Marcus Tulius T. Silva

The HTLV-1 neurological complex

Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about 20 million people worldwide and causes immune-mediated diseases of the nervous system. The classic neurological presentation of HTLV-1 infection is a myelopathy called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, HAM/TSP is not the only neurological outcome that can result from HTLV-1 infection. In this Personal View, we show that HTLV-1 has a broader neurological spectrum than the names HAM/TSP suggest and that people infected with this virus can present with various isolated or assorted syndromes.

Human T Lymphotropic Virus Type 1 (HTLV-1) Proviral Load in Asymptomatic Carriers, HTLV-1–Associated Myelopathy/Tropical Spastic Paraparesis, and Other Neurological Abnormalities Associated with HTLV-1 Infection

Recent reports have demonstrated that human T lymphotropic virus type 1 (HTLV-1) is associated with other neurological abnormalities in addition to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It has been well established that high HTLV-1 proviral loads are associated with the development of HAM/TSP. We now demonstrate, for the first time, to our knowledge, that HTLV-1 proviral loads in patients with other neurological abnormalities are also significantly higher than in asymptomatic HTLV-1 carriers.

Molecular detection, quantification and characterization of human polyomavirus JC from waste water in Rio De Janeiro, Brazil

Polyomavirus JC (JCPyV) is largely excreted by the human population through the urinary route and has been recognized as a potential viral marker for human waste contamination. This study aims to investigate the dissemination of JCPyV in waste water from a sewage treatment plant (STP) located in Rio de Janeiro, Brazil, and to describe the prevalence of JCPyV subtypes currently present in this population. Raw and treated sewage samples were collected bimonthly during one year, and examined for the presence of JCPyV using nested polymerase chain reaction (nPCR) and quantitative real time PCR (qPCR). JCPyV was detected by nPCR in 96% and 43% of raw and treated sewage samples, respectively. The concentration of JCPyV present in the samples ranged from 1.2x10(3) to 3.2x10(5) and 2.6x10(2) to 6.2x10(3) genome copies per 2 ml of concentrated raw and treated sewage sample, respectively. The strains were characterized and the obtained nucleotide sequences indicated that the detected JCPyV strains clustered with subtypes of East African, West African and European origin. To our knowledge, this is the first study describing the incidence and diversity of JCPyV strains in raw and treated sewage in Brazil.

Peripheral neuropathy in HTLV-I infected individuals without tropical spastic paraparesis/HTLV-I-associated myelopathy.

Tropical spastic paraparesis/ HTLV-I-associated myelopathy (TSP/HAM) is the classical neurological manifestation of HTLV-I. Only a few studies have described isolated peripheral neuropathy (PN) among HTLV-I infected individuals. 335 infected individuals without TSP/HAM were evaluated for the presence of PN and 45 of them showed evidences of peripheral nervous system involvement. Of these 21 patients had isolated PN, defined by clinical and/or electrophysiological criteria. Sural nerve biopsies revealed inflammatory infiltrates in 2, axonal degeneration in 2 and segmental demyelination in 1. Therefore, peripheral neuropathy can be found as an isolated manifestation of HTLV-I infection. We conclude that HTLV-I infection should be investigated in patients with PN of unknown origin.

ALS syndrome in HTLV-I infection

Human T-cell lymphotrophic virus (HTLV)-I causes tropical spastic paraparesis/HTLV-I associated myelopathy (HAM/TSP) and may have other neurologic manifestations such as isolated peripheral neuropathy.1 An HTLV-I-associated ALS-like syndrome (ALS-S) has been rarely reported.2 We now describe the features of ALS-S in a cohort of HTLV-I infected individuals. From May 1992 to September 2004, 606 HTLV-I infected individuals who fulfilled international criteria for serologic positivity at both ELISA and Western blot tests were admitted to our institution. The clinical diagnosis of HAM/TSP was based on World Health Organization guidelines,3 which basically define it as a chronic, slowly progressive spastic paraparesis, with bladder disturbances, sensory symptoms, and low back pain. EMG of at least three limbs and nerve conduction studies were performed. Diagnosis of ALS-S was made by El Escorial criteria.4 Informed consent was obtained from all individuals. Of 606 infected individuals, 259 had some neurologic abnormality; 169 had HAM/TSP (65.2%) and 90 (34.7%) had other neurologic abnormalities. Five patients …

Sporothrix schenckii meningitis in AIDS during immune reconstitution syndrome

Sporotrichosis is a fungal disease usually restricted to the cutaneous and lymphatic systems. Visceral involvement is unusual. To date, only 21 cases of sporotrichosis meningitis have been reported, some of these associated with immunosuppression. According to the reported cases, difficulty establishing the correct diagnosis is almost the rule which, undoubtedly, is associated with a worse prognosis. In this report, two HIV infected patients are described who developed meningitis due to Sporothrix schenckii associated with immune reconstitution inflammatory syndrome. This is the first report of sporotrichosis meningitis associated with immune reconstitution inflammatory syndrome in AIDS patients.

