Prevalence and Risk Factors for Human T-Cell Lymphotropic Virus (HTLV) in Blood Donors in Brazil-A 10-Year Study (2007-2016).

It is unknown whether HTLV-1/2 prevalence has been stable or changing with time in Brazil. We present a 10-year (2007-2016) analysis of HTLV-1/2 infection in first-time blood donors from four blood banks in Brazil. The Brazilian blood centers participating in this multicenter Recipient Epidemiology and Donor Evaluation Study (REDS) are located in Recife in the Northeast and in São Paulo, Rio de Janeiro and Belo Horizonte located in the Southeast of the country. A previous REDS study using the same database from 2007 to 2009 showed that the prevalence per 100,000 donors was 222 in Recife, 83 in Belo Horizonte and 101 in São Paulo. From 2007 to 2016, HTLV-1/2 prevalence was calculated by year, blood center and birth cohort. Covariates included age, gender, schooling, self-reported skin color and type of donation. From 1,092,174 first-blood donations, in the general analysis, HTLV-1/2 infection predominated in females, donors over 50 years of age, black skin color and less educated. The average prevalence was 228 per 100,000 donors in Recife, 222 in Rio de Janeiro, 104 in Belo Horizonte and 103 in São Paulo. In the 10-year analysis, HTLV-1/2 prevalence was stable, but a trend was observed toward an increase in HTLV-1/2 infection among younger people (p < 0.001), males (p = 0.049), those with white skin color (p < 0.001), and higher education (p = 0.014). Therefore, this 10-year surveillance of the infection showed stable HTLV-1/2 prevalence overall but a trend toward increased prevalence among the younger and more educated donors despite Brazilian policies to control sexually transmitted infections being in place for more than 10 years.

Cognitive screening in HTLV-1-infected people using a self-perceived memory score and auditory P300.

The HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is the most common neurological manifestation associated with human T-cell lymphotropic virus type-1 (HTLV-1) infection. Although cognitive impairment has been highlighted in the spectrum of HTLV-1 neurological manifestations, it may go unnoticed in those who do not spontaneously report it. We aimed at evaluating the applicability of a self-perceived memory score (SMS) and the cognitive event-related potential (P300) for early detection of cognitive impairment in HTLV-1-infected people. The SMS was measured by a 0-10 point numeric scale combined with a sad-happy face rating scale. The higher the number, the better was the SMS. The P300 was obtained through an oddball paradigm with a mental counting task. The participants were 15 (21.4%) individuals with HAM/TSP, 20 (28.6%) HTLV-1 asymptomatic carriers, and 35 (50%) seronegative controls. We found that SMS (p < 0.001) and P300 latency (p < 0.001) got progressively worse from the seronegative controls to the asymptomatic carriers and then to the HAM/TSP. The results that indicated cognitive impairment were SMS < 7.2 points and P300 latency > 369.0 ms. The HAM/TSP group showed the highest prevalence of altered P300 (80%) and SMS (87%). Interestingly, the asymptomatic group also presented significantly higher prevalence of altered SMS (60%) and P300 (35%) when compared to controls (< 10%). The frequency of cognitive impairment was 16 times higher in the HTLV-1 asymptomatic group and 69 times higher in the HAM/TSP group when compared to controls. The use of SMS in the medical consultation was a useful and easy-to-apply method to screen HTLV-1-infected subjects for everyday memory complaints.

Vestibular Evoked Myogenic Potential on Ocular, Cervical, and Soleus Muscles to Assess the Extent of Neurological Impairment in HTLV-1 Infection.

