladder dysfunctions, dizziness and vertigo, fatigue, depression, pain, and cognitive dysfunction; however, other neurological signs and symptoms can also be seen1,3.
In a great majority of MS patients, the diagnosis is made based on clinical features or a combination of clinical and imaging manifestations10. Proper diagnosis always requires the exclusion of any other possible cause of symptoms. Several tools have been developed in order to help with making the diagnosis, such as McDonald MS diagnostic criteria, which utilizes a combination of clinical and paraclinical evidence11. Magnetic resonance imaging (MRI) has become an important technique to detect MS lesions12. Meanwhile, the introduction of MRI has also led to a significant increase in the number of false positives. Patients without MS with white matter lesions similar to those seen in MS may be misdiagnosed. In particular, the presence of clinical features that are atypical for MS should raise a red flag for clinicians13. Other tests such as blood work, CSF analysis, or evoked potentials may be required to either confirm the diagnosis or rule out other conditions. After all, MS still remains a diagnosis of exclusion10.
Acute attacks of MS are often managed by high doses of intravenous (sometimes oral) corticosteroids. The treatment appears to be effective in relieving the symptoms, but its long-term positive impacts are uncertain. In some cases, plasmapheresis may be used to control those attacks that do not respond to the usual corticosteroid therapy6,14,15. Proper rehabilitation and emotional support are also important parts of relapse management.
Several injectable and oral disease-modifying agents are currently approved by the U.S. Food and Drug Administration as first-line treatments for relapsing forms of MS such as interferon beta-1a (Avonex, Rebif), interferon beta-1b (Betaserone), glatiramer acetate (Copaxone), and fingolimod (Gilenya). Disease-modifying agents in relapsing-remitting MS can decrease the number of attacks. If started early, they are also thought to improve long-term outcomes in these patients6. In patients with secondary-progressive MS, mitoxanterone (Novantrone) is approved, as it has been shown to slow the progression of disease16.
Proper management of patients’ symptoms is crucial in MS. While disease-modifying agents are aimed at changing the course of the disease, adequate symptom management allows patients to optimize their daily functioning and improve their quality of life. Symptom management in patients with MS often requires a multi-disciplinary approach given the broad spectrum of symptoms these patients face17.
Despite recent advances in the treatment of MS, including the introduction of disease-modifying treatments, most patients with MS develop different degrees of disability that limits their daily activities and affects their quality of life. Rehabilitation strategies are key approaches in dealing with such limitations in patients with MS. This is another treatment paradigm for MS patients that requires a multi-disciplinary approach by a group of healthcare professionals. It is also important to provide patients with adequate psychosocial support in dealing with the disease and its complications18.
Studies show that many patients with MS seek other therapies including complementary and alternative therapies for which clear evidence of effectiveness is not available19. A study published by Zamboni et al. in 2009 suggested that chronic cerebrospinal venous insufficiency plays an important role in pathogenesis of MS. The authors also suggested that a correctional surgery widely known as “liberation procedure” can significantly improve patients’ outcomes20. The study has received wide attention among patients, healthcare professionals, researchers in the field, and members of media. However, other studies have raised questions on the merit of this concept at different levels21,22.
The treatment paradigm of MS has changed dramatically over the past two decades. In 1993, no approved treatment was available for these patients. Nowadays, there are several therapies approved for MS, and many other compounds are being assessed in multiple clinical trials with the hope of bringing even more options to the table 6.