Immunological alterations in tuberculosis associated immune reconstitution inflammatory syndrome in HIV infected patients

The tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS) frequently complicates the course of HIV/AIDS and HIV-TB treatment and its immunological mechanisms are poorly understood. Here, we investigated T-cells frequencies, their secreted chemokines and cytokines. In this prospective case-control study, HIV/AIDS and HIV-TB patients during treatment with highly active antiretroviral treatment (HAART) and anti-TB treatment were followed for TB-IRIS development. Age, gender and BMI-matched patients without IRIS constituted as “Controls” (non-IRIS). Activation and proliferation were assessed in CD4 and CD8 cell compartments. CCR4, CCR6 and T-reg cells were also analysed in PBMCs. Cytokines (IL-2, IL-4, IL-10, IFN-γ and TGF-β1) and chemokines (IP-10, MCP-1, MIG and RANTES) were measured in culture supernatants. Of 560 enrolled HIV/AIDS patients, TB-IRIS developed in 50 (8.9%) patients (25-paradoxical and 25-unmasking) at a median interval of 35-days (IQR, 24-78). After ART therapy, CD8+ T-cell proportion decreased in both paradoxical and unmasking-TB-IRIS as compared to non-IRIS. Simultaneously, activation of CD4+ T-cells was observed in unmasking TB-IRIS only. Similarly, CD161+ T-cells, Th17-cells and inflammatory cytokines like IFN-γ, IP-10 and MIG elevated in both TB-IRIS subgroups as compared to non-IRIS.In conclusion, during HAART treatment the dominance of pro-inflammatory cells and cytokines in TB-IRIS patients favours the development of IRIS event. On the other hand, in non-IRIS patients relative increase of anti-inflammatory cells and cytokines prevents the development of IRIS event.

Aetiology, outcomes & predictors of mortality in acute respiratory distress syndrome from a tertiary care centre in north India.

Background & objectives: Acute respiratory distress syndrome (ARDS) is a common disorder in critically ill patients and is associated with high mortality. There is a paucity of literature on this condition from developing countries. This prospective observational study was designed to find out the aetiology, outcomes and predictors of mortality in ARDS. Methods: Sixty four consecutive patients who satisfied American-European Consensus Conference (AECC) definition of ARDS from medical Intensive Care Unit (ICU) of a tertiary care centre in New Delhi, India, were enrolled in the study. Demographic, biochemical and ventilatory variables were recorded for each patient. Baseline measurements of serum interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α), procalcitonin (PCT) and high sensitivity C-reactive protein (hsCRP) were performed. Results: Common causes of ARDS included pneumonia [44/64 (68.7%)], malaria [9/64 (14.1%)] and sepsis [8/64 (12.5%]. Eight of the 64 (12.5%) patients had ARDS due to viral pneumonia. The 28-day mortality was 36/64 (56.2%).Independent predictors of mortality included non-pulmonary organ failure, [Hazard ratio (HR) 7.65; 95% CI 0.98-59.7, P=0.05], Simplified Acute Physiology Score (SAPS-II) [HR 2.36; 95% CI 1.14-4.85, P=0.02] and peak pressure (Ppeak) [HR 1.13; 95% CI 1.00-1.30, P = 0.04] at admission. Interpretation & conclusions: Bacterial and viral pneumonia, malaria and tuberculosis resulted in ARDS in a considerable number of patients. Independent predictors of mortality included non-pulmonary organ failure, SAPS II score and Ppeak at baseline. Elevated levels of biomarkers such as TNF-α, PCT and hsCRP at admission might help in identifying patients at a higher risk of mortality.

Malignancies in human immunodeficiency virus infected patients in India: Initial experience in the HAART era.

