Talakad N. Sathyaprabha

Heart rate variability and outcome in acute severe stroke: role of power spectral analysis.

AbstractIntroduction: Heart rate variability (HRV) is a predictor of outcome in acute myocardial infarction and head trauma. Its efficacy in predicting outcome in stroke has not been well documented. Materials and Methods: Twenty-five patients (mean age 39 years) with acute stroke treated in a stroke intensive care unit were studied. Continuous echocardiogram recorded for a 1-hour period was digitized and stored for off-line analysis. Time and frequency domain HRV measures were derived for the filtered and rectified ECG data for each patient. Clinical and HRV profiles were compared among patients who died or survived. Results: At admission, 16 patients were comatose (Glasgow Coma score <9 at admission), 16 had focal weakness, and all had abnormal brain computed tomography. Of the 25 patients, 11 died, 10 had a poor outcome, and 4 had good outcome. Two variables—low-frequency (LF) spectral power and very low-frequency (VLF) spectral power—correlated with mortality. After adjustment for mechanical ventilation and vasopressor administration, LF, VLF, and Triangular index of RR interval (TINN) correlated with mortality. On multiple regression analysis weighted for mechanical ventilation and vasopressor administration, the eye-opening score on Glasgow Coma Scale and LF spectral power were factors that were independently predictive of mortality. Conclusion: HRV measurements are independent predictors of outcome in acute severe stroke.

Evidence of endoplasmic reticular stress in the spinal motor neurons exposed to CSF from sporadic amyotrophic lateral sclerosis patients

We have earlier reported that intrathecal injection of cerebrospinal fluid (CSF) from sporadic Amyotrophic Lateral Sclerosis patients (ALS-CSF) into neonatal rats and supplementation of rat spinal cord cultures with ALS-CSF induces motor neuron degeneration via aberrant neurofilament phosphorylation and Golgi apparatus fragmentation. Intracellular aggregates immunoreactive to ubiquitin, phosphorylated neurofilaments and choline acetyl transferase (ChAT) were prominently seen in NSC-34 cells exposed to ALS-CSF. Protein aggregation could cause stress on endoplasmic reticulum (ER) and may precede Golgi fragmentation. Here we assessed the effect of ALS-CSF on the expression of GRP-78 and caspase-12 proteins, the markers of ER stress responses, in NSC-34 cells and rat spinal cords by immunochemistry and immunoblotting. Both in vitro and in vivo, increased expression of these proteins accompanied elevated active caspase-12 levels. Apoptotic nuclei and nuclear translocation of caspase-12 were noted in some cells. In vitro, the occurrence of ER stress was supported by electron microscopic observations of numerous free polyribosomes and fragmented ER cisternae. Aggregated mSOD1 protein causes ER stress in familial ALS. ER stress is also reported in the autopsy samples of sporadic ALS. Thus our observation of ER stress may be linked to the protein aggregation, viz. phosphorylated neurofilaments and ChAT, reported earlier.

Modulation of cardiac autonomic balance with adjuvant yoga therapy in patients with refractory epilepsy

The practice of yoga regulates body physiology through control of posture, breathing, and meditation. Effects of yoga on autonomic functions of patients with refractory epilepsy, as quantified by standardized autonomic function tests (AFTs), were determined. The yoga group (n=18) received supervised training in yoga, and the exercise group (n=16) practiced simple routine exercises. AFTs were repeated after 10 weeks of daily sessions. Data were compared with those of healthy volunteers (n=142). The yoga group showed significant improvement in parasympathetic parameters and a decrease in seizure frequency scores. There was no improvement in blood pressure parameters in either group. Two patients in the yoga group achieved normal autonomic functions at the end of 10 weeks of therapy, whereas there were no changes in the exercise group. The data suggest that yoga may have a role as an adjuvant therapy in the management of autonomic dysfunction in patients with refractory epilepsy.

Pattern of subclinical pulmonary dysfunctions in Parkinson's disease and the effect of levodopa.

