Central Disorders of Hypersomnolence in Children and Adults: A Comparative Study from South India.

BACKGROUND: Narcolepsy and idiopathic hypersomnolence (IHS) are rare disorders. In Western populations, the reported prevalence of narcolepsy is 0.02%-0.05%. In Indian subcontinent, there are few reports on narcolepsy and none on IHS so far. Here, we compared the clinical and polysomnographic profile of narcolepsy/IHS among the pediatric and adult groups. MATERIALS AND METHODS: The patients presenting with excessive daytime sleepiness (EDS) attending sleep clinic from January 2010 to December 2015 were included. Patients were diagnosed with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and IHS based on the International Classification for Sleep Disorders criteria. Patients with secondary causes of EDS were excluded from the study. RESULTS: A total of 56 patients were included in the study (29 males and 27 females). The mean age of symptom onset was 29 years (males - 34 years and females - 24 years). Twelve (21%) patients had NT1, five (9%) patients had NT2, whereas 38 (68%) patients had IHS compared to narcolepsy, the IHS had an older mean age at presentation. The average time from symptom onset to diagnosis was 71 months. Classical tetrad of narcolepsy was rarely found in pediatric cohort, but they had more behavioral problems and weight gain. Pediatric cohort of IHS also reported behavioral problems. The mean sleep-onset latency was 3.1 min, while the mean rapid eye movement latency was 7.2 min. CONCLUSION: The pediatric narcolepsy patients tend to have less classical symptoms and more behavioral/eating problems as compared to adult cohort. There is significant delay in diagnosing narcolepsy, indicating the need to increase awareness among the physicians about this rare treatable disorder.

Do quantified sleep architecture abnormalities underlie cognitive disturbances in amnestic mild cognitive impairment?

The study was designed to gauge association between occult sleep-related breathing disturbances and sleep architecture changes on cognitive trajectories in subjects with amnestic mild cognitive impairment (aMCI) relative to cognitively normal healthy controls, phenotyped by neuroimaging. Subjects with aMCI and normal cognition were prospectively recruited. Following standardized neuropsychological and sleep questionnaire assessment they underwent a single overnight polysomnography (PSG); multimodality MRI was used to ascertain age-corrected radiological differences between the 2 groups. The aMCI cohort was followed up longitudinally with serial cognitive assessments for the next 3 years. Thirty seven subjects with aMCI and 24 control subjects consented for evaluation. Although occult moderate to severe obstructive sleep apnea (OSA) was more prevalent in aMCI (43.6%) as opposed to controls (22.7%); higher median apnea-hypopnea index (AHI = 11.5) and total apnea-hypopnea time (26.6 min) were also noted in aMCI relative to controls (6.6 and 11.4 min respectively), the differences were not statistically significant. In the aMCI group, better sleep efficiency, longer duration of REM sleep correlated with higher associative learning, free-recall/recognition memory performance. Higher AHI had negative correlation with visual memory scores. However longitudinal cognitive trends in the aMCI group over 3 years reflected relative stability (only 5% progressed to AD) notwithstanding imaging differences from controls and appeared to be independent of sleep parameters. The study concluded that despite associations between sleep efficiency, REM sleep and sleep-related breathing variables with neuropsychological test-scores in aMCI, these appear to be comorbidities rather than causative factors for the degree of cognitive impairment or its longitudinal trajectory.

Post-stroke Fatigue is an Independent Predictor of Post-stroke Disability and Burden of Care: A Path analysis Study.