Background & objectives: Limited data are available on malignancies in human immunodeficiency virus (HIV)-infected patients from India. We undertook this study to assess the frequency and spectrum of malignancies in HIV-infected adult patients during the first eight years of highly active antiretroviral therapy (HAART) rollout under the National ART Programme at a tertiary care centre in New Delhi, India. Methods: Retrospective analysis of records of patients registered at the ART clinic between May 2005 and December 2013 was done. Results: The study included 2598 HIV-infected adult patients with 8315 person-years of follow up. Malignancies were diagnosed in 26 patients with a rate of 3.1 (IQR 2.1-4.5) cases per 1000 person-years. The median age for those diagnosed with malignancy was 45 (IQR 36-54) yr, which was significantly (P<0.01) higher compared with those not developing malignancies 35 (IQR 30-40) yr. The median baseline CD4+ T-cell count in patients with malignancy was 135 (IQR 68-269) cells/μl compared to 164 (IQR 86-243) cells/μl in those without malignancies. AIDS-defining cancers (ADCs) were seen in 19 (73%) patients, while non-AIDS-defining cancers (NADCs) were observed in seven (27%) patients. Malignancies diagnosed included non-Hodgkin’s lymphoma (16), carcinoma cervix (3), Hodgkin’s lymphoma (2), carcinoma lung (2), hepatocellular carcinoma (1), and urinary bladder carcinoma (1). One patient had primary central nervous system lymphoma. There was no case of Kaposi’s sarcoma. Interpretation & conclusions: Malignancies in HIV-infected adult patients were infrequent in patients attending the clinic. Majority of the patients presented with advanced immunosuppression and the ADCs, NHL in particular, were the commonest malignancies.

Consensus & Evidence-based INOSA Guidelines 2014 (First edition).

Obstructive sleep apnoea (OSA) and obstructive sleep apnoea syndrome (OSAS) are subsets of sleep-disordered breathing. Awareness about OSA and its consequences amongst the general public as well as the majority of primary care physcians across India is poor. This necessiated the development of the INdian initiative on Obstructive Sleep Apnoea (INOSA) guidelines under the auspices of Department of Health Research, Ministry of Health & Family Welfare, Government of India. OSA is the occurrence of an average five or more episodes of obstructive respiratory events per hour of sleep with either sleep related symptoms or comorbidities or >15 such episodes without any sleep related symptoms or comorbidities. OSAS is defined as OSA associated with daytime symptoms, most often excessive sleepiness. Patients undergoing routine health check-up with snoring, daytime sleepiness, obesity, hypertension, motor vehicular accidents and high risk cases should undergo a comprehensive sleep evaluation. Medical examiners evaluating drivers, air pilots, railway drivers and heavy machinery workers should be educated about OSA and should comprehensively evaluate applicants for OSA. Those suspected to have OSA on comprehensive sleep evaluation should be referred for a sleep study. Supervised overnight polysomnography (PSG) is the “gold standard” for evaluation of OSA. Positive airway pressure (PAP) therapy is the mainstay of treatment of OSA. Oral appliances are indicated for use in patients with mild to moderate OSA who prefer oral appliances to PAP, or who do not respond to PAP or who fail treatment attempts with PAP or behavioural measures. Surgical treatment is recommended in patients who have failed or are intolerant to PAP therapy.

Central venous catheter related bloodstream infections in medical intensive care unit patients in a tertiary referral centre.

