Multiple Sclerosis And Migraines

Introduction 

Multiple Sclerosis (MS) and migraines are both neurological conditions that often coexist, affecting a patient’s life. More specifically, MS is an autoimmune disease that affects over 130,000 people in the UK (MS Society). Autoimmunity is where the body’s immune system attacks itself. In MS, your body specifically targets your brain and spinal cord (the central nervous system, CNS). This causes common symptoms such as cognitive dysfunction. In contrast to this, migraines are characterised as moderate or severe headaches. Approximately 31% of individuals with MS experience migraines in which the prevalence varies from 2% - 67%.¹ Both conditions impact the brain, indicating potential underlying connections. Understanding the relationship between them can provide valuable insights for improving your health.

Understanding multiple sclerosis 

Multiple Sclerosis (MS) is a chronic autoimmune disease that affects your CNS, which includes your spinal cord and brain. In MS, your immune system attacks the protective layer (myelin) that covers your neurons in the CNS. As a result, the disease is typically characterised by inflammation, demyelination, gliosis, and neuronal loss.² Depending on the location of the affected neurons in the CNS, the neurological symptoms an individual experiences may vary. The onset of MS begins between the ages of 20-40 and affects more than 2.5 million people globally.³ Due to its relatively early onset and progressive worsening, MS can impose a significant burden on individuals and their families.

Autoimmunity & the blood-brain barrier 

The exact cause of MS is not fully understood, but it is believed to involve a combination of genetic susceptibility and environmental factors that cause an autoimmune response. This attack is mediated by the activation of a wide range of immune cells such as Th1 and Th17 cells as well as B cells and macrophages.⁴ In MS, immune cells can release small proteins called cytokines or chemokines that function as signalling molecules that can induce inflammation by the activation, further recruitment, and regulation of the inflammatory response. These proteins can also disrupt your blood-brain barrier (BBB).⁵ The BBB is a selective permeability barrier that protects the CNS from potentially harmful substances in the blood. As a result of the BBB disruption, immune cells infiltrate your CNS, where they mistakenly identify myelin as a foreign antigen and attack it. 

Myelin & demyelination 

Myelin is a fatty, insulating protective layer that surrounds the axons of neurons, which are the long projections that carry electrical signals necessary for signal transmission and communication across the CNS. Myelin is essential for the proper functioning of the nervous system for several reasons:

1. Increased Signalling: Myelin allows for electrical signals to travel much faster along the axon via a process called saltatory conduction. During this process, the electrical impulse jumps between the gaps in the myelin sheath called Nodes of Ranvier. 
2. Protection and Support: Myelin provides structural integrity and supplies metabolic support for the axons, helping maintain their health and function. 
3. Efficient Signal Transmission: Myelin ensures the electrical signals travel the entire axon without losing strength, enabling efficient signal transmission.

However, MS is an autoimmune condition that targets the myelin sheath in your CNS. This process is known as demyelination and results in the degradation of myelin. This process damages your nerve fibres by enzymes and reactive oxygen species produced by activated immune cells. This process creates lesions and plaques in the CNS. Without myelin, axons are vulnerable to damage. High or chronic inflammation can cause axonal degeneration, contributing to the long-term effects observed in MS.

The genetic factors of MS

MS is a complex disease influenced by numerous genetic predispositions and environmental factors. However, children cannot directly inherit the condition from their parents (MS Society). Despite not being an entirely heritable disease, multiple genes can affect your chances of developing MS. The strongest genetic association with MS is found in the MHC class II HLA-DRB1 gene, HLA-DRB1*15:01, which increases the risk of developing MS threefold.⁶ This gene is crucial for presenting antigens to T cells, playing a vital role in the autoimmune response. Other genetic variants have also been identified. Genome-wide association studies (GWAS) have identified over 200 genetic variants associated with MS.⁷ These genes are often related to the immune system, ranging from T cell activation, cytokine signalling, and immune cell migration such as the interleukin-2 receptor alpha (IL2RA).⁸

Symptoms

Due to its complex background, MS has a wide range of symptoms that can vary widely from person to person. The symptoms can also vary or change in severity over time. The NHS has listed the following symptoms as the main symptoms of MS:

1. Fatigue
2. Pain
3. Vision problems
4. Numbness, muscle spasms, stiffness and weakness
5. Mobility problems
6. Bowel and bladder problems
7. Problems with thinking, planning, and learning
8. Depression and anxiety

Some people experience a steady worsening of symptoms, while others have symptoms that come and go. When your symptoms worsen, that period is called a relapse. But when your symptoms improve or disappear, that is known as remission. People with MS have a relapsing-remitting disease course, meaning they experience relapses that occur over days or weeks which is then followed by months or years of partial or complete improvement. 

