Pathology of chronic myelopathy associated with HTLV-I infection (HAM/TSP)

doi:10.1016/0022-510X(90)90060-Z

Journal of the Neurological Sciences

Volume 96, Issue 1, April 1990, Pages 103-123

https://doi.org/10.1016/0022-510X(90)90060-Z Get rights and content

Abstract

The CNS pathology of 10 autopsy cases of Japanese HAM/TSP patients with a serological confirmation of HTLV-I infection was reviewed. The essential histopathological feature was a chronic progressive inflammatory process with marked parenchymal exudation of lymphocytes and monocytes into both the grey and white matter of the spinal cord, uniquely perpetuating for more than 3 years after the onset of neurological symptoms, and resulting in severe degeneration of the white matter accompanied by marked glio-mesenchymal tissue reactions. Both the inflammation and the white matter degeneration were most conspicuous in the lower thoracic cord. The lateral column was always and most severely affected. Although the parenchymal tissue degeneration was not confined to any particular long tracts, symmetrical degeneration of the lateral pyramidal tract was evident in all cases. Diffuse myelin pallor was also seen in the anterior column but it was usually mild. The posterior column was commonly involved but the severity and extent of the white matter degeneration were variable. Neurons were relatively well preserved. These histopathological features of HAM/TSP in Japan largely agree with those previously described for HAM/TSP in tropical regions. In the absence of detectable amount of HTLV-I antigens at the sites of inflammation, “chronic progressive parainfectious myelitis” seems to be the most appropriate descriptive term for this unique histopathology of HAM/TSP.

References (62)

R.D. Adams et al.
The morbid anatomy of the demyelinative diseases
Am. J. Med.
(1952)
S. Akizuki et al.
Necropsy findings in HTLV-I associated myelopathy
Lancet
(1987)
S. Akizuki et al.
An autopsy case of human T-lymphotropic virus type I-associated myelopathy
Hum. Pathol.
(1988)
S. Hirose et al.
Isolation of HTLV-I from cerebrospinal fluid of a patient with myelopathy
Lancet
(1986)
N. Imamura et al.
Multiple primary neoplasms in patients with adult T-cell leukemia
Lancet
(1989)
K.S. Mani et al.
A spastic paraplegic syndrome in South India
J. Neurol. Sci.
(1969)
M. Osame et al.
HTLV-I associated myelopathy, a new clinical entity
Lancet
(1986)
G.C. Román et al.
Identity of HTLV-I-associated tropical spastic paraparesis and HTLV-I associated myelopathy
Lancet
(1988)
M. Sugimoto et al.
T-lymphocyte alveolitis in HTLV-I associated myelopathy
Lancet
(1987)
H. Terunuma et al.
Neurotoxic activity in HTLV-I carrier lymphocyte culture
J. Neurol. Sci.
(1989)

R.D. Adams et al.

Subacute degeneration of the brain in pernicious anemia

New Engl. J. Med.

(1944)

S. Akizuki et al.

The neuropathology of human T-lymphotropic virus type I-associated myelopathy

I.V. Allen

Demyelinating diseases

S. Bhagavati et al.

Detection of human T-cell lymphoma/leukemia virus type I DNA and antigen in spinal fluid and blood of patients with chronic progressive myelopathy

New Engl. J. Med.

(1988)

L.J. Couderc et al.

Lymphocytic alveolitis in HTLV-I associated tropical spastic paraparesis

J.K. Cruickshank et al.

Tropical spastic paraparesis and human T cell lymphotropic virus type I in the United Kingdom

Brain

(1989)

E. DeFreitas et al.

HTLV-I infection of cerebrospinal fluid T cells from patients with chronic neurologic disease

AIDS Res. Hum. Retrovir.

(1987)

C. Foix et al.

La myélite nécrotique subaïgué

Rev. Neurol.