Aims. To determine the incidence of central line associated bloodstream infections (CLABSIs) in the medical intensive care unit (ICU) and ward setting at All India Institute of Medical Sciences (AIIMS), New Delhi. Settings and Design. The study was conducted in the medical ICU, a 9-bedded ICU at the AIIMS, a tertiary care teaching hospital. The study design was a prospective observational study. Methods. One hundred patients admitted to medical ICU and the ward at AIIMS with an indwelling, non-tunnelled central venous catheter (CVC) in place at admission and those with a hospital stay with indwelling CVC for more than 48 hours were monitored. These patients were followed daily for the development of new onset sepsis 48 hours after insertion of CVC, in which case three sets of blood samples for culture were drawn over a span of 24 hours. Statistical Methods. Incidence of CLABSIs was measured per 1000 central line days. Results. One hundred patients hospitalised for an aggregate 1119 days acquired 29 hospital-acquired infections (HAIs), a rate of 38.8% or 31.2 HAIs per 1000 hospital days. The incidence of bloodstream infections (BSIs) in this group was 6.8%. No case of laboratory confirmed CLABSIs could be demonstrated. Incidence of clinical sepsis was 27.6% or 8.2 per 1000 CVC days. There were 9 cases out of the 29 patients (39.7%) who had evidence of HAIs with no apparent focus of infection. Only one of these cases had evidence of BSI with isolation of Staphylococcus aureus in both CVC tip culture and the simultaneous blood culture; however the antibiograms were different. Conclusions. The low rate of BSIs in the present study and the absence of occurrence of a laboratory confirmed CLABSI should be interpreted in the light of the small sample size of the study and the multitude of antibiotics received before the development of HAI.

Clinical profile & predictors of poor outcome of adult HIV-tuberculosis patients in a tertiary care centre in north India.

Background & objectives: There is a paucity of data from India on response to treatment of tuberculosis (TB) in patients with human immunodeficiency virus (HIV)-TB co-infection. This study was done to assess the frequency and pattern of TB, outcome of anti-tuberculosis treatment, and the factors related to poor outcome of TB treatment in adult patients with HIV infection. Methods: Retrospective review of case records of HIV-TB co-infected patients attending the antiretroviral therapy (ART) clinic in a tertiary care centre in north India was done. Results: Of the 1754 patients included in the study, 583 (33.2%) were diagnosed with active TB and 466 (79.9%) of them had CD4 count less than 200/μl at diagnosis. Extrapulmonary TB was diagnosed in 372 (63.8%) patients [76 (20.4%) had disseminated TB], and pulmonary TB in 211 (36.2%) patients. “Favourable outcome” (cure and completed treatment) was observed in 332 (77%) patients. Unfavourable outcome included default (8.1%), treatment failure (1.6%), and death (13.2%). At 1-year post-treatment follow up, 12 (3.6%) patients had disease relapse. CD4 count of less than 200/ μl at diagnosis [OR-2.32, CI (1.06-5.09)], and retreatment cases [OR-2.91, CI (1.22-6.89)] were independent predictors of unfavourable outcome. Interpretation & conclusions: There is an urgent need to strengthen the information, education, communication activities and expand the ART services to meet the requirement of early testing and treatment initiation in patients co-infected with HIV-TB. The findings highlight the need for performing drug susceptibility testing (DST) for patients starting retreatment regimen to improve treatment outcome.

Tuberculosis: From an incurable scourge to a curable disease - journey over a millennium.

Globally, tuberculosis (TB) still remains a major public health problem. India is a high TB burden country contributing to 26 per cent of global TB burden. During 1944-1980, TB became treatable and short-course chemotherapy emerged as the standard of care. When TB elimination seemed possible in the early 1980s, global human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) pandemic resulted in a resurgence of TB. Widespread occurrence of multidrug-resistant and extensively drug-resistant TB (M/XDR-TB) is threatening to destabilize TB control globally. Atypical clinical presentation still poses a challenge. Disseminated, miliary and cryptic TB are being increasingly recognized. Availability of newer imaging modalities has allowed more efficient localization of lesions and use of image guided procedures has facilitated definitive diagnosis of extrapulmonary TB. Introduction of liquid culture, rapid drug-susceptibility testing (DST), molecular diagnostic methods has helped in rapid detection, speciation and DST profiling of Mycobacterium tuberculosis isolates. While treatment of TB and HIV-TB co-infection has become simpler, efforts are on to shorten the treatment duration. However, drug toxicities and drug-drug interactions still constitute a significant challenge. Recently, there has been better understanding of anti-TB drug-induced hepatotoxicity and its frequent confounding by viral hepatitis, especially, in resource-constrained settings; and immune reconstitution inflammatory syndrome (IRIS) in HIV-TB. Quest for newer biomarkers for predicting a durable cure, relapse, discovery/repurposing of newer anti-TB drugs, development of newer vaccines continues to achieve the goal of eliminating TB altogether by 2050.

