Multiple sclerosis
Progress, promises and the way forward
New horizons for multiple sclerosis
In global terms, approximately 2.8 million people are affected by the neurological disease multiple sclerosis, or MS for short. In Denmark, nearly 18,000 individuals live with the condition[1]. Women are more often affected (2/3) than men in adulthood. Multiple sclerosis rarely follows the same course, making therapy and treatment challenging for both patients and doctors.
MS is an inflammatory disease in the central nervous system, typically developing in relapses. The nerve structures in the brain and spinal cord constitute the central nervous system, abbreviated as CNS. It regulates the central processing of stimuli in the body, including the following tasks:
Transmission and processing of messages (stimuli) from the surroundings and the body's internal functions. For example, feeling hungry when seeing food.
Coordination of motor movements. For example, waving to someone while walking and greeting them.
Cognitive functions - referring to everything related to language, thinking, memory, motivation, and emotions.
Regulation of the harmonious interaction between all vital systems in the human body. For example, an increase in breathing during exertion or the body adjusting to the day-night rhythm.
The Latin term for multiple sclerosis is encephalomyelitis disseminata. It means disseminated (from Latin disseminare 'scatter, spread', from dis- and seminare 'sow seeds') inflammation of the brain and spinal cord, aptly describing what happens in the disease:
The immune system attacks and destroys parts of the nerve fibres in the CNS, crucial for transmitting impulses. The nerve fibres and cells themselves are also targeted. This damage is called demyelination[2]. Diseases where the body's immune system attacks itself are termed autoimmune diseases.
What are the possible causes of MS?
Researchers have not yet been able to fully explain why people develop multiple sclerosis. According to current data, it is assumed that various factors contribute to the occurrence of multiple sclerosis. These factors include:
Genetic predisposition: Family members do not transmit the disease to their offspring but pass on an increased risk of the disease[3].
External influences, so-called environmental factors: Experts suspect that factors such as smoking, excessive vitamin D, and viral infections (e.g., Epstein-Barr virus) may promote the occurrence of the disease[4].
What MS symptoms can occur?
MS symptoms vary and differ for each individual; no two diseases are the same. Because the functions of the central nervous system are so extensive, multiple sclerosis can affect all these functions[5].
Some symptoms are called early symptoms. These are signs that typically appear at the beginning of the neurological disease. These include[6]:
Spastic (cramp-like) paralysis
Coordination problems
Sensory disturbances such as numbness or "tingling" throughout the body, often occurring sporadically
Visual disturbances, where there is a vision loss in the visual field or blurred vision. Occasionally, patients also describe double vision.
Rapid fatigue and exhaustion
Concentration difficulties
The early symptoms continue to occur in the advanced course of the disease.
If the autonomic nervous system is also affected during an episode, patients often lose control over their bladder and bowel function. The disease course usually has an impact on mental health, and patients often develop depression.
Most symptoms usually disappear when the episode is over. However, if the inflicted damage is significant, permanent neurological impairments may remain.
MS Diagnosis – Useful Things to Know About Diagnosis
There is no single clinical feature or diagnostic procedure to identify multiple sclerosis. The diagnosis of MS is based on a combination of clinical, imaging, and laboratory findings[5].
The diagnosis of MS is made by exclusion. Neurologists first rule out all differential diagnoses, i.e., diagnoses that cause similar symptoms.
A first indication of an inflammatory disease may be elevated blood inflammation levels (CRP) during a relapse. However, the value alone is too nonspecific to draw accurate conclusions; many relatively harmless diseases also cause the value to rise. An essential part of the diagnosis[7] is the examination of the fluid in the brain and spinal cord, known as cerebrospinal fluid. Specific proteins and cells are examined in the cerebrospinal fluid. Additionally, an MRI (magnetic resonance imaging) is performed to detect any changes in the brain. Electrophysiological measurements, especially the determination of the capacity of the optic nerves, are also part of the diagnosis.
A valuable tool for diagnosing MS is the McDonald criteria, which require signs of damage or dysfunction in at least two of four areas of the central nervous system at different times: On or beside the cortex, around the spaces in the brain (ventricles), in the cerebellum, and the spinal cord[8].
