Transverse myelitis: what is it, causes, symptoms, treatment, prognosis

What is transverse myelitis?

Transverse myelitis (PM) is a rare inflammatory disorder that causes spinal cord injury with varying degrees of weakness, sensory changes, and autonomic dysfunction (the part of the nervous system that controls involuntary activities such as heart rate, breathing, digestive system, and reflexes).

The first cases of acute myelitis were described in 1882. and are associated with vascular damage and acute inflammation. In England, between 1922 and 1923, more than 200 post-vaccination cases were reported as a complication of smallpox vaccine and rabies. Later reports showed that transverse myelitis is post-infectious in nature, and pathogens such as measles, rubella and mycoplasmawere directly isolated from the cerebrospinal fluid of sick patients. The term "acute transverse myelitis" was first used by an English neurologist in 1948 to describe a case rapidly progressing paraparesis at the level of the sense organs of the chest, which arose as a post-infectious complication 

pneumonia.

Signs and symptoms

The spinal cord carries motor nerve fibers to the limbs and trunk, and sensory fibers from the body back to the brain. Spinal cord inflammation interrupts these pathways and causes general symptoms. Transverse myelitis usually presents with rapidly progressive muscle weakness or paralysis of varying severity, starting in the legs and potentially extending into the arms. The lesion of the arm depends on the level of the spinal cord lesion. Sensitivity to light touch decreases below the level of spinal cord injury in most patients. Pain (as determined by a neurologist using a pinprick) and fever, usually decrease, and the sensation of vibration (when checking with a tuning fork) and the feeling of joint position.

In most patients, a sensory level is recorded, most often in the mid-thoracic region in adults or in the cervical region in children. Back, limb, or abdominal pain, and tingling, numbness, and burning (paresthesias) are common. Sexual dysfunction is also the result of sensory and autonomic disturbances. Increased urge to urinate, bowel or bladder incontinence, difficulty or inability to urinate, incomplete bowel movement, or constipation - other characteristic vegetative symptoms of the disorder. Other common symptoms of transverse myelitis are spasticity and fatigue. In addition, patients with the disease often have depressionand it needs to be treated to prevent devastating effects.

In some patients, symptoms progress over several hours, while in other cases, symptoms appear over several days. Neurological function tends to decrease during the 4-21 day acute phase, while in In 80 percent of patients, the maximum deficiency is reached within 10 days of the onset of symptoms. In the worst case, 50% of patients lose all leg movements, 80-94% experience numbness, paresthesias, tangles or shinglesand almost all have some degree of bladder dysfunction.

Causes and risk factors

The possible causes of transverse myelitis can be very different. The disease can occur in isolation or against the background of another disease. Idiopathic transverse myelitis is thought to result from inadequate and over-activation immune response against the spinal cord, leading to inflammation and tissue damage (the exact cause of which has not yet been installed).

Transverse myelitis may be a hallmark multiple sclerosis. In people with acute partial transverse myelitis and a normal MRI of the brain, about 10-33 percent will develop multiple sclerosis within 5-10 years. If MRI of the brain shows lesions, it is known that the frequency of transition to clinical certain multiple sclerosis is quite high, ranging from 80 to 90 percent during several years. Those who are eventually diagnosed with multiple sclerosis are more likely to have asymmetric clinical signs, predominant sensory symptoms with relative economy of motor systems, MRI lesions covering less than 2 segments of the spine, brain MRI abnormality and oligoclonal bands in cerebrospinal fluid.

Transverse myelitis is often seen in patients who test positive for NMO-IgG (autoantibodies that are a highly specific biomarker for an immune-mediated disease called optical spectrum disorder neuromyelitis (opticomyelitis), as well as in patients who test positive for MOG-IgG (another marker of autoimmune antibodies). In patients with this condition, myelitis symptoms are often symmetrical (as opposed to multiple sclerosis, in which myelitis symptoms are usually asymmetric). In patients with opticomyelitis, at least 3 segments of the spine are most often affected (and therefore called longitudinally extended transverse myelitis).

Transverse myelitis often develops with viral and bacterial infections, especially those that may be associated with a rash (for example, measles, rubella, chickenpox, smallpox, flu and parotitis). The term parainfectious transverse myelitis suggests that neurological damage associated with the disorder may be associated with direct microbial infection and trauma resulting from infection, a microbial infection with an immune-mediated systemic response that causes damage to the nervous systems. About one third of patients with transverse myelitis report a febrile illness (flu-like illness with fever), which over time is closely associated with the appearance neurological symptoms. In some cases, there is evidence that there is direct invasion and damage to the umbilical cord by the infectious agent itself (especially polio, shingles, AIDS and Lyme neuroborreliosis). However, a causal relationship cannot always be established.

Experts believe that in many patients, the infection causes a compromised immune system, leading to an autoimmune attack on the spinal cord rather than a direct attack from the body. One theory that explains this abnormal activation of the immune system in relation to human tissue is called molecular mimicry. This theory postulates that an infectious agent may have a common molecule that resembles or mimics a molecule in the spinal cord. When the body develops an immune response to an invading virus or bacterium, it also responds to a spinal cord molecule with which it shares structural characteristics. This leads to inflammation and injury to the spinal cord.