Contribution of medical colleges to tuberculosis control in India under the Revised National Tuberculosis Control Programme (RNTCP): Lessons learnt & challenges ahead.

Medical college faculty, who are academicians are seldom directly involved in the implementation of national public health programmes. More than a decade ago for the first time in the global history of tuberculosis (TB) control, medical colleges of India were involved in the Revised National TB Control Programme (RNTCP) of Government of India (GOI). This report documents the unique and extraordinary course of events that led to the involvement of medical colleges in the RNTCP of GOI. It also reports the contributions made by the medical colleges to TB control in India. For more than a decade, medical colleges have been providing diagnostic services (Designated Microscopy Centres), treatment [Directly Observed Treatment (DOT) Centres] referral for treatment, recording and reporting data, carrying out advocacy for RNTCP and conducting operational research relevant to RNTCP. Medical colleges are contributing to diagnosis and treatment of human immunodeficiency virus (HIV)-TB co-infection and development of laboratory infrastructure for early diagnosis of multidrug-resistant and/or extensively drug-resistant TB (M/XDR-TB) and DOTS-Plus sites for treatment of MDR-TB cases. Overall, at a national level, medical colleges have contributed to 25 per cent of TB suspects referred for diagnosis; 23 per cent of ‘new smear-positives’ diagnosed; 7 per cent of DOT provision within medical college; and 86 per cent treatment success rate among new smear-positive patients. As the Programme widens its scope, future challenges include sustenance of this contribution and facilitating universal access to quality TB care; greater involvement in operational research relevant to the Programme needs; and better co-ordination mechanisms between district, state, zonal and national level to encourage their involvement.

Challenges in the diagnosis & treatment of miliary tuberculosis.

Miliary tuberculosis (TB) is a potentially lethal disease if not diagnosed and treated early. Diagnosing miliary TB can be a challenge that can perplex even the most experienced clinicians. Clinical manifestations are nonspecific, typical chest radiograph findings may not be evident till late in the disease, high resolution computed tomography (HRCT) shows randomly distributed miliary nodules and is relatively more sensitive. Ultrasonography, CT and magnetic resonance imaging (MRI) are useful in discerning the extent of organ involvement by lesions of miliary TB in extra-pulmonary locations. Fundus examination for choroid tubercles, histopathological examination of tissue biopsy specimens, conventional and rapid culture methods for isolation of Mycobacterium tuberculosis, drug-susceptibility testing, along with use of molecular biology tools in sputum, body fluids, other body tissues are useful in confirming the diagnosis. Although several prognostic markers have been described which predict mortality, yet untreated miliary TB has a fatal outcome within one year. A high index of clinical suspicion and early diagnosis and timely institution of anti-tuberculosis treatment can be life-saving. Response to first-line anti-tuberculosis drugs is good but drug-induced hepatotoxicity and drug-drug interactions in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients pose significant problems during treatment. However, sparse data are available from randomized controlled trials to define the optimum regimen and duration of treatment in patients with drug-sensitive as well as drug-resistant miliary TB, including those with HIV/AIDS.

Rare manifestations of sarcoidosis in modern era of new diagnostic tools.

