HTLV-1 Associated Myelopathy - Clinical Features, Diagnosis, and Management

Introduction:

HTLV-1-associated myelopathy is a slowly progressive disorder caused by the human T-lymphotropic virus -1. It usually results in symmetrical progressive spasticity of the legs. It has a female predilection over males. It is also known as tropical spastic paraparesis (TSP).

What Is the Pathogenesis of HTLV-1 Associated Myelopathy?

When the virus enters the body, it usually infects the T-cell lymphocytes. As a result, the immune response of the body activates by producing antibodies that target the virus. As a result, most infected individuals do not develop illness, but a very few might develop a condition related to defective T-cells.

What Are the Clinical Manifestations of HTLV-1 Infection?

Individuals with HTLV-1 infection are usually asymptomatic. However, various serious diseases are strongly associated with the virus. These diseases present with specific symptoms that may indicate the presence of HTLV-1. These are as follows:

Adult T-cell Leukemia/Lymphoma (ATL): It is a white blood cell neoplasm that may progress slowly or rapidly. It is most commonly seen among people with HTLV-1 infection. It has been classified into several clinical subtypes:

• Acute.

• Lymphomatous.

• Chronic.

• Smoldering.

Clinical presentation depends on the subtype. Individuals with HTLV-1 may present with

• Fatigue.

• Fever.

• Lymphadenopathy or enlarged lymph nodes.

• Hepatosplenomegaly.

• Hypercalcemia.

HTLV-1 Associated Myelopathy (HAM) or Tropical Spastic Paraparesis (TSP): It is a chronic inflammatory disorder of the central nervous system. It is typically characterized by

• Progressive spastic weakness of the lower limbs.

• Upper limb spasticity is insignificant.

• Lower back pain.

• Bowel and bladder dysfunction.

• Urinary incontinence.

• Muscle weakness.

• Hyperreflexia and clonus in the lower limbs.

• Extensor plantar response.

• Spastic gait or gait disturbances.

• Stumbling.

Other diseases associated with HTLV-1 infection include

• HTLV-1 Associated Uveitis (HAU).

• Infectious Dermatitis.

• Bronchiectasis.

• Bronchitis.

• Bronchiolitis.

• Seborrheic Dermatitis.

• Sjögren’s Syndrome.

• Rheumatoid Arthritis.

• Fibromyalgia.

• Ulcerative Colitis.

What Are the Risk Factors Associated with HTLV-1 Infection?

Risk factors for HTLV-1 infection are

• Intravenous drug abusers.

• Immigrants from high-risk areas.

• Often associated with co-infection with HIV.

• Endemic in some parts of the United States.

• History of blood transfusion.

• Multiple sexual partners.

How Is HTLV-1 Transmitted?

HTLV-1 infection can be transmitted via

Vertical Transmission:

• From mother to fetus during pregnancy or especially during breastfeeding.

SexualTransmission:

• It has a male predilection over females.

• More common in ages more than thirty.

Parenteral Transmission:

• It can also be transmitted through exposure to contaminated blood, as occurs in cases of shared needles during intravenous drug usage.

What Are the Diagnostic Tests to Be Carried Out?

Confirmatory tests for the diagnosis of HTLV-1 should follow screening tests for HTLV-1. Most screening tests are done with the help of immunoassays, which depend upon detecting anti-HTLV-1 antibodies. Confirmatory tests usually detect antibody against specific HTLV-1 antigens. The test includes the following:

• Enzyme Immunoassay (EIA) Test: It is a method used to detect antibodies in the blood against HTLV-I and HTLV-II antigens.

• Western Blot: If the initial test is positive, a second test or confirmatory test, known as, Western blot, is done to confirm the finding and to help differentiate between HTLV-I and HTLV-II.

• Polymerase Chain Reaction (PCR) or Molecular Test: In cases where HTLV-I and HTLV-II cannot be differentiated, a molecular test is usually performed to detect the virus's genetic material.

Testing can be more complicated due to the time between acquiring the virus and the seroconversion of the virus to appear on tests. This period may be as long as sixty-five days.

• If the CSF-to-serum ratio of HTLV-1 antibodies is more than one or if HTLV-1 antigen appears in CSF, the diagnosis is most likely to be HTLV-1 infection.

• Protein and Immunoglobulin levels in CSF may also be increased, frequently with oligoclonal bands. Also, lymphocytic pleocytosis may be seen in many patients.

• Magnetic Resonance Imaging (MRI): It shows atrophy of the spinal cord and T2-weighted images of the anterior nerve roots an lateral columns, which often appear hyperintense on MRI. The most common radiographic feature of HTLV-1-associated myelopathy is cord atrophy and increased signal. It is most prominent in the lateral columns involving the white matter, adjacent gray matter, and anterior nerve roots. In cases of acute exacerbation, the cord is characteristically swollen and of high T2 signal with peripheral contrast enhancement.

What Is HTLV-1 Associated Myelopathy Managed?

No effective treatment has been proven beneficial in altering the disease outcome. The mainstay of treatment includes

• Corticosteroids.

• Plasmapheresis is a method that involves removing the plasma from the blood, then separating it into plasma and cells, and then transfusing the cells back into the bloodstream. It is specifically done to remove the antibodies from the blood that helps in treating autoimmune conditions.

• Danazol.

• Interferon-gamma has proven beneficial in treating a few cases of HTLV-1-associated myelopathy.

• Highly active antiretroviral therapy (HAART).

What Are the Differential Diagnosis of HTLV-1 Associated Myelopathy?

The differential diagnosis for HAM/TSP includes

• Multiple Sclerosis (MS): Differentiating primary progressive multiple sclerosis from HTLV-1-associated myelopathy is challenging as both conditions clinically mimic each other, and the mere presence of positive HTLV-1 serology does not compulsorily confirm a neurological disease.

• Neuromyelitis Optica (NMO): It shows more rapid progression than HTLV-1-associated myelopathy. HTLV-1-associated myelopathy usually does not present with optic neuritis, and the patients with HTLV-1-associated myelopathy are negative for a specific antibody known as NMO-IgG or anti-aquaporin-4 antibodies.

• Spinal cord compression, such as cervical spondylosis and spinal tumors.

• Transverse myelitis.

• Collagen vascular disease.

• Sjogren syndrome.

• Hereditary spastic paraparesis.

• Primary lateral sclerosis.

• Subacute combined degeneration due to folate deficiency and vitamin B12 deficiency.

• Human immunodeficiency virus-associated neurosyphilis, Lyme disease, and vacuolar myelopathy.

Conclusion

HTLV-1-associated myelopathy is a slowly progressive disorder caused by the human T-lymphotropic virus. The characteristic features include progressive spasticity of lower limbs with bowel and urinary dysfunction. Therefore, screening tests for HTLV-1 are done followed by confirmatory tests for the diagnosis of HTLV-1. No effective treatment has been proven beneficial.