Age-stratified norms for Raven's standard progressive matrices for Sri Lankan adults.

OBJECTIVE: The aim of this study was to create age-stratified norms for the Raven's Standard Progressive Matrices (SPM) for Sri Lankan adults. METHODS: A sample of 610 adults (age: 18-72 years; education: 1-19 years), underwent the 60-item version of the SPM under individual supervision of a test administrator. The sample was stratified into 5-year age bands, and the norms are presented as percentile tables and percentile curves. RESULTS: The age-related changes were more accurately predicted by a curvilinear model (overall R2 = 0.961) than a linear regression model (R2 = 0.639). The SPM norms are presented as age-stratified percentile tables, as well as sex-, age- and education-adjusted multiple regression equations. The highest percentiles in the younger end of the age spectrum showed a ceiling effect. In the context of age-stratified US (1993) and British (1992) norms, older individuals in the Sri Lankan sample scored much lower than their Western counterparts. However, the difference narrowed in the younger age bands, showing no difference among the 18-to-22-year age bands in the three countries. CONCLUSIONS: This age-by-country interaction can be partly explained by poorer education in the older individuals in the present sample compared to those in the US and UK standardization samples. SPM norms presented in this paper fill a hiatus in assessment of general intellectual ability in Sri Lankan adults. Given that Sri Lanka improves its educational, socioeconomic and health standards faster than the nations who have already reached higher standards, these norms would require re-standardization in the coming decades.

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.

Psychometric properties of the Sinhala version of the Swanson, Nolan, and Pelham rating scale (SNAP-IV) Parent Form in healthy children and children with ADHD.

OBJECTIVE: The present study aimed to translate and adapt the Parent Form of the MTA Version of the Swanson, Nolan, and Pelham ADHD/ODD rating scale (SNAP-IV) into Sinhala and examine its psychometric properties. METHOD: The MTA version of the SNAP-IV was translated into the Sinhala language by adhering to the WHO translation and adaptational process. The final Sinhala SNAP-IV (S-SNAP-IV) was administered to parents of 412 healthy children and adolescents (age: 6-18 years), and 272 children and adolescents with ADHD (age: 4-19 years). Internal consistency and factor structure of the S-SNAP-IV were determined in each sample. RESULTS: Conforming to that of the original English version, the S-SNAP-IV showed a three-factor structure (inattention, hyperactivity/impulsivity, and oppositional defiant disorder) in each sample, except for three item deviations (10,11, and 13) in the healthy sample. The S-SNAP-IV showed excellent internal consistency in the total sample (Cronbach's alpha = 0.97), healthy sample (Cronbach's alpha = 0.90), and the clinical sample (Cronbach's alpha = 0.94). The S-SNAP-IV also showed good discriminative validity: Only 1.5% of the healthy sample exceeded the cut-off scores in any domain, whereas all newly diagnosed, unmedicated children were S-SNAP-IV positive in at least one domain. CONCLUSIONS: The findings suggest that the three-factor model fits the S-SNAP-IV, and it clearly distinguishes children with ADHD from non-ADHD children. We conclude that the S-SNAP-IV possesses satisfactory psychometric properties-consistent with the MTA English version and its translations into other languages-making it a reliable and valid instrument for screening children with ADHD.

Subclinical memory impairment in unaffected siblings of patients with dementia.

Objective: Family history of dementia is a known risk factor for dementia. The cognitive performance of unaffected siblings of dementia patients has been poorly studied. We aimed to determine whether clinically unaffected siblings of dementia patients have significant cognitive impairment compared to individuals who do not have first-degree relatives with dementia. Methods: We compared the cognitive performance of 67 patients with dementia (24 males; mean age 69.5), 90 healthy siblings of those patients (34 males; mean age 61.56) and 92 healthy adults (35 males; mean age 60.96) who have no first-degree relatives with dementia. We assessed learning and memory (Rey Auditory Verbal Learning Test (RAVLT)), short-term/working memory (Digit Span) executive functions (Stroop Test) and general intelligence (Raven Progressive Matrices). Test scores were compared among three groups, with regression-based adjustments for age, sex, and education. Results: As expected, the patients with dementia were impaired in all cognitive domains. In the Sibling Group, RAVLT total learning was significantly lower compared to controls (B = -3.192, p = .005). In a subgroup analysis, compared to controls, RAVLT delayed recall was poorer in the siblings of patients with early-onset (<65 years) dementia. No significant differences were observed in other cognitive domains. Conclusion: Clinically unaffected siblings of dementia patients seem to have a selective subclinical impairment in memory encoding. This impairment seems to be more prominent in siblings of patients with early-onset dementia who also have deficits in delayed recall. Future studies are needed to determine if the observed cognitive impairment deteriorates to dementia.