Background & objectives: Growing body of literature on sarcoidosis in India has led to an increased awareness of the disease. With the advent of better imaging tools hitherto under-recognized manifestations of sarcoidosis are likely to be better recognized. We sought to study the rare clinical and radiological manifestations (<5%) in patients with sarcoidosis. Methods: Retrospective review of records of 164 patients with histopathologically proven sarcoidosis seen over six years in a tertiary care centre in north India, was done. Results: Fifty four rare manifestations were observed in 164 patients. Acute presentation in the form of Lofgren syndrome was seen in eight (4.9%) and Heerfordt's syndrome in two (1.2%) patients. Musculoskeletal manifestations included chronic sarcoid arthritis in three (1.8%), deforming arthritis and bone erosion in one (0.6%) each. Rare initial presentation with dilated cardiomyopathy in one (0.6%), complete heart block in two (1.2%), bilateral sequential facial nerve palsy in two (1.2%), and pyrexia of unknown origin was seen in one (0.6%) patient. Other rare manifestations included chronic respiratory failure in one (0.6%), dysphagia in one (0.6%), sicca syndrome in five (3%), massive splenomegaly in one (0.6%), portal hypertension in two (1.2%), hypersplenism, gastric sarcoidosis, ninth and tenth cranial nerve palsies, moderate pericardial effusion and nephrocalcinosis in one (0.6%) each, and pulmonary artery hypertension in two (1.2%) patients. Rare radiological manifestations included moderate pleural effusion in two (1.2%), pleural thickening in five (3%), calcification of intrathoracic lymph nodes in four (2.4%), alveolar (nodular) sarcoidosis in three (1.8%), and myocardial uptake of 18F-fluorodeoxyglucose (F-18 FDG) in two (1.2%) patients. Fourteen patients had airways obstruction and behaved typically like seasonal bronchial asthma with excellent response to corticosteroids. Interpretation & conclusions: Increased awareness of rare manifestations will facilitate better management of these patients. With increasing use of modern diagnostic tools, manifestations hitherto considered rare, are likely to be recognized more frequently in the future.

HIV & immune reconstitution inflammatory syndrome (IRIS).

Antiretroviral therapy (ART) initiation in HIV-infected patients leads to recovery of CD4+T cell numbers and restoration of protective immune responses against a wide variety of pathogens, resulting in reduction in the frequency of opportunistic infections and prolonged survival. However, in a subset of patients, dysregulated immune response after initiation of ART leads to the phenomenon of immune reconstitution inflammatory syndrome (IRIS). The hallmark of the syndrome is paradoxical worsening of an existing infection or disease process or appearance of a new infection/disease process soon after initiation of therapy. The overall incidence of IRIS is unknown, but is dependent on the population studied and the burden of underlying opportunistic infections. The immunopathogenesis of the syndrome is unclear and appears to be result of unbalanced reconstitution of effector and regulatory T-cells, leading to exuberant inflammatory response in patients receiving ART. Biomarkers, including interferon-γ (INF-γ), tumour necrosis factor-α (TNF-α), C-reactive protein (CRP) and inter leukin (IL)-2, 6 and 7, are subject of intense investigation at present. The commonest forms of IRIS are associated with mycobacterial infections, fungi and herpes viruses. Majority of patients with IRIS have a self-limiting disease course. ART is usually continued and treatment for the associated condition optimized. The overall mortality associated with IRIS is low; however, patients with central nervous system involvement with raised intracranial pressures in cryptococcal and tubercular meningitis, and respiratory failure due to acute respiratory distress syndrome (ARDS) have poor prognosis and require aggressive management including corticosteroids. Paradigm shifts in management of HIV with earlier initiation of ART is expected to decrease the burden of IRIS in developed countries; however, with enhanced rollout of ART in recent years and the enormous burden of opportunistic infections in developing countries like India, IRIS is likely to remain an area of major concern.

Prevalence of metabolic syndrome in a north Indian hospital-based population with obstructive sleep apnoea.

