Multiple Sclerosis: Related Diseases

There are many different conditions that can mimic multiple sclerosis (MS) closely, with similar neurologic symptoms being displayed.

As MS does not have a diagnostic test that is 100% specific, careful assessment is needed to enable your doctor to rule out other possible disorders that could be causing these symptoms. Arriving at a correct diagnosis, whether it is MS or something else, is very important so that appropriate treatment can begin straight away.

Sometimes, conditions can be ruled out with a simple blood test, while for others, a careful review of medical history and a neurological examination and MRI scans are sufficient. However, sometimes additional tests, such as a biopsy, are required to arrive at a correct diagnosis. Some diseases that are often mistaken for MS are detailed below. In many autoimmune diseases, treatments are similar and include immunosuppression.

Neuromyelitis Optica Spectrum Disorder (NMOSD, or simply NMO) and Myelin Oligodendrocyte Glycoprotein Antibody Associated Disease (MOGAD) are two neurological conditions that cause symptoms that are similar to MS. An accurate diagnosis is required as soon as possible, so that the most appropriate treatment can begin.

Neuromyelitis Optica Spectrum Disorder (NMO)

What is Neuromyelitis Optica Spectrum Disorder?

Neuromyelitis Optica Spectrum Disorder (NMOSD) or Neuromyelitis Optica (NMO), is a disease that resembles MS. The main symptoms are loss of sight due to inflammation of the optic nerve (optic neuritis) or weakness of the arms and legs due to inflammation of the spinal cord (transverse myelitis). Some patients may experience severe episodes of nausea and vomiting for no apparent reason. Other symptoms can include nerve pain, spasms, and stiffness, as we as bladder, bowel and sexual problems.

How is NMO different from MS?

Most cases of NMO are caused by a specific protein in the blood called NMO antibody (anti-aquaporin-4 antibody), which is produced by the white blood cells. This antibody attacks parts of the nervous system and is a specific marker for the disease. It is not known why the white blood cells of the immune system mistakenly attack the nervous system. The immune attacks in NMO are typically more severe and may leave permanent damage, compared to MS attacks which are often associated with a better recovery. MS has a secondary progressive stage, which means that the condition worsens gradually over time – often years – after a long period of relapsing disease if left untreated. This is not the case with NMO as it is a relapsing-remitting disease and there is no progressive phase. This means that if we can prevent the relapses, then patients can remain stable.

Causes of NMO

While we understand the mechanisms that cause NMO (specifically the NMO antibody), just like in MS, we do not know what causes NMO. It is more common in women, and occurs all over the world, with African, Asian, and Native American populations being more at risk.

Diagnosing NMO

If a patient presents with loss of sight or weakness, an MRI scan is usually performed first, sometimes with spinal fluid tests. Blood is tested for NMO antibodies and if present, confirms the disease. However, one third of patients may not have the antibody despite otherwise being typical for NMO, so if other symptoms are present and diagnostic tests have ruled out other possible causes, a diagnosis of seronegative NMO can be made.

Treatment of NMO

There is no cure for NMO, but a relapse or attack can be treated with medication. A high-dose steroid is given which suppresses the immune system. A plasma exchange (a treatment like dialysis that cleans the blood of antibodies) can also be given to prevent further damage and speed up recovery.

In order to prevent further attacks, many drugs can be given which suppress the immune system. These drugs are different to the ones given to MS patients. The drugs proven to be most effective include rituximab, inebilizumab, eculizumab, satralizumab, and tocilizumab. Commonly used oral medications include prednisone, azathioprine, and mycophenolate mofetil. All these medications may require blood monitoring.

Myelin Oligodendrocyte Glycoprotein Antibody Associated Disease (MOGAD)

What is Myelin Oligodendrocyte Glycoprotein Antibody Associated Disease (MOGAD)?

MOGAD is a disorder that may appear identical to NMO and MS. The most common symptoms are vision loss due to inflammation of the optic nerve (optic neuritis), or a weakness of the arms and legs, due to inflammation of the spinal cord (transverse myelitis). Some patients may suffer from seizures or stroke-like episodes.

How is MOGAD different to MS?

The attacks caused by MOGAD can be more severe and may leave permanent damage, compared to those seen in MS, which are usually followed by good recovery. Sometimes MOGAD is a self-limiting illness, which means it can resolve itself without treatment.

What causes MOGAD?

MOGAD is caused by a specific protein in the blood called the MOG antibody (Myelin Oligodendrocyte Glycoprotein antibody), which is produced by our white blood cells. This antibody attacks the myelin within the nervous system, and causes damage and inflammation. It is not known why the white blood cells of the immune system mistakenly attack the nervous system. This antibody is a specific marker for the disease and can be tested for in the blood.

Diagnosing MOGAD

Typically, when a patient presents with loss of sight or weakness, an MRI scan is performed, sometimes accompanied by a spinal fluid test. MOG antibodies are present in the blood, so a blood test can confirm a diagnosis.

Treatment of MOGAD

• Treatment of relapse or attack involves high-dose steroids given over a period of a few months. A plasma exchange (a treatment like dialysis that cleans the blood of antibodies) can also be given to prevent further damage and speed-up recovery.
• Preventing further attacks involves suppressing the immune system through the use of medications. These are different to the ones used in the treatment of MS. Immunosuppressants can include prednisone, azathioprine, mycophenolate, rituximab, and intravenous immunoglobulin tocilizumab.
• Not all patients with MOGAD will need long-term treatment.