We performed a detailed evaluation of pulmonary function in 53 patients with idiopathic Parkinsons disease (PD) who did not have symptoms of pulmonary or cardiac dysfunction. There was a significant pulmonary dysfunction of restrictive type which partially responded to levodopa. Compared to men, women were more severely affected. Pulmonary function assessment is recommended in PD, irrespective of severity of disease.

Cerebrospinal Fluid from sporadic Amyotrophic Lateral Sclerosis patients induces degeneration of a cultured motor neuron cell line

We investigated the effect of Cerebrospinal Fluid (CSF) from sporadic Amyotrophic Lateral Sclerosis patients (SALS-CSF) on motor neuron-like cells to delineate the pathomechanism of SALS. Exposure of NSC-34 cells to SALS-CSF caused lower viability, reduction in differentiation and enhanced lactate dehydrogenase activity. Additionally, reduced choline acetyl transferase expression alongside intracellular aggregation of phosphorylated neurofilaments was prominently seen. The aggregates were immunopositive for ubiquitin. These findings are comparable to the pathological changes seen in the postmortem tissue of ALS patients. Unlimited supply of NSC-34 cells and their vulnerability to SALS-CSF render them to be a good bioassay system to identify new therapeutic agents conferring protection to motor neurons.

Exposure to cerebrospinal fluid of sporadic Amyotrophic Lateral Sclerosis patients alters Nav1.6 and Kv1.6 channel expression in rat spinal motor neurons

Cerebro Spinal Fluid (CSF) from patients with ALS has been documented to have a toxic effect on motor neurons both in vivo and in vitro. Here we show that the CSF from Amyotrophic Lateral Sclerosis (ALS) patients (ALS-CSF) has the potential to perturb ion channel expression, specifically the Na(v)1.6, and K(v)1.6 channels in newborn rat spinal motor neurons both in vivo and in vitro. ALS-CSF and CSF from nonALS patients (nonALS-CSF) were intrathecally injected into 3-day-old rat pups at the rate of 1 microl/2.5 min using a microinjector. In addition, embryonic rat spinal cord cultures were also exposed to 10% ALS or nonALS-CSF on the 9th day in vitro (9DIV) in serum free DMEM medium. After 48 h of CSF exposure, the cultures and the spinal cord sections were processed for immunostaining of the above mentioned ion channels. We observed a decrease in the expression of Na(v)1.6 and K(v)1.6 channels in motor neurons in ALS-CSF treated group, and the presence of trophic factors like Brain Derived Neurotrophic Factor (BDNF) and Ciliary Neurotrophic Factor CNTF partially reversed the effects produced by ALS-CSF. Altered expression of these voltage-gated channels may interfere with the electrical activity of motor neurons, and thereby lead to the degeneration of neurons.

Chitotriosidase - a putative biomarker for sporadic amyotrophic lateral sclerosis

BackgroundPotential biomarkers to aid diagnosis and therapy need to be identified for Amyotrophic Lateral Sclerosis, a progressive motor neuronal degenerative disorder. The present study was designed to identify the factor(s) which are differentially expressed in the cerebrospinal fluid (CSF) of patients with sporadic amyotrophic lateral sclerosis (SALS; ALS-CSF), and could be associated with the pathogenesis of this disease.ResultsQuantitative mass spectrometry of ALS-CSF and control-CSF (from orthopaedic surgical patients undergoing spinal anaesthesia) samples showed upregulation of 31 proteins in the ALS-CSF, amongst which a ten-fold increase in the levels of chitotriosidase-1 (CHIT-1) was seen compared to the controls. A seventeen-fold increase in the CHIT-1 levels was detected by ELISA, while a ten-fold elevated enzyme activity was also observed. Both these results confirmed the finding of LC-MS/MS. CHIT-1 was found to be expressed by the Iba-1 immunopositive microglia.ConclusionElevated CHIT-1 levels in the ALS-CSF suggest a definitive role for the enzyme in the disease pathogenesis. Its synthesis and release from microglia into the CSF may be an aligned event of neurodegeneration. Thus, high levels of CHIT-1 signify enhanced microglial activity which may exacerbate the process of neurodegeneration. In view of the multifold increase observed in ALS-CSF, it can serve as a potential CSF biomarker for the diagnosis of SALS.