(1926)

G. Georgsson et al.

Primary demyelination in visna

An ultrastructural study of Icelandic sheep with clinical signs following experimental infection

Acta Neuropathol.

(1982)

A. Gessain et al.

Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis

Lancet

(1985)

G. Goudreau et al.

Inflammatory myopathy in association with chronic myelopathy in HTLV-I seropositive patients

Neurology

(1988)

J.G. Greenfield

Acute disseminated encephalomyelitis as a sequel to “influenza”

J. Pathol. Bacteriol.

(1930)

J.G. Greenfield et al.

Acute and subacute necrotic myelitis

Brain

(1939)

T. Hashiguchi et al.

Skin manifestations in HTLV-I-associated myelopathy (HAM): xerosis and erythema

Y. Itoyama et al.

Altered subsets of peripheral blood lymphocytes in patients with HTLV-I-associated myelopathy (HAM)

Neurology

(1988)

Y. Itoyama et al.

Spontaneous proliferation of peripheral blood lymphocytes increased in patients with HTLV-I-associated myelopathy

Neurology

(1988)

S. Izumo et al.

The neuropathology of HTLV-I-associated myelopathy in Japan: Report of an autopsy case and review of the literature

S. Jacobson et al.

Isolation of an HTLV-I-like retrovirus from patients with tropical spastic paraparesis

Nature

(1988)

B. Jubelt et al.

Viral infections

I. Kobayashi et al.

An autopsy case of HTLV-I associated myelopathy

Neurol. Med.

(1989)

G. McKhann et al.

Isolation and characterization of HTLV-I from symptomatic family members with tropical spastic paraparesis (HTLV-I encephalomyeloneuropathy)

Neurology

(1989)

Cited by (215)

