Multiple Sclerosis

What is Multiple Sclerosis?

Multiple sclerosis, often referred to as MS, is a long-term disease where the body’s immune system attacks the central nervous system, which consists of the brain and spinal cord. People with MS experience inflammation and damage to the protective covering of nerve fibers, called myelin, leading to a variety of symptoms like vision problems, numbness, tingling, weakness, problems with bladder and bowel control, and difficulties with memory and thinking.

In MS, certain immune cells called lymphocytes and macrophages harm the myelin sheath around the neurons in the brain and spinal cord. The symptoms of MS depend on where this damage occurs. MS often starts with sudden symptoms and can lead to permanent disabilities within 10 to 15 years.

MS is a complex disease with different types and stages:

• Relapsing-remitting (RR): Most people with MS, about 70-80%, first experience this type. It causes new or reoccurring symptoms that last 24 to 48 hours or even a few weeks.
• Primary progressive (PP): About 15-20% of patients have this type, which shows a steady progression of symptoms without periods of remission.
• Secondary progressive (SP): This type follows the relapsing-remitting phase and involves a slow but steady worsening of symptoms. Additional relapses may occur.
• Progressive-relapsing (PR): This is the least common type, seen in about 5% of patients. It involves a steady worsening of the disease with occasional relapses.

Other possible types of MS are clinically isolated syndrome (one instance of symptoms related to demyelization), fulminant (severe MS with frequent relapses and swift progression), and benign MS (mild symptoms with infrequent relapses).

Doctors often focus on the relapsing-remitting course of MS as it’s the most common. Though symptoms can partially or even fully improve over time, patients might still experience lasting symptoms adding to overall disability. In diagnosing MS, doctors look for at least two separate instances of inflammation in the brain or spinal cord. They consider the timing of these episodes and the specific areas of the brain or spinal cord that are affected.

Early diagnosis allows for prompt treatment, which is crucial in managing the disease. The main goals of treatment are to reduce episodes of symptoms and prevent permanent disability. Treatment also focuses on managing other problems that can come with MS, such as issues with bladder and bowel control, depression and other emotional changes, fatigue, sexual problems, sleep issues, and balance problems.

What Causes Multiple Sclerosis?

The exact cause of multiple sclerosis is not known, but researchers think that it has to do with a combination of immune system problems, environmental factors, and genetic elements.

For the immune factors, doctors believe that the immune system attacks the central nervous system, which includes the brain, spine, and optic nerves. This attack is thought to start due to certain immune cells mistakenly attacking the body’s own tissues. The theory is that something unknown activates these cells, which then attach to the lining of the brain, cross the brain’s protective barrier and start an immune attack. Another theory suggests that an abnormality within the central nervous system itself could be the initial trigger, leading to inflammation and tissue damage.

Environmental factors, such as where a person lives, may also play a significant role. For example, people living further away from the equator, where there’s less sunlight, might be at a higher risk for multiple sclerosis, perhaps due to a lack of vitamin D. Certain infections, including the Epstein-Barr virus, could also be linked to the disease. Exploring the interactions between these environmental factors and people’s genes is an ongoing area of research.

Genetic factors can also contribute to multiple sclerosis. If you have close family relatives with multiple sclerosis, you have a higher risk of developing the condition. For instance, having a parent or sibling with multiple sclerosis increases your risk to 2% to 4%, compared to only 0.1% in the general population. Similarly, identical twins have a higher chance of both having multiple sclerosis compared to fraternal twins.

With respect to genetics, a specific variation in the human leukocyte antigen (HLA), mostly found in our immune system, called DRB1*1501, has a strong link to multiple sclerosis. Genetic research in multiple sclerosis is complex, as it isn’t inherited in a straightforward way and many genes might be involved. Certain genes associated with the immune system, vitamin D metabolism, mitochondrial DNA, fibrinolysis (the process of dissolving blood clots), and brain function and repair have been identified to slightly increase the risk of multiple sclerosis.

Risk Factors and Frequency for Multiple Sclerosis

Multiple sclerosis is a disease that damages the protective covering of nerve cells in your brain and spinal cord. It’s the most common of such diseases, affecting around 400,000 people in the United States and 2.5 million people worldwide. Women are three times more likely to have multiple sclerosis than men.

• Multiple sclerosis usually starts between the ages of 20 and 40, however, it can start at any age.
• The average ages to develop the most common types of multiple sclerosis are 25 to 29 for “relapsing-remitting” and 39 to 41 for “primary progressive”.
• About 10% of cases are diagnosed before age 18.
• The disease is found in about 1 out of 1000 people of European heritage.

Not a lot is known about how common multiple sclerosis is in non-European populations. It seems to be less common in people of East Asian and African heritage, but recent studies have found that it’s just as common in African-Americans as it is in people of European heritage. There seems to be a pattern with how common multiple sclerosis is around the world. It’s more common in northern Europe and North America. Other factors that affect the disease pattern could be different genes in different people and influences from the environment.

Several studies have shown that people who move to areas where multiple sclerosis is more common during their childhood are at a higher risk of developing the disease. However, there’s still controversy over this finding. Neither genetic nor external risks alone can explain the patterns of multiple sclerosis around the world. Interestingly, multiple sclerosis is the top cause of permanent disability in young adults. A single study reported that the rate of children diagnosed with multiple sclerosis was 0.51 per 100,000 people per year.

Signs and Symptoms of Multiple Sclerosis

Multiple sclerosis is a disease that affects the central nervous system, leading to a wide range of symptoms. The intensity and variety of these symptoms depend on the extent and location of damage within the system. Symptoms may not always match up with MRI scans due to the brain’s ability to repair itself and adapt to damage.

Patients with multiple sclerosis often experience the following symptoms:

• Vision issues, such as loss of sight, double vision, optic neuritis, and eye pain
• Dizziness and balance problems
• Bulbar dysfunction, causing speech and swallowing difficulties
• Muscle-related issues, like weakness, tremors, and fatigue
• Sensory symptoms, like the loss of sensation, abnormal sensations, and a band-like feeling around the chest or abdomen
• Changes in urinary and bowel control, including incontinence, urgency, and bladder and bowel irregularities
• Memory problems, difficulty in focusing, and executive function impairment
• Psychiatric conditions like depression and anxiety
• Brainstem issues, like facial weakness, reduced facial sensations, and visual disturbances

Atypical symptoms of multiple sclerosis are seizures, continuous symptom progression, quick development of deficits, onset before age 10 or after 50, early onset dementia, and certain motor and sensory deficiencies.

The most common type of multiple sclerosis is relapsing-remitting, where patients experience episodes of worsening neurological symptoms with periods of stability in between. These episodes include new or recurring symptoms developing over days to weeks and lasting between 24 and 48 hours. Over time, residual symptoms from these episodes accumulate, leading to a more gradual and persistent disabling condition.

A minority of multiple sclerosis patients experience a consistent worsening of their disability, known as the primary progressive course. Patients on this course commonly have symptoms related to myelopathy (spinal cord disease), cognitive issues, and visual impairments.

For isolated cases, patients may appear to have multiple sclerosis, either based on MRI evidence or clinical symptoms, but do not meet the full diagnostic criteria. However, these isolated cases can eventually progress to full-blown multiple sclerosis.

If multiple sclerosis is suspected but typical symptoms are not present, further investigation should be prompted by unusual symptoms like seizures, sleep disorders, brief neurological events, taste disturbances, or body temperature abnormalities.

There are also symptoms that might lead to an incorrect diagnosis of MS. If a patient presents quickly-developing symptoms, rapidly progressive disease, transient symptoms, failure to improve, or systemic disease symptoms like night sweats and fever, other diagnoses should be considered.

Testing for Multiple Sclerosis

Multiple sclerosis is a complex disease and currently, there are no specific tests that can definitively diagnoses it. The process of diagnosing this disease involves looking into your past health history, conducting physical examinations, and performing tests like MRI scans, evoked potential tests, and checking the fluid in your spine (cerebrospinal fluid) or blood studies. All this is done while also ensuring that other diseases causing similar symptoms are ruled out.

For a diagnosis to be made, your doctor needs to find evidence of one or more instances of disease flare-ups, or ‘relapses’. These can be confirmed through signs of one or more lesions in your body, or through signs of a lesion coupled with your account of a past relapse.

Two key criteria for diagnosing multiple sclerosis are ‘Dissemination in Space (DIS)’ and ‘Dissemination in Time (DIT)’. DIS involves determining the locations in the central nervous system (CNS – the brain and spinal cord) that are affected by the disease. This is done by looking at your medical history, physical examination, and MRI scans. DIT is established by tracking the course of the disease over time through detailed medical history and noting several disease flare-ups.

In order to establish DIS, doctors look for a specific type of lesion in at least two out of four key areas of the CNS – spinal cord, infratentorial (the lower part of the brain), juxtacortical (near the cerebral cortex), and periventricular (around the fluid-filled cavities in the brain) regions. Revised criteria from 2017 have improved diagnosis sensitivity by including certain proteins (oligoclonal bands) in CSF analysis as a marker to establish DIT and allow lesions causing symptoms to be used to establish both DIS and DIT.

Evoked potentials are tests that measure the electrical activity of your brain in response to stimulation of specific sensory nerve pathways. They help detect any delayed response which can indicate the involvement of the disease not picked up in other testing. MRI, CSF, and blood studies help in ruling out other causes of the symptoms. It is recommended that all patients undergo an MRI if possible and specific blood studies might include complete blood count, thyroid-stimulating hormone levels, vitamin B12 levels, erythrocyte sedimentation rate, and antinuclear antibody testing.

Characteristic features of multiple sclerosis lesions noticeable in brain MRI include: lesions appearing bright on T2 images and normal or dark on T1 images (also known as black holes), lesions being oval or patchy in shape, a high preference for white matter around the fluid cavities in the brain, lesions oriented perpendicular to the ependymal surface (known as Dawson fingers), and active lesions often showing gadolinium enhancement, indicating active inflammation.

In addition to brain MRI, spinal cord lesions are often observed in patients with multiple sclerosis. These lesions are typically found in the cervical or thoracic cord, often in the dorsolateral region (the back and side part of the spinal cord). These lesions are generally focal, meaning they’re limited to one specific area, with clearly defined boundaries visible in MRI scans. Their size can range from 3mm to less than 2 vertebral segments in length.

Also, testing the spinal fluid (CSF) can show characteristic features of multiple sclerosis, which typically include raised protein and myelin basic protein levels, occasional white cells (mainly mononuclear cells), and increased levels of total immunoglobulin G (IgG), free kappa light chains, and oligoclonal bands. These are all signs of an immune response taking place in the CNS.

When clinical, imaging, or laboratory features don’t fully align with typical multiple sclerosis symptoms, patients are tested for specific antibodies like aquaporin-4 (AQP4) IgG serum autoantibody and the myelin oligodendrocyte glycoprotein IgG autoantibody (MOG-IgG).

Treatment Options for Multiple Sclerosis

Glatiramer acetate, dimethyl fumarate, fingolimod, interferon-beta, natalizumab, and mitoxantrone are some of the main drugs used to manage multiple sclerosis. As soon as multiple sclerosis is diagnosed, it is important to start treatment right away. In the short-term, the aim is to decrease activity seen on MRI scans, whereas in the long-term, the aim is to prevent the disease from progressing. Challenges encountered after treatment include making sure patients stick to their treatment plans, and monitoring for any harmful effects of the drugs.

Let’s look closer at some of these medications:

– Glatiramer acetate is a mix of synthetic proteins that may help control the immune cells that cause damage in multiple sclerosis. It can be great in protecting nerve cells and potentially helping them repair. However, it does not work for all forms of multiple sclerosis.

– Interferon-beta works in many ways to control cell activity and potentially repair the blood-brain barrier, which is often damaged in people with multiple sclerosis. However, it may cause flu-like side effects and temporary worsening of neurological symptoms.

– Natalizumab is a drug that basically blocks the movement of immune cells into the central nervous system. It is generally well-tolerated but may cause mild headaches and flushing while it is being given.

– Mitoxantrone is a chemotherapy drug used for multiple sclerosis because of its effects on DNA repair and protein production. However, it has many side effects which limit its usage.

– Fingolimod is an oral drug with effects on the immune system, possibly by preventing harmful immune cells from moving around. Still, it does have potential side effects like low lymphocyte count, slow heart rate, and liver damage, so it needs careful monitoring.

In cases of progressive multiple sclerosis, these therapies have varying effectiveness, with limited impact on disease progression. Younger patients with a shorter duration of the disease seem to benefit more from these treatments.

When an acute relapse occurs (sudden worsening of symptoms), several guiding principles should be followed:

– Address any underlying issues like infections or metabolic issues that could’ve triggered the relapse.
– Provide specific treatments based on the neurological symptoms.
– Administer a short course of steroids to help with recovery.
– Implement rehabilitation programs such as physical and occupational therapy for comprehensive management.

Certain drugs should be avoided by women of childbearing age due to potential risks.

During an acute exacerbation of multiple sclerosis (a sudden flare-up of symptoms), treatment can include medications like corticosteroids, either IV or oral, that help reduce inflammation and potentially speed up recovery. If corticosteroids are not effective, a process known as plasma exchange (PLEX) may be recommended. This process involves removing and replacing the liquid part of the blood, which can help clear harmful substances related to multiple sclerosis.