Although a causal relationship has not been established, transverse myelitis has been informally reported following influenza vaccination and booster vaccination. hepatitis B. One theory suggests that vaccination may have triggered an autoimmune process. It is extremely important to remember that extensive research has shown that vaccination is safe and the potential connection with the disease can only be accidental or, in the worst case, exclusively a rare complication.

Cancer-related myelitis (called paraneoplastic syndrome) is rare. There are several reports of severe myelitis associated with malignant neoplasm in the medical literature. In addition, there are increasing reports of cases of cancer-related myelopathy when the immune system produces antibodies to fight cancer, and this leads to cross-reactions with molecules in the neurons of the spinal cord brain.

Vascular causes are noted as they are associated with the same problems as transverse myelitis. However, in reality, this is a separate issue, primarily due to insufficient blood flow to the spinal cord, rather than actual inflammation. Blood vessels in the spinal cord may be blocked by blood clots (blood clots) or atherosclerosis or burst and bleed. In fact, it is “stroke»The spinal cord.

Affected populations

Conservative estimates of the incidence of transverse myelitis range from 1 to 8 new cases per million per year, or about 1400 new cases annually. Although this disease affects people of all ages, from 6 months to 88 years old, there are bimodal peaks between the ages of 10 to 19 and 30 to 39 years. In addition, approximately 25% of cases are in children. The disease has no gender or family connection. In 75-90% of cases, transverse myelitis is monophasic, but a small percentage of cases relapse, especially if there is a predisposing underlying disease.

Related disorders

As mentioned above, transverse myelitis can be a relatively rare manifestation of several autoimmune diseasesincluding systemic lupus erythematosus (SLE), Sjogren's syndrome and sarcoidosis.

• SLE Is an autoimmune disease of unknown cause that affects several organs and tissues of the body. SLE can cause transverse myelitis, which can recur periodically.
• Sjogren's disease Is another autoimmune disease characterized by invasion and infiltration of the lacrimal and salivary glands with leukocytes, which leads to a decrease in the production of these fluids, which causes dry mouth and eyes. Several tests can confirm this diagnosis: presence of SS-A / SS-B antibodies in the blood, ophthalmologic examinations confirming decreased tear production and the presence of lymphocytic infiltration in small salivary gland biopsies (minimally invasive procedure). Neurologic manifestations in Sjogren's syndrome are uncommon, but spinal cord inflammation can occur.
• Sarcoidosis - multisystem inflammatory disease of unknown cause, manifested by swollen lymph nodes, pneumonia, various skin lesions, lesions liver and other organs. In the nervous system, various nerves can be affected, as well as the spinal cord. The diagnosis is usually confirmed by biopsy confirming signs of inflammation typical of sarcoidosis.

Diagnostics

The diagnosis of transverse myelitis is based on clinical and radiographic findings. The clinical characteristics of myelopathy are signs and / or symptoms of sensory, motor, or autonomic dysfunction related to the spinal cord. Evidence of inflammation is often observed, either on MRI with increased gadolinium, or with lumbar puncture in the form of an increase in leukocytes in cerebrospinal fluid or IgG index, or the presence of oligoclonal IgG bands unique to cerebrospinal liquids.

If myelopathy is suspected based on history and physical examination, an MRI of the spinal cord with gadolinium enhancement is first done to assess if there is a compression or inflammatory (gadolinium-intensifying) lesion or stroke of the spinal cord, as signs and symptoms may be similar. It is important to rule out compression myelopathy (compression of the spinal cord), which can be caused by a tumor, herniated disc, hematoma, or abscess. Identifying these abnormalities is critical because immobilization to prevent further damage and early surgery to remove compression can sometimes reverse neurological damage to the spinal cord brain.

Lumbar puncture is used to look for surrogate markers of inflammation in the cerebrospinal fluid. These include an increased number of leukocytes in the cerebrospinal fluid, an increased protein content in cerebrospinal fluid and an increased IgG index / or the presence of oligoclonal IgG bands unique to cerebrospinal liquids. However, it should be noted that a significant percentage of patients with a clinical picture that otherwise resembles transverse myelitis does not correspond to these inflammatory characteristics, and therefore the absence of inflammatory markers does not exclude transverse myelitis.

To determine the underlying cause of the inflammatory process, special tests are recommended to evaluate having a systemic inflammatory disease such as Sjogren's syndrome, lupus erythematosus (SLE), and neurosarcoidosis. It is important to check your vitamin B12 and copper levels. NMO-IgG should be tested and, if negative, MOG-IgG assay ordered. It is necessary to exclude the causes of infection.

An MRI of the brain is done to look for lesions suggestive of multiple sclerosis or other conditions (opticomyelitis, acute disseminated encephalomyelitis, neurovascular erythematosus, neuro-Sjogren's syndrome, neurosarcoidosis), which can affect not only the spinal cord, but also brain. If a clear cause cannot be established, the diagnosis is idiopathic transverse myelitis.

