Tropical spastic paraparesis (TSP) stems from an infection by the human T-cell lymphotropic virus 1 (HTLV-1) [1] [2] [3] [4]. The condition has been recognized throughout all parts of the world but is most prevalent in Caribbean islands, South America, Africa, and in Japan [2] [4] [5] [6]. The clinical presentation has been well-described in the literature but the diagnosis is delayed for years in many patients [5]. Patients are mainly diagnosed in their fourth and fifth decade of life and the main manifestation is spastic paraparesis accompanied by impaired sphincter control and paresthesias [1] [2] [4]. Constipation, weakness of lower extremities, hyperreflexia, pain in the lumbar region, gait disturbances that often require a need for assisting devices (some patients may be in wheelchairs or bedridden), as well as sexual dysfunction, are accompanying features of tropical spastic paraparesis [1] [5] [7]. For this reason, the term HTLV-1 associated myelopathy (HAM) is also used to describe TSP [2]. Less common findings are nystagmus and atrophy of the optic nerve [7]. A slowly progressive course is observed in the majority of individuals, but severe neurological disability developing within a period of a few years is encountered in approximately 20% of patients [5] [7].

• Virilization

  Danazol is an attenuated androgen with minimal virilizing effects. It is used in the treatment of endometriosis and various autoimmune hematologic diseases shown to be responsive to prednisone. [ncbi.nlm.nih.gov]

• Lower Extremity Pain

  Conversely, descriptors for lower extremities pain suggest a neuropathic origin. [ncbi.nlm.nih.gov]

• Mobility Impairment

  All patients presented with long-term mobility impairment with a DSS score (expanded disability status scale) of between 5 and 7.5. VPA was administrated orally at a maximal dose of 20 mg/kg/day. [bloodjournal.org]

• Vascular Disease

  cervical spondylosis and spinal tumors), transverse myelitis, collagen vascular disease, Sjögren syndrome, hereditary spastic paraparesis, primary lateral sclerosis, subacute combined degeneration secondary to vitamin B12 and folate deficiency, human [dx.doi.org]

• Protein S Deficiency

  We report the case of a 35-year-old woman with HTLV-I and the unusual combination of cutaneous T-cell lymphoma, tropical spastic paraparesis, cerebral vasculitis, and protein S deficiency. We discuss the relationship of all her diseases to HTLV-I. [ncbi.nlm.nih.gov]

• Lordosis

  Here, we described the clinical presentations, muscle biopsy studies and laboratory results of two siblings with HTLV-1-associated myelopathy / tropical spastic paraparesis (HAM/TSP) who were affected with lumbar lordosis. [ncbi.nlm.nih.gov]

• Scissoring Gait

  At the age of 32, the gait disturbance improved during her second pregnancy, but became worse after delivery and eventually resulted in a scissoring gait. [ncbi.nlm.nih.gov]

• Eczema

  Infective dermatitis associated to the HTLV-I (IDH) is a chronic eczema of childhood occurring in vertically infected carriers. Here we describe a 7-year-old boy with HAM/TSP and IDH. [ncbi.nlm.nih.gov]

  Miyamura et al (2009) reported on a female patient who developed ATL along with chronic refractory eczema and corneal injury. She was subsequently treated with allogeneic hematopoietic stem cell transplantation. [emedicine.medscape.com]

  Successful treatment of young-onset adult T cell leukemia/lymphoma and preceding chronic refractory eczema and corneal injury by allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2009 Aug 25. [Medline]. Willems L. [emedicine.com]

• Papule

  ATLL is a mature CD4 CD25 CCR4 T-cell neoplasm, and approximately half of patients have direct skin involvement manifesting patch, plaque, tumor, multiple papules, erythroderma and purpura. [ncbi.nlm.nih.gov]

• Round Face

  Neither round face nor obesity was found in these patients. A younger brother of Patient 14 (aged 44 years, height 150 cm [ 3.3 SD]) and two sisters of Patient 2 had HAM/TSP and short stature; however, extensive examination was not allowed. [dx.doi.org]

• Neglect

  Our results identify the cytoplasmic localization of HBZ in HAM/TSP patient as a possible biomarker of this rather neglected tropical disease, and raise important hypotheses on the role of HBZ in the pathogenesis of the neuromyelopathy associated to HTLV [ncbi.nlm.nih.gov]

