Serial repetitive nerve stimulation studies in organophosphorus poisoning indicate two distinct pathophysiological processes occur at the neuromuscular junction in the intermediate syndrome.

INTRODUCTION: Intermediate syndrome is an important cause of respiratory failure following acute organophosphorus pesticide poisoning. The objective of this study was to examine the pathophysiology of this syndrome by analysis of sequential repetitive nerve stimulation studies in patients with acute organophosphorus pesticide poisoning. METHODS: Thirty-four consenting symptomatic patients with acute organophosphorus pesticide poisoning with intermediate syndrome (n = 10) or a milder forme fruste intermediate syndrome (n = 24) were assessed prospectively with daily physical examination and repetitive nerve stimulation done on the right and left median and ulnar nerves. The compound muscle action potential at 1, 3, 10, 15, 20 and 30 Hertz was measured with a train of ten stimuli. The amplitudes of the resulting stimuli were normalized to the first stimulus (100 per cent) and plotted against time. The decrease in the area under the curve of all the second stimulus compound muscle action potentials in the first 0.3 seconds was measured as a means of quantifying the refractory block. The decrease in the area under the curve under the 10, 15, 20 and 30 Hertz compound muscle action potentials relative to this pooled second stimulus compound muscle action potentials-area under the curve indicated the extent of additional rate-dependent block (decreasing compound muscle action potential-area under the curve over the first 0.3 seconds after the first stimulus with increasing Hertz). RESULTS: These new measurements strongly correlated with the severity of weakness. Refractory block was seen in most patients but was more severe in those with intermediate syndrome than those with forme fruste (partial) intermediate syndrome (median 55 per cent versus 16 per cent, P = 0.0001). Similar large differences were found for rate-dependent block (30 per cent versus 7 per cent, P = 0.001), which was uncommon in forme fruste intermediate syndrome but found in nine out of 10 patients with intermediate syndrome. Rate dependent block was generally only observed after 24 hours. The simplest strong predictor was total block at 30 Hertz repetitive nerve stimulation (89 per cent [interquartile range 73 to 94 per cent] versus 21 per cent [4 to 55 per cent]; P < 0.0001), which was very similar to total block calculated by summing other calculations. DISCUSSION: These findings likely represent depolarization and desensitization block from prolonged excessive cholinergic stimulation but it is not clear if these are from pre- or post-synaptic pathology. An animal model of intermediate syndrome with repetitive nerve stimulation studies might enable a better pathophysiological understanding of the two types of block. LIMITATIONS: The limited number of repetitive nerve stimulation studies performed were sufficient to demonstrate proof-of-concept, but further studies with more patients are needed to better define the correlates, clinical relevance and possible diagnostic/prognostic roles for the use of this technique. CONCLUSION: There are two easily distinguishable pathophysiological abnormalities in the neuromuscular block in intermediate syndrome. While they often coincide, both may be observed in isolation. The total and rate-dependent block at 30 Hertz are strongly associated with more severe weakness.

Emotional intelligence and academic performance of medical undergraduates: a cross-sectional study in a selected university in Sri Lanka.

BACKGROUND: Emotional intelligence (EI) has been linked with academic and professional success. Such data are scarce in Sri Lanka. This study was conducted to describe the pattern of EI, to determine its predictors and to determine the effect of EI on academic performance at the final MBBS examination, in medical undergraduates of a Sri Lankan university. METHODS: This is a cross-sectional study in a selected university, involving those who did final MBBS examination in 2016. Consecutive sampling was done. EI was assessed with self-administered Genos Emotional Intelligence Full Version (7 domains; 70 questions equally weighted; total score 350). Socio-demographic data were obtained using a self-administered questionnaire. Academic performance was assessed with final MBBS results in the first attempt. RESULTS: Of 148 eligible students 130 responded (response rate-88%); 61.5% were females; mean age was 26.3 ± 1 years. Mean total EI score was 241.5 (females-245.5, males-235.1; p = 0.045).Among different domains, mean score was highest for Emotional Self-Awareness (36.8/50) and lowest for Emotional Expression (32.6/50). Multiple linear regression analysis indicated that having good family support (p = 0.002), socializing well in university (p = 0.024) and being satisfied with facilities available for learning (p = 0.002), were independent predictors of EI. At the final MBBS examination 51.6% obtained classes, 31.5% passed the examination without classes and 16.9% got repeated. Females had better academic performance than males (p = 0.009). Mean EI of second-class upper division, second-class lower division, pass and repeat groups were 249.4, 246.6, 240.2 and 226.9, respectively (with one-way ANOVA p = 0.015). After adjusting for gender, ordinal regression analysis indicated that, total EI score was an independent predictor of final MBBS results [ß-0.018 (95% CI 0.005-0.031); p = 0.006]. CONCLUSIONS: In the study population, both EI and academic performance were higher among females. Independent of gender, academic performance was better in those who were more emotionally intelligent. Several psychosocial factors were found to be independent predictors of EI. These results suggest that emotional skills development might enhance academic performance of medical undergraduates in Sri Lanka. Further research is needed in this under-explored area.