Non-inflammatory myelopathies include myelopathies caused by arterial or venous ischemia (blockage), vascular malformations, radiation, or nutritional / metabolic causes, and appropriate investigations in these situations may include aortic ultrasound, spinal angiography, or evaluation prothrombotic risk factors.

Within the category of idiopathic transverse myelitis, it may be helpful to distinguish between acute partial (partial), acute full form and longitudinally extensive transverse myelitis, since these syndromes represent different differential diagnoses and forecasts.

Acute partial transverse myelitis refers to mild to severely asymmetric spinal cord dysfunction with fewer than 3 vertebral segments on MRI. Acute full disorder refers to complete or nearly complete clinical dysfunction below the lesion and MRI lesions of less than 3 vertebral segments. Longitudinally extensive transverse myelitis has a complete or incomplete clinical picture, but the lesion on MRI is longer than or equal to 3 vertebral segments.

Standard treatments

- Intravenous steroids.

Intravenous steroid (corticosteroid) treatment is the first line of therapy often used for acute transverse myelitis. Corticosteroids have a variety of mechanisms of action, including anti-inflammatory activity, immunosuppressive properties, and antiproliferative effects. Although there is no randomized, double-blind, placebo-controlled study that supports this approach, data on related disorders and clinical experience support this treatment. At the Johns Hopkins Center, the standard of care includes intravenous administration of methylprednisolone (1000 mg) or dexamethasone (200 mg) for 3-5 days unless there is a compelling reason to refuse this therapy. The decision to continue steroid use or add a new treatment is often based on the clinical course, the underlying cause, and the MRI findings after 5 days of steroid use.

- Plasmapheresis.

Plasmapheresis often begins with moderate to severe transverse myelitis (eg, inability to walk, markedly impaired autonomic function, and loss of sensation in lower extremities) in patients in whom, after the administration of intravenous steroids for 5-7 days, clinical improvement was insignificant, but can also be prescribed first procedure. It is believed that plasmapheresis acts in autoimmune diseases of the central nervous system by removing specific or nonspecific soluble factors that may mediate, be responsible for, or contribute to the inflammatory lesion target organ. It has been shown that plasmapheresis is effective in adults with transverse myelitis and other acute inflammatory diseases of the central nervous system.

- Other immunomodulatory treatments.

If progression continues despite intravenous steroid therapy and plasmapheresis, pulsed intravenous cyclophosphamide (800-1000 mg / m2) should be considered. Cyclophosphamide is known to have immunosuppressive properties. From the experience of the Johns Hopkins Center, it has been reported that plasmapheresis provides additional steroid benefit in patients who have not had disability A (complete injury) on the American Spinal Injury Association scale and who did not have an autoimmune disease in anamnesis. For those rated A disability on the American Spinal Injury Association scale, they showed significant improvement with the appointment of combination therapy with steroids, plasmapheresis and cyclophosphamide intravenously. Cyclophosphamide should be administered under the supervision of an experienced team of oncologists, and caregivers should closely monitor the patient for hemorrhagic cystitis and cytopenia.

In case of recurrence of transverse myelitis, the possibility of chronic immunomodulatory therapy should be considered. The ideal treatment regimen is unknown, so it is important for your neurologist to consult with a specialist with significant experience in the treatment of these rare, recurring neuroimmunological diseases.

- Rehabilitation.

After the acute phase, rehabilitation assistance to improve functional skills and prevent secondary complications associated with immobility include both psychological and physical adaptation. Very little has been written in the medical literature about rehabilitation after transverse myelitis. However, in general, much has been written about recovery from spinal cord injury, and the literature is applicable. Physical problems include bowel and bladder control, problems with sexual activity, maintaining skin integrity, spasticity, daily activities (such as dressing), mobility, and pain.

It is important to start occupational therapy and physical therapy early in your recovery to prevent problems associated with lack of physical activity, such as destruction of the skin and soft tissue contractures that lead to decreased range movements. Assessment and placement of splints designed to passively maintain optimal position of limbs that cannot be actively moved is an important part of treatment at this stage.

Forecast

Recovery from transverse myelitis may be absent, partial, or complete, and usually begins within 1-3 months after acute treatment. Significant improvement is unlikely if there is no improvement by 3 months. After an initial attack, about 1/3 of people recover with little or no symptoms, 1/3 remain with a moderate degree of permanent disability, and 1/3 practically does not recover and remains with severe functional disability. Most patients show good and satisfactory recovery. Rapid progression of clinical symptoms, back pain and spinal shock, as well as paraclinical signs such as lack of central motor response conductivity in the study of evoked potentials and the presence of an increased 14-3-3 protein in the cerebrospinal fluid (CSF) in the acute phase, are often indicators of less complete recovery.

Although it is usually a monophasic disorder, transverse myelitis may recur in some patients. Relapse can often be predicted at the initial acute onset based on multifocal spinal cord lesions, brain lesions the brain, the presence of an underlying mixed connective tissue disease, the presence of oligoclonal bands in the cerebrospinal fluid and / or antibodies NMO-IgG.