The correlation between the severity of paroxysmal sympathetic hyperactivity and plasma catecholamine levels in patients with severe traumatic brain injury.

BACKGROUND: There is limited literature investigating the catecholamine levels in patients with paroxysmal sympathetic hyperactivity (PSH) after traumatic brain injury (TBI). The primary objective of this study was to correlate the severity of PSH (assessed using the PSH-Assessment measure [AM]) with plasma catecholamine levels at a resting state. METHODS: In this prospective case-control study, blood samples for epinephrine and norepinephrine estimation were obtained at rest on three consecutive days, only for 'cases' of PSH after severe TBI (s-TBI) and for control patients (matched for age, gender, and Glasgow coma scale [GCS]. RESULTS: Twenty-seven patients with PSH and 16 controls were recruited. The median PSH-AM score was 20 and 9 in cases and controls, respectively. The epinephrine and norepinephrine levels at rest did not correlate with the severity of PSH assessed during PSH paroxysms (p = 0.949 and 0.975). Norepinephrine levels increased in PSH patients over the 3 consecutive days, once PSH was diagnosed (p = 0.022). The length of hospital stay was longer and the motor-GCS score was lower in PSH patients, with no differences in other outcomes between the groups. CONCLUSION: Catecholamine levels in the inter-paroxysmal interval cannot be correlated with PSH severity assessed during the paroxysms. However, the results of the study need to be confirmed by a larger sample size as the study is underpowered.

Etiogenic factors present in the cerebrospinal fluid from amyotrophic lateral sclerosis patients induce predominantly pro-inflammatory responses in microglia.

BACKGROUND: Microglial cell-associated neuroinflammation is considered as a potential contributor to the pathophysiology of sporadic amyotrophic lateral sclerosis. However, the specific role of microglia in the disease pathogenesis remains to be elucidated. METHODS: We studied the activation profiles of the microglial cultures exposed to the cerebrospinal fluid from these patients which recapitulates the neurodegeneration seen in sporadic amyotrophic lateral sclerosis. This was done by investigating the morphological and functional changes including the expression levels of prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), TNF-α, IL-6, IFN-γ, IL-10, inducible nitric oxide synthase (iNOS), arginase, and trophic factors. We also studied the effect of chitotriosidase, the inflammatory protein found upregulated in the cerebrospinal fluid from amyotrophic lateral sclerosis patients, on these cultures. RESULTS: We report that the cerebrospinal fluid from amyotrophic lateral sclerosis patients could induce an early and potent response in the form of microglial activation, skewed primarily towards a pro-inflammatory profile. It was seen in the form of upregulation of the pro-inflammatory cytokines and factors including IL-6, TNF-α, iNOS, COX-2, and PGE2. Concomitantly, a downregulation of beneficial trophic factors and anti-inflammatory markers including VEGF, glial cell line-derived neurotrophic factor, and IFN-γ was seen. In addition, chitotriosidase-1 appeared to act specifically via the microglial cells. CONCLUSION: Our findings demonstrate that the cerebrospinal fluid from amyotrophic lateral sclerosis patients holds enough cues to induce microglial inflammatory processes as an early event, which may contribute to the neurodegeneration seen in the sporadic amyotrophic lateral sclerosis. These findings highlight the dynamic role of microglial cells in the pathogenesis of the disease, thus suggesting the need for a multidimensional and temporally guarded therapeutic approach targeting the inflammatory pathways for its treatment.

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.

Astroglia acquires a toxic neuroinflammatory role in response to the cerebrospinal fluid from amyotrophic lateral sclerosis patients.

BACKGROUND: Non-cell autonomous toxicity is one of the potential mechanisms implicated in the etiopathogenesis of amyotrophic lateral sclerosis (ALS). However, the exact role of glial cells in ALS pathology is yet to be fully understood. In a cellular model recapitulating the pathology of sporadic ALS, we have studied the inflammatory response of astroglia following exposure to the cerebrospinal fluid from ALS patients (ALS-CSF). METHODS: Various inflammatory markers including pro-inflammatory and anti-inflammatory cytokines, COX-2, PGE-2, trophic factors, glutamate, nitric oxide (NO), and reactive oxygen species (ROS) were analyzed in the rat astroglial cultures exposed to ALS-CSF and compared with the disease control or normal controls. We used immunofluorescence, ELISA, and immunoblotting techniques to investigate the protein expression and real-time PCR to study the messenger RNA (mRNA) expression. Glutamate, NO, and ROS were estimated using appropriate biochemical assays. Further, the effect of conditioned medium from the astroglial cultures exposed to ALS-CSF on NSC-34 motor neuronal cell line was detected using the MTT assay. Statistical analysis was carried out using one-way ANOVA followed by Tukey's post hoc test, or Student's t test, as applicable. RESULTS: Here, we report that the ALS-CSF enhanced the production and release of inflammatory cytokines IL-6 and TNF-α, as well as COX-2 and PGE-2. Concomitantly, anti-inflammatory cytokine IL-10 and the beneficial trophic factors, namely VEGF and GDNF, were down-regulated. We also found impaired regulation of glutamate, NO, and ROS in the astroglial cultures treated with ALS-CSF. The conditioned medium from the ALS-CSF exposed astroglial cultures induced degeneration in NSC-34 cells. CONCLUSIONS: Our study demonstrates that the astroglial cells contribute to the neuroinflammation-mediated neurodegeneration in the in vitro model of sporadic ALS.

Prevalence and predictors of preoperative cardiac autonomic dysfunction among elective neurosurgical patients: A prospective observational study.

Background and Aims: The autonomic nervous system (ANS) is cardinal for systemic homeostasis. Autonomic dysfunction is prevalent in as high as 65% of patients presenting for cardiac surgery in the Indian scenario. Pre-existing cardiac autonomic dysfunction (CAD) in surgical patients can accentuate perioperative haemodynamic fluctuations during stressful intraoperative events, predispose to adverse cardiac events, and contribute to morbidity and mortality. The prevalence and predictors of CAD in the elective neurosurgical population are unknown in the Indian scenario. The current study was conducted to bridge this knowledge gap. Methods: In this single-centre prospective observational study conducted at a tertiary care neurosciences centre, among 400 consenting adult patients of either gender, between 18 and 80 years of age, undergoing elective neurosurgery, the preoperative ANS function at the bedside was assessed as the primary outcome measure. The ANS status was evaluated using ANSiscope™-derived indices of heart rate variability. The diagnosis of CAD was made when the ANS index exceeded a threshold of 13.5. Data regarding predictors of CAD were collected from patient records as the secondary outcome measure. Statistical analysis was done using the R software. A P-value of <0.05 was considered statistically significant. Results: The prevalence of preoperative CAD in our study population was 79.7% (319/400 patients). None of the demographic and baseline clinical characteristics we studied predicted CAD in our study. Conclusion: We observed a significant prevalence of preoperative CAD among elective neurosurgical patients. None of the parameters we evaluated predicted CAD in our study.

Development and validation of Ayurveda based assessment scale for anxiety.

BACKGROUND: Anxiety scale based on Ayurveda would help Ayurveda physicians to measure and initiate appropriate treatment strategies. OBJECTIVES: The objective of the study was to develop a clinical assessment scale for anxiety based on Ayurveda science. MATERIALS AND METHODS: Ayurveda assessment scale for anxiety (AAA) was developed and subjected to various psychometric evaluations. Patients of generalized anxiety disorder with social phobia (GAD with SP) (n = 31) meeting DSM-IV-TR criteria and age, sex-matched healthy subjects (n = 31) were enrolled from NIMHANS Psychiatry OPD. Two independent Ayurveda experts evaluated both patients and healthy subjects using AAA, Hamilton Anxiety Rating Scale (HARS), and Beck Anxiety Inventory (BAI). Reliability and validity assessments were carried out. The sensitivity to treatment-induced change was evaluated in a randomized controlled clinical trial. 72 patients of GAD with SP meeting DSM-IV-TR criteria, aged between 20 and 55 years, and either sex participated in the study. The duration of intervention was 30 days. The assessments were done through HARS, BAI, Beck Depression Inventory (BDI), AAA and Clinical Global Impression scales (Severity, Improvement, and Efficacy). RESULTS: The Interrater reliability was between - good to very good score. Validity of AAA with HARS and BAI was significant (p < 0.001). Scales recorded significant differences when compared between patients and healthy subjects (p < 0.001). AAA also recorded the sensitivity to treatment-induced changes in a randomized controlled study and noted a large effect size (>0.60). CONCLUSIONS: The psychometric properties such as interrater reliability, validity (criteria, convergent, divergent, face) and sensitivity to change of AAA were promising.