Dose-response effect of L-theanine on psychomotor speed, sustained attention, and inhibitory control: a double-blind, placebo-controlled, crossover study.

BACKGROUND: L-theanine is a non-protein-forming amino acid found in tea. Previous research shows high doses (100-400 mg) of L-theanine enhances attention, mainly by reducing mind wandering and distracter processing. We hypothesized that these indirect mechanisms could significantly improve the performance of low-level attentional tasks, whereas the relative contribution could be less in complex attentional tasks that require active, higher-order processing of target stimuli. METHODS: To test this hypothesis, we conducted a double-blind, placebo-controlled, counterbalanced, four-way crossover study in 32 healthy young adults, where we compared the effects of three doses of L-theanine (100, 200 and 400 mg) with a placebo (distilled water), administered before and 50 min after dosing, on three attentional tasks from the Cambridge Neuropsychological Test Automated Battery [viz. Reaction Time (RTI)-visuomotor speed, Rapid Visual Information Processing (RVP)-sustained attention, and Stop Signal Task (SST)-inhibitory control]. Results were analyzed in dose × time repeated measures ANOVA models, with subsequent pairwise comparisons. RESULTS: Active doses significantly improved reaction times in the RTI (100-200 mg) and RVP (200-400 mg) tasks from baseline (p < 0.05), but once controlled for the change-from-baseline caused by placebo, only the RTI simple reaction times showed significant improvements, following 100 mg (Δ = 16.3 ms, p = 0.009) and 200 mg (Δ = 16.9 ms, p = 0.009) of L-theanine. CONCLUSIONS: Consistent with our hypothesis, these findings suggest that L-theanine significantly improves attention in simple visuomotor tasks, but not in more complex sustained attention tasks, or executive control tasks that require top-down inhibition of pre-active responses.

Effect of balance training on footwork performance in badminton: An interventional study.

Badminton is a racket sport that requires a wide variety of proficient postural changes and moves including jumps, lunges, quick changes in direction, and rapid arm movements. Efficient movement in badminton court entails reaching the shuttlecock in as few steps as possible while maintaining good balance. Balance training is an unexplored component in badminton training protocol, though balance is important in injury prevention and performance enhancement. We aimed to investigate the effectiveness of balance training on sport-specific footwork performance of school-level competitive badminton players. We conducted a controlled trial involving 20 male badminton players (age 12.85±0.67 years). Participants were stratified according to their level of performance in the game, and payers from each stratum were randomly assigned to control and intervention groups. The control group (n = 8) engaged in 2 hours of ordinary badminton training, whereas the intervention group (n = 12) underwent 30 minutes of balance training followed by 1 hour and 30 minutes of ordinary badminton training, 2 days per week for 8 weeks. We tested the participants at baseline and after 8 weeks for static balance (Unipedal Stance Test), dynamic balance (Star Excursion Balance Test) and sport-specific footwork performance (shuttle run time and push-off times during stroke-play). On pre- vs. post-intervention comparisons, both groups improved in static balance (eyes opened) (p<0.05), but only the intervention group improved in dynamic balance (p = 0.036) and shuttle-run time (p = 0.020). The intervention group also improved push-off times for front forehand (p = 0.045), side forehand (p = 0.029) and rear around-the-head shots (p = 0.041). These improvements in push-off times varied between 19-36% of the baseline. None of the footwork performance measures significantly improved in the control group. Our findings indicate that incorporating a 30-minute balance training program into a regular training schedule improves dynamic balance, and on-court sport-specific footwork performance in adolescent competitive badminton players, after 8 weeks of training.

L-theanine improves neurophysiological measures of attention in a dose-dependent manner: a double-blind, placebo-controlled, crossover study.