Managing symptoms of NMO and MOGAD attacks

• Symptoms from MS, NMO, MOGAD, optic neuritis or myelitis of other causes, are all similar and are managed in a very similar way.
• Pain can be managed by a variety of drugs and behavioral pain management strategies.
• Muscle stiffness spasms can be improved with medication.
• Bladder problems can be effectively managed with many medications and lifestyle changes.
• Weakness can be improved with physiotherapy, strength and balance training, and assistive devices such functional electrical stimulation by a neurorehabilitation team.
• Vision problems including double vision can be managed to some degree by ophthalmologists.

Other related diseases

Optic Neuritis

Optic Neuritis is inflammation of the nerve that connects the eye to the brain and causes a loss or blurring of vision. While MS is a common cause, there are many other conditions that can cause the optic nerve to become inflamed, such as Neuromyelitis Optica, MOG antibody disease, and infections or inflammation of blood vessels that affect the eye. In many cases, doctors don’t know the exact cause. However, thorough investigations are needed to determine the cause and risk of recurrence, which will then determine if long-term treatment is required.

Transverse Myelitis

Transverse Myelitis is a rare neurological condition caused by inflammation of the spinal cord. Symptoms can include pain or numbness in the back, a tingling and weakness in the legs and arms, bladder problems and sometimes paralysis. While MS is a common cause, there are many other conditions that can cause the spinal cord to become inflamed or swollen. These include Neuromyelitis Optica, MOG antibody disease, infection, problems with the blood vessels that supply the spinal cord, sarcoidosis, cancer and Behcet’s disease. In many cases, the exact cause is not known, and thorough examinations are required. The exact cause and risk of recurrence will then determine if long-term treatment is needed.

Acute Disseminated Encephalomyelitis

Acute Disseminated Encephalomyelitis (ADEM) is a disease similar to MS. It causes a short but intense inflammation of the brain and spinal cord, and sometimes the optic nerve, but typically it is not progressive or relapsing. Symptoms are similar to MS, including behavior and neurological changes, leading to vision and coordination loss. ADEM usually occurs after infection and is considered a misdirected immune response against a virus or bacteria. Children are more commonly affected by ADEM than adults. ADEM is often misdiagnosed as an early, severe attack of MS and it is hard to distinguish if the brain inflammation is a single episode or recurrent, and investigations and follow-up are needed.

Neurosarcoidosis

Sarcoidosis is a disease of unknown cause, that can affect various parts of the body. Typically though, it affects the lungs and lymph nodes where it causes inflammation. Sometimes it affects the central nervous system and is referred to as Neurosarcoidosis, a condition that displays similar symptoms to MS. In order to achieve an accurate diagnosis, doctors may perform tests including an MRI scan, spinal fluid studies, and a biopsy. There is no cure for Neurosarcoidosis, but there are effective treatments available.

Vasculitis

Vasculitis refers to inflammation of the blood vessels. It can affect many areas of the body, and cause inflammation in the small, medium, and major blood vessels. It can be mild and resolve itself without treatment, but if it affects major vessels, it can be life-threatening. There are two types of Vasculitis that can affect the central nervous system; Systemic Vasculitis, which can affect the vessels of any organ including the brain and spinal cord, and Primary CNS Vasculitis, in which only the brain is affected. Symptoms of both conditions may include stroke, weakness, and loss of vision. An accurate diagnosis may require extensive testing, including spinal fluid studies, an angiogram and a brain biopsy. Treatment may include immunosuppressive medications.

Neuro Behcet’s

Also known as Silk Road disease, Behcet’s disease is named after Huluci Behcet, a Turkish neurologist, and is common in the Middle East. The exact cause of the disease is not known. It can affect various parts of the body, but typically causes ulcers in the mouth and genital area, skin rashes and joint pains. Sometimes the central nervous system is the first to be affected and achieving an accurate diagnosis may require a variety of tests including MRI scans, spinal fluid studies, and a biopsy. There is no cure for Behcet’s, but there are effective treatments available.

Susac’s Syndrome

This is a rare disease named after John Susac, an American neurologist, in which your immune system attacks the very small blood vessels in the brain, inner ear, and retina (eye). These vessels become inflamed, causing damage within these areas. This can result in visual disturbance, loss of hearing, and brain inflammation. There is no cure for Susac’s Syndrome, but there are many medications that can suppress the immune system and ease the symptoms.

GFAP Disease or Autoimmune Meningoencephalomyelitis

This is a recently discovered inflammatory disease that causes inflammation of the brain and spinal cord in response to an immune reaction. Antibodies are produced by the immune system which attack a protein of the nervous system, called Glial Fibrillary Acidic Protein (GFAP). It can cause headaches, weakness, blurred vision, and confusion. Most cases have a typical MRI appearance in the brain, and it can sometimes occur in association with certain cancers.

Other disorders

There are many other conditions that can affect the brain and spinal cord, and some may mimic MS. These include deficiencies of vitamins, genetic disorders, cancers, infections, toxins and the side effects of some drugs. Always discuss any symptoms you are experiencing with your doctor.