Electrophysiological correlates of respiratory failure in acute organophosphate poisoning: evidence for differential roles of muscarinic and nicotinic stimulation.

BACKGROUND: Respiratory failure in acute organophosphate (OP) poisoning can occur early and also relatively late in the clinical course, and the pathophysiology of respiratory failure at these different phases may have important clinical implications. Objective. To compare the electrophysiological findings in patients with early and late respiratory failure following acute OP poisoning. METHODS: A prospective observational case series of consenting symptomatic patients with acute OP poisoning were assessed with daily physical examinations and repetitive nerve stimulation (RNS) studies. RNS was done on right and left median and ulnar nerves at 1, 3, 10, 15, 20, and 30 Hz. Outcomes such as need for ventilation and development of intermediate syndrome (IMS) were noted. Early respiratory failure was defined as occurring within 24 hours of ingestion. RESULTS: Seventy-eight patients were recruited for the clinical and electrophysiological study and of those 59 (75.6%) patients had ingested chlorpyrifos. Seven patients developed respiratory failure within 24 hours of ingestion with overt muscarinic signs. They had no electrophysiological abnormalities at median and ulnar nerves before intubation. Three of them later developed "forme fruste" IMS. Five other patients developed late respiratory failure after 24 hours of ingestion, and all of them showed progressive RNS changes indicating severe IMS prior to intubation. CONCLUSION: The normal RNS in all patients developing early respiratory failure suggests that it is due to a central nervous system (CNS) and muscarinic effect. This emphasizes the need for early rapid atropinisation as a priority, combating the nicotinic effects being less urgent. This is in contrast with the late respiratory failure, which has been shown to be associated with neuromuscular dysfunction. Further studies are needed to quantify CNS and muscarinic dysfunction to assist in the development of better treatments for the severe and early OP poisoning.

Electrophysiological correlates of intermediate syndrome following acute organophosphate poisoning.

INTRODUCTION: Organophosphate (OP) poisoning is a major global health problem. The late onset of respiratory failure associated with intermediate syndrome (IMS) is a major contributor to the high morbidity, mortality, and cost of OP poisoning. This is particularly important as most poisoning occurs in the under-resourced developing world. Repetitive nerve stimulation studies. An understanding of the abnormalities observed in repetitive nerve stimulation studies during the progression and development of IMS spectrum disorder may help clinicians to utilize electrodiagnostic testing in the better management of their patients with acute OP poisoning. In addition, it will allow researchers to interpret future research that utilizes repetitive nerve stimulation as an outcome measure. A review of the clinical and experimental electrophysiological studies in the IMS shows that subclinical electrophysiological abnormalities are common, progressive, and precede the onset of the clinical IMS. Serial repetitive nerve stimulation studies have been most commonly used and are the most accessible for clinicians. Clinical and experimental studies demonstrate a progression through early initial decrement-increment patterns at high rates of stimulations, which correlate with moderate muscle weakness, to decrement-increment patterns at intermediate- and low-frequency stimulations. Progression to a combination of decrement-increment and repetitive fade patterns correlates with clinical deterioration; severe decrement pattern is usually observed immediately before the onset of respiratory failure. Although electrophysiological features closely parallel clinical severity during progression of IMS, the same is not true during recovery. Electrophysiological changes sometimes improve long before the patient recovers normal strength and respiratory function. Intermediate syndrome. Thus, IMS can be regarded as a spectrum disorder affecting the neuromuscular junction (NMJ) with two main forms: a forme fruste variety associated with mild weakness and the classical IMS with weakness of 3/5 or less than 3/5 on the Medical Research Council (MRC) grading; patients in the latter category are at risk of developing late onset respiratory failure. While IMS remains a clinically important entity, the early occurrence of abnormalities on repetitive nerve stimulation studies suggest that this is part of the continuum of nicotinic receptor stimulation. CONCLUSIONS: Reviewing the anatomical and the functional structure of the NMJ and neuromuscular transmission helps to provide an understanding of the pathophysiological nature of the neuromuscular transmission failure observed in IMS. This includes potential mechanisms of presynaptic feedback which may reduce acetylcholine release and postsynaptic receptor desensitization and provides some explanation for the time course of IMS. It also suggests other potential strategies to reduce OP-induced NMJ toxicity in which repetitive nerve stimulation is likely to be an important tool in judging efficacy.