Background & objectives: Obstructive sleep apnoea (OSA) is known to be associated with cardiovascular risk factors and metabolic syndrome (MS). The burden of MS in patients with OSA in India is unknown. We investigated the prevalence of MS and its components in a cross-sectional study in patients with and without OSA in a hospital-based population of a tertiary health care centre in New Delhi, India. Methods: Consecutive patients undergoing overnight polysomnography in the Sleep Laboratory of the Department of Internal Medicine of All India Institute of Medical Sciences (AIIMS) hospital, New Delhi, were studied. Anthropometry and body composition analysis, blood pressure (BP), fasting blood glucose, insulin resistance by homeostasis model assessment (HOMA-IR) and fasting blood lipid profile were measured. MS was defined using the National Cholesterol Education Program Adult treatment panel III criteria, with Asian cut-off values for abdominal obesity. Results: Of the 272 subjects recruited, 187 (82%) had OSA [apnoea-hypopnoea index (AHI)>5 events/h] while 40 (18%) had a normal sleep study. Prevalence of MS in OSA patients was 79 per cent compared to 48 per cent in non-OSA individuals [OR 4.15, (2.05-8.56), P<0.001]. Prevalence of OSA in mild, moderate and severe OSA was 66, 72 and 86 per cent, respectively (P<0.001). Patients with OSA were more likely to have higher BP [OR: 1.06 (1.02-1.11)], fasting insulin [OR: 1.18 (1.05-1.32)], HOMA-IR [OR: 1.61 (1.11-2.33)] and waist circumference [OR: 1.20 (1.13-1.27)]. Interpretation & conclusions: Our findings suggest that OSA is associated with a 4-fold higher occurrence of MS than patients without OSA. The prevalence of MS increases with increasing severity of OSA, therefore, early detection will be beneficial.

Prevalence of multidrug-resistant tuberculosis among Category II pulmonary tuberculosis patients.

Background & objectives: Multidrug-resistant tuberculosis (MDR-TB) has emerged as a significant global health concern. The most important risk factor for the development of MDR-TB is previous anti-tuberculosis therapy. Category II pulmonary TB includes those patients who had failed previous TB treatment, relapsed after treatment, or defaulted during previous treatment. We carried out this study to ascertain the prevalence of MDR-TB among category II pulmonary TB patients. Methods: This was a cross-sectional, descriptive study involving category II pulmonary TB patients diagnosed between 2005 and 2008. All sputum-positive category II TB cases were subjected to mycobacterial culture and drug-susceptibility testing (DST). MDR-TB was defined as TB caused by bacilli showing resistance to at least isoniazid and rifampicin. Results: A total of 196 cases of sputum-positive category II pulmonary tuberculosis patients were included. Of these, 40 patients (20.4%) had MDR-TB. The mean age of MDR-TB patients was 33.25 ± 12.04 yr; 9 patients (22.5%) were female. Thirty six patients showed resistance to rifampicin and isoniazid; while 4 patients showed resistance to rifampicin, isoniazid and streptomycin. The prevalence of MDR-TB among category-II pulmonary tuberculosis patients was 20.4 per cent. Interpretation & conclusions : The prevalence of MDR-TB in category II TB patients was significant. However, nation-wide and State-wide representative data on prevalence of MDR-TB are lacking. We stress the importance of continuous monitoring of drug resistance trends, in order to assess the efficacy of current interventions and their impact on the TB epidemic.

Prevalence of multidrug-resistant tuberculosis among newly diagnosed cases of sputum-positive pulmonary tuberculosis.

Background & objectives: The prevalence of multidrug-resistant tuberculosis (MDR-TB) is increasing throughout the world. Although previous treatment for TB is the most important risk factor for development of MDR-TB, treatment-naïve patients are also at risk due to either spontaneous mutations or transmission of drug-resistant strains. We sought to ascertain the prevalence of MDR-TB among new cases of sputum-positive pulmonary TB. Methods: This was a prospective, observational study involving newly diagnosed cases of sputum-positive pulmonary tuberculosis diagnosed between 2008 and 2009 carried out in New Delhi, India. All sputum-positive TB cases were subjected to mycobacterial culture and first-line drug-susceptibility testing (DST). MDR-TB was defined as TB caused by bacilli showing resistance to at least isoniazid and rifampicin. Results: A total of 218 cases of sputum-positive pulmonary tuberculosis were enrolled between 2008 and 2009. Of these, 41 cases had negative mycobacterial cultures and DST was carried out in 177 cases. The mean age of the patients was 27.8 ± 10.2 yr; 59 patients (27%) were female. All patients tested negative for HIV infection. Out of 177 cases, two cases of MDR-TB were detected. Thus, the prevalence of MDR-TB among newly diagnosed pulmonary tuberculosis patients was 1.1 per cent. Interpretation & conclusions: MDR-TB prevalence is low among new cases of sputum-positive pulmonary TB treated at primary care level in Delhi. Nation-wide and State-wide representative data on prevalence of MDR-TB are lacking. Efforts should be directed towards continued surveillance for MDR-TB among newly diagnosed TB cases.

