Spinal cord anteroposterior atrophy in HAM/TSP: Magnetic resonance imaging and neuropathological analyses

Taniguchi, Akitoshi; Mochizuki, Hitoshi; Yamashita, Atsushi; Shiomi, Kazutaka; Asada, Yujiro; Nakazato, Masamitsu

doi:10.1016/j.jns.2017.08.3243

Cited by 15 publications

(16 citation statements)

References 14 publications

(21 reference statements)

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“…Although the hematological malignancy, ATLL, is associated with latent viral infections and the clonal proliferation of an HTLV-1-transformed subpopulation of T-cells, [34][35][36][37][38]87,88 the HTLV-1-associated inflammatory diseases, such HAM/TSP, infectious dermatitis, rheumatoid arthritis, uveitis, and others, are caused by autoreactive immune-responses to persistent virus replication and the chronic production of viral antigens. [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] It is thus possible that oleandrin and its ability to enter the CNS 7,57,58 could provide a plausible therapeutic strategy for the future clinical treatment and management of HTLV-1-induced inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

“…[35][36][37][38][39] The HTLV-1 also causes a progressive demyelinating neuroinflammatory disease, known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)-associated with an autoimmune response against virus replication and viral antigens in the central nervous system (CNS), which results in the demyelination of the lower spinal cord and possible paralysis or coma. [40][41][42][43][44][45][46][47] HTLV-1-infections are also etiologically linked with other auto-inflammatory diseases, including infectious dermatitis, rheumatoid arthritis, uveitis, keratoconjunctivitis, sicca syndrome, and Sjögren's syndrome. [48][49][50][51][52][53][54] Based upon the demonstrated ability of oleandrin to inhibit the replication and infectivity of HIV-1 -a related human retrovirus, 17 investigators examined whether oleandrin or a phytoextract from N. oleander could inhibit the infectivity and transmission of HTLV-1.…”

Section: Htlv-1mentioning

confidence: 99%

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<p>Antiviral Effects of Oleandrin</p>

Newman¹,

Sastry²,

Arav‐Boger³

et al. 2020

JEP

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Over the past 15 years, investigators have reported on the utility and safety of cardiac glycosides for numerous health benefits including those as treatments for malignant disease, stroke-mediated ischemic injury and certain neurodegenerative diseases. In addition to those, there is a growing body of evidence for novel antiviral effects of selected cardiac glycoside molecules. One unique cardiac glycoside, oleandrin derived from Nerium oleander , has been reported to have antiviral activity specifically against ‘enveloped’ viruses including HIV and HTLV-1. Importantly, a recent publication has presented in vitro evidence for oleandrin’s ability to inhibit production of infectious virus particles when used for treatment prior to, as well as after infection by SARS-CoV-2/COVID-19. This review will highlight the known in vitro antiviral effects of oleandrin as well as present previously unpublished effects of this novel cardiac glycoside against Ebola virus, Cytomegalovirus , and Herpes simplex viruses.

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Section: Discussionmentioning

confidence: 99%

Section: Htlv-1mentioning

confidence: 99%

<p>Antiviral Effects of Oleandrin</p>

Newman¹,

Sastry²,

Arav‐Boger³

et al. 2020

JEP

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“…The spinal cord atrophy seen in magnetic resonance imaging (MRI) and clinical disability have been correlated in advanced HAM [43], but not in early stage HAM [44]. The serum inflammatory profile that is typical of HAM does not present a good validity to be used in the clinical practice to differentiate the real HTLV-1-aymptomatic carrier from those who are developing HAM [45,46].…”

Section: Discussionmentioning

confidence: 99%

“…In HTLV-1-asymptomatic infection, subclinical alterations can be disclosed by electrophysiological tests but not by MRI [44].…”

Section: Discussionmentioning

confidence: 99%

Ocular vestibular evoked myogenic potential (VEMP) reveals mesencephalic HTLV-1-associated neurological disease