Evaluation of Cardiac, Autonomic Functions in Ambulant Patients with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder caused by dystrophin gene mutation resulting in muscle weakness, motor delays, difficulty in standing, and inability to walk by 12 years. As disease progresses, it leads to cardiac and respiratory failure. Evaluation of cardiac autonomic status and echocardiography in DMD patients at a young age can be a potential biomarker to assess disease progression. This study aimed to investigate the younger DMD population of 5-11years of age with mild to moderate cardiac involvement for early detection using non-invasive and cost-effective tools. Genetically confirmed male DMD patients, aged 5-11 years (n = 47), screened from the outpatient department of a tertiary neuroscience institution were subjected to heart rate variability and echocardiographic analysis, and values were correlated with their clinical variables. DMD patients showed a significantly higher difference in HR, interventricular septum, E m/s, and E-wave to A-wave (E/A) ratio than normal values (p < 0.001). Significantly higher HR indicates initial sinus tachycardia and decreased IVD (d), and increased E m/s and E/A ratio mark the onset of cardiac symptoms in DMD patients even though its chamber dimension remains normal and are associated with cardiac muscle fibrosis.

Incidence, predictors, and impact of acute post-operative pain after cranial neurosurgery: A prospective cohort study.

Objectives: Pain is common after craniotomy. Its incidence and predictors in developing nations are not adequately studied. We aimed to assess the incidence, predictors, and impact of acute post-operative pain after intracranial neurosurgeries. Materials and Methods: This prospective observational study was conducted in adult patients undergoing intracranial neurosurgeries. After patient consent, ethics committee approval, and study registration, we assessed the incidence of post-operative pain using numerical rating scale (NRS) score. Predictors and impact of pain on patient outcomes were also evaluated. Results: A total of 497 patients were recruited during 10-month study period. Significant (4-10 NRS score) post-operative pain at any time-point during the first 3 days after intracranial neurosurgery was reported by 65.5% (307/469) of patients. Incidence of significant pain during the 1st post-operative h, on the 1st, 2nd, and 3rd post-operative days was 20% (78/391), 50% (209/418), 38% (152/401), and 24% (86/360), respectively. Higher pre-operative NRS score and pain during the 1st h post-operatively, predicted the occurrence of pain during the first 3 days after surgery, P = 0.003 and P < 0.001, respectively. Pain was significantly associated with poor sleep quality on the first 2 post-operative nights (P < 0.001). Patient satisfaction score was higher in patients with post-operative pain, P = 0.002. Conclusion: Every two in three patients undergoing elective intracranial neurosurgery report significant pain at some point during the first 3 postoperative days. Pre-operative pain and pain during 1st post-operative h predict the occurrence of significant post-operative pain.

Immediate Effects of OM Chanting on Heart Rate Variability Measures Compared Between Experienced and Inexperienced Yoga Practitioners.