Progression in Multiple Sclerosis
When MS-typical changes are detected for the first time via MRI or CSF examination, neurologists speak of a clinically isolated syndrome (CIS). CIS can develop into MS, but it can also occur only once.
Once the diagnosis is confirmed, neurologists categorise the disease into different courses[9]:
Relapsing-remitting multiple sclerosis (RMS): This type of multiple sclerosis is characterised by episodes of symptoms where the effects of the MS episode disappear entirely or at least partially within a few weeks.
Secondary progressive multiple sclerosis (SPMS): Most people with MS develop secondary progressive MS as the disease progresses. The main characteristic is a slow clinical deterioration of the patient's condition independent of relapses.
Primary progressive multiple sclerosis (PPMS): Primary progressive MS is characterised by patients experiencing gradual disability right from the start. This form of multiple sclerosis often develops without relapses.
Benign multiple sclerosis: A small portion of MS patients are spared significant disabilities for several decades after diagnosis. With this disease, monitoring cognitive abilities and concentration is essential.
MS Therapy and Treatment Options
Multiple sclerosis cannot be cured, according to current medical knowledge. However, comprehensive treatment can slow the progression and alleviate symptoms. Neurologists currently treat patients according to a three-phase therapy model, taking individual courses into account. The three phases are attack treatment, disease-modifying treatment, and symptomatic therapy[10].
During a relapse, the use of corticosteroids for the treatment of acute symptoms has proven to be effective. Cortisone has an anti-inflammatory effect and can thus contribute to alleviating symptoms. However, the treatment also has side effects. If cortisone is not adequate, so-called plasma exchange (blood washing) is considered an alternative relapse treatment. The procedure is similar to dialysis - during plasma exchange, some components of blood plasma are isolated, and the purified blood flows back through the attached access.
Disease-modifying treatment can prevent relapses and can have a positive effect on the course of the disease. The goal is to slow down the course of the disease. For disease-modifying treatment, drugs that affect the immune system are used.
Symptomatic treatments address the symptoms of multiple sclerosis with occupational therapy, physiotherapy, and speech therapy. Rehabilitation is an integral part of therapy, and in some cases, medication is also used, e.g., for the treatment of depression or bladder weakness.
MS therapies without medication are not effective. Only symptomatic treatment remains, which cannot slow the course of the disease. Although a diet tailored to the condition may, under certain circumstances, have a positive effect on the course of the disease, it is not influential enough on its own.
Medical Cannabis in the Treatment of Multiple Sclerosis
The (endogenous) endocannabinoid system is, among other things, a part of the nervous system in the human body. It includes the so-called cannabinoid receptors CB1 and CB2. While CB1 receptors are mainly found in nerve cells in various parts of the brain and the peripheral (surrounding) nervous system, CB2 receptors are found primarily in the immune system and other body parts. In patients suffering from spastic disorders due to multiple sclerosis, the endocannabinoid system may be altered. There is suspicion that there is a lack of the body's own cannabinoids (endocannabinoids), such as anandamide. These are important for signal transmission between nerve cells[11].
The system is involved in processes such as nerve tissue inflammation, neuronal repair mechanisms, and the protection of nerve cells (neuroprotection), all of which are essential processes in connection with multiple sclerosis[12]. Cannabis' effect on the body is based on the fact that the cannabis plant also contains cannabinoids that can bind to the respective receptors. The most well-known of these active substances are THC (delta-9-tetrahydrocannabinol) and CBD (cannabidiol). THC can have a euphoric effect but also, among other things, a pain-relieving effect. CBD, on the other hand, has no euphoric effect and can have an anti-inflammatory, anticonvulsant, calming, and anxiety-relieving effect.
The results of several studies especially point to cannabis having an antispasmodic effect. Particularly interesting: 2017 New Zealand researchers reported on subjects who did not respond adequately to standard medication for multiple sclerosis. After the patients had received medicinal cannabis with equal parts CBD and THC for three months, the research team reported a significant improvement in spasticity[13].
