RESUMO
BACKGROUND: The late-onset efavirenz neurotoxicity syndrome (LENS) presents as ataxia and/or encephalopathy with supratherapeutic efavirenz plasma concentrations (>4 µg/mL). Efavirenz is primarily metabolized by cytochrome P450 2B6 (CYP2B6), with CYP2A6 as an accessory pathway. We hypothesized that participants with LENS would predominantly be CYP2B6 slow metabolizers. The aim of our study was to determine the frequency of CYP2B6 slow metabolizers in participants with LENS. METHODS: Adult HIV-positive participants on efavirenz-based antiretroviral therapy presenting with LENS were prospectively enrolled. Genetic polymorphisms known to be associated with increased efavirenz plasma concentrations in CYP2B6 (rs3745274, rs28399499, rs4803419) and CYP2A6 (rs28399433) were selected and used to determine proportions of slow metabolizers. Pharmacokinetic analyses were performed using liquid chromatography-tandem mass spectrometry. Median (IQR) plasma efavirenz and 8-hydroxyefavirenz were described. RESULTS: Fifteen participants were enrolled. Thirteen (13/15) were Black-African and 13 were female. Median weight was 49.9kg with a median duration on efavirenz of 2.2 years. All 15 participants were successfully genotyped as slow CYP2B6 metabolizers, with 6 participants additionally having CYP2A6 heterozygous genotype. Thirteen were receiving the CYP2A6 enzyme inhibitor isoniazid, and all 15 were genotypic NAT2 slow or intermediate acetylators. Efavirenz plasma concentration was markedly increased at 50.5 (47.0-65.4) µg/mL; 8-hydroxyefavirenz concentration was markedly decreased at 0.10 (0.07-0.15) µg/mL. CONCLUSIONS: Our cohort provides definitive evidence that LENS is associated with the CYP2B6 slow metabolizer genotype, with a median efavirenz plasma concentrationâ >12-fold higher than the defined upper limit of the therapeutic range. Isoniazid and low body weight are important contributors to LENS development.
Assuntos
Fármacos Anti-HIV , Arilamina N-Acetiltransferase , Infecções por HIV , Síndromes Neurotóxicas , Adulto , Alcinos/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Arilamina N-Acetiltransferase/genética , Benzoxazinas/efeitos adversos , Ciclopropanos/uso terapêutico , Citocromo P-450 CYP2B6/genética , Feminino , Humanos , Isoniazida/uso terapêutico , Masculino , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/genética , Farmacogenética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
INTRODUCTION: This study seeks to determine whether the use of Eulerian video magnification (EVM) increases the detection of muscle fasciculations in people with amyotrophic lateral sclerosis (PALS) compared with direct clinical observation (DCO). METHODS: Thirty-second-long video recordings were taken of 9 body regions of 7 PALS and 7 controls, and fasciculations were counted by DCO during the same 30-s period. The video recordings were then motion magnified and reviewed by 2 independent assessors. RESULTS: In PALS, median fasciculation count per body region was 1 by DCO (range 0-10) and 3 in the EVM recordings (range 0-15; P < 0.0001). EVM revealed more fasciculations than DCO in 61% of recordings. In controls, median fasciculation count was 0 for both DCO and EVM. DISCUSSION: Compared with DCO, EVM significantly increased the detection of fasciculations in body regions of PALS. When it is used to supplement clinical examination, EVM has the potential to facilitate the diagnosis of ALS. Muscle Nerve 56: 1063-1067, 2017.
Assuntos
Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/fisiopatologia , Fasciculação/diagnóstico , Fasciculação/fisiopatologia , Estudo de Prova de Conceito , Gravação em Vídeo/normas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Software/normas , Gravação em Vídeo/métodosRESUMO
BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described autoimmune inflammatory disorder of the central nervous system (CNS). There is limited data on the association between Human Immunodeficiency virus (HIV) infection and MOGAD. We report three patients with HIV infection and myelin oligodendrocyte glycoprotein (MOG) antibodies in the setting of other central nervous system infections. CASE DESCRIPTIONS: The first patient, a 44-year-old black African man, presented with acute disseminated encephalomyelitis (ADEM) with positive serum MOG antibodies. He made a significant recovery with corticosteroids but had a quick relapse and died from sepsis. The second patient, an 18-year-old black woman, presented with paraplegia and imaging revealed a longitudinally extensive transverse myelitis and had positive serum MOG antibodies. She remained paraplegic after methylprednisone and plasmapheresis treatments. Her rehabilitation was complicated by development of pulmonary embolism and tuberculosis. The third patient, a 43-year-old mixed-race woman, presented with bilateral painless visual loss. Her investigations were notable for positive MOG antibodies, positive Varicella Zoster Virus on cerebral spinal fluid (CSF) and hyperintense optic nerves on magnetic resonance imaging (MRI). Her vision did not improve with immunosuppression and eventually died from sepsis. CONCLUSION: Our cases illustrate the diagnostic and management challenges of MOGAD in the setting of advanced HIV infection, where the risk of CNS opportunistic infections is high even without the use of immunosuppression. The atypical clinical progression and the dilemmas in the diagnosis and treatment of these cases highlight gaps in the current knowledge of MOGAD among people with HIV that need further exploration.
