Neuroimmunologic Disorders of the Central Nervous System

The Transverse Myelitis Association advocates for people who have Transverse Myelitis, Recurrent Transverse Myelitis, Neuromyelitis Optica (NMO or Devic’s Disease); Acute Disseminated Encephalomyelitis (ADEM) and Optic Neuritis - and their caregivers. People with these disorders and their families are members of The Transverse Myelitis Association. Multiple sclerosis is also a neuroimmunologic disorder of the central nervous system.

All of these conditions are neuroimmunologic disorders of the central nervous system (brain, spinal cord and optic nerves). Each of these disorders occurs when a person experiences an inflammatory attack at some location in their central nervous system. In patients with these disorders, the immune system, which is supposed to keep a person free of infections, attacks parts of the nervous system by mistake. The inflammatory attacks are also referred to as demyelinating attacks because the immune system attacks and destroys myelin, the insulating material that surrounds nerves.

Transverse Myelitis is an inflammatory attack in the spinal cord only; there is no brain or optic nerve involvement. It is primarily a monophasic condition; the attack only occurs once. In rare cases, a person can have more than one inflammatory attack in their spinal cord; this is Recurrent TM. In each unique episode, the inflammatory attack occurs only in the spinal cord. There is no brain or optic nerve involvement in any of the episodes. Some people have an inflammatory attack in the spinal cord in association with an underlying rheumatic disorder, i.e., Lupus or Sjögren’s syndrome. This is sometimes referred to as disease associated TM. When no underlying cause is found, it is referred to as Idiopathic TM; the cause is unknown.

Neuromyelitis Optica or Devic’s disease involves inflammatory attacks in the spinal cord and optic nerve. A person with NMO is at risk for multiple attacks of spinal cord inflammation or Optic Neuritis or both. There is ordinarily no brain involvement, but this is not always the case. There is a blood test for NMO called NMO-IgG that is available at Mayo Clinic Laboratories. If a person tests positive for NMO-IgG, they have NMO. In approximately 30% of cases, a person may test negative but still have NMO; thus a negative NMO-IgG does not definitively rule out NMO.

If a person with Transverse Myelitis presents with a lesion (inflammation) that extends to 3 vertebrae in length or longer, they are at risk for multiple attacks, i.e., it is possible that the attack in the spinal cord is a first attack of Neuromyelitis Optica. This condition is called Longitudinally Extensive Transverse Myelitis (LETM). People who have LETM should probably receive the NMO-IgG test to rule in or out Neuromyelitis Optica. Infants and young children seem to be the exception to this situation. Infants and young children tend to have very long lesions that may begin high in the cord (cervical region), and yet they do not seem to have the same risk for multiple attacks as adults with LETM. They have Transverse Myelitis. As children can also have Neuromyelitis Optica, this remains an area that is in need of critical research focus.

Multiple Sclerosis involves an inflammatory attack that can occur anywhere within the central nervous system (i.e., brain, spinal cord and/or optic nerves). Most patients will have brain lesions at the time of onset or early in the course of the disease. The lesions in the brain are ordinarily identified in a specific pattern; although lesions may be present anywhere in the white matter. MS involves more than one episode (i.e., recurrent attacks) and the multiple episodes occur in different locations in the central nervous system.

Acute Disseminated Encephalomyelitis (ADEM) involves inflammation and demyelination in the brain and often involves inflammation in the spinal cord. In some instances there can be optic nerve involvement. ADEM may occur after a bacterial or viral infection (post infectious) or following an immunization (post vaccination). The demyelination in the brain is different than a demyelinating attack from MS; white matter lesions tend to be diffuse. ADEM is most often monophasic, although there are recurrent variants of ADEM. It can be characterized by headache or seizures and may involve vision loss. The spinal cord involvement is the same as Transverse Myelitis, as are the associated symptoms.

Finally, Optic Neuritis (ON) involves a demyelinating attack of the optic nerve. In isolated ON, there is no brain or spinal cord involvement. An episode of ON may be a first attack of NMO or a first attack of MS. Working through a differential diagnosis is important. A person may have Optic Neuritis or Recurrent Optic Neuritis and never have an attack in the spinal cord or brain.

While these disorders are all categories of demyelinating attacks of the central nervous system, each can be clinically distinguished and defined based upon the location of the attack and whether the attacks are a monophasic or recurring event.

