Wild-Type Yellow Fever Virus RNA in Cerebrospinal Fluid of Child.

We report a 3-year-old child who was hospitalized because of severe manifestations of the central nervous system. The child died after 6 days of hospitalization. Analysis of postmortem cerebrospinal fluid showed the presence of yellow fever virus RNA. Nucleotide sequencing confirmed that the virus was wild-type yellow fever virus.

A non-functional galanin receptor-2 in a multiple sclerosis patient.

Multiple Sclerosis (MS) is an inflammatory neurodegenerative disease that affects approximately 2.5 million people globally. Even though the etiology of MS remains unknown, it is accepted that it involves a combination of genetic alterations and environmental factors. Here, after performing whole exome sequencing, we found a MS patient harboring a rare and homozygous single nucleotide variant (SNV; rs61745847) of the G-protein coupled receptor (GPCR) galanin-receptor 2 (GALR2) that alters an important amino acid in the TM6 molecular toggle switch region (W249L). Nuclear magnetic resonance imaging showed that the hypothalamus (an area rich in GALR2) of this patient exhibited an important volumetric reduction leading to an enlarged third ventricle. Ex vivo experiments with patient-derived blood cells (AKT phosphorylation), as well as studies in recombinant cell lines expressing the human GALR2 (calcium mobilization and NFAT mediated gene transcription), showed that galanin (GAL) was unable to stimulate cell signaling in cells expressing the variant GALR2 allele. Live cell confocal microscopy showed that the GALR2 mutant receptor was primarily localized to intracellular endosomes. We conclude that the W249L SNV is likely to abrogate GAL-mediated signaling through GALR2 due to the spontaneous internalization of this receptor in this patient. Although this homozygous SNV was rare in our MS cohort (1:262 cases), our findings raise the potential importance of impaired neuroregenerative pathways in the pathogenesis of MS, warrant future studies into the relevance of the GAL/GALR2 axis in MS and further suggest the activation of GALR2 as a potential therapeutic route for this disease.

Factors influencing cerebrospinal fluid and plasma HIV-1 RNA detection rate in patients with and without opportunistic neurological disease during the HAART era.

BACKGROUND: In the central nervous system, HIV replication can occur relatively independent of systemic infection, and intrathecal replication of HIV-1 has been observed in patients with HIV-related and opportunistic neurological diseases. The clinical usefulness of HIV-1 RNA detection in the cerebrospinal fluid (CSF) of patients with opportunistic neurological diseases, or the effect of opportunistic diseases on CSF HIV levels in patients under HAART has not been well defined. We quantified CSF and plasma viral load in HIV-infected patients with and without different active opportunistic neurological diseases, determined the characteristics that led to a higher detection rate of HIV RNA in CSF, and compared these two compartments. METHODS: A prospective study was conducted on 90 HIV-infected patients submitted to lumbar puncture as part of a work-up for suspected neurological disease. Seventy-one patients had active neurological diseases while the remaining 19 did not. RESULTS: HIV-1 RNA was quantified in 90 CSF and 70 plasma samples. The HIV-1 RNA detection rate in CSF was higher in patients with neurological diseases, in those with a CD4 count lower than 200 cells/mm3, and in those not receiving antiretroviral therapy, as well as in patients with detectable plasma HIV-1 RNA. Median viral load was lower in CSF than in plasma in the total population, in patients without neurological diseases, and in patients with toxoplasmic encephalitis, while no significant difference between the two compartments was observed for patients with cryptococcal meningitis and HIV-associated dementia. CSF viral load was lower in patients with cryptococcal meningitis and neurotoxoplasmosis under HAART than in those not receiving HAART. CONCLUSION: Detection of HIV-1 RNA in CSF was more frequent in patients with neurological disease, a CD4 count lower than 200 cells/mm3 and detectable plasma HIV-1. Median HIV-1 RNA levels were generally lower in CSF than in plasma but some patients showed higher CSF levels, and no difference between these two compartments was observed in patients with cryptococcal meningitis and HIV-associated dementia, suggesting the presence of intrathecal viral replication in these patients. HAART played a role in the control of CSF HIV levels even in patients with cryptococcal meningitis and neurotoxoplasmosis in whom viral replication is potentially higher.

Modified sphygmomanometer test for the assessment of strength of the trunk, upper and lower limbs muscles in subjects with subacute stroke: reliability and validity.