Background: Chanting "OM" is a form of meditation that has numerous health benefits. However, the neurophysiological mechanisms underpinning its effect are surprisingly scarce. The present study aimed to investigate the effect of OM chanting on autonomic modulation, using heart rate variability (HRV), on experienced yoga practitioners and yoga naïve persons. Methods: This prospective study included 19 yoga practitioners (9 females and 10 males; group mean age ± standard deviation [SD]; 25.9 ± 3.2 years) and 17 yoga naïve persons (8 females and 9 males; group mean age ± SD; 24.8 ± 3.6 years) of both sexes and similar age range. Both the groups were assessed for HRV indices (time and frequency domain measures) before and after loud OM chanting for 5 min. Results: Baseline comparison using Mann-Whitney U test between groups showed yoga practitioners had significantly increased high frequency (HF) power (P < 0.029) than nonyoga practitioners, signifying a state of tranquility before the chanting of OM. After 5 min of loud chanting of OM, a comparison between groups assessed using Wilcoxon Signed Ranks test revealed: HF Power, a component of the parasympathetic nervous system, was further amplified with a significantly increase (P < 0.001) in the yoga practitioners group compared to nonyoga practitioners. Furthermore, this increase in HF power was positively correlated with the years of experience in yoga. Conclusion: The present study showed that a brief chanting of OM (5 min) might enhance parasympathetic nervous system activity, promote relaxation, and provide calmness. Further, this experience may be achieved effectively in individuals experienced in yoga than nonyoga practitioners.

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.

Down regulation of trophic factors in neonatal rat spinal cord after administration of cerebrospinal fluid from sporadic amyotrophic lateral sclerosis patients.

Accumulating evidence supports neuroprotective role of trophic factors in amyotrophic lateral sclerosis (ALS). Previous studies from our laboratory report that the CSF of patients with sporadic ALS (ALS-CSF) induces degenerative changes in the rat spinal motor neurons and reactive astrogliosis in the surrounding gray matter. The present study was aimed to investigate if the ALS-CSF affected the expression of trophic factors namely, brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2) and insulin-like growth factor 1 (IGF1) in the newborn rat spinal cords. ALS-CSF was intrathecally injected into the neonatal rats and the mRNA levels of the trophic factors were determined by quantitative real-time polymerase chain reaction. Here, we report significant down regulation in the gene expression of trophic factors for BDNF, FGF2 and IGF1. BDNF mRNA levels were found to be reduced by 6.8-fold in the ALS-CSF injected group compared to control groups. The levels of IGF1 and FGF2 mRNA were also decreased by 3.91- and 2.13-fold, respectively, in the ALS group. We further found that exogenous supplementation of BDNF considerably reduced the aberrant phosphorylation of neurofilaments, complementing our earlier findings of restored expression of voltage gated sodium channel. Reduced expression of trophic factors indicates an altered microenvironment of the motor neurons and could possibly be one of the contributing factors in the degeneration process.

Vascular endothelial growth factor attenuates neurodegenerative changes in the NSC-34 motor neuron cell line induced by cerebrospinal fluid of sporadic amyotrophic lateral sclerosis patients.

BACKGROUND: Motor neuron disease or amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons in the spinal cord as well as motor cortex. Recently, vascular endothelial growth factor (VEGF) has been identified as a neurotrophic factor in animal models of familial ALS and other neurological diseases. OBJECTIVE: The present study was designed to investigate the neuroprotective role of VEGF in the more prevalent sporadic form of ALS. METHODS: We studied the effect of VEGF on the NSC-34 cell line exposed to cerebrospinal fluid (CSF) from sporadic ALS patients (ALS-CSF) in terms of lactate dehydrogenase (LDH) assay as well as choline acetyltransferase (ChAT) and phosphorylated neurofilament expression by immunocytochemistry and confocal microscopy. NSC-34 cells were exposed to CSF from patients with definite ALS and compared to controls. LDH activity was assessed in the growth media, prior to and 24 h after the addition of VEGF to the cells. At similar time points, the cells were fixed and processed for immunocytochemistry to evaluate ChAT and phosphorylated neurofilament expression. RESULTS: Exposure to ALS-CSF caused morphological changes of NSC-34 cells like reduced differentiation and aggregation of phosphorylated neurofilaments. Enhanced LDH activity and reduced ChAT immunoreactivity were also observed. Addition of VEGF to NSC-34 cells exposed to ALS-CSF was protective in terms of reduced LDH activity and restoration of ChAT expression. CONCLUSION: The present study confirms that VEGF exerts a neuroprotective effect on the NSC-34 cell line by attenuating the degenerative changes induced by ALS-CSF. It thus has therapeutic potential in sporadic ALS.