Pilates exercise improves the clinical and immunological profiles of patients with human T-cell lymphotropic virus 1 associated myelopathy: A pilot study
2020, Journal of Bodywork and Movement Therapies
Citation Excerpt :
HTLV-1-associated myelopathy/tropical spastic paraparesis is a neurological syndrome associated with human T-cell lymphotropic virus 1 (HTLV-1), characterized by chronic inflammation and demyelination of the central nervous system (CNS), mainly the lower thoracic spinal cord (Gessain and Gout, 1992; Iwasaki, 1990; Bangham, 2018).
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an infectious chronic-inflammatory disease, which can lead to lower limb motions.
The study evaluated the effects of serial Pilates exercises on the clinical and immunological profiles of patients with HAM/TSP. Eight patients with ages ranging from 39 to 70 years old (2 males and 6 females), 2 wheelchair users and 6 with compromised gait, were evaluated. The patients were submitted to 20 Pilates sessions for 10 weeks. Data were collected at 3 time points (beginning of the study, after Pilates sessions and after 10 weeks without Pilates) and consisted of evaluations of the pain level, spasticity, motor strength, balance, mobility, functional capacity, quality of life and quantification of IFN-γ, IL-10 and IL-9 cytokines levels.
After the Pilates sessions, significant improvements in pain level, static and dynamic balance, trunk control, mobility and quality of life were observed, with simultaneous and significant reductions in the serum levels of the cytokines IFN-γ and IL-10. However, after 10 weeks without Pilates, there were significant changes in terms of increasing pain and regression of mobility, with no changes in strength, spasticity, functional capacity in any of the periods of the study.
The results suggest that Pilates may be a promising auxiliary physical therapy for patients with HAM/TSP.
Retroviral envelope proteins: Involvement in neuropathogenesis
2017, Journal of the Neurological Sciences
Citation Excerpt :
TSP/HAM manifests as a chronic myelopathy with a progressive course in many ways similar to primary progressive multiple sclerosis. It is characterised by inflammatory infiltrates in the spinal cord with neuroaxonal degeneration and demyelination [155]. The factors involved in the pathogenesis compounds host genotype, environmental, and viral factors, the initial route of infection, the target cells and/or the primary immune response, as well as immune mechanisms such as molecular mimicry [8,15,152,153,156–158].
The primary disease caused by infection with the exogenous human retroviruses, human immunodeficiency virus 1 (HIV-1) or human T-cell lymphotropic virus 1 (HTLV-1), may overlay manifestations of additional autoimmune pathogenesis. Currently, a role for human endogenous retroviruses (HERVs) is also emerging in some autoimmune/immune-mediated diseases, particularly in multiple sclerosis (MS).
Both exogenous and endogenous retroviruses have the potential to elicit the processes leading to autoimmune disease. The pathogenicity of the retroviral envelope protein (Env) is a key player with notable importance in neuroimmune diseases. An essential prerequisite of retroviral infection is the interactions between Env (the retroviral adhesion) proteins on the virion and specific surface receptors on the host cell. These interactions facilitate fusion of the viral envelope and cellular membranes. Additional fusiogenic activities mediated by Env may be beneficial (establishment of the syncytiotrophoblast induced by a HERV-encoded Env) or detrimental to the host (syncytia formation, induction of apoptosis), and Envs are further implied in the direct induction of proinflammatory cytokines, the regulation of autophagy, and pathways of cell death.
The pathogenic potential of retroviral Env is therefore not limited to the pathogenetics of infection but also comprise the pathogenic/toxic capacity of the Env protein itself.
Factors associated with pain in individuals infected by human T-cell lymphotropic virus type 1 (HTLV-1)
2017, Brazilian Journal of Infectious Diseases
Citation Excerpt :
This group usually has a higher pro-viral load and increased cytokines expression that indicates an inflammatory process.29,30 The inflammation mainly affects the thoracic spinal cord segment31 and leads to weakness in the lower limbs (paraparesis) accompanied by hyperreflexia and Babinski signal.7,10,12 The worsening of neurological symptoms cause muscle impairment, postural and joint instability18,21,32 that are potential sources of pain and also lead to adjacent tissue injury, such as joint capsules and ligaments, muscles and peripheral nerves.
Despite the high prevalence of chronic pain in individuals infected with HTLV-1, predictive and protective factors for its development are still unclear.
To identify factors associated with chronic pain in individuals with HTLV-1.
This cross-sectional study was conducted in a reference center for treatment of patients infected with HTLV-1 in Salvador, Bahia, Brazil. The study included individuals infected with HTLV-1, over 18 years, and excluded those with difficulty to respond the pain protocol. Data on sociodemographic, health behavior, and clinical characteristics were collected in a standardized way. The prevalence ratio (PR) of pain is described, as well as the factors independently associated with the presence of pain, which were assessed by multiple logistic regression.
A total of 142 individuals were included in the study, mostly female (62.7%), aged 20–64 years (73.2%), married (61.3%), with less than eight years of education (54.2%), and with a steady income (79.6%). Multivariate analysis showed that being symptomatic for HTLV-1 – sensory manifestations, erectile dysfunction, overactive bladder, and/or HAM/TSP (PR = 1.21, 95% CI: 1.05 to 1.38), self-medication (PR = 1.29, 95% CI: 1.08–1.53), physiotherapy (PR = 1.15, 95% CI: 1.02–1.28), and depression (PR = 1.14, 95% CI: 1.01–1.29) were associated with an increased likelihood of presenting pain. On the other hand, physical activity (PR = 0.79, 95% CI: 0.67–0.93) and religious practice (PR = 0.83, 95% CI: 0.72–0.95) were associated with a decreased likelihood of having pain.
The use of self-medication, physiotherapy and the presence of depression are independently associated with neurological symptoms in HTLV-1 infected patients. Religious practice and physical activity are both protective for the development of pain.
Neuropathology of viral infections
2014, Handbook of Clinical Neurology
Citation Excerpt :
The inflammation of the spinal white matter is bilateral and diffuse but most severe in the lateral aspects of the cord, including the lateral corticospinal tracts (Iwasaki, 1990; Izumo, 2010). The spinal gray matter is also affected by inflammation, but tissue damage, evident as loss of myelinated axons, is seen preferentially in the white matter (Fig. 8.12A and B) (Iwasaki, 1990). The anterior horns are relatively spared from inflammatory lesions (Izumo, 2010).
Advancements in diagnostic methods, particularly polymerase chain reaction (PCR)-based testing of cerebrospinal fluid for viral nucleic acids, have diminished the role of neuropathologic examination in the diagnosis of viral infections of the central nervous system (CNS). Nevertheless, neuropathologic examination of CNS tissue remains important in the diagnosis of atypical viral encephalitides and in the exclusion of non-infectious etiologies. In addition to routine hematoxylin and eosin stains on tissue sections, the neuropathologist may utilize immunohistochemistry, in situ hybridization, electron microscopy, and PCR-based testing of the tissue specimen. In this review, we cover the general pathologic features of viral infections of the CNS as well as the specific features of CNS infections caused by poliovirus, herpes simplex virus, varicella-zoster virus, Epstein–Barr virus, cytomegalovirus, rabies virus, West Nile virus, Eastern equine encephalitis virus, measles virus, JC virus, human immunodeficiency virus, and human T lymphotropic virus type 1.
Infectious Myelopathies
2024, CONTINUUM Lifelong Learning in Neurology
Th17/IL-17 Axis in HTLV-1-Associated Myelopathy Tropical Spastic Paraparesis and Multiple Sclerosis: Novel Insights into the Immunity During HAMTSP
2023, Molecular Neurobiology

View all citing articles on Scopus

View full text

Pathology of chronic myelopathy associated with HTLV-I infection (HAM/TSP)

Abstract

Am. J. Med.

Lancet

Hum. Pathol.

Lancet

Lancet

J. Neurol. Sci.

Lancet

Lancet

Lancet

J. Neurol. Sci.

Subacute degeneration of the brain in pernicious anemia

New Engl. J. Med.

The neuropathology of human T-lymphotropic virus type I-associated myelopathy

Demyelinating diseases

Detection of human T-cell lymphoma/leukemia virus type I DNA and antigen in spinal fluid and blood of patients with chronic progressive myelopathy

New Engl. J. Med.

Lymphocytic alveolitis in HTLV-I associated tropical spastic paraparesis

Tropical spastic paraparesis and human T cell lymphotropic virus type I in the United Kingdom

Brain

HTLV-I infection of cerebrospinal fluid T cells from patients with chronic neurologic disease

AIDS Res. Hum. Retrovir.

La myélite nécrotique subaïgué

Rev. Neurol.

Primary demyelination in visna

An ultrastructural study of Icelandic sheep with clinical signs following experimental infection

Acta Neuropathol.

Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis

Lancet

Inflammatory myopathy in association with chronic myelopathy in HTLV-I seropositive patients

Neurology

Acute disseminated encephalomyelitis as a sequel to “influenza”

J. Pathol. Bacteriol.

Acute and subacute necrotic myelitis

Brain

Skin manifestations in HTLV-I-associated myelopathy (HAM): xerosis and erythema

Altered subsets of peripheral blood lymphocytes in patients with HTLV-I-associated myelopathy (HAM)

Neurology

Spontaneous proliferation of peripheral blood lymphocytes increased in patients with HTLV-I-associated myelopathy

Neurology

The neuropathology of HTLV-I-associated myelopathy in Japan: Report of an autopsy case and review of the literature

Isolation of an HTLV-I-like retrovirus from patients with tropical spastic paraparesis

Nature

Viral infections

An autopsy case of HTLV-I associated myelopathy

Neurol. Med.

Isolation and characterization of HTLV-I from symptomatic family members with tropical spastic paraparesis (HTLV-I encephalomyeloneuropathy)

Neurology