BACKGROUND: Limitations in activities have been related to weakness of the upper limbs (UL), lower limbs (LL) and trunk muscles after stroke. Therefore, the measurement of strength after stroke becomes essential. The Modified Sphygmomanometer Test (MST) is an alternative method for the measurement of strength, since it is cheap and provides objective values. However, no studies have investigated the measurement properties of the MST in sub-acute stroke. AIM: To investigate the test-retest and inter-rater reliabilities and criterion-related validity of the MST for the measurement of strength of the UL, LL, and trunk muscles in subjects with sub-acute stroke, and verify whether the number of trials would affect the results. DESIGN: Diagnostic accuracy. SETTING: Local community, out-patient clinics, and university laboratory. POPULATION: Sixty- five subjects with sub-acute stroke (62±14 years) participated of the present study. METHODS: The strength of 36 muscular groups was measured with the MST and dynamometers (criterion standard). To investigate whether the number of trials would affect the results, analysis of variance was applied. For the test-retest and inter-rater reliabilities and criterion-related validity of the MST, intra-class correlation coefficients (ICC), Pearson correlation coefficients, and coefficients of determination were calculated. RESULTS: Similar results were found for all muscular groups and number of trials (0.01≤F≤0.14; 0.87≤p≤0.99) with significant and adequate values of test-retest (0.57≤ICC≥0.98) (exception: first trial of the non-paretic ankle dorsiflexors) and inter-rater (0.50≤ICC≥0.99) (exception: non-paretic ankle plantar flexors) reliabilities and validity (0.70≤r≥0.95; p≤0.001). The values obtained with the MST were good predictors of those obtained with the dynamometers (0.54≤r2≤0.90). CONCLUSIONS: In general, the MST showed adequate reliabilities and criterion-related validity for measuring strength of subjects with sub-acute stroke, and only one trial, after familiarization, provided adequate values. CLINICAL REHABILITATION IMPACT: The MST can be used by health professionals within several clinical contexts to objectively measure strength of the UL, LL, and trunk muscles in subjects with sub-acute stroke. Besides providing objective, reliable, and valid strength measures, the MST is also feasible. The aneroid sphygmomanometer used for the MST assessment is portable, easily found worldwide, and commonly acquired by health professionals. Furthermore, its adaptation is simple, reversible, and cheap.

HIV-1 RNA levels in cerebrospinal fluid and plasma and their correlation with opportunistic neurological diseases in a Brazilian AIDS reference hospital.

BACKGROUND: Plasma HIV RNA levels reflect systemic viral replication but in CNS it may occur relatively independent of systemic infection, yet clinical application of CSF HIV-1 RNA levels is less clear. OBJECTIVE: To compare CSF and plasma HIV-1 RNA levels of patients with different opportunistic neurological diseases to those without neurological disease, as well as to correlate these levels with the outcome of the disease and use of HAART. METHOD: 97 patients who had lumbar puncture for routine work up of suspected neurological diseases, were divided in 2 groups: without neurological disease (23) and with neurological disease (74). NASBA was used for plasma and CSF HIV RNA. RESULTS: Median CSF viral load was higher in toxoplasmic encephalitis, cryptococcal meningitis, HIV dementia and neurological diseases without a defined etiology when compared to patients without neurological disease. There was no difference between plasma viral load in patients with and without neurological diseases. Median viral load was higher in plasma and CSF among patients who died when compared to those successfully treated. CSF and plasma viral load were lower in patients with opportunistic diseases on HAART than without HAART. CONCLUSION: CSF viral load was higher in patients with any neurological disease, but this difference was not present in plasma viral load, suggesting that neurological disease influences more the CSF than plasma compartments. Notwithstanding different neurological diseases were not possible to be differentiated by the levels of CSF HIV-1.

Cerebral macroabscess caused by Candida albicans in an immunocompetent patient: A diagnostic challenge.

We describe the history of a 24-year-old immunocompetent man with an expansive lesion in the brainstem that, after many misdiagnoses, was found to be caused by a Candida albicans abscess. One year after surgery and 3 months of fluconazole treatment, the patient was asymptomatic and all image and laboratory tests were normal.

HIV-1 RNA levels in cerebrospinal fluid and plasma and their correlation with opportunistic neurological diseases in a Brazilian AIDS reference hospital

INTRODUÇÃO: Os níveis de RNA do HIV-1 no plasma refletem a replicação viral sistêmica e a replicação no sistema nervoso central pode ocorrer independentemente da infecção sistêmica, mas a utilidade da medida destes níveis no líquido cefalorraqueano (LCR) permanece indefinida. OBJETIVO: Comparar os níveis de RNA do HIV-1 no LCR e plasma de pacientes sem doenças neurológicas e com diferentes doenças neurológicas, bem como correlacionar estes níveis com a sua evolução e o uso de antiretrovirais. MÉTODO: Foram avaliados 97 pacientes com suspeita de doença neurológica que realizaram punção lombar e que foram divididos em dois grupos: sem doenças neurológicas (23) e com doenças neurológicas (74). Metodologia NASBA foi usada para quantificação do RNA do HIV-1. RESULTADOS: A mediana da carga viral do LCR foi maior em pacientes com neurotoxoplasmose, neurocriptococose, demência pelo HIV e doença neurológica sem etiologia definida quando comparada aos pacientes sem doenças neurológicas. Não houve diferença da carga viral do plasma entre os pacientes com e sem doença neurológica. A mediana da carga viral do plasma e LCR foi maior nos pacientes que faleceram em relação aos tratados com sucesso. A carga viral do LCR e plasma foi menor nos pacientes com doenças oportunísticas que usavam HAART em relação aos que não a usavam. CONCLUSÃO: A carga viral no LRC foi maior nos pacientes com qualquer doença neurológica em relação aos sem doenças neurológicas, mas isto não ocorreu no plasma, sugerindo que doença neurológica influencia mais o compartimento do LCR que o do plasma, mas não foi possível diferenciar as doenças neurológicas pelos níveis de RNA do HIV-1 do LCR.