WHAT YOU NEED TO KNOW ABOUT HTLV-I-ASSOCIATED
MYELOPATHY/TROPICAL SPASTIC PARAPARESIS?

What is HAM/TSP?

HAM/TSP (HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis) is an inflammation of the spinal cord seen in some people infected with the Human T-Lymphotropic Virus Type I.

The condition TSP had been recognised in the Caribbean for many decades but the cause was unknown until 1985 when evidence of HTLV-I infection was found in the blood of the majority of patients with TSP in Martinique. At about the same time, and quite separately, neurologists in Japan found that patients with a particular pattern of neurological symptoms were infected with HTLV-I. They called this condition HTLV-I-associated myelopathy (HAM). TSP and HAM are in fact the same disease and the names have been combined. Although a few patients with a disease resembling TSP are not infected with HTLV-I the information presented here is only about HAM/TSP and not about HTLV-I negative TSP.

Most of the research into the cause of HAM/TSP suggests that the disease is caused by the immune system trying to clear the HTLV-I infection. In patients with HAM/TSP there is evidence of inflammation in the spinal cord with many cells called lymphocytes moving to the site of inflammation. These lymphocytes, which are part of the response to infection with a virus, release chemicals called cytokines to control the infection and to kill cells infected with HTLV-I. However some of these cytokines also cause damage to the nerves. It seems that in HAM/TSP the nerves are 'innocent by-standers' caught up in the immune system's fight against the virus.

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Who is likely to be affected?

In the UK we have calculated that approximately 3 out of every 100 people infected with HTLV-I will develop HAM/TSP at some stage in their life. Similar rates of disease (1.7-7%) have been reported from Africa, the Caribbean, South America and the USA. The disease seems less common in Japanese carriers of HTLV-I. There are additional factors that make the development of HAM/TSP more or less likely:

  • Gender - women infected with HTLV-I are more likely to develop HAM/TSP than men (3 women to every 2 men).


  • Time or route of infection - initial infection with HTLV-I in adult life is a risk factor.


  • The amount of virus in the blood (this is known as viral load) - the risk increases if more than 1 lymphocyte per 100 in the blood is infected with HTLV-I.


  • Immune system genetics - certain HLA types (these are also called Tissue types and are like blood types on white blood cells rather than on red blood cells) seem to increase protection against HAM/TSP whereas others may increase susceptibility.

How does HAM/TSP start?

Most people who develop HAM/TSP will have been infected with the HTLV-I for months, years or even decades. We do not know what triggers the inflammation to start.

The symptoms of HAM/TSP most often present for the first time between the ages of thirty and fifty years, but may occur at any time after childhood. Disease in childhood although reported is very rare.

The earliest symptoms of HAM/TSP are often mild and could be caused by a number of other more common diseases, or are simply attributed to getting older. This often results in a delay in the correct diagnosis being made. Damage to nerves in the spinal cord causes a variety of symptoms, such as, stiffness or weakness of the legs, partial loss of bladder or bowel control, impotence and lower back pain. Bladder symptoms or backache are often the first symptoms to appear.

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What are the symptoms of HAM/TSP?

The commonest bladder problems are:
  • Increased frequency - this refers to the number of visits to the toilet to pass urine (every 3-4 hours is normal).
  • Urgency - needing to pass urine with very little "warning", often the volume of urine passed is only small.
  • Nocturia - having to get up at night to pass urine more than once.
  • Incontinence - not being able to get to the toilet in time.

Primary sites of inflammation in HTLV-I - Effects of inflammation in the spinal cord

These symptoms are usually due to an "overactive bladder" and occur when the bladder wants to empty before it is properly full. In some patients with HAM/TSP the bladder is "underactive" or partially paralysed, in which case the sensation (urge) to empty the bladder is very weak or absent despite the bladder being full. Urine retained in the bladder may become infected causing cystitis.

This can lead to generalised illness with fever and sometimes to infection of the kidneys. An overfull bladder should be emptied by a catheter to protect the kidneys from back pressure. In some HAM/TSP patients the bladder contracts actively but the urethra (the tube through which urine is expelled) does not relax (open). This leads to patients experiencing an urge to pass urine, but being unable to empty the bladder completely, because of poor and interrupted urine flow. In this disorder a considerable amount of urine could be retained in the bladder.



Any bladder symptoms should be fully investigated as they may be caused by other health problems and not HAM/TSP. Bowel function can slow down resulting in troublesome constipation in some patients.

Inflammation of the nerves can result in pain. This is most commonly in the lumbar spine (low back) but can also be felt in the buttocks and back of the legs.

HAM/TSP may not be diagnosed until the nerves that carry instructions from the brain to the leg muscles are affected. This will manifest as a change in walking. The first complaint may be that the legs feel stiff, a tendency to trip or difficulty on the stairs or getting out of a low chair. The weakness in the legs is usually most marked at the hips and then the knees rather than around the ankles.

Men with HAM/TSP may complain of impotence or erectile dysfunction. This is likely to be due to the inflammation affecting the nerves responsible for the maintenance of sexual function.

The nerves responsible for feeling in the legs are, however, not usually affected, particularly at the start. Although the arms can be affected this is not usually the case and even when the legs are very weak or stiff the strength in the arms remains normal.

How is HAM/TSP diagnosed?

The diagnosis of HAM/TSP is made by:
  • Recognising the pattern of symptoms.
  • Diagnosing HTLV-I or HTLV-II infection by detecting HTLV-I or HTLV-II antibodies in the blood.
  • Ruling out other conditions, particularly pressure on the spinal cord.
It is also helpful to confirm the diagnosis by:
  • Detecting HTLV-I or HTLV-II antibodies in the cerebrospinal fluid (CSF), fluid which bathes the brain and spinal cord.
  • Measuring the HTLV-I viral load in the blood and CSF.

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What is the normal course of HAM/TSP?

The natural course of HAM/TSP is very variable but usually most change occurs during the first couple of years after the first symptoms.

Thereafter the condition is more stable or worsens only very slowly. The level of disability varies greatly from person to person. Some patients have very mild disability that hardly interferes with their lives. However, up to half of all patients with HAM/TSP may eventually need to use a wheelchair. It can take many years before this becomes necessary.

Can HAM/TSP be treated?

Although there is no cure for HAM/TSP a number of treatments are available. There are two approaches to treatment: treatment for the symptoms (e.g. pain or stiffness) and treatment of the cause (i.e. the inflammation in the spinal cord).

Symptomatic treatments, i.e. relieves symptoms like bladder frequency and urgency, constipation, impotence, back pain, stiffness of the legs.

Frequency, urgency and nocturia due to an overactive bladder can be improved with a drug called Oxybutytin or related medications that reduce bladder muscle activity. Similar symptoms of urgency and frequency (usually also with pain on passing urine and or fever or generally feeling unwell) may indicate the presence of a bladder infection that will require antibiotic treatment.

A "floppy bladder" may be best managed by intermittent self-catheterisation using an "in-and-out" urinary catheter (tube) to empty the bladder.

Constipated bowels are treated with changing the diet to increase the amount of roughage. If required laxatives, suppositories or enemas can be prescribed.

Treatments such as Sildenafil are available to help maintain sexual function.

Pain is managed by analgesics (painkillers) such as Paracetamol or Codeine, by anti-inflammatory treatments, by specialised drugs for nerve pain, by injection of local anaesthetics or steroids and be a variety of physical methods (physiotherapy).

Painful spasms and stiffness of the legs are treated with Tizanidine or Baclofen.

Walking can be helped by reducing stiffness or pain, by physiotherapy and by appropriate walking aids. Restoring muscle strength after any illness is important to maintain mobility.

STEROIDS - Corticosteroids - that have been used in many other inflammatory conditions, like asthma and arthritis, are commonly used to reduce the inflammation in the spinal cord in HAM/TSP. How best to use this type of treatment, which can have important side-effects if used for a long time, needs to be determined by properly conducted research with patients.

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OTHER ANTI-INFLAMMATORY

Interferon-alpha (IFN-&alpha) is a protein made in the body in a response to infections. A synthetic copy of this protein is often given to boost the immune response. It has been tried in patients with HAM/TSP, but the benefits were mostly found to be short-term.

Other anti-inflammatory agents that have been used with success in a wide-range of conditions have yet to be properly studied in patients with HAM/TSP.

Anti-viral drugs - Anti-viral drugs are designed to reduce the amount of the virus in the blood of an infected person. Unfortunately the anti-virals tried so far have not been able to reduce HTLV-I viral load.

A series of studies, sponsored by the Medical Research Council, are now underway. If you are interested in taking part in such a study (clinical trial) please ask your doctor or contact the National Centre for Human Retrovirology for more information.

What tests and investigations are usual?

A number of tests are needed to diagnose HAM/TSP and to exclude other diseases which may present with similar symptoms. These include blood tests, CT and MRI scans, nerve studies, ultrasound and a lumbar puncture.

BLOOD TESTS
- Evidence of HTLV-I/HTLV-II infection-antibodies is essential, but not sufficient to a make a diagnosis of HAM/TSP.

Quantifying the amount of virus is helpful.

Other blood tests are needed to exclude other possible causes.

SCANS - CT and MRI are imaging techniques to visualise the spinal cord and the brain, to look for signs of inflammation and to exclude other diseases especially any cause of pressure on the spinal cord, such as a prolapsed disc.

CT Scans - CT is a computer-enhanced x-ray technique. CT can detect a wide range of brain and spinal cord disorders.

MRI - magnetic resonance imaging - uses a magnetic field and very high frequency radio waves to produce high quality pictures that show more details than CT.

ULTRASOUND IMAGING is a method of obtaining images from inside the body through the use of high frequency sound waves. The reflected sound waves echoes are recorded and displayed as a real time visual image. No radiation (x-ray) is involved. Ultrasound is a useful way of examining many organs, including the heart, liver, gallbladder, spleen, kidneys and bladder. In HAM/TSP ultrasound is used to evaluate the bladder, especially its capacity and the ability to empty completely.

LUMBAR PUNCTURE - (spinal tap) involves passing a fine needle carefully into the spinal canal below the end of the spinal cord. This allows a sample of the fluid that surrounds the brain and spinal cord (cerebrospinal fluid) to be safely withdrawn for laboratory examination. Examination of the cerebrospinal fluid can detect evidence of infections, injury, tumours, and bleeding in the brain and spinal cord.

In patients with HAM/TSP examination of the cerebrospinal fluid gives information about the degree of inflammation in the spinal cord and is useful to exclude other infections or causes of inflammation. Detecting antibodies to HTLV-I and quantifying the HTLV-I viral load in the CSF can be important in making the right diagnosis in some cases.

ELECTROMYOGRAPHY (EMG) - measures electrical impulses of muscles at rest and during contraction. EMG helps diagnose diseases that damage muscle tissue, nerves or the junctions between nerve and muscle.

NERVE CONDUCTION STUDIES - measure the speed at which motor or sensory impulses travel through the nerve to the brain and back. Nerve conduction studies are used to determine whether symptoms are caused by disease of muscles or nerves.

Other inflammatory conditions associated with HAM/TSP

Persons with HAM/TSP may also develop other inflammatory conditions such as:
  • "uveitis " (inflammation of the eye)
  • "arthritis" (inflammation of one or more joints)
  • "alveolitis" (inflammation of lung tissue)
  • "polymyositis" (inflammation of muscle)
  • "keratoconjuctivitis " (inflammation of the cornea and conjunctiva)
  • and "infectious dermatitis " (inflammation of the skin)

Summary

HAM/TSP is a chronic inflammation of the spinal cord caused by a virus called HTLV-I. Early diagnosis of HAM/TSP is important to enable early use of treatments that may halt or reverse the disease.

The diagnosis of HAM/TSP is made by recognising the pattern of symptoms and signs, diagnosing HTLV-I infection by an antibody test, by confirming the presence of HTLV-I antibodies in the CSF and by the exclusion of other diseases that may cause similar presentations.

Although there is currently no cure for HAM/TSP many treatments are available to relieve symptoms. New treatments are under investigation.

Patients with HAM/TSP are usually cared for by a multidisciplinary team including a neurologist, infection specialist, physiotherapist and a nurse-specialist with access to other specialists especially for bladder and pain management.

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Updated: February 2009