Differential Diagnoses
ADEM
Acute Disseminated Encephalomyelitis (ADEM) involves inflammation and demyelination in the brain and often involves inflammation in the spinal cord. In some instances, there can also 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 rare 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 TM, as are the associated symptoms. ADEM is more common in children than in adults. Antibodies to Myelin Oligodendrocyte Glycoprotein or anti-MOG have been found in individuals diagnosed with ADEM, and those with persistent detection of anti-MOG may be more likely to have a relapsing rather than monophasic disease course. More information about anti-MOG can be found in the MOG Antibody Disease section.
AFM
Acute Flaccid Myelitis (AFM) is a variant or sub-type of transverse myelitis. AFM is inflammation of the spinal cord and generally presents with unique clinical and MRI features that are not typical of classical transverse myelitis. AFM abnormalities noted on MRI are predominantly found in the gray matter of the spinal cord.
MOGAD
MOG antibody disease (MOGAD) is a neuro-inflammatory condition that preferentially causes inflammation in the optic nerve but can also cause inflammation in the spinal cord and brain. Myelin oligodendrocyte glycoprotein (MOG) is a protein that is located on the surface of myelin sheaths in the central nervous system. While the function of this glycoprotein is not exactly known, MOG is a target of the immune system in this disease. The diagnosis is confirmed when MOG antibodies in the blood are found in patients who have repeated inflammatory attacks of the central nervous system. Those with MOG Antibody Disease may previously have been diagnosed with neuromyelitis optica spectrum disorder (NMOSD), transverse myelitis (TM), acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), or multiple sclerosis (MS) because of the pattern of inflammation it causes including brain, spinal cord and optic nerve damage. Patients with persistently positive antibodies are at risk for recurrent events. Those with MOG Antibody Disease do not test positive for the NMO antibody called aquaporin 4 (AQP-4). MOG antibody disease and AQP-4 positive NMOSD are thought to have distinct immunological mechanisms.
MS
Multiple Sclerosis (MS) involves an inflammatory attack that can occur anywhere within the central nervous system (i.e., brain, spinal cord and/or optic nerves). Brain lesions at the time of onset or early in the course of the disease are common. The lesions in the brain are ordinarily identified in a specific pattern; however, 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.
NMOSD
Neuromyelitis Optica Spectrum Disorder (NMOSD) involves immune-mediated inflammatory attacks in the spinal cord and/or the optic nerve. A person with NMOSD is at risk for multiple attacks of spinal cord inflammation or ON, or both. There is ordinarily no brain involvement, but this is not always the case. It is typically characterized by longitudinally extensive transverse myelitis (LETM, myelitis which is 3 vertebral segments in length or greater), which can leave one quite debilitated at presentation, and unilateral or bilateral optic neuritis. There is a blood test for NMOSD called NMO-IgG that is clinically available. It is highly specific (>99%) and its sensitivity ranges from 48-72%, depending on the assay used. Antibodies to Myelin Oligodendrocyte Glycoprotein or anti-MOG have been found in individuals diagnosed with NMOSD. Those with MOG Antibody Disease do not test positive for the NMO antibody called aquaporin 4 (AQP-4). MOG Antibody Disease and AQP-4 positive NMOSD are thought to have distinct immunological mechanisms. More information about anti-MOG can be found in the MOG Antibody Disease section.
ON
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 MOGAD, NMOSD or a first attack of MS. Working through a differential diagnosis is important. A person may have ON or Recurrent ON and never have an attack in the spinal cord or brain.
TM
Transverse Myelitis (TM) is an immune-mediated inflammatory attack of a person’s spinal cord. Sometimes the inflammation has no clear cause and is referred to as Idiopathic TM. The majority of these cases are probably post infectious events, but this can be difficult to prove. In general, individuals with Idiopathic TM do not have recurrences or future inflammatory events. At other times, TM is part of a larger autoimmune process, such as MOGAD, NMOSD, MS, Sarcoidosis, Sjogren’s Syndrome, Lupus, or ADEM. When presenting with TM, clinical care should focus on reducing inflammation acutely and trying to determine if there is an underlying cause.
In rare cases, a person can have more than one inflammatory attack in their spinal cord; this is called Recurrent Transverse Myelitis (RTM). 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. It is important in these cases that the inflammatory attack in the spinal cord be identified; the diagnosis cannot be based solely on clinical symptoms, as there can be a worsening of symptoms apart from a new attack in the spinal cord. It is also important that the attack be identified as a unique attack and not associated with an unresolved initial attack. For example, if a person experiences an inflammatory attack and then two weeks later, the inflammation worsens; this cannot be considered a second attack. The first attack must completely resolve over time and the next attack must occur after this resolution to be considered a subsequent attack. Everyone with recurrent TM must have MOGAD and NMOSD ruled out. There should also be a rule out of an underlying rheumatic disorder, discussed below.