Pattern & correlates of neurocognitive dysfunction in Asian Indian adults with severe obstructive sleep apnoea.

Background & objectives: No published data are available on neurocognitive dysfunction in Asian Indians with obstructive sleep apnoea (OSA). We therefore, studied the pattern and correlates of neurocognitive dysfunction in Indian adults with severe OSA. Methods: Fifty patients aged 25-65 yr with severe OSA (apnoea-hypopnoea index > 30) and 25 age, sex, and education level-matched normal controls were studied. Both groups were administered a standardized battery of neurocognitive tests. Results: Patients with severe OSA had significantly impaired performance on tests of alertness, working memory, response inhibition, problem solving, and executive function. However, the difference in executive function between the groups disappeared after adjusting for delayed information processing. The test scores did not correlate with apnoea-hypopnoea index, arousal index, or Epworth sleepiness score. However, the percentage of time spent at < 90 per cent oxygen saturation had a weak correlation with the number of stroop errors (Spearman’s rho = 0.64; P = 0.033), number of trials required (rho = 0.05; P = 0.02), and perseverative errors on Wisconsin card sorting test (rho = 0.36; P = 0.02). Interpretation & conclusions: Our results suggested that delayed information processing rather than impaired abstract thinking was probably the cause of impaired performance on composite tests of neurocognitive function in patients with severe OSA.

Proton magnetic resonance spectroscopy of brain in obstructive sleep apnoea in north Indian Asian subjects.

Background & objectives: Repeated apnoeic/hypoapnoeic episodes during sleep may produce cerebral damage in patients with obstructive sleep apnoea (OSA). The aim of this study was to determine the absolute concentration of cerebral metabolites in apnoeic and non-apnoeic subjects from different regions of the brain to monitor the regional variation of cerebral metabolites. Methods: Absolute concentration of cerebral metabolites was determined by using early morning proton magnetic resonance spectroscopy (1H MRS) in 18 apnoeic patients with OSA (apnoeics) having apnoea/hypopnoea index (AHI) >5/h, while 32 were non-apnoeic subjects with AHI< 5/h. Results: The absolute concentration of tNAA [(N-acetylaspartate (NAA)+N-acetylaspartylglutamate (NAAG)] was observed to be statistically significantly lower (P<0.05) in apnoeics in the left temporal and left frontal gray regions compared to non-apnoeics. The Glx (glutamine, Gln + glutamate, Glu) resonance showed higher concentration (but not statistically significant) in the left temporal and left frontal regions of the brain in apnoeics compared to non-apnoeics. The absolute concentration of myo-inositol (mI) was significantly high (P<0.03) in apnoeics in the occipital region compared to non-apnoeics. Interpretation & conclusions: Reduction in the absolute concentration of tNAA in apnoeics is suggestive of neuronal damage, probably caused by repeated apnoeic episodes in these patients. NAA showed negative correlation with AHI in the left frontal region, while Cho and mI were positively correlated in the occipital region and Glx showed positive correlation in the left temporal region of the brain. Overall, our results demonstrate that the variation in metabolites concentrations is not uniform across various regions of the brain studied in patients with OSA. Further studies with a large cohort of patients to substantiate these observations are required.