Effect of Partial Weight–Supported Treadmill Gait Training on Balance in Patients With Parkinson Disease

OBJECTIVE To investigate the role of conventional gait training and partial weight-supported treadmill gait training (PWSTT) in improving the balance of patients with Parkinson disease (PD). DESIGN Prospective randomized controlled design. SETTING National-level university tertiary hospital for mental health and neurosciences. PATIENTS Sixty patients with PD fulfilling the United Kingdom Brain Bank PD diagnostic criteria were recruited from the neurology outpatient department and movement disorder clinic. METHODOLOGY The patients were randomly assigned into 3 equal groups: (1) a control group that only received a stable dosage of dopaminomimetic drugs; (2) a conventional gait training (CGT) group that received a stable dosage of dopaminomimetic drugs and conventional gait training; and (3) a PWSTT group that received a stable dosage of dopaminomimetic drugs and PWSTT with unloading of 20% of body weight. The sessions for the CGT and PWSTT groups were provided for 30 minutes per day, 4 days per week, for 4 weeks (16 sessions). OUTCOME MEASURES The Unified Parkinson Disease Rating Scale (UPDRS) motor score, dynamic posturography, Berg Balance Scale, and Tinetti performance-oriented mobility assessment (POMA) were used as main outcome measures. RESULTS A significant interaction effect was observed in the UPDRS motor score, mediolateral index, Berg Balance Scale, limits of stability (LOS) total score, POMA gait score, and balance score. Post-hoc analysis showed that in comparison with the control group, the PWSTT group had a significantly better UPDRS motor score, balance indices, LOS in 8 directions, POMA gait, and balance score. The CGT group had a significantly better POMA gait score compared with control subjects. Compared with the CGT group, the PWSTT group had a significantly better UPDRS motor score, mediolateral index, POMA gait score, and LOS total score. CONCLUSION PWSTT may be a better interventional choice than CGT for gait and balance rehabilitation in patients with PD.

Spinocerebellar ataxias type 1, 2 and 3: a study of heart rate variability

Objective –  To detect cardiac autonomic dysfunction, using analysis of heart rate variability in genetically defined spinocerebellar ataxias (SCA).

Study of cardiac autonomic function in drug-naïve, newly diagnosed epilepsy patients

BackgroundEpilepsy is associated with ictal autonomic dysfunction which may extend into the inter-ictal period. Antiepileptic drugs have often been blamed for cardiac autonomic dysfunction in epilepsy patients. In this study we have investigated cardiac autonomic parameters in order to evaluate autonomic functions of drug-naïve epilepsy patients.MethodTwenty drugnaïve patients (15 males and 5 females) with epilepsy, and an equal number of age and gender matched controls, were evaluated for short-term resting heart rate variability and conventional cardiovascular autonomic measurements.ResultsThe mean age of patients was 29.30 ± 9.80 yrs (17–55 yrs), mean age at seizure onset was 19.70 ± 9.15 yrs (3–40 yrs) and mean length of time since last seizure was 5.60 ± 7.00 days (1–30 days). While there was no difference in the resting heart rate or conventional autonomic test parameters, time domain heart rate variability measurements showed a decreased percentage of R-R intervals of less than 50 ms and root mean square of R-R intervals in patients, when compared to controls. Frequency domain parameters showed a decreased total power (patients: 1,796.58 ± 1,052.45 ms2; controls: 2,934.23 ± 1,767.06 ms2, p = 0.008). Parameters indicative of decreased vagal tone, i.e. decreased high frequency power and increased low to high frequency ratio (patients: 1.69 ± 0.94; controls: 1.14 ± 0.64, p = 0.045), were observed among patients compared to controls.ConclusionSubtle but definite cardiac autonomic dysfunction, especially in vagal tone, was identified in drug-naïve, new-onset epilepsy patients. Seizures can cause long-term and often progressive cardiac autonomic dysfunction which may be independent of concomitant antiepileptic drugs.