Adjunct yoga therapy: Influence on heart rate variability in major depressive disorder - A randomized controlled trial.

HRV is inversely proportional to severity of depression. Effect of 12-weeks adjunct yoga therapy on HRV in patients with MDD was assessed through a randomized controlled trial. Sixty-eight subjects (40 females) with mean age 31.58 ± 8.79 years, scoring ≥ 18 on HDRS were randomized to either (YG; n = 35) or (WG; n = 33). Linear mixed model analysis showed no significant difference between groups. On comparing change in mean percentage, substantial more decrease could be elicited only for LF/HF ratio in YG compared to WG, while being comparable for other variables across the groups. Findings suggest Yoga therapy may help in bringing parasympathetic dominance in patients with MDD.

Clinical Profile and Treatment Response in Patients with CASPR2 Antibody-Associated Neurological Disease.

BACKGROUND: The clinical spectrum of contactin-associated protein-like 2 (CASPR2) antibody-associated disease is wide and includes Morvan syndrome. Studies describing treatment and long-term outcome are limited. AIMS: We report the clinical profile and emphasize response to treatment and long-term outcome in eight patients with CASPR2-antibody-associated disease. METHODS: Clinical, radiological, electrophysiological, treatment, follow-up, and outcome data were collected by retrospective chart review. RESULTS: Clinical manifestations included Morvan syndrome (n = 7) and limbic encephalitis (n = 1). None of the patients were positive for LGI1 antibody. Associated features included myasthenia (n = 1), thymoma (n = 1), and dermatological manifestations (n = 4). Patients were treated with intravenous methylprednisolone and plasma exchange during the acute symptomatic phase followed by pulsed intravenous methyl prednisolone to maintain remission. Mean-modified Rankin score at admission (pre-treatment), discharge, and last follow-up were 3.75, 2.5, and 0.42, respectively. One patient with underlying thymoma and myasthenic crisis died. The other seven patients were followed up for a mean duration of 19.71 months. All of them improved completely. Relapse occurred in one patient after 13 months but responded favorably to steroids. CONCLUSION: CASPR2 antibody-associated disease has favorable response to immunotherapy with complete improvement and good outcome. Underlying malignancy may be a marker for poor prognosis.

CASPR2-Related Morvan Syndrome: Autonomic, Polysomnographic, and Neuropsychological Observations.

OBJECTIVE: Morvan syndrome is characterized by central, autonomic, and peripheral hyperexcitability due to contactin-associated protein 2 (CASPR2) antibody. Our objective was to study the clinical spectrum, electrophysiologic, autonomic, polysomnographic, and neuropsychological profile in patients with CASPR2-related Morvan syndrome. METHODS: Serum and CSF samples that were CASPR2 antibody positive from 2016 to 2019 were assessed. Among them, patients with Morvan syndrome diagnosed based on clinical and electrophysiologic basis were included. RESULTS: Fourteen (M:F = 10:4) patients with Morvan syndrome were included with age at onset of 37.1 ± 17.5 years. The clinical features were muscle twitching (12), insomnia (12), pain (11), paresthesias (9), hyperhidrosis (7), hypersalivation (6), double incontinence (3), spastic speech (2), dysphagia (2), behavioral disturbances (2), seizures (1), and cold intolerance (1). Neurologic examination revealed myokymia (12), hyperactive tendon reflexes (10), and tremor (6). EMG revealed neuromyotonia (12) and increased spontaneous activity (7). Autonomic function tests conducted in 8 patients revealed definite autonomic dysfunction (4), orthostatic hypotension (2), early dysfunction (1), and postural orthostatic tachycardia syndrome (1). Polysomnography findings in 6 patients revealed insomnia (3), absence of deep sleep (1), high-frequency beta activity (1), REM behavior disorder (1), and periodic leg movements (1). Neuropsychological evaluation showed subtle involvement of the left frontal and temporal lobe. Malignancy workup was negative. All patients were treated with steroids. There was complete neurologic resolution in follow-up with persistent neuropathic pain in 5 patients. CONCLUSIONS: This study has contributed to the growing knowledge on CASPR2-related Morvan syndrome. It is important for an increased awareness and early recognition as it is potentially treatable by immunotherapy.