A multinational study of neurological performance in antiretroviral therapy-naïve HIV-1-infected persons in diverse resource-constrained settings

Little is known about how the prevalence and incidence of neurological disease in HIV-infected patients in resource-limited settings. We present an analysis of neurological and neurocognitive function in antiretroviral naïve individuals in multinational resource-limited settings. This prospective multinational cohort study, a substudy of a large international randomized antiretroviral treatment trial, was conducted in seven low- and middle-income countries in sub-Saharan Africa, South America, and Asia. Subjects were HIV-infected and met regional criteria to initiate antiretroviral therapy. Standardized neurological examination and a brief motor-based neuropsychological examination were administered. A total of 860 subjects were studied. Overall 249 (29%) had one or more abnormalities on neurological examinations, but there was a low prevalence of HIV-associated dementia (HAD) and minor neurocognitive disorder (MND). Twenty percent of subjects had evidence of peripheral neuropathy. There were significant differences across countries (p < 0.001) in neuropsychological test performance. In this first multinational study of neurological function in antiretroviral naïve individuals in resource-limited settings, there was a substantial prevalence of peripheral neuropathy and low prevalence of dementia and other CNS diseases. There was significant variation in neurocognitive test performance and neurological examination findings across countries. These may reflect cultural differences, differences in HIV-related and unrelated diseases, and variations in test administration across sites. Longitudinal follow-up after antiretroviral treatment initiation may help to define more broadly the role of HIV in these differences as well as the impact of treatment on performance.

Neurological manifestations of Chikungunya and Zika infections.

The epidemics of Chikungunya virus (CHIKV) and Zika virus (ZIKV) infections have been considered the most important epidemiological occurrences in the Americas. The clinical picture of CHIKV infection is characterized by high fever, exanthema, myalgia, headaches, and arthralgia. Besides the typical clinical picture of CHIKV, atypical manifestations of neurological complications have been reported: meningo-encephalitis, meningoencephalo-myeloradiculitis, myeloradiculitis, myelitis, myeloneuropathy, Guillain-Barré syndrome and others. The diagnosis is based on clinical, epidemiological, and laboratory criteria. The most common symptoms of ZIKV infection are skin rash (mostly maculopapular), fever, arthralgia, myalgia, headache, and conjunctivitis. Some epidemics that have recently occurred in French Polynesia and Brazil, reported the most severe conditions, with involvement of the nervous system (Guillain-Barré syndrome, transverse myelitis, microcephaly and meningitis). The treatment for ZIKV and CHIKV infections are symptomatic and the management for neurological complications depends on the type of affliction. Intravenous immunoglobulin, plasmapheresis, and corticosteroid pulse therapy are options.

HTLV-1 AND NEUROLOGICAL CONDITIONS : When to suspect and when to order a diagnostic test for HTLV-1 infection?

HTLV-1 is a retrovirus associated with a myriad of clinical conditions, especially hematological and neurological ones. Regarding nervous system diseases, it is of utmost importance to select those cases in which HTLV-1 infection could really be associated. This is particularly true for patients from endemic areas and for HIV-infected patients and drug users, since that these groups are at a higher risk for HTLV infection. This caution in selecting neurological patients for HTLV diagnostic tests is justified by the fact that in some circumstances the seropositivity may merely represent an epiphenomenon. In this paper we enroll some neurological conditions that have been associated with HTLV-1/2 infection in the literature and discuss the real need for HTLV-1/2 diagnostic tests in each one. Because HIV/HTLV-co-infected patients seem to be at an increased risk for neurological diseases development, a special consideration about this matter is also made.

Long-term outcome of neuroparacoccidioidomycosis treatment

INTRODUCTION Neuroparacoccidioidomycosis (NPCM) is a term used to describe the invasion of the central nervous system by the pathogenic fungus Paracoccidioides brasiliensis. NPCM has been described sporadically in some case reports and small case series, with little or no focus on treatment outcome and long-term follow-up. METHODS All patients with NPCM from January 1991 to December 2006 were analyzed and were followed until December 2009. RESULTS Fourteen (3.8%) cases of NPCM were identified out of 367 patients with paracoccidioidomycosis (PCM). A combination of oral fluconazole and sulfamethoxazole/trimethoprim (SMZ/TMP) was the regimen of choice, with no documented death due to Paracoccidioides brasiliensis infection. Residual neurological deficits were observed in 8 patients. Residual calcification was a common finding in neuroimaging follow-up. CONCLUSIONS All the patients in this study responded positively to the association of oral fluconazole and sulfamethoxazole/trimethoprim, a regimen that should be considered a treatment option in cases of NPCM. Neurological sequela was a relatively common finding. For proper management of these patients, anticonvulsant treatment and physical therapy support were also needed.