Effect of Yoga and Physiotherapy on Pulmonary Functions in Children with Duchenne Muscular Dystrophy - A Comparative Study.

CONTEXT: Abnormal respiratory function is known to be detectable almost as soon as it can be measured reliably. Studies have identified the effect of respiratory muscle training as well as breathing exercises in improving pulmonary functions in children with Duchenne muscular dystrophy (DMD). AIMS: This study aims to identify the add-on effect of yoga over physiotherapy on pulmonary functions in children with DMD. SETTINGS AND DESIGN: One hundred and twenty-four patients with DMD were randomized to two groups. Group I received home-based physiotherapy and Group II received physiotherapy along with yoga intervention. MATERIALS AND METHODS: Pulmonary function test (PFT) was assessed before the intervention (baseline data) and at regular intervals of 3 months for a period of 1 year. STATISTICAL ANALYSIS USED: Normality was assessed using Shapiro-Wilk normality test. The baseline data were analyzed using Mann-Whitney U-test to identify the homogeneity. Repeated measures analysis of variance was used to assess significant changes in study parameters during the assessment of every 3 months, both within and between the two groups of patients. RESULTS: A total of 88 participants completed all the 5 assessments, with a mean age of 7.9 ± 1.5 years. PFT parameters such as forced vital capacity (FVC), peak expiratory flow rate, maximum voluntary ventilation (MVV), and tidal volume during maximum voluntary ventilation (MVt) demonstrated significant improvements in Group I. In Group II, FVC and MVt significantly improved from baseline up to 1 year, whereas MVV improved from baseline up to 9 months. Tidal volume did not show any changes in both the groups. CONCLUSIONS: The findings suggest that introduction of yoga with physiotherapy intervention at an early age can be considered as one of the therapeutic strategies in improving pulmonary functions in patients with DMD.

Effect of Yoga as an Add-on Therapy in the Modulation of Heart Rate Variability in Children with Duchenne Muscular Dystrophy.

BACKGROUND: Duchene muscular dystrophy (DMD) is a progressive muscular disorder. Cardiac disorder is the second-most common cause of death in children with DMD, with 10%-20% of them dying of cardiac failure. Heart rate variability (HRV) is shown to be a predictor of cardio-autonomic function. Physiotherapy (PT) is advised for these children as a regular treatment for maintaining their functional status. The effect of yogic practices on the cardio-autonomic functions has been demonstrated in various neurological conditions and may prove beneficial in DMD. MATERIALS AND METHODS: In this study, 124 patients with DMD were randomized to PT alone or PT with yoga intervention. Home-based PT and yoga were advised. Adherence was serially assessed at a follow-up interval of 3 months. Error-free, electrocardiogram was recorded in all patients at rest in the supine position. HRV parameters were computed in time and frequency domains. HRV was recorded at baseline and at an interval of 3 months up to 1 year. Repeated-measures ANOVA was used to analyze longitudinal follow-up and least significant difference for post hoc analysis and P < 0.05 was considered statistically significant. RESULTS: In our study, with PT protocol, standard deviation of NN, root of square mean of successive NN, total power, low frequency, high-frequency normalized units (HFnu), and sympathovagal balance improved at varying time points and the improvement lasted up for 6-9 months, whereas PT and yoga protocol showed an improvement in HFnu during the last 3 months of the study period and all the other parameters were stable up to 1 year. Thus, it is evident that both the groups improved cardiac functions in DMD. However, no significant difference was noted in the changes observed between the groups. CONCLUSION: The intense PT and PT with yoga, particularly home-based program, is indeed beneficial as a therapeutic strategy in DMD children to maintain and/or to sustain HRV in DMD.

Effects of craniopharyngioma cyst fluid on neurons and glial cells cultured from rat brain hypothalamus.