The immune system functions to distinguish between ‘self’ and ‘not-self’ – to protect the body from foreign invaders, such as from bacterial, viral or fungal infections. For people with these neuroimmunologic disorders, the immune system becomes dysfunctional and attacks self; the immune system begins to destroy some part or multiple parts (multi-focal) of the central nervous system. The only treatment for these disorders in their acute or early stages is to quiet down the immune system as quickly as possible, before damage is done. These treatments need to be considered in the context of the correct diagnosis and administered as quickly as possible. Time is critical. Unfortunately, there is very little research available on the most effective treatments for any one of these disorders or on the neuroimmunologic disorders in general. It is important to be working with a physician who has good experience with these disorders, because acute treatment is going to involve primarily or exclusively clinical judgment. If your physician does not have this experience, it is important to ask your physician to consult with a physician who does. There are very few physicians who specialize in TM or NMO (e.g., Johns Hopkins, Mayo Clinic, University of Texas Southwestern), but there are numerous Multiple Sclerosis Centers associated with prominent medical centers and medical schools. A specialist from one of these centers should be considered, as they have experience in demyelinating disorders of the central nervous system. After the inflammation has begun to resolve and the person is medically stable, the next course of treatment for a person who has an inflammatory attack in their spinal cord (ADEM, NMO or TM) involves intensive rehabilitation therapy. Centers devoted to spinal cord injury and disease or stroke offer comprehensive rehabilitation programs for people who have suffered significant spinal cord deficits from the inflammatory attack. The Christopher and Dana Reeve Paralysis Foundation web site provides excellent information regarding the factors that should be considered in selecting a rehabilitation hospital.

ADEM and TM are considered monophasic. It is important to have a regular appointment with your neurologist to monitor your condition. Over time and depending on symptoms, a yearly exam might be sufficient for many people.

People with Neuromyelitis Optica or recurrent TM or recurrent ADEM, are at risk for multiple attacks and should be monitored more closely. People with these disorders will likely receive medication to either diminish the chance of another attack or lessen its severity should it occur. It is important that a definitive differential diagnosis from MS be made by your physician. The MS treatments (i.e., Copaxone, Avonex, Rebif, Tysabri, and Betaseron) have not proven to be effective in the treatment of people with NMO or recurrent TM. Most often, people with recurrent TM or NMO are considered for immune suppressant therapies. Which therapies a person is placed on is based entirely on the clinical judgment of the physician. Again, it is important to be working with a physician who has experience with recurrent TM and NMO.

For people who have had a demyelinating attack in their spinal cord from TM, ADEM or NMO, the symptoms are going to be the same. In fact, in some of the medical literature, the attack in the spinal cord from ADEM or NMO is referred to as transverse myelitis. Those symptoms may include, muscle weakness to paralysis, inability to breathe (due to diaphragm muscle weakness), spasticity (tightness), parasthesias (tingling), nerve pain, bowel, bladder and sexual dysfunction, fatigue, or depression. The specific nature of symptoms depends on the level of inflammatory attack in the spinal cord and the severity of the attack. The treatments for each of these symptoms, regardless of the condition, are going to be the same.

Each of these neuroimmunologic disorders remains a challenge to diagnose. Only NMO has a distinct and defined marker and this auto-antibody is present in about 70% of cases that are diagnosed as Neuromyelitis Optica. The diagnostic criteria for the other disorders are neither entirely clear-cut nor universally accepted in medicine, i.e., there appear to be numerous exceptions to every rule. The relationships between each of these disorders are also not well understood; is each of these disorders a unique disease or are some of them variants of the same disease. No one understands the cause of any of these disorders. No one has the answer to what is TM, what is ADEM, what is NMO, what is ON? It is believed that there is a genetic susceptibility in an individual that allows the immune system to become dysfunctional, and that environmental triggers are involved in pushing the immune system into this dysfunctional state. No genes have been identified as being implicated in TM, ADEM, NMO or ON and not a single environmental trigger has been proven to be implicated in TM, ADEM, NMO or ON. No one knows the cause or causes of any of these disorders. No one understands why a person is impacted at their particular level of the spinal cord and no one understands why some people have a good recovery from the attack, while others have no recovery. No one understands why a person may have just one attack of TM, while another person can have multiple attacks.

While much about these disorders remains a mystery, there is much that is understood. Our great hope comes from the fact that there are excellent researchers and clinicians who are focused on the neuroimmunologic disorders and more is learned about the immune system and these disorders every single day.

There is a great deal of information about each of these disorders on our web site. We urge you to learn as much as you possibly can about your disorder and believe that this will help you to become the most effective advocate for your medical care.

The members of the TMA include people with idiopathic TM, ADEM, NMO, ON, recurrent TM, TM and NMO with HIV, people who have TM and NMO with an underlying rheumatic disorder (Lupus or Sjögren’s syndrome), people who have Neurosarcoidosis, and people who have various myelopathies of the spinal cord (radiation, spinal stroke), as well as family members of people with these disorders.