What else can Multiple Sclerosis be?

When trying to diagnose multiple sclerosis, doctors must carefully consider and rule out a wide range of other conditions that resemble it. These potential misdiagnoses fall under seven categories:

• Demyelinating or inflammatory syndromes of the central nervous system (CNS), such as optic neuritis, Marburg disease, acute disseminated encephalomyelitis
• Wider inflammatory and autoimmune syndromes like systemic lupus erythematosus and Wegener granulomatosis
• Conditions caused by infections, such as Lyme disease, syphilis and HIV
• Vascular disorders, including migraine headaches, small vessel ischemia, and ischemic optic neuropathy
• Metabolic causes, for instance, vitamin deficiencies, thyroid disease, and adult-onset adrenoleukodystrophy
• Uncommon genetic conditions like mitochondrial cytopathy, Fabry disease, and Alexander disease
• Cancerous causes, including primary central nervous system malignancies like gliomas and meningiomas, or metastasis

Doctors would perform various tests to consider each of these possibilities, in order to arrive at the accurate diagnosis.

What to expect with Multiple Sclerosis

The outcome and severity of multiple sclerosis, a disease that impacts your brain and spinal cord, can greatly differ from one person to another. Some people might have only mild symptoms at the beginning, but these typically get worse over time.

Some factors suggest a person’s multiple sclerosis may become worse over time, including being male, if the disease gets progressively worse, having symptoms that primarily impact movement or coordination, more frequent relapses of the disease, little to no improvement between these relapses, and multiple symptoms starting at once. When a doctor takes an MRI (a scan of the brain), if they see a lot of damage or there’s shrinking in the brain, these can also suggest a worse outcome.

On the other hand, there are several factors suggesting the disease may be easier to manage, including being female, if the disease comes and goes, if the relapses of the disease are mild and recovery in between relapses is good, having symptoms that impact only sensation, and a longer time span between the first and second relapses. An MRI scan showing low level of damage, first sign of the disease being optic neuritis (an inflammation that damages the optic nerve), and full recovery from relapses can also suggest a favorable prognosis.

Possible Complications When Diagnosed with Multiple Sclerosis

In multiple sclerosis, long-term disability usually results from the buildup of symptoms over time. This happens when the patient doesn’t fully recover after each flare-up.

• Most people with long-term multiple sclerosis have restricted mobility. This can be due to factors like flawed motor control and balance issues.
• Problems in the brain’s oculomotor pathways might lead to chronic double vision. This condition can be treated with prism glasses or surgery.
• Chronic dizziness, which is also common, can potentially impact a person’s wellbeing. Medications like meclizine, ondansetron, or diazepam can help manage this issue.
• Chronic swallowing difficulties due to a condition called bulbar dysfunction might cause persistent aspiration.
• Cerebellar tremors could significantly contribute to a person’s disability. Wrist weights may assist in managing these tremors, although any existing weakness can limit their use.
• Urinary tract infections are potential long-term complications due to bladder dysfunction. A urologist’s consultation is often needed for tackling this issue.
• Constipation is a common gastrointestinal problem. It can be addressed through patient education, increased fiber intake, and bulk-forming agents.
• If a person faces erectile dysfunction, it is usually treated with oral medications known as phosphodiesterase-5 inhibitors.
• Cognitive issues, mood disorders, and generalized fatigue are seen as long-term complications. Their management often requires specialized care.

Preventing Multiple Sclerosis

Diagnosing multiple sclerosis, a disease of the nervous system, can be difficult for patients, and doctors play a very important role in providing support and guidance. Since it’s hard to predict how the disease will progress, doctors should also help patients understand the different ways it might develop and change. Plus, it’s important for doctors to remind patients that many people with multiple sclerosis respond well to treatment and can help explain the role of effective medications. Patients can also look for credible information online from places like the Multiple Sclerosis International Federation and the National Multiple Sclerosis Society to learn more about their condition. Educating patients about the potential of disease relapses and long-term complications is also crucial.

Patients should know that they should get in touch with their doctor right away if they have any new symptoms related to their nerves that last for more than 24 hours. This can sometimes mean they’ll need treatment with corticosteroids, which are medications that can help reduce inflammation. Doctors also should emphasize the importance of quitting smoking, taking vitamin D supplements, eating a balanced diet, and making healthy lifestyle changes. Patients should also be advised about the importance of sticking to their treatment plan, while also considering the potential side effects of these medications.