Introduction: Vestibular Evoked Myogenic Potential (VEMP) can be used to test central vestibular pathways from the midbrain to the lumbar spine, according to the muscle tested. Purpose: to compare the spinal cord alteration in individuals with HTLV-1-associated myelopathy (HAM) and with HTLV-1-asymptomatic infection using the VEMP recorded from different muscles. Methods: VEMP was recorded in 90 individuals of whom 30 had HAM, 30 were HTLV-1 asymptomatic carriers, and 30 negative controls. VEMP was recorded in the oculomotor muscle (oVEMP), testing the vestibulo-ocular reflex, and in the cervical muscle (cVEMP) and soleus muscle (sVEMP), testing the vestibulospinal reflex, respectively, in the cervical and in the lumbar spinal level. The type of stimulation was auditory for oVEMP and cVEMP, and galvanic for sVEMP. The compared variables were the latencies of the electrophysiological waves. Results: HTLV-1-asymptomatic group was similar to the controls regarding oVEMP (p = 0.461), but different regarding cVEMP (p < 0.001) and sVEMP (p < 0.001). HAM group has presented the worst latencies and was different from the HTLV-1-asymptomatic group in the VEMP of all the tested muscles (p < 0.001). The concomitant occurrence of VEMP alterations in the three recorded muscles of the same individual was found in 2 (6.7%) asymptomatic carriers and in 20 (66.7%) patients with HAM (p = 0.001). The analysis of VEMP alteration per group and per muscle has showed that, in HTLV-1-asymptomatic group, oVEMP was altered in 3 (10.0%) individuals, cVEMP in 10 (33.3%) and sVEMP in 13 (43.3%). In HAM group, oVEMP was altered in 23 (76.6%) individuals, cVEMP in 27 (90%), and sVEMP in 30 (100%). Conclusion: HTLV-1-neurological damage has followed an ascendant progression beginning at the lumbar spine in the stage of a clinically asymptomatic infection, whereas HAM has affected not only the spine, but also the midbrain.

Case Report: Cognitive Impairment without Clinical Spinal Disease May Be the First Sign of HTLV-1 Neurological Alteration.

Human t-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM) is a progressive neurological disease whose diagnosis is defined by clinical manifestations and seropositivity for HTLV-1 infection. Cognitive impairment (CI) is considered to occur after spinal impairment. A 51-year-old HTLV-1-infected man classified as an asymptomatic carrier presented difficulties in listening comprehension and executive memory. He was assessed for central auditory processing (CAP), cognition (event-related auditory evoked potential [P300]), and otoneurological functions (galvanic vestibular-evoked myogenic potential [gVEMP]). Altered responses were found in CAP, P300, and gVEMP, but the neurological examination and cognitive screening were normal. After a 2-year follow-up, we disclosed a positive Babinski sign, a mild CI, worsened P300, and gVEMP latencies, and the patient reported progressive lumbar pain and difficulty running. He was, then, reclassified as HAM. The first examination, in 2016, had already shown abnormal results in P300 and gVEMP despite the HTLV-1-asymptomatic carrier status. Therefore, tests that provide subclinical measures of neurological disease progression can be useful tools for an early diagnosis and intervention in HTLV-1 patients. Electrophysiological results had worsened as well as the clinical status and the cognitive function and the progression from asymptomatic status to an HTLV-1-associated neurological disease occurred within 2 years. Thus, HTLV-1-infected individuals with complaints of CI, hearing, or otoneurological manifestations should be submitted to neuropsychological and electrophysiological tests, allowing them to be properly cared in case of HAM progression.

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

PURPOSE: Vestibular 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 METHODS: This 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. RESULTS: Ocular 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. CONCLUSION: Neurological 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.

Intrarater and interrater agreement and reliability of vestibular evoked myogenic potential triggered by galvanic vestibular stimulation (galvanic-VEMP) for HTLV-1 associated myelopathy testing.