et al. 2019

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PurposeVestibular Myogenic Evoked Potential (VEMP) evaluates vestibulo-ocular and vestibulo-collic reflexes involved in the function of the otolithic organs and their afferent pathways. We compared the results of cervical and ocular VEMP in HTLV-1 associated myelopathy (HAM) and HTLV-1-asymptomatic infection.Participants and methodsThis cross-sectional study included 52 HTLV-1-infected individuals (26 HAM and 26 asymptomatic carriers) and 26 seronegative controls. The groups were similar regarding age and gender. Participants underwent simultaneous ocular and cervical VEMP. The stimulus to generate VEMP was a low-frequency tone burst sound tone burst, with an intensity of 120 decibels normalized hearing level, bandpass filter from 10 to 1,500 Hertz (Hz), with 100 stimuli at 500 Hz and 50 milliseconds recording time. The latencies of the electrophysiological waves P13 and N23 for cervical VEMP and N10 and P15 waves for ocular VEMP were compared among the groups. The absence or delay of the electrophysiological waves were considered abnormal results.ResultsOcular VEMP was similar among the groups for N10 (p = 0.375) and different for P15 (p≤0.001). Cervical VEMP was different for P13 (p = 0.001) and N23 (p = 0.003). About ocular VEMP, in the HTLV-1-asymptomatic group, normal waves were found in 23(88.5%) individuals; in HAM group, normal waves were found in 7(26.9%). About cervical VEMP, 18(69.2%) asymptomatic carriers presented normal waves and only 3(11.5%) patients with HAM presented normal waves. Abnormalities in both VEMPs were found in 1(3.8%) asymptomatic carrier and in 16(61.5%) patients with HAM.ConclusionNeurological impairment in HAM was not restricted to the spinal cord. The mesencephalic connections, tested by ocular VEMP, have been also altered. Damage of the oculomotor system, responsible for eye stabilization during head and body movements, may explain why dizziness is such a frequent complaint in HAM.

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“…In a sensitivity analysis, the model was also run using relative efficacy of teriflunomide versus placebo from Chinese subgroup of patients in the TOWER study with hazard ratio (HR) = 0.32 (0.07, 1.51) for confirmed disability worsening and risk ratio (RR) = 0.29 (0.15, 0.57) relative annualized relapse rates [ 26 ]. The treatment efficacy for interferon beta-1b was assumed to be similar to that of the pooled RMS population in Table 1 , as no similar data source was found regarding interferon beta-1b efficacy in Chinese patients.…”

Section: Methodsmentioning

confidence: 99%

Cost-effectiveness of Teriflunomide Compared to Interferon Beta-1b for Relapsing Multiple Sclerosis Patients in China

Ningying

Chirikov

et al. 2019

Clin Drug Investig

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Background and Objective Teriflunomide is a once-daily oral immunomodulatory agent approved in 80 countries for the treatment of patients with relapsing multiple sclerosis (RMS). The study objective was to estimate the cost effectiveness of teriflunomide (14 mg tablet, daily) versus interferon beta-1b (250 mcg subcutaneous injection, every other day) among RMS patients from the Chinese healthcare system perspective. Methods A Markov model with annual cycles and a lifetime horizon was utilized to assess cost-effectiveness of teriflunomide in comparison with interferon beta-1b in RMS patients. Treatment effects, including 3-month confirmed disability worsening and annualized relapse rate, were derived from a network meta-analysis. Cost inputs included costs related to treatment acquisition, administration, monitoring, natural disease management through Expanded Disability Status Scale states, relapse treatment, and adverse event management. These costs were calculated as the product between unit costs from published sources and healthcare resource utilization patterns identified in a survey conducted among 11 neurologists across different areas in China. Health effects were expressed as quality-adjusted life years (QALYs) with costs in local currency (¥) and US dollars (US$), 2018. Results Teriflunomide dominated interferon beta-1b and was associated with lower total costs (teriflunomide ¥1,887,144 vs interferon beta-1b ¥2,061,393) and higher QALYs (teriflunomide 9.60 QALYs vs interferon beta-1b 8.88 QALYs). In probabilistic sensitivity analysis, teriflunomide was dominant in 62.2% of model runs. Conclusion Teriflunomide is a cost-effective therapy over a lifetime time horizon compared to interferon beta-1b in the treatment of RMS patients in China. Results should be interpreted with caution as head-to-head comparisons are not available. Electronic supplementary material The online version of this article (10.1007/s40261-019-00750-3) contains supplementary material, which is available to authorized users.

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Spinal cord anteroposterior atrophy in HAM/TSP: Magnetic resonance imaging and neuropathological analyses

Cited by 15 publications

References 14 publications

<p>Antiviral Effects of Oleandrin</p>

<p>Antiviral Effects of Oleandrin</p>

Ocular vestibular evoked myogenic potential (VEMP) reveals mesencephalic HTLV-1-associated neurological disease

Cost-effectiveness of Teriflunomide Compared to Interferon Beta-1b for Relapsing Multiple Sclerosis Patients in China

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