Craniopharyngiomas (CPs) are rare, epithelial tumors of the central nervous system (CNS) that could lead to manifestation of multiple post-operative symptoms, ranging from hormonal imbalance to obesity, diabetes, visual, neurological and neurocognitive impairments. CP is more frequent in children, and has been reported in middle aged adults as well. In fact, arterial laceration and/or brain stroke which may occur following the removal of some CPs is mainly due to calcification of that CPs along with strong attachments to the blood vessels. The dense oily fluid content of CPs is reported to cause brain tissue damage, demyelination and axonal loss in the hypothalamus; however, its exact effect on different cell types of CNS is still unexplored. In this study, we have collected CP cyst fluid (CCF) from mostly young patients during surgical removal and exposed it 9-10 days in vitro to the primary cultures derived from rat brain hypothalamus for 48 h. A gradual decline in cell viability was noted with increasing concentration of CCF. Moreover, a distinct degenerative morphological transformation was observed in neurons and glial cells, including appearance of blebbing and overall reduction of the cell volume. Further, enhanced expression of Caspase-3 in neurons and glial cells exposed to CCF by immunofluorescence imaging, supported by Western blot experiment suggest CCF induced apoptosis of hypothalamic cells in culture. In this study, we have demonstrated the deleterious effects of the cyst fluid on various cell types within the tumors originating region of the brain and its surroundings for the first time. Taken together, this finding could be beneficial towards identifying the region specific toxic effects of the cyst fluid and its underlying mechanism.

VEGF alleviates ALS-CSF induced cytoplasmic accumulations of TDP-43 and FUS/TLS in NSC-34 cells.

Cytoplasmic mislocalisation and aggregation of TDP-43 and FUS/TLS proteins in spinal motor neurons contribute to the pathogenesis of the highly fatal disorder amyotrophic lateral sclerosis (ALS). We investigated the neuroprotective effect of VEGF on expression of these proteins in the motor neuronal cell line NSC-34 modelled to reminisce sporadic form of ALS. We studied the expression of TDP-43 and FUS/TLS proteins after exposure to ALS-CSF and following VEGF supplementation by quantitative confocal microscopy and electron microscopy. ALS-CSF caused cytoplasmic overexpression of both the proteins and stress-granule formation in the cells. These alterations were alleviated by VEGF supplementation. The related ultrastructural changes like nuclear membrane dysmorphism and p-bodies associated changes were also reversed. However the protein expression did not completely translocate to the nucleus, as some cells continued to show to cytoplasmic mislocalisation. Thus, the present findings indicate that VEGF alleviates TDP43 and FUS pathology by complimenting its role in controlling apoptosis and reversing choline acetyl transferase expression. Hence, VEGF appears to target multiple pathogenic processes in the neurodegenerative cascade of ALS.

Brain-Derived Neurotrophic Factor Facilitates Functional Recovery from ALS-Cerebral Spinal Fluid-Induced Neurodegenerative Changes in the NSC-34 Motor Neuron Cell Line.

BACKGROUND: The survival of motor neurons is dependent upon neurotrophic factors both during childhood and adolescence and during adult life. In disease conditions, such as in patients with amyotrophic lateral sclerosis (ALS), the mRNA levels of trophic factors like brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), fibroblast growth factor-2 (FGF-2), and vascular endothelial growth factor are downregulated. This was replicated in our in vivo experimental system following the injection of cerebral spinal fluid (CSF) of sporadic ALS (ALS-CSF) patients. OBJECTIVE: To evaluate the protective role of BDNF in a model of sporadic ALS patients. METHODS: The expressions of endogenous BDNF, its receptor TrkB, the enzyme choline acetyl transferase (ChAT), and phosphorylated neurofilaments were studied in NSC-34 cells. The calcium-buffering and proapoptotic effects were assessed by calbindin-D28K and caspase-3 expression, respectively. RESULTS: ALS-CSF considerably depleted the endogenous BDNF protein, while its effect on IGF-1 and FGF-2 was inconsequential; this indirectly indicates a key role for BDNF in supporting motor neuronal survival. The exogenous supplementation of BDNF reversed autocrine expression; however, it may not be completely receptor mediated, as the TrkB levels were not restored. BDNF completely revived ChAT expression. It may inhibit apoptosis by restoring Ca2+ homeostasis, since caspase-3 and calbindin-D28K expression was back to normal. The organellar ultrastructural changes were only partially reversed. CONCLUSION: Our study provides evidence that BDNF supplementation ameliorates most but not all degenerative changes. The incomplete revival at the ultrastructural level signifies the requirement of factors other than BDNF for near-total protection of motor neurons, and, to an extent, it explains why only a partial success is achieved in clinical trials with BDNF in ALS patients.

Influence of hydrotherapy on clinical and cardiac autonomic function in migraine patients.