BACKGROUND: The vestibular evoked myogenic potential triggered by galvanic vestibular stimulation (galvanic-VEMP) has been used to assess the function of the vestibulospinal motor tract and is a candidate biomarker to predict and monitor the human T-cell lymphotropic virus type 1 (HTLV-1) associated myelopathy (HAM). This study determined the agreement and reliability of this exam. METHODS: Galvanic-VEMP was performed in 96 participants, of which 24 patients presented HAM, 27 HTLV-1-asymptomatic carriers, and 45 HTLV-1-negative asymptomatic controls. Galvanic vestibular stimulation was achieved by passing a binaural and bipolar current at a 2 milliamperes (mA) intensity for 400 milliseconds (ms) between the mastoid processes. Galvanic-VEMP electromyographic wave responses of short latency (SL) and medium latency (ML) were recorded from the gastrocnemius muscle. Intrarater (test-retest) and interrater (two independent examiners) agreement and reliability were assessed by standard error of measurement (SEM), coefficient of repeatability (CR), intraclass correlation coefficient (ICC), and Kappa coefficient. RESULTS: In the total sample (n = 96), SL and ML medians were 56 ms (IQR 52-66) and 120 ms (IQR 107-130), respectively. The intrarater repeatability measures for SL and ML were, respectively: SEM of 6 and 8 ms; CR of 16 and 22 ms; ICC of 0.80 (p<0.001) and 0.91 (p<0.001); and a Kappa coefficient of 0.53 (p<0.001) and 0.82 (p<0.001). The interrater reproducibility measures for SL and ML were, respectively: SEM of 3 and 10 ms; CR of 8 and 27 ms; ICC of 0.95 (p<0.001) and 0.86 (p<0.001); and a Kappa coefficient of 0.77 (p<0.001) and 0.88 (p<0.001). CONCLUSION: Galvanic-VEMP is a reliable and reproducible method to define the integrity of the vestibulospinal tract. Longitudinal studies will clarify its validity in the clinical context, aimed at achieving an early diagnosis and the monitoring of HAM.

Vestibular-evoked myogenic potential triggered by galvanic vestibular stimulation may reveal subclinical alterations in human T-cell lymphotropic virus type 1-associated myelopathy.

BACKGROUND: Vestibular-evoked myogenic potential triggered by galvanic vestibular stimulation (galvanic-VEMP) evaluates the motor spinal cord and identifies subclinical myelopathies. We used galvanic-VEMP to compare spinal cord function in individuals infected with human T-cell lymphotropic virus type 1 (HTLV-1) from asymptomatic status to HTLV-1-associated myelopathy (HAM). METHODOLOGY/PRINCIPAL FINDINGS: This cross-sectional study with 122 individuals included 26 HTLV-1-asymptomatic carriers, 26 individuals with possible HAM, 25 individuals with HAM, and 45 HTLV-1-seronegative individuals (controls). The groups were similar regarding gender, age, and height. Galvanic stimuli (duration: 400 ms; intensity: 2 mA) were applied bilaterally to the mastoid processes and VEMP was recorded from the gastrocnemius muscle. The electromyographic parameters investigated were the latency and amplitude of the short-latency (SL) and medium-latency (ML) responses. While SL and ML amplitudes were similar between groups, SL and ML latencies were delayed in the HTLV-1 groups compared to the control group (p<0.001). Using neurological examination as the gold standard, ROC curve showed an area under the curve of 0.83 (p<0.001) for SL and 0.86 (p<0.001) for ML to detect spinal cord injury. Sensibility and specificity were, respectively, 76% and 86% for SL and 79% and 85% for ML. Galvanic-VEMP disclosed alterations that were progressive in HTLV-1-neurological disease, ranging from SL delayed latency in HTLV-1-asymptomatic carriers, SL and ML delayed latency in possible HAM group, to absence of VEMP response in HAM group. CONCLUSIONS/SIGNIFICANCE: The worse the galvanic-VEMP response, the more severe the myelopathy. Galvanic-VEMP alteration followed a pattern of alteration and may be a prognostic marker of progression from HTLV-1-asymptomatic carrier to HAM.

Vestibular Evoked Myogenic Potential (VEMP) Triggered by Galvanic Vestibular Stimulation (GVS): A Promising Tool to Assess Spinal Cord Function in Schistosomal Myeloradiculopathy.

BACKGROUND: Schistosomal myeloradiculopathy (SMR), the most severe and disabling ectopic form of Schistosoma mansoni infection, is caused by embolized ova eliciting local inflammation in the spinal cord and nerve roots. The treatment involves the use of praziquantel and long-term corticotherapy. The assessment of therapeutic response relies on neurological examination. Supplementary electrophysiological exams may improve prediction and monitoring of functional outcome. Vestibular evoked myogenic potential (VEMP) triggered by galvanic vestibular stimulation (GVS) is a simple, safe, low-cost and noninvasive electrophysiological technique that has been used to test the vestibulospinal tract in motor myelopathies. This paper reports the results of VEMP with GVS in patients with SMR. METHODS: A cross-sectional comparative study enrolled 22 patients with definite SMR and 22 healthy controls that were submitted to clinical, neurological examination and GVS. Galvanic stimulus was applied in the mastoid bones in a transcranial configuration for testing VEMP, which was recorded by electromyography (EMG) in the gastrocnemii muscles. The VEMP variables of interest were blindly measured by two independent examiners. They were the short-latency (SL) and the medium-latency (ML) components of the biphasic EMG wave. RESULTS: VEMP showed the components SL (p = 0.001) and ML (p<0.001) delayed in SMR compared to controls. The delay of SL (p = 0.010) and of ML (p = 0.020) was associated with gait dysfunction. CONCLUSION: VEMP triggered by GVS identified alterations in patients with SMR and provided additional functional information that justifies its use as a supplementary test in motor myelopathies.