Pulmonary function tests and diaphragmatic compound muscle action potential in patients with sporadic amyotrophic lateral sclerosis.

BACKGROUND: Respiratory failure is the primary cause of death in patients with amyotrophic lateral sclerosis (ALS). Diaphragmatic compound muscle action potentials (DCMAP) are valid parameters to assess the respiratory muscle innervation. AIM: In this study we propose to establish evidence of pulmonary dysfunction in patients with ALS and its relation to DCMAP parameters among patients with sporadic ALS. MATERIALS AND METHODS: Twenty nine patients (M-20, F-9) diagnosed to have sporadic ALS by El. Escorial criteria, without symptoms of pulmonary dysfunction, and able to perform the PFT satisfactorily, were studied. Thirty controls (M-20, F-10) were selected from patient's relatives. Forced vital capacity (FVC), forced expiratory volume in one second (FEV(1)), peak expiratory flow rate (PEFR) and maximum voluntary ventilation (MVV) were measured by spirometry. Maximum expiratory pressure (MEP) was measured by digital peak pressure monitor. Right phrenic nerve conductions (DCMAP) were performed and the latencies and amplitude of diaphragmatic com-pound action potential (DCMAP) was recorded in controls and ALS patients. RESULTS: The mean age of patients was 51.41 +/- 10.72 years (37-82) and control was 53.57 +/- 8.85 years (30-68). None of the patients had symptoms or clinical evidence of respiratory dysfunction. The FVC, FEV1, PEFR, MVV, MIP and MEP were significantly (P < 0.001) reduced in ALS. The mean DCMAP amplitude was reduced among patients (610 +/- 506.231 muv) as compared to controls (1303.33 +/- 584.56, P < 0.001) and mean latency was increased in patients (9.73 +/- 2.57 ms) compared to controls (7.69 +/- 0.87, P = 0.001). There was significant negative correlation between PFTs and latencies of DCMAP. Amplitude of DCMAP did not correlate with PFTs. CONCLUSION: There is significant negative correlation between DCMAP latencies and PFTs suggesting early loss of myelinated fibres and diaphragmatic dysfunction. DCMAP latencies may be a good indicator of early respiratory muscle involvement and also of disease progression in ALS.

Subclinical pulmonary dysfunction in spinocerebellar ataxias 1, 2 and 3.

OBJECTIVES: Evaluation of pulmonary function in patients with spinocerebellar ataxias (SCA) 1, 2 and 3 without clinical evidence of pulmonary dysfunction. METHODS: Thirty patients (F:M = 7:23; age: 35 ± 11.3 years; SCA1 - 13, SCA2 - 9 and SCA3 - 8) without clinical manifestations of respiratory dysfunction and 30 controls underwent pulmonary function tests. The percentage predicted values of forced vital capacity (FVC), volume of air exhaled during first second of FVC (FEV1), peak expiratory flow rate (PEFR) and maximal voluntary ventilation (MVV), actual values of maximal inspiratory and expiratory pressures (MIP and MEP in mmHg), and ratios of actual values of FEV1/FVC (%) and FEV1/PEFR (ml/l/min) were analyzed. RESULTS: Compared with controls SCA patients had significant reductions of FVC (71.1 ± 17.5 vs 85.5 ± 18.7; P < 0.01), PEFR (51.5 ± 20.7 vs 77.1 ± 24.9; P < 0.001), MVV (64.4 ± 21.6 vs 97.2 ± 22.7; P < 0.001), MIP (27.7 ± 16.8 vs 50.1 ± 15.1; P < 0.001) and MEP (38.1 ± 18.7 vs 74.7 ± 16.0; P < 0.001), elevation of FEV1/PEFR (10.5 ± 2.8 vs 7.4 ± 2.1; P < 0.001), but no significant change of FEV1 and FEV1/FVC. FEV1/PEFR correlated positively with illness duration and MVV negatively with severity of illness. CONCLUSIONS: The present study showed subclinical restrictive type of pulmonary dysfunction in SCA, and possible presence of upper airway obstruction. Chest physiotherapy and breathing exercises should be introduced early in management of SCA.

Transthoracic electrical bioimpedence cardiac output: comparison with multigated equillibrium radionuclide cardiography.

INTRODUCTION: Thoracic electrical bioimpedance (TEB) for measuring cardiac output (CO) is being explored increasingly as an alternative to pulmonary artery catheter. The major advantage of this technology is that it is non-invasive and easy to perform. Several studies have compared it to thermodilution cardiac output using PA catheter, with variable correlation. Multigated radionuclide equilibrium cardiography (RNEC) method of cardiac output measurement is known to be reliable. OBJECTIVE: To compare cardiac output measured by thoracic electrical bioimpdenace with that measured by multigated radionuclide equilibrium cardiography. PATIENTS AND METHODS: CO studies were performed sequentially at a single sitting by TEB and RNEC methods among patients with cardiac symptoms referred for radionuclide study as part of their evaluation. TEB CO was measured by placing two pairs of electrodes on either side of neck and two other pairs on either side of the lower chest. Stroke volume was estimated from the sequential changes in transthoracic electrical bioimpedance induced by rhythmic aortic blood flow, using Kubicek equation. RNEC-CO was measured by intravenous injection of radio-active Technitium-tagged RBCs followed by ECG gated blood pool imaging over the chest (MUGA study). Bland-Altman analysis was used to compare the measurements. RESULTS: A total of 32 subjects with proven or suspected ischemic heart disease, but without overt cardiac failure, edema or arrhythmias were studied (M:F::26:6; mean age: 48 +/- 12 years). The mean TEB-CO was 3.54 +/- 1.052 l/min and mean RNEC-CO was 3.907 +/- 0.952 l/min. Correlation coefficient (r) for these measurements was 0.67 (p < 0.01), with bias: -0.421 l/min; precision: 1.557 l/min; and percentage error of measurement: 42.35%. CONCLUSIONS: This study observed a moderate correlation between TEB and RNEC methods of CO measurement. Further studies are indicated to explore the relative utility of TEB in comparison with RNEC as well as other methods of CO measurement before considering its use in patients with ischemic heart disease.

A comparative study of cardiac dysautonomia in autosomal dominant spinocerebellar ataxias and idiopathic sporadic ataxias.

OBJECTIVES: Comparative evaluation of cardiac dysautonomia in spinocerebellar ataxias (SCA) and idiopathic sporadic ataxias (IA) not fulfilling the criteria of multiple system atrophy. MATERIAL AND METHODS: Cardiac autonomic functions were evaluated in 14 SCA (SCA1 = 6, SCA2 = 5 and SCA3 = 3) and 10 IA patients, comparable for age, age at onset, duration and severity of illness. The results were categorized as early, definitive, or severe autonomic involvement (EI, DI and SI respectively) based on the degree of abnormalities on tests of parasympathetic and sympathetic pathways. RESULTS: Cardiac autonomic dysfunction was present in all (EI = 25.0%, DI = 41.7% and SI = 33.3%), parasympathetic dysfunction being an early feature. SI was most often present in SCA3 (100%), followed by those with SCA1 (66.7%), and SCA2 (20%) and none in IA. CONCLUSIONS: Cardiac dysautonomia was common in both SCA and IA, although the severity was greater in SCA. Among SCAs, the severity was greatest in SCA3, followed by SCA2 and least in SCA1.