BACKGROUND: Migraine is associated with autonomic symptoms. The growing body of literature suggests that the dysfunctional autonomic nervous system might play a pivotal role in the pathogenesis of migraine. Thermal therapies have been hypothesized to modulate these changes and alleviate pain. However, data regarding the efficacy of hydrotherapy in migraine remain scant. We evaluated the effect of add on hydrotherapy procedure (a hot arm and foot bath with ice massage to head) in migraine patients. METHODS: Forty chronic migraine patients fulfilling the International Classification of Headache Disorders II criteria were recruited from the neurology outpatient clinic. Patients were randomized to receive either hydrotherapy plus conventional pharmacological care (n = 20) or conventional medication only (n = 20). Hydrotherapy group received treatment with hot arm and foot bath (103°F to 110°F) and ice massage to head daily for 20 min for 45 days. Patients were assessed using headache impact test (HIT), visual analog scale for pain and cardiac autonomic function by heart rate variability (HRV) before and after intervention period. RESULTS: There was a significant decrease in HIT score, frequency, and intensity of headaches following treatment in both the groups. However, it was more evident in add on hydrotherapy group compared to pharmacological treatment alone group. There was also significant improvement in the HRV parameters. In particular, there was a significant decrease in heart rate (P = 0.017), increase in high frequency (HF) (P = 0.014) and decrease in low frequency/HF ratio (P = 0.004) in add on hydrotherapy group. CONCLUSION: Our study shows that add on hydrotherapy enhanced the vagal tone in addition to reducing the frequency and intensity of headaches in migraine patients.

Spirometry Changes in Cold Climatic Conditions of Antarctica.

BACKGROUND: Pulmonary function is one of the important physiological measures that is known to be affected during the changes in the altitude. There is dearth of literature on changes in the pulmonary function variables in the cold climate conditions of Antarctica. We carried out spirometry before, during and after one year stay at Antarctica in members of the Indian expedition. METHODS: Spirometry was carried out on 23 members of the XXVI Indian Scientific Expedition to Antarctica at baseline, after six months of expedition and at the end of one year, using standard guidelines. The tests were carried out indoor in temperature controlled laboratory. RESULTS: The pulmonary function test parameters did not vary across the period. Although, both forced vital capacity (FVC) and forced expiratory volume in first second (FEV1) showed a decreasing trend but did not attain any statistical significance. However, peak expiratory flow (PEFR) rate was reduced significantly. CONCLUSION: Our study did not show consistently significant change in the pulmonary function parameters in the members of the Indian Antarctic expedition.

Evaluation of the influence of ayurvedic formulation (Ayushman-15) on psychopathology, heart rate variability and stress hormonal level in major depression (Vishada).

INTRODUCTION: Ayurveda (Indian-complimentary and alternative medicine) is still most sought after in India and has promising potential in management of Vishada [major depressive disorder (MDD)]. But, systematic research is lacking. In this study we evaluated of influence of ayurvedic treatment (Panchakarma and Ayushman-15) on psychopathology, heart rate variability (HRV) and endocrinal parameters in patients with major depression. METHODS: 81 drug naive patients diagnosed as Vishada by ayurvedic physician and MDD according to DSM IV-TR were given ayurvedic Virechana module (therapeutic purgation) and were randomized into two groups. Patients in group A (n=41) received Ayushman-15A while group B (n=40) received Ayushman-15B for two months and Shirodhara (forehead-oil pouring therapy). Patients were assessed with Hamilton Depression Rating Scale (HDRS), Montgomery Asberg Depression Rating Scale (MADRS), Heart Rate Variability (HRV). Cortisol and adrenocorticotropic hormone (ACTH) were estimated at baseline and after ayurvedic therapy. HRV and endocrinal parameters were compared with age and gender matched healthy volunteers. RESULTS: HRV parameters showed significant sympathetic dominance in patients compared to healthy volunteers. Two months of ayurvedic treatment significantly decreased psychopathology, showed increase in vagal tone, decrease in sympathetic tone and reduced cortisol levels. However, there was no significant difference between groups receiving Ayushman A and B. CONCLUSION: This study provides evidence for antidepressant, cardiac (HRV) and beneficial neuroendocrine modulatory influence of Ayurveda therapy in patients of Vishada (MDD). Further studies are needed to confirm these findings. Greater insight into the neurobiology behind this therapy might provide valuable information about newer drug target.