UNLABELLED: Post-stroke fatigue (PSF) is a common and one of the most distressing symptoms in stroke survivors. However, little is known about the relationship between severity of fatigue and the overall impact it has on post-stroke disability and burden of care. We aimed to examine the role of PSF in post-stroke disability and burden of care among stroke survivors after their first-ever stroke. METHODS: We prospectively recruited 163 subjects (35 females) from patients examined consecutively in a tertiary stroke care center in India, after their first-ever ischemic or hemorrhagic stroke (>3 months after event). In addition to demographic and clinical characteristics, the following assessments were done - SF-36 vitality domain (fatigue), Modified Rankin Scale (functional recovery), Hospital anxiety and depression scale (depression), Functional independence measure (disability and burden of care). We used path analysis to identify a model that will capture the interactions of fatigue, depression, and degree of functional recovery in stroke survivors. RESULTS: The severity of PSF positively correlated with the severity of disability and PSF had significant contribution to disability over and above functional recovery and depression, with all three factors accounting for 43% of the variance. Among the four models that were proposed to explore these relationships, the best fitting model showed that the effect of PSF is mediated through both the direct effect of fatigue on disability and through its interaction with depression, which remained a separate contributor to post-stroke disability and burden of care. CONCLUSIONS: PSF, therefore, is an important determinant of post-stroke disability and should be evaluated for successful post-stroke rehabilitation.

Employment status, social function decline and caregiver burden among stroke survivors. A South Indian study.

UNLABELLED: Stroke leaves at least 60% of the survivors with moderate to severe disability limiting their employment status and social functioning leading to high levels of caregiver burden. AIM: We sought to study the employment status and level of change of social functioning of stroke survivors and their principal caregiver and correlate it with severity of stroke, functional disability, and anxiety and depression scores. METHODS: One hundred and fifty stroke survivors and principal caregivers (3 months-2 years post-stroke) were recruited for the study. The employment status pre- and post-stroke was assessed. The social function of the patient and caregiver was analyzed using a 6 item social function scale developed for the study, encompassing culturally relevant questions. A 20 point scale adapted from Burden assessment schedule was used to assess the caregiver burden. RESULTS: Mean age of the study group was 54.37±12.072 (range 22-75 years), with 116 males and 34 females. Spouse was the principal caregiver for 142/150 patients (94.6%). In the stroke survivors, compared to the pre-stroke employment status of 62.7%, only 20.7% were employed post-stroke with half having change of job. But the employment status of caregiver was not reduced post-stroke (34.7% vs 33.3%). Employment loss in stroke survivors had a statistically significant association with severity of functional disability, male gender and presence of limb weakness (p values 0.037, 0.0001 and 0.043 respectively). There was an overall decline in social functions among the 6 parameters assessed in both the stroke survivors and caregivers. Of the caregiver burden, financial burden was more among female and older caregivers. The functional status and motor weakness of the stroke survivors did not tend to worsen the overall caregiver burden. CONCLUSIONS: Loss of occupation among stroke survivors is high. The decline in social function among stroke survivors and caregivers was significant. Even though functional disability contributed to employment loss and social function decline among stroke survivors, it did not have a significant impact on caregiver burden.

Clinical and functional outcome and factors predicting prognosis in osmotic demyelination syndrome (central pontine and/or extrapontine myelinolysis) in 25 patients.

AIMS: To assess the functional and clinical outcome in a sizeable cohort of patients with osmotic demyelination syndrome (ODS) and to characterise the factors which could predict the final outcome. METHODS: Twenty five consecutive patients with ODS formed the study cohort. The diagnosis of ODS was based on clinical features with corroborating imaging findings. Two functional scales--Functional Independent Measure (FIM) and Disability Rating Scale (DRS)--were applied to assess the functional status at the time of admission, discharge and last follow-up. Patients who became independent for activities of daily living (ADL) at last follow-up were classified as favourable outcome, and those who died or became dependent for ADL were classified as a poor outcome group respectively. The Fisher exact test and Mann-Whitney U test were used to assess categorical and continuous variables respectively. RESULTS: The mean age at diagnosis was 53 ± 14 years. Five (20%) had central pontine myelinolysis, seven (28%) had extrapontine myelinolysis, and 13 (52%) had both. Hyponatraemia and hypokalaemia were noted in 20 (80%) and 10 (40%) patients respectively. Six (24%) received intravenous methylprednisolone. Eleven (46%) had a favourable outcome at a mean follow-up of 2.2 ± 2.5 years. Hyponatraemia ≤ 115 mEq (p=0.04), associated hypokalaemia (p=0.04) and low Glasgow Coma Scale (GCS) (p=0.008) at presentation were predictive of poor outcome. The mean FIM score at admission (p=0.05) and at discharge (p=0.01), and mean DRS at admission (p=0.05) were predictive of poor outcome. CONCLUSIONS: Higher GCS scores, better scores in functional scales in hospital, less severe hyponatraemia and absence of superadded hypokalaemia predicted favourable outcome.