Objective: L-theanine, a non-proteinic amino acid found in tea, is known to enhance attention particularly in high doses, with no reported adverse effects. We aimed to determine whether oral administration of L-theanine acutely enhances neurophysiological measures of selective attention in a dose-dependent manner.Methods: In a double-blind, placebo-controlled, counterbalanced, 4-way crossover study in a group of 27 healthy young adults, we compared the effects of 3 doses of L-theanine (100, 200 and 400 mg) with a placebo (distilled water) on latencies of amplitudes of attentive and pre-attentive cognitive event-related potentials (ERPs) recorded in an auditory stimulus discrimination task, before and 50 min after dosing.Results: Compared to the placebo, 400 mg of theanine showed a significant reduction in the latency of the parietal P3b ERP component (p < 0.05), whereas no significant changes were observed with lower doses. A subsequent exploratory regression showed that each 100-mg increase in dose reduces the P3b latency by 4 ms (p < 0.05). No dose-response effect was observed in P3b amplitude, pre-attentive ERP components or reaction time.Discussion: The findings indicate L-theanine can increase attentional processing of auditory information in a dose-dependent manner. The linear dose-response attentional effects we observed warrant further studies with higher doses of L-theanine.

Changes of attention-related brain activity over 6 months after acute organophosphate pesticide poisoning: a prospective follow-up study.

CONTEXT: Ingestion of organophosphate (OP) pesticides is a common method of self-harm in developing countries. Apart from acute cholinergic effects, limited evidence implicates OP poisoning in long-term neurocognitive deficits. However, prospective neurophysiological evidence of long-term deficits is scarce in humans. We aimed to determine long-term cognitive changes of acute OP pesticide self-poisoning in a prospective follow-up study, using event-related potentials (ERPs), an electroencephalographic index of cognitive functioning. METHODS: We recruited 203 patients (147 men) hospitalised with OP pesticide ingestion (OP group; all had significant erythrocyte cholinesterase inhibition) and 50 patients (23 men) with paracetamol overdose (control group) as a means of self-harm. We recorded their ERPs and behavioural performance in a selective attention task at three post-exposure time points: on discharge from hospital (around 14 days post-ingestion), 6 weeks and 6 months post-ingestion. We compared the reaction time and ERP components of the two groups at each time point, adjusting for sex, age, education and comorbid depression in multiple regression models. RESULTS: OP group had significantly slower reaction times than the control group on discharge and at 6 weeks, but not at 6 months. On discharge, the OP group also showed significantly prolonged latency of the parietal P3b component, signifying delayed attentional processing. P3b amplitudes were also significantly smaller in the OP group on discharge and at 6 months. Within the OP group, greater clinical severity of poisoning was associated with smaller P3b amplitudes. Early pre-attentive cortical processing (as indexed by N1 ERP component) showed no significant intergroup differences. CONCLUSIONS: Acute OP pesticide poisoning was associated with impaired behavioural and neurophysiological indices of selective attention. These deficits outlast the cholinergic phase of intoxication. The neurobehavioral impairment disappears over months, but neurophysiological deficits seem to last even after 6 months. This impairment could potentially compromise the performance and safety of patients for months following clinical recovery.

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.

The effect of optic neuritis treatment trial (ONTT) combined corticosteroid regimen on pattern reversal visual evoked potentials: a prospective follow-up study.

BACKGROUND: The combined corticosteroid regimen of the original Optic Neuritis Treatment Trial (ONTT) is used in many centers to treat optic neuritis. Though pattern reversal visual evoked potentials (PRVEPs) are a sensitive, standard measure of visual conduction in optic neuritis, no studies hitherto have investigated the effect of combined ONTT regimen on PRVEPs. We aimed to determine the effect of combined corticosteroid regimen of the ONTT on changes of PRVEPs in patients with first-episode optic neuritis over 3 months post-treatment. METHODS: This is a prospective, observational study in which 44 patients with optic neuritis were seen pre-treatment (baseline) and follow-up, at 1 month (FU1) and 3 months (FU2). Twenty-nine patients were treated with ONTT combined regimen (ONTT+ Group) while 15 were conservatively managed without corticosteroids (ONTT- Group). The median latency and amplitude values of the P100 PRVEP component and the visual acuity (i.e. LogMAR values) at pre-treatment, FU1 and FU2 were compared in the two groups using Friedman's rank test and Wilcoxon Signed Ranks test. RESULTS: Median P100 latency improved significantly (to the normal range) as early as by 1 month after the commencement of treatment in the ONTT+ Group, and then remained significantly lower than the baseline over next 2 months. In the ONTT- Group, the median P100 latency improved more slowly over the two follow up assessments and reached the normal range by 3 months. Median visual acuity values also improved significantly at 1 and 3 months after the commencement of treatment in the ONTT+ Group but not in the ONTT- Group. CONCLUSION: ONTT combined corticosteroid regimen improves conduction in the visual pathways of patients with first-episode optic neuritis earlier than does conservative management. We provide electrodiagnostic evidence that combined ONTT regimen-compared with conservative management-results in early remission of visual conduction abnormalities in first-episode optic neuritis.

