Description
Transverse myelitis (TM) is a neuroinflammatory syndrome of the spinal cord characterised by damage to the myelin sheath, the insulating layer surrounding nerve cell fibres. This damage leads to disruption of neuronal communication between the spinal cord and the rest of the body, resulting in an array of neurological manifestations.
Pathogenesis
TM occurs when the body’s immune system mistakenly attacks the spinal cord, leading to inflammation and damage to the myelin sheath. This can occur as an isolated event or be associated with other diseases, such as multiple sclerosis or neuromyelitis optica. The specific trigger for this immune response is often not identified, but it can occur after viral infections or in association with systemic autoimmune conditions.
The primary pathology of transverse myelitis is inflammation leading to damage within the spinal cord, primarily in the white matter. Inflammatory cells, such as lymphocytes and macrophages, infiltrate the spinal cord, leading to the loss of myelin – the insulating layer around neurons. This demyelination impairs the ability of neurons to transmit signals efficiently.
Over time, the inflammatory process can also lead to direct damage to the neurons themselves, a process known as axonal loss or axonal degeneration. This axonal damage can cause more permanent deficits and is a major factor in the severity of the disease.
Severe forms of transverse myelitis may exhibit necrotic changes within the spinal cord. Necrosis typically occurs in more severe, acute forms of the disease and can lead to significant, permanent neurological damage.
In response to the inflammatory process and subsequent damage, there can be an overproduction of a type of cell called astrocytes in a process known as gliosis. These astrocytes form a glial scar, which can inhibit repair processes within the spinal cord.
Pathologically, transverse myelitis is characterised by the formation of a lesion, or several lesions, within the spinal cord. These lesions can be detected radiologically and are typically found in the thoracic spinal cord. However, they can occur at any level. The term “transverse” refers to the fact that the lesion often affects both sides of the same spinal cord level.
Epidemiology, Risk Factors & Associations
- Annual incidence rate of transverse myelitis is estimated to be around 1-5 per million individuals globally.
- Can occur at any age, but displays a bimodal distribution, with incidence peaks in young adults (aged 10-19 years) and in mid-adulthood (aged 30-39 years).
- Slight predilection for females, with a female-to-male ratio of approximately 3:2.
- Autoimmune associations: TM can be a manifestation of other autoimmune disorders. Its frequency in association with other conditions is as follows (from most to least common):
- Neuromyelitis optica (NMO): Up to 20% of NMO patients can present with TM as an initial symptom.
- Multiple sclerosis (MS): Around 15-20% of MS patients might initially present with symptoms of TM.
- Systemic lupus erythematosus (SLE): Approximately 1-2% of SLE patients might develop TM.
- Certain viral infections, including herpes viruses, influenza, and HIV, have been associated with TM, albeit less frequently.
- A significant proportion of TM cases are idiopathic, with no identifiable cause or association.
Clinical Features
- Sensory disturbances such as paraesthesia or hypersensitivity, often corresponding to specific dermatomal levels.
- Motor weakness in the limbs, progressing from difficulty with fine motor tasks to potential paralysis. Changes in muscle tone, either spasticity or flaccidity, may also occur.
- Autonomic dysfunction resulting in bowel and bladder irregularities, such as urgency, incontinence, or retention. Sexual dysfunction may also be present.
- Pain, particularly in the back or neck, that may be exacerbated by movement or palpation, and radicular pain along a nerve’s distribution.
- Other neurological signs like abnormal reflexes (hyperreflexia, Babinski’s sign, or absent reflexes) and positive Hoffman’s sign, indicative of an upper motor neuron lesion.
- Typically, symptoms are bilateral due to inflammation affecting both sides of a spinal cord segment. The onset of symptoms can be acute (hours to days) or subacute (days to weeks).
Complications
Complications from TM can include permanent neurological damage, such as paralysis and sensory loss, chronic pain, and bladder and bowel dysfunction.
Pathological Features
Histopathology
- Inflammation causing damage predominantly in the spinal cord white matter.
- Infiltration of lymphocytes and macrophages initiating demyelination.
- Axonal degeneration over time due to persistent inflammation.
- Necrotic changes in severe cases within the spinal cord.
- Gliosis forming glial scars in response to the inflammatory process.
- Lesion formation, often thoracic but can be found at any level, typically bilateral.
Serology
Certain serological markers may be positive in cases of TM, such as antinuclear antibodies (ANAs) in cases associated with systemic lupus erythematosus, or AQP4-IgG in cases associated with neuromyelitis optica.
Biochemistry
There are no specific biochemical markers for TM.
Genetics
There is no known genetic predisposition for developing TM.
Radiological Features
General Features
- MRI of the spine is the primary imaging study for TM.
- It often reveals an area of inflammation within the spinal cord, typically extending over multiple spinal segments.
MRI
- T2WI: Hyperintense signal within the spinal cord, often extending over multiple spinal segments.
- T1WI C+: Lesions may show enhancement, indicating active inflammation.
CT
CT is not the primary imaging modality for TM, but it may be used to rule out other causes of symptoms, such as spinal cord compression from a tumour or herniated disc.
Grading and Staging
There is no specific grading or staging system for TM. The severity of the condition is determined by the extent of the spinal cord inflammation and the resulting neurological deficits.
Diagnosis
Diagnosis of TM requires a clinical presentation consistent with the disorder, along with supportive findings on MRI and spinal fluid analysis. Additional tests may be performed to rule out other causes of symptoms and to identify potential triggers.
Differential Diagnosis
- Multiple Sclerosis (MS): MS can present with similar symptoms to TM but typically has a relapsing and remitting course, and brain MRI often shows additional lesions.
- Neuromyelitis Optica (NMO): NMO can present with transverse myelitis, but it is also associated with optic neuritis. The presence of AQP4-IgG is suggestive of NMO rather than TM.
- Spinal cord compression: This can mimic TM but is usually caused by physical abnormalities such as a herniated disc or tumour, which can be identified on imaging.
Management
The acute phase of TM is usually managed with high-dose corticosteroids to reduce inflammation. Plasma exchange may be considered if symptoms do not improve with steroids. Long-term management focuses on rehabilitation, including physiotherapy and occupational therapy, to manage symptoms and improve function. Pain management and treatment of bladder and bowel dysfunction are also important components of management. In cases where TM is associated with another autoimmune condition, treatment of the underlying condition is also necessary.