Electrophysiological analysis shows dizziness as the first symptom in human T cell lymphotropic virus type-associated myelopathy/tropical spastic paraparesis.

Dizziness is a symptom in human T cell lymphotropic virus type-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and may occur due to vestibulospinal tract dysfunction. This tract can be assessed by an electrophysiological test called vestibular-evoked myogenic potential (VEMP). The aim was to correlate the result of VEMP generated by acoustic stimuli and dizziness in individuals with human T cell lymphotropic virus type 1 (HTLV-1)-asymptomatic infection and HAM/TSP. VEMP was recorded from the sternocleidomastoid muscle of 60 HTLV-1-negative adults (60±8 years) and 60 individuals infected with HTLV-1, 30 being asymptomatic (59±8 years) and 30 with HAM/TSP (59±8 years). In all groups, 90% of the participants were women. VEMP was generated by acoustic stimuli (short tone bursts), with an intensity of 118 dBHL and band-pass filter from 10 Hz to 1,500 Hz, and presented 200 stimuli at a frequency of 1,000 Hz with a record time of 60 ms. Of 60 HTLV-1-negative individuals, 14 (23%) reported dizziness; VEMP was normal in all. In the HTLV-1-asymptomatic group, 11(37%) complained of dizziness (p=0.31); VEMP was altered in four (40%) subjects with dizziness and in one (5%) without dizziness (p=0.00). In the group with HAM/TSP, dizziness was reported by 17 (57%) subjects (p=0.002); VEMP was altered in 11 (64%) with dizziness and in 5 (38%) without dizziness (p=0.15). Dizziness without an apparent etiology in HTLV-1-asymptomatic carriers deserves attention in terms of a possible subclinical spinal cord involvement that can be clarified through spinal electrophysiological tests. Damage of the vestibulospinal tract seems to occur in the early stages of HAM/TSP.

Contribution of Galvanic Vestibular Stimulation for the Diagnosis of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis.

BACKGROUND AND PURPOSE: Galvanic vestibular stimulation (GVS) is a low-cost and safe examination for testing the vestibulospinal pathway. Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a slowly progressive disease that affects the vestibulospinal tract early in its course. This study compared the electromyographic (EMG) responses triggered by GVS of asymptomatic HTLV-1-infected subjects and subjects with HAM/TSP. METHODS: Bipolar galvanic stimuli (400 ms and 2 mA) were applied to the mastoid processes of 39 subjects (n=120 stimulations per subject, with 60 from each lower limb). Both the short latency (SL) and medium latency (ML) components of the EMG response were recorded from the soleus muscles of 13 healthy, HTLV-1-negative adults (56±5 years, mean±SD), and 26 individuals infected with HTLV-1, of whom 13 were asymptomatic (56±8 years) and 13 had HAM/TSP (60±6 years). RESULTS: The SL and ML EMG components were 55±4 and 112±10 ms, respectively, in the group of healthy subjects, 61±6 and 112±10 ms and in the HTLV-1-asymptomatic group, and 67±8 and 130±3 ms in the HAM/TSP group (p=0.001). The SL component was delayed in 4/13 (31%) of the examinations in the HTLV-1-asymptomatic group, while the ML component was normal in all of them. In the HAM/TSP group, the most common alteration was the absence of waves. CONCLUSIONS: A pattern of abnormal vestibular-evoked EMG responses was found in HTLV-1-neurological disease, ranging from delayed latency among asymptomatic carriers to the absence of a response in HAM/TSP. GVS may contribute to the early diagnosis and monitoring of nontraumatic myelopathies.