Incidence, types, risk factors, and outcome of stroke in a developing country: the Trivandrum Stroke Registry.

BACKGROUND AND PURPOSE: Despite increasing burden of stroke in developing countries, population-based data are rare. Through the Trivandrum Stroke Registry, we intend to assess incidence, types, risk factors, and outcome of stroke among urban and rural dwellers of a South Indian community. METHODS: We ascertained all first-ever strokes occurring among 741,000 urban and 185,000 rural inhabitants of Trivandrum, Kerala. In addition to Steps 1 and 2 of World Health Organization STEPS Stroke Manual, we used multiple supplementary methods to maximize ascertainment of nonfatal and nonhospitalized fatal stroke events in the community. RESULTS: During a 6-month period, 541 strokes were registered, 431 in the urban and 110 in the rural communities. Stroke occurred at a median age of 67 years; only 3.8% of patients were aged

Effects of caloric restriction on mitochondrial function and gene transcripts in rat muscle.

Rodent skeletal muscle mitochondrial DNA has been shown to be a potential site of oxidative damage during aging. Caloric restriction (CR) is reported to reduce oxidative stress and prolong life expectancy in rodents. Gene expression profiling and measurement of mitochondrial ATP production capacity were performed in skeletal muscle of male rats after feeding them either a control diet or calorie-restricted diet (60% of control diet) for 36 wk to determine the potential mechanism of the beneficial effects of CR. CR enhanced the transcripts of genes involved in reactive oxygen free radical scavenging function, tissue development, and energy metabolism while decreasing expression of those genes involved in signal transduction, stress response, and structural and contractile proteins. Real-time PCR measurements confirmed the changes in transcript levels of cytochrome-c oxidase III, superoxide dismutase (SOD)1, and SOD2 that were noted by the microarray approach. Mitochondrial ATP production and citrate synthase were unaltered by the dietary changes. We conclude that CR alters transcript levels of several genes in skeletal muscle and that mitochondrial function in skeletal muscle remains unaltered by the dietary intervention. Alterations in transcripts of many genes involved in reactive oxygen scavenging function may contribute to the increase in longevity reported with CR.

Impact of high-fat diet and antioxidant supplement on mitochondrial functions and gene transcripts in rat muscle.

High-fat diets are reported to increase oxidative stress in a variety of tissues, whereas antioxidant supplementation prevents many diseases attributed to high-fat diet. Rodent skeletal muscle mitochondrial DNA has been shown to be a potential site of oxidative damage. We hypothesized that the effects of a high-fat diet on skeletal muscle DNA functions would be attenuated or partially reversed by antioxidant supplementation. Gene expression profiling and measurement of mitochondrial ATP production capacity were performed in skeletal muscle from male rats after feeding one of three diets (control, high-fat diet with or without antioxidants) for 36 wk. The high-fat diet altered transcript levels of 18 genes of 800 surveyed compared with the control-fed rats. Alterations included reduced expression of genes involved in free-radical scavenging and tissue development and increased expression of stress response and signal transduction genes. The magnitude of these alterations due to high-fat diet was reduced by antioxidant supplementation. Real-time PCR measurements confirmed the changes in transcript levels of cytochrome c oxidase subunit III and superoxide dismutase-1 and -2 noted by microarray approach. Mitochondrial ATP production was unaltered by dietary changes or antioxidant supplementation. It is concluded that the high-fat diet increases the transcription of genes involved in stress response but reduces those of free-radical scavenger enzymes, resulting in reduced DNA repair/metabolism (increased DNA damage). Antioxidants partially prevent these changes. Mitochondrial functions in skeletal muscle remain unaltered by the dietary intervention due to many adaptive changes in gene transcription.