The spectrum of intermediate syndrome following acute organophosphate poisoning: a prospective cohort study from Sri Lanka.

BACKGROUND: Intermediate syndrome (IMS) is a major cause of death from respiratory failure following acute organophosphate poisoning. The objective of this study was to determine repetitive nerve stimulation (RNS) predictors of IMS that would assist in patient management and clinical research. METHODS AND FINDINGS: Seventy-eight consenting symptomatic patients with organophosphate poisoning were assessed prospectively with daily physical examination and RNS. RNS was done on the right and left median and ulnar nerves at 1, 3, 10, 15, 20, and 30 Hz. The study was conducted as a prospective observational cohort study in the Central Province, Sri Lanka. IMS was diagnosed in ten out of 78 patients using a priori clinical diagnostic criteria, and five of them developed respiratory failure. All ten patients showed progressive RNS changes correlating with the severity of IMS. A decrement-increment was observed at intermediate and high frequencies preceding the onset of clinical signs of IMS. As the patient developed clinical signs of IMS, decrement-increment was progressively noted at low and intermediate frequencies and a combination of decrement-increment and repetitive fade or severe decrement was noted at high frequencies. Severe decrement preceded respiratory failure in four patients. Thirty patients developed forme fruste IMS with less severe weakness not progressing to respiratory failure whose RNS was characterized by decrement-increment or a combination of decrement-increment and repetitive fade but never severe decrements. CONCLUSIONS: Characteristic changes in RNS, preceding the development of IMS, help to identify a subgroup of patients at high risk of developing respiratory failure. The forme fruste IMS with the characteristic early changes on RNS indicates that IMS is a spectrum disorder. RNS changes are objective and precede the diagnosis and complications of IMS. Thus they may be useful in clinical management and research.

Methylphenidate in children with attention-deficit hyperactivity disorder (ADHD): experience from a Sri Lankan Tertiary Children's Hospital.

The response to methylphenidate was assessed in children diagnosed as having attention-deficit hyperactivity disorder (ADHD) in 2000 at the Lady Ridgeway Tertiary Hospital for Children in Sri Lanka. They were managed in outpatient child psychiatry clinics. ADHD was diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV). The severity of the symptoms was determined with a validated Sinhala assessment form based on DSM-IV criteria. The data on problems experienced by the diagnosed children and their families were obtained using an interviewer-administered questionnaire. The severity of the symptoms and problems experienced by the children and their families were reassessed at 6 weeks and 6 months of methylphenidate therapy. Thirty-seven new subjects were diagnosed as having ADHD in 2000, and 36 of them were treated with methylphenidate. The severity of the symptoms and the number of subjects receiving frequent complaints from school were significantly lower 6 weeks after methylphenidate treatment. At 6 months of treatment, the severity of the symptoms was not significantly reduced when compared with the severity assessed 6 weeks after treatment. Methylphenidate did help with school-related problems in the short term, but the long-term effects of methylphenidate were not convincing in this group of subjects and showed poor long-term compliance, probably owing to inadequate improvement seen in symptoms.