Neurological complications of varicella-zoster virus infection in adults with human immunodeficiency virus infection

This multicentre retrospective study describes the clinical features and prognostic significance of Varicella-zoster virus (VZV)-associated neurological complications. The study was performed in patients with human immunodeficiency virus (HIV) infection, hospitalized for VZV neurological complications, confirmed in every case by positive VZV polymerase chain reaction (PCR) in cerebrospinal fluid (CSF). Between 1990 and 1995, 34 HIV-infected patients were included in the study. At diagnosis, 59% had AIDS, with a median CD4 count of 11 x 10(9)/l. A past history of zoster was noted in 35% of cases. A concomitant herpes zoster rash and/or acute retinal necrosis were noted in 71% and 12% of patients, respectively. The predominant neurological manifestations were encephalitis (13), myelitis (8), radiculitis (7) and meningitis (6). The mean CSF white blood cell count was 126/mm3 and the mean CSF protein concentration was 2.3 g/l. Interferon-alpha level was increased in 36% of patients. VZV was isolated from CSF cultures in 2/6 cases. Magnetic resonance imaging was abnormal, demonstrating encephalitis lesions. After intravenous antiviral therapy, complete recovery was obtained in 18 cases (53%), serious sequelae were observed in 10 cases (29%) and 6 patients died (18%). Severe symptoms and a low CD4 cell count appeared to be associated with death or sequelae. In conclusion, VZV should be considered as a possible cause of encephalitis, myelitis, radiculitis or meningitis in HIV-infected patients, especially in patients with a history of or concomitant herpes zoster or acute retinal necrosis. VZV-PCR in the CSF may allow rapid diagnosis and early specific antiviral treatment.     

Prevalence and Correlates of Metabolic Acidosis among Patients with Homozygous Sickle Cell Disease

Background and objectives

Very few studies report acid base disorders in homozygous patients with sickle cell anemia (SCA) and describe incomplete renal acidosis rather than true metabolic acidosis, the prevalence of which is unknown and presumably low. This study aimed to assess the prevalence of metabolic acidosis and to identify its risk factors and mechanisms.

Design, setting, participants, & measurements

This study retrospectively analyzed 411 homozygous patients with SCA with a GFR≥60 ml/min per 1.73 m², referred in a single center between 2007 and 2012. Acidosis and nonacidosis groups were compared for clinical and biologic data including SCA complications and hemolytic parameters. A subgroup of 65 patients with SCA, referred for a measured GFR evaluation in the setting of sickle cell–associated nephropathy, was further analyzed in order to better characterize metabolic acidosis.

Results

Metabolic acidosis was encountered in 42% of patients with SCA, with a higher prevalence in women (52% versus 27% in men; P<0.001). Several hemolytic biomarkers, such as lactate dehydrogenase, were different between the acidosis and nonacidosis groups (P=0.02 and P=0.03 in men and women, respectively), suggesting higher hemolytic activity in the former group. To note, fasting urine osmolality was low in the whole study population and was significantly lower in men with SCA in the acidosis group (392 versus 427 mOsm/kg; P=0.01). SCA subgroup analysis confirmed metabolic acidosis with a normal anion gap in 14 patients, characterized by a lower urinary pH (P<0.02) and no increase in urinary ammonium. Serum potassium, plasma renin, and aldosterone were similar between the two groups and thus could not explain impaired urinary ammonium excretion.

Conclusions

These results suggest that the prevalence of metabolic acidosis in patients with SCA is underestimated and related to impaired ammonium availability possibly due to an altered corticopapillary gradient. Future studies should evaluate whether chronic metabolic acidosis correction may be beneficial in this population, especially in bone remodeling.     

Subclinical left ventricular systolic impairment in steady state young adult patients with sickle-cell anemia

Chronic volume overload in sickle-cell anemia (SCA) is associated with left ventricular (LV) enlargement and hypertrophy. The effect of the disease on LV systolic function remains debated. The aim of our study was to investigate LV systolic function in SCA patients using 2D speckle-tracking imaging. We compared 30 steady state asymptomatic adult SCA patients (17 women, mean age 24.7 ± 5.1 years) with 30 age and sex-matched healthy subjects (17 women, mean age 25.0 ± 4.9 years). In addition to conventional echocardiographic parameters including LV ejection fraction (LVEF) and LV mass index (LVMi), global longitudinal strain (GLS) and strain rate (GLSR) were measured. GLS (?17.9 ± 2.0 vs. ?19.7 ± 2.5 %, p = 0.004) and GLSR (?0.92 ± 0.09 vs. ?1.07 ± 0.17 s^?1, p < 0.0001) values were lower in SCA patients while LVEF values (60.1 ± 3.8 vs. 61.7 ± 4.7 %, p = 0.30) were not different. LVMi was increased in SCA patients (100.7 ± 23.5 vs. 72.4 ± 15.2 g/m², p = 0.0001) and GLSR was significantly lower in the subgroup of patients with LV hypertrophy (?0.88 ± 0.09 vs. ?0.96 ± 0.08 s^?1, p = 0.02). In SCA patients LVMi was correlated to GLS (r = 0.58, p = 0.001) and GLSR (r = 0.45, p = 0.015) pleading in favor of a pathological LV remodeling. Asymptomatic SCA patients exhibited a subclinical alteration of LV systolic function. Myocardial dysfunction appears to be linked to the degree of LV hypertrophy. 2D speckle-tracking imaging might be useful for long-term follow-up and to study the natural course of LV dysfunction in SCA patients.