Many neurological conditions share similar symptoms, so your symptoms may not necessarily indicate MS. However, if you do experience any symptoms or early signs of MS, it's advisable to consult your local GP.

Migraines 

Migraines are a prevalent health condition that affects a majority of individuals in the population. They are typically characterised by intense headaches often accompanied by nausea, vomiting, and sensitivity to light and sound (NHS). These headaches differ from your average headaches and can last between four hours to three days (Brain & Spine Foundation). Despite not being life-threatening, they can greatly affect an individual's standard of living and their ability to perform day-to-day tasks. 

There are different subtypes of migraines (NHS):⁹ 

• Migraine with aura: this is where there are signs or symptoms (aura) before the migraine attack itself 
• Migraine without aura: this is when the migraine attack occurs without any warning signs 
• Migraine aura without headache (silent migraines): this is when an individual experiences aura or other symptoms without experiencing the headache

The frequency of migraines varies from person to person. People can experience migraine multiple times a week, have occasional migraines, or experience them with years in between. 

The connection between MS and migraines

The relationship between MS and migraines is complex and multifaceted. Researchers are still investigating the background of this relationship to identify the cause of the two conditions. Approximately 43% of MS patients experience a significantly higher level of migraines as well as other subtypes of headaches than the general population.^10,11,12 Both conditions involve neurological dysfunction and are believed to share certain underlying mechanisms related to inflammation and immune system dysregulation. 

Potential mechanisms

The exact relationship between MS and migraines requires further ​​exploration. However, scientists have observed that patients with MS and migraines have abnormalities in their immune response causing the activation of pro-inflammatory mechanisms that cause lesions in the white matter of their brain.^13,14 It has also been hypothesised that individuals experiencing migraine may also have a disrupted blood-brain barrier (BBB) due to an elevated production of pro-inflammatory cytokines and chemokines.^15,16 Your BBB is a barrier that functions as a protective shield that maintains a stable environment for the brain by regulating what substances can pass from the bloodstream into the brain. When your BBB is disrupted, activated immune cells can enter your brain. If these immune cells target myelin, they can also demyelinate your neurons and induce the onset of MS. Hence, scientists are considering the possibility of migraines potentially being a risk factor for MS that can potentially promote MS onset.¹⁷ Other factors can also disrupt the BBB and contribute to the risk of MS, meaning migraines are not the sole risk factor for the disease. 

Further research needs to be conducted l to pinpoint the exact relationship between migraines and MS. Scientists are currently utilising advanced MRI scans,¹⁸ among other brain imaging techniques, to help answer this question. These scans generate detailed images of the body and brain, enhancing our understanding of the relationship between MS and migraines.

Summary

Multiple Sclerosis (MS) and migraines are neurological conditions that often coexist, affecting many patients. MS is an autoimmune disease where the immune system attacks myelin, an important protective sheath found in the neurons of your central nervous system (CNS). This can lead to symptoms like fatigue and cognitive dysfunction as well as some individuals with MS experiencing migraines. Migraines impact the quality of life with intense headaches and other symptoms. The exact relationship between MS and migraines is mostly unknown. However, scientists have hypothesised that the relationship between MS and migraines includes shared mechanisms of immune dysregulation and inflammation, potentially involving blood-brain barrier (BBB) disruption. This process allows activated immune cells to enter the CNS and attack myelin. Despite these hypotheses, no definitive conclusions have been identified. Scientists are using advanced MRI scans and other imaging techniques to explore this complex relationship, aiming to improve understanding and treatment of MS and migraines.