Assuntos
Encefalomielite Aguda Disseminada , Infecções por HIV , Sepse , Masculino , Feminino , Humanos , Adulto , Adolescente , Glicoproteína Mielina-Oligodendrócito , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , AutoanticorposRESUMO
A man in his 20s presented with headache and acute deterioration in visual acuity. He was found to have panuveitis and raised intracranial pressure with papilloedema. MRI and F-fluorodeoxyglucose positron emission tomography confirmed a subclinical, but active, inflammatory mastoid process. Histology of the mastoid showed immunoglobulin G4 (IgG4) cells, plasma cells and storiform fibrosis.This presentation of IgG4 disease has not been previously described.Treatment with high-dose steroids was initiated, followed by long-term immunosuppressive therapy. The patient's symptoms improved, although he remains dependent on azathioprine and low dose oral steroids for symptom control. To date, there has been no progression of the disease.
Assuntos
Doenças do Sistema Imunitário , Doença Relacionada a Imunoglobulina G4 , Masculino , Humanos , Processo Mastoide/diagnóstico por imagem , Processo Mastoide/patologia , Doença Relacionada a Imunoglobulina G4/diagnóstico , Imunoglobulina G , Plasmócitos/patologia , Tomografia por Emissão de Pósitrons , Doenças do Sistema Imunitário/patologiaRESUMO
BACKGROUND AND OBJECTIVES: Antiretroviral treatment (ART) era HIV-associated stroke data from sub-Saharan Africa are limited. We determined the prevalence of HIV in patients presenting with acute symptomatic stroke and compared risk factors, clinical characteristics, and brain imaging with age-matched stroke patients without HIV. METHODS: We conducted a retrospective study of adults presenting with any type of stroke to Tygerberg Hospital in a 12-month period. Patients living with HIV (PLWH) and HIV-uninfected (HIV-) patients were matched based on age group (1:2 ratio). Patients were identified by keyword search, while HIV status was ascertained from laboratory data. Clinical and imaging data were extracted from medical records. RESULTS: Among 884 patients presenting with acute strokes, the minimum prevalence of HIV infection was 9.3% (95% CI: 7.4%-11.2%), with 496 patients (56.1%) with negative HIV status and 306 patients with unknown HIV status (34.6%). The mean age at presentation in PLWH was 46 (±11) years compared with 55 (±14) years in HIV- patients (p < 0.001). Smoking was less prevalent in PLWH with an adjusted relative risk ratio of RR = 0.58 (95% CI: 0.39-0.86). Concurrent infection was more prevalent in PLWH (25.6% vs 4.9%, p ≤ 0.001) with an adjusted relative risk ratio of RR = 2.07 (95% CI: 1.49-2.84), largely in patients with a CD4 count <200 cells/µL. PLWH with higher CD4 counts (≥200 cells/µL, 51.3%) had more traditional risk factors and less concurrent infection. Among PLWH, 68.3% were on ART, and 39.3% of them had been started or restarted on ART within the past 6 months. Basal ganglia infarcts (35.6% vs 18.3%, p = 0.014) and multiple vascular territory involvement (25.4% vs 7.7%, p = 0.002) were more common in PLWH. Clinical presentation, ischemic stroke type, and in-hospital outcomes did not differ between the groups. DISCUSSION: Stroke patients with HIV were younger, had less traditional cardiovascular risk factors, and more concurrent infections than patients without HIV, especially those with a lower CD4 count. Recent ART initiation or reinitiation rates were high. Significant differences in CT brain imaging findings were seen. Understanding the multifactorial mechanisms underlying increased stroke risk, including associated infections and potential ART-associated immune reconstitution, is crucial and needs further study.
Assuntos
Infecções por HIV , Acidente Vascular Cerebral , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Prevalência , Estudos Retrospectivos , África do Sul/epidemiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Centros de Atenção TerciáriaRESUMO
Severe hypertriglyceridemia is the third most common cause of acute pancreatitis and is strongly associated with an increased risk of cardiovascular disease. In infants, the most common cause of severe hypertriglyceridemia is lipoprotein lipase deficiency. We describe a 7-week-old infant with severe hypertriglyceridemia, who presented with frequent gastrointestinal bleeding, respiratory distress, a decreased level of consciousness and lipemia retinalis. Triglycerides were reduced from 734 to 2 mmol/L (64,956-177 mg/dL), by exchange transfusions. The infant made a remarkable recovery with no sequelae. This case highlights atypical, protean presentations and a potential treatment when established therapies are unavailable.
Assuntos
Hipertrigliceridemia/terapia , Insuficiência de Múltiplos Órgãos/etiologia , Troca Plasmática , Transfusão de Sangue , Hemorragia Gastrointestinal/complicações , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/diagnóstico , Hipertrigliceridemia/complicações , Hipertrigliceridemia/patologia , Lactente , Masculino , Índice de Gravidade de Doença , Triglicerídeos/sangueRESUMO
In this case report, we describe the course of a female patient who is known to have neuromyelitis optica (NMO) and developed left hemiparesis and unilateral diaphragmatic paralysis. She was initially treated with intravenous methylprednisolone 1 g daily for 5 days without improvement. Subsequently, she received five sessions of a plasmapheresis. Her hemiparesis had improved after few days. however, the phrenic nerve palsy remained.