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.

Regression-based, demographically adjusted norms for Victoria Stroop Test, Digit Span, and Verbal Fluency for Sri Lankan adults.

OBJECTIVE: Lack of test norms is a major limitation in neuropsychological assessment in many non-English-speaking countries. Our objective was to generate sex-, age-, and education-adjusted, regression-based norms for three pen-and-paper-based executive function/working memory tests, viz. Victoria Stroop Test (VST), Digit Span, and Verbal Fluency, for Sinhala-Speaking Sri Lankan adults. METHOD: Six-hundred and six healthy, community-living, Sinhala-speaking adults (273 men) aged 19-83 years completed VST, Digit Span (forward and backward), and Phonemic (Sinhala phonemes "N," "P," and "S") and Category (animals and vegetables) Fluency tests. We conducted multiple linear regression analyses with sex, age, and years of education fitted as predictors to model the test outcome variables. RESULTS: Younger age was associated with better performance in all tests except in Phonemic Fluency. Longer education was associated with better performance in all outcomes except VST errors and interference. Women had a significant but small advantage over men in VST Neutral and Color Word tests, and Phonemic Fluency. We report regression equations to predict norms for the test performance measures based on sex, age, and years of education; and the test variances accounted by these factors. CONCLUSIONS: We propose demographically adjusted norms for VST, Digit Span, and Verbal Fluency for Sinhala-speaking Sri Lankans aged 19-83 years, and supplement the regression formulae with a calculator that produces predicted and standard scores. These norms would help in interpreting the results of clinical samples in the future, taking into account the variability introduced by sex, age, and education.

Sex-, age- and education-adjusted norms for the WHO/UCLA version of the Rey Auditory Verbal Learning Test for Sinhala-speaking Sri Lankan adults.

OBJECTIVE: The aim of this study was to create sex-, age- and education-adjusted norms for the WHO/UCLA version of the Rey Auditory Verbal Learning Test (RAVLT) for Sinhala-speaking Sri Lankan adults. METHODS: Five-hundred and sixty-one healthy, community-living adults (252 men), aged 19-83 years, and had 0-23 years of education completed the WHO/UCLA RAVLT in Sinhala language. We conducted multiple linear regression analyses with sex, age and years of education to predict RAVLT list A1-A5 individual trial scores; trials A1-A5 total learning; list B score; immediate and delayed recall and recognition trial scores; and retroactive interference. RESULTS: We report regression equations to predict RAVLT norms based on sex, age and years of education; and the test variances accounted by those variables. Accordingly, all measures, except retroactive interference had a significant age-related decline. All measures, except the recognition trial hits, significantly improved with more years of education. Women had significantly higher scores in all measures except in trial B and retroactive interference. Proactive interference, learning rate, learning over trials were not associated with sex, age or education. A confirmatory factor analysis loaded the RAVLT outcome measures into two factors: acquisition and retention. CONCLUSIONS: We report sex-, age- and education-adjusted WHO/UCLA RAVLT norms for Sinhala-speaking Sri Lankans aged 19-83 years; and supplement the regression formulae with a calculator that produces predicted and standard scores for given test participant. These norms would help clinicians accurately interpret individual test results, accounting for the variability introduced by sex, age and education.

Sex-, age-, and education-adjusted norms for Cambridge Neuropsychological Test Automated Battery in literate Sri Lankan adults.

Objective: Neuropsychological test batteries validated for Sri Lankan population are extremely scarce. Cambridge Neuropsychological Test Automated Battery (CANTAB) is a language-independent test battery used in many countries, but the original UK norms may not be representative in the local setting due to sociocultural differences. Our aim was to generate age-, sex-, and education-adjusted norms for the CANTAB for Sri Lankan adults.Method: Three-hundred and eleven healthy, community-living adults aged 20-64 years completed CANTAB subtests of visual attention (Reaction Time and Rapid Visual Information Processing), visual memory (Paired Associates Learning and Delayed Matching to Sample); and executive functions (Stockings of Cambridge, Stop Signal Task, and Spatial Working Memory). We conducted multiple linear regression analyses with sex, age and years of education fitted as predictors to model the CANTAB outcome variables.Results: Younger age and longer education were associated with better performance in most CANTAB measures. Men outperformed women in few measures of psychomotor speed and visuospatial skills, but sex explained only a small proportion of test variance. We report regression equations to predict CANTAB norms based on sex, age and years of education; and the test variances accounted by these factors.Conclusions: We propose sex-, age- and education-adjusted CANTAB norms for Sri Lankans aged 20-64 years and supplement the regression formulae with a calculator that produces predicted and standard scores of a given test subject. These norms would help in interpreting the results of clinical samples in future studies, taking into account the variability introduced by sex, age and education.

Can we predict intermediate syndrome? A review.

INTRODUCTION: Ingestion of organophosphorus insecticides (OPI) is a common method of deliberate self harm in the developing world. Deaths mainly follow as a result of the respiratory failure associated with both cholinergic crisis and the intermediate syndrome. Even though death can be prevented by early mechanical ventilation of these patients, limited studies are available regarding the prediction of intermediate syndrome and subsequent respiratory failure. OBJECTIVE: To systematically review articles that are published with regard to possible prediction of intermediate syndrome using clinical, biochemical and electrophysiological parameters. METHODS: A systematic review on literature published in English language was done in the PubMed database without a date limitation. Two sets of search terms were used. The first set consisted of MeSH Terms "organophosphates", "organophosphate poisoning", "op poisoning" "organophosphate insecticide poisoning" and "organophosphorus". The second set included the MeSH Terms "Intermediate syndrome", "proximal muscle weakness", "cranial nerve palsies", "respiratory depression" and "neck muscle weakness". Articles containing at least one word from each set were reviewed. RESULTS: At least one MeSH term from each set was incorporated in 179 articles. Of these, 69 were rejected as they were not related to organophosphate poisoning or intermediate syndrome. PREDICTION OF IMS: Clinical prediction is mostly based on ICU scoring systems. Biochemical markers such as reduced levels of serum and erythrocyte acetylcholine esterase have been studied many times. Both clinical and biochemical markers show a modest relationship in predicting IMS. Single fibre electromyography show promising results as it directly assesses neuromuscular junction. CONCLUSION: The intermediate syndrome which follows organophosphate poisoning still remains a significant problem with its high morbidity. Clinical and biochemical markers show modest results in predicting IMS. Neurophysiological markers such as single fibre EMG should be studied further as they measure activity of affected nicotinic receptors directly.