A large number of multiple sclerosis patients also suffer from pain. This can be a result of spasticity or damaged nerve fibres. Various studies have already examined and concluded the effectiveness of cannabis as a medicine for nerve pain[12,14,15].
It is not uncommon for those affected to develop depression as a result of their disease. Here, too, cannabis as medicine can have a supportive effect along with psychotherapy: In a study on the impact of medical cannabis on nausea and vomiting during chemotherapy, researchers state that the mood-lifting effect of cannabis with THC is a wholly desirable side effect[16].
In the future, treatment with high doses of CBD could also alleviate the suffering of MS patients. Although research is not yet mature enough to make a final statement, initial studies provide hope: Israeli researchers gave mice with MS-like symptoms highly concentrated CBD. The mice showed less inflammation and could move their legs again after CBD treatment[17].
Criteria for the Prescription of Medical Cannabis
The responsibility for medical treatment with cannabis always lies with the treating physician. Therefore, it is the doctor who determines whether a patient should be treated with medical cannabis.
According to the cannabis guidance from the Danish Medicines Agency, the following should be considered:
Relevant approved marketed drugs should be tested before attempting treatment with medical cannabis.
Cannabis should not be used for children and young people under 18 years of age due to a lack of knowledge about long-term effects, including cognitive development.
A doctor can prescribe a maximum of one month's supply on a prescription.
As a rule, doctors do not treat medical cannabis outside their area of expertise.
Furthermore, the Danish Medicines Agency has approved a few patient groups and indications, including multiple sclerosis, for the use of medical cannabis by patients in Denmark. You can read more about relevant indications for prescription here.
References
Skleroseforeningen https://www.scleroseforeningen.dk/viden-om/hvad-er-sclerose/faa-alle-tallene-om-sclerose
Zalc, Bernard. One hundred and fifty years ago Charcot reported multiple sclerosis as a new neurological disease. Brain : a journal of neurology vol. 141,12 (2018).
Patsopoulos, Nikolaos A et al. Fine-mapping the genetic association of the major histocompatibility complex in multiple sclerosis: HLA and non-HLA effects. PLoS genetics vol. 9,11 (2013).
Olsson, T., Barcellos, L. & Alfredsson, L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nat Rev Neurol 13, 25–36 (2017).
Brownlee, Wallace J et al. Diagnosis of multiple sclerosis: progress and challenges. Lancet (London, England) vol. 389,10076 (2017).
Rommer, Paulus Stefan et al. Symptomatology and symptomatic treatment in multiple sclerosis: Results from a nationwide MS registry. Multiple sclerosis (Houndmills, Basingstoke, England) vol. 25,12 (2019).
Hoffmann, S. et al. Multiple Sklerose: Epidemiologie, Pathophysiologie, Diagnostik und Therapie. ISSN 1861- 6704 Prakt. Arb.med. (2009).
Thompson, Alan J et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. The Lancet. Neurology vol. 17,2 (2018).
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Centonze, D. et al. The endocannabinoid system is dysregulated in multiple sclerosis and in experimental autoimmune encephalomyelitis. Brain 130, 2543–2553 (2007).
Mecha, M., Carrillo-Salinas, F. J., Feliú, A., Mestre, L. & Guaza, C. Perspectives on Cannabis-Based Therapy of Multiple Sclerosis: A Mini-Review. Front Cell Neurosci 14, 34 (2020).
Keating, Gillian M. Delta-9-Tetrahydrocannabinol/Cannabidiol Oromucosal Spray (Sativex®): A Review in Multiple Sclerosis-Related Spasticity. Drugs vol. 77,5 (2017).
Lakhan, Shaheen E, and Marie Rowland. Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review. BMC neurology vol. 9 59. (2009).
Iskedjian, Michael et al. Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain. Current medical research and opinion vol. 23,1 (2007).
Tramèr, M. R. et al. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ 323, 16 (2001).
Kozela, Ewa et al. Cannabidiol inhibits pathogenic T cells, decreases spinal microglial activation and ameliorates multiple sclerosis-like disease in C57BL/6 mice. British journal of pharmacology vol. 163,7 (2011).