  Loading metrics Citation: Casseb J (2009) Is Human T Cell Lymphotropic Type 1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Syndrome a Neglected Disease? PLoS Negl Trop Dis 3(11): e487. [journals.plos.org]

• Amenorrhea

  Toxicities noted were mild elevations in liver enzymes in 4 patients; these responded to a decrease in dose of danazol; amenorrhea in one and mild fluid retention in one. We conclude that danazol is a useful agent in the management of TSP. [ncbi.nlm.nih.gov]

The differential diagnosis of tropical spastic paraparesis is quite broad and includes multiple sclerosis (MS), human immunodeficiency virus (HIV)-associated myelopathy, motor neuron disease (MND), hereditary spastic paraplegia (HSP), CNS tumors, and many other inflammatory and neurodegenerative conditions [1]. Thus, it is of critical importance to obtain a detailed patient history that will assess the onset and progression of symptoms and perform a thorough physical examination, particularly focused on the neurological exam. Laboratory studies, however, are necessary to make a definite diagnosis of tropical spastic paraparesis. Findings from cerebrospinal fluid (CSF) evaluation are nonspecific but CSF, as well as serum, should be used for detecting HTLV-1 specific IgG antibodies through enzyme-linked immunosorbent assay (ELISA) [1]. Western blot analysis may be used for a confirmation of the diagnosis [1], whereas the detection of HTLV-1 viral load carried out by molecular laboratory studies might be useful for prognostic purposes [2] [8]. Electromyography (EMG) shows normal results in the peripheral nerves, which might be one of the main discriminating features of tropical spastic paraparesis [1]. Magnetic resonance imaging (MRI) is of limited benefit for identifying TSP [2] [3].

• Lymphocytic Infiltrate

  Magnetic resonance imaging revealed multiple spotty lesions in the cervical spinal cord, probably reflecting pathological changes known as perivascular lymphocytic infiltrations of the spinal cord. [ncbi.nlm.nih.gov]

  Akizuki et al demonstrated perivascular lymphocytic infiltration in the CNS, suggesting that vasculitis is an important pathological feature of TSP/HAM. 24 This may explain the diffuse nature of such lesions, suggesting that TSP/HAM is in fact a chronic [jnnp.bmj.com]

  The lesions are associated with perivascular and mild parenchymal lymphocytic infiltration with the presence of foamy macrophages, proliferation of astrocytes, and fibrillary gliosis. [dx.doi.org]

• HLA-B15

  Recognition of the immunodominant epitope was restricted by human leukocyte antigen (HLA) B15, and recognition of all the others was by HLA A2. [ncbi.nlm.nih.gov]

1. Ali A. Tropical spastic paraparesis and polymyositis--a still unfolding story. West Indian Med J. 2006;55(6):459-463.
2. Gessain A, Mahieux R. Tropical spastic paraparesis and HTLV-1 associated myelopathy: clinical, epidemiological, virological and therapeutic aspects.Rev Neurol (Paris). 2012;168(3):257-269.
3. Bagnato F, Butman JA, Mora CA, et al. Conventional magnetic resonance imaging features in patients with tropical spastic paraparesis. J Neurovirol. 2005;11(6):525-534.
4. Gotuzzo E, De Las Casas C, Deza L, Cabrera J, Castañeda C, Watts D. Tropical spastic paraparesis and HTLV-I infection: clinical and epidemiological study in Lima, Peru. J Neurol Sci. 1996;143(1-2):114-117.
5. Casseb J. Is Human T Cell Lymphotropic Type 1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Syndrome a Neglected Disease? Brooker S, ed. PLoS Negl Trop Dis. 2009;3(11):e487.
6. Proietti FA, Carneiro-Proietti AB, Catalan-Soares BC, Murphy EL. Global epidemiology of HTLV-I infection and associated diseases. Oncogene. 2005;24:6058–6068.
7. Oh U, Jacobson S. Treatment of HTLV-I-Associated Myelopathy / Tropical Spastic Paraparesis: Towards Rational Targeted Therapy. Neurol Clin. 2008;26(3):781-x.
8. Zunt J, Montano S, Beck I, et al. Human T-lymphotropic virus type 1–associated myelopathy/tropical spastic paraparesis: Viral load and muscle tone are correlated. J Neurovirol. 2006;12(6):466-471.