Dysfunction in macula, retinal pigment epithelium and post retinal pathway in acute organophosphorus poisoning.

CONTEXT: Organophosphorus (OP) insecticide poisoning is a significant health problem in South Asian countries. Although cholinergic receptors are present at the junction between photoreceptors and the retinal pigment epithelium (RPE), human studies of the effects of OP poisoning on the visual pathways are very few. This study aims to demonstrate the pattern of changes in retina and post retinal pathways in patients with acute OP poisoning using visual electrophysiological tests. METHODS: This is an observational, cross-sectional study conducted at the Neurophysiology Unit, Teaching Hospital, Peradeniya, Sri Lanka. We tested 16 patients recovered from cholinergic phase, at least 24 h after deatropinization and within 8 weeks of OP ingestion. We assessed the functional integrity of the photoreceptors and ganglion cells of the macula by pattern electroretinography (PERG); RPE by electro-oculography (EOG); and post retinal pathways by pattern reversal visual evoked potentials (PR-VEP). Latencies and amplitudes of PR-VEP and PERG, light peak (LP), dark trough (DT) and Arden ratio of EOG were determined in patients and compared with 16 controls using the Mann-Whitney U test. RESULTS: Of the 16 OP-poisoned patients (median age of 37 ± IQR 20 years), six (37.5%) had reduced Arden ratio with reference to the International Society of Clinical Electrophysiology of Vision cut-off value of 1.7. The median Arden ratio in patients (1.69 ± IQR 0.36) was significantly lower compared to controls (1.90 ± IQR 0.4). The median latencies and amplitudes of PR-VEP or PERG were not significantly different between patients and controls. However, three patients had prolonged P100 latencies in PR-VEP and one had prolonged P50 latency in PERG. CONCLUSIONS: Acute OP poisoning seems to affect the functions of the RPE and the visual electrophysiological changes outlast the cholinergic phase. Limited evidence suggests that photoreceptors of the macula region and post retinal pathway might be affected in some patients.

Subacute and chronic neuropsychological sequalae of acute organophosphate pesticide self-poisoning: a prospective cohort study from Sri Lanka.

CONTEXT: Some epidemiological evidence implicates acute organophosphate (OP) pesticide poisoning in long-term neurocognitive deficits. However, no study has prospectively followed up poisoned patients long-term from the time of intoxication. We aimed to determine whether clinically significant acute OP self-poisoning leads to subacute and chronic neurocognitive deficits, in a prospective follow up study. METHODS: Employing Mini Mental State Examination, Digit Span and Cambridge Neuropsychological Test Automated Battery (CANTAB), we compared multiple cognitive functions in 222 patients hospitalized with acute OP pesticide self-poisoning with a control group of 52 patients hospitalized with paracetamol overdose, at three time points: on discharge following clinical recovery, 6 weeks and 6 months post-ingestion. Intergroup comparisons at each time point were done in multiple regression models, adjusting for sex, age, education and psychiatric comorbidities. OP within-group analysis was done to determine a dose-response relationship. RESULTS: After adjusting for covariates, the OP poisoned group had significantly poorer working memory (Digit Span) and episodic memory (CANTAB Paired Associates Learning); impaired spatial planning (CANTAB Stocking of Cambridge); and slower response speed in the sustained attention task (CANTAB Rapid Visual Information Processing), in the post-discharge assessment. Only working memory and episodic memory measures were impaired in the OP group at 6 weeks, whereas no significant intergroup differences were observed at 6 months. The OP subgroup who had complete red cell acetylcholinesterase inhibition on admission had poorer episodic memory when tested post-discharge than those who had partial inhibition, but no significant subgroup differences were observed at 6 weeks or 6 months. DISCUSSION: Acute OP pesticide poisoning may cause neuropsychological impairment that outlasts the cholinergic phase on a subacute time scale; but does not cause measurable chronic neuropsychological deficits.

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.

Effects of L-theanine-caffeine combination on sustained attention and inhibitory control among children with ADHD: a proof-of-concept neuroimaging RCT.

We examined the acute effects of L-theanine, caffeine and their combination on sustained attention, inhibitory control and overall cognition in boys with attention deficit hyperactivity disorder (ADHD). L-Theanine (2.5 mg/kg), caffeine (2.0 mg/kg), their combination and a placebo were administered in a randomized four-way repeated-measures crossