Tropical Spastic Paraplegia

Synonyms include Jamaican neuropathy, tropical myeloneuropathy, Human T lymphotropic virus1 (HTLV-1) associated myelopathy (HAM/TSP).

There are two types of tropical myeloneuropathies that are quite different in aetiology and clinical features although there can be some overlap. They both occur predominantly in tropical countries although tropical spastic paraplegia has been described in temperate southern Japan.

• Tropical spastic paraparesis (TSP), is also called HAM/TSP, the HAM standing for HTLV-1 associated myelopathy. It affects predominantly the spinal cord, resulting in an upper motor neurone syndrome.
• Tropical ataxic neuropathy (TAN) is predominantly a sensory neuropathy. It is not the subject of this article.

HAM/TSP results in inflammation, demyelination and necrotic lesions in the spinal cord. Although a form of chronic myeloneuropathy found in the West Indies had been recognised as a distinct entity for over a hundred years, it was not until 1985 that a link was first made with HTLV-1. In a study in Martinique, looking at the epidemiology of adult T cell leukaemia, 59% of those patients who had tropical spastic paraplegia (TSP) were found to have antibodies to HTLV-1 as opposed to 13% of controls.¹ Since then several other studies have confirmed these findings, and a set of clinical criteria have been established to describe what is now referred to as HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a progressive disease involving the degeneration of neurons in the spinal cord leading to a gradual paralysis of the lower limbs. Three hypotheses exist to explain the association of HTLV-1 with HAM/TSP^2,3

1. That there is a direct toxic effect on infected glial cells by cytokines from primed specific cytotoxic lymphocytes.
2. That a T cell immune response is initiated by the HTLV-1 virus.
3. That "collateral" damage occurs in the central nervous system due to cytokines and autoantibodies.

HAM/TSP is associated with HTLV-1 infection. This infection is usually asymptomatic, although it may be dormant and produce disease many decades later in the form of adult T cell leukaemia or HAM/TSP. Of the 10 to 20 million people in the world thought to have HTLV-1, only 1 to 4% will go on to develop HAM/TSP. In Japan that figure is lower at 0.25%. The outcome is probably dependent upon the individual's immune response.⁴

Populations at risk include those in areas where the HTLV-1 virus is endemic such as the Caribbean, Colombia, India, Africa and Japan, and those at risk of coming into contact with the virus by transfusion of contaminated blood products, needle sharing, substance abuse, breast feeding and unprotected sex with a seropositive partner.

It tends to affect lower social classes. There is about a 30 years latency between acquiring the infection and manifesting the disease. Women outnumber men by 3:1.

The presentation of HAM/TSP may be the same as for other forms of spastic paraparesis, and patients may be mis-diagnosed for a period of time until HTLV-1 serology is tested.

Symptoms

These may include:

• Gradual onset of weakness of the legs.
• Some loss of sensation.
• Incontinence or urinary dysfunction. There is urinary frequency with detrusor instability.
• Constipation
• Back pain
• Erectile dysfunction

Signs

These are largely signs of UMN lesions:

• Increased lower limb tone.
• Increased reflexes with extensor plantar response.
• Muscular weakness, especially of the lower limb.
• Decreased touch and pinprick sensation, often in poorly defined thoracic areas.
• Loss of vibratory and position sense. Sensory loss appears to originate in the CNS (probably spinal cord) rather than peripheral nerves⁵ but it seems likely that peripheral nerves are also involved.⁶
• Less common features include cerebellar signs such as intention tremor, optic atrophy, deafness, nystagmus, cranial nerve deficits, upper extremities tremor and absent or diminished ankle jerk.

Other features which may be associated with HTLV-1 infection, although not part of HAM/TSP per se include:-

• Uveitis
• Keratoconjunctivitis-sicca
• Arthritis
• Myositis
• Alveolitis
• Dermatitis

HAM/TSP is often mis-diagnosed initially as one of the following:

• Transverse myelitis
• Motor neurone disease
• Primary progressive multiple sclerosis

First get a full history with particular reference to place of birth, countries lived in and social history and then perform a full neurological examination.

• An initial diagnosis of an UMN lesion of the lower limbs may demand imaging studies. MRI of the spinal cord is needed to exclude other causes of myelopathy. In this condition MRI is usually normal but it may show evidence of demyelination. Cord swelling or atrophy has been noted in a few cases.
• Electrophysiological studies of the lower limb may show abnormalities.
• Lumbar puncture may show a mild lymphocytosis (<50 cells/mL) in the CSF of 25 to 60% of patients. Slightly more have mild protein elevation. Most patients have CSF oligoclonal bands.
• High titres of antibody to HTLV-1 is found in both serum and CSF.

HAM/TSP may be seen in association with adult T cell leukaemia or T cell lymphoma as both have an association with the HTLV-1 virus.

Non-Drug

As with other forms of spastic paresis, patients will require support over a long period of time from many members of the health care team. Early introduction to all agencies should be established. This includes physiotherapy, occupational therapy and continence nurses.
Plasma exchange is one form of treatment that has been used in the treatment of HAM/TSP although the improvements seen after treatment tend to be short lived.

Drugs

• There is no specific treatment for the disease but a number of therapeutic options do have merit. Oral methylprednisolone appears to give a good response in about two thirds.
• Interferon-α is reported to have given some good results.⁷
• Antiretroviral agents have been used. It seems that zidovudine can reduce the viral load⁸ but demonstrating clinical improvement is not so forthcoming.⁹ It may be necessary to treat earlier, before nerve damage becomes established.
• Pentoxifylline has been used with apparrent success but in an uncontrolled trial.
• Many different agents have been tried with varying results but few have been subjected to the rigors of a proper RCT.¹⁰
• Symptomatic treatment is also important. Spasticity may be treated with drugs such as baclofen. Detrusor instability may be helped by oxybutynin.

These are related to spastic paraplegia and include pressure sores, venous thrombo-embolism and recurrent urinary tract infections.

The disease is a slowly progressive disorder primarily affecting the lower limbs. Although not life threatening in itself, death may occur as a complication of infection or immobility e.g. septicaemia from urinary infections or infected pressure sores, pneumonia and pulmonary emboli secondary to immobility. Survival for 10 to 40 years is not uncommon.

Prevention is based on curtailing transmission of the virus, especially from those who are known to be infected. It may be sexually transmitted or transmitted by blood, including the sharing of equipment for intravenous drug abuse. It seems that it may occur from blood transfusion but not via plasma. In an infected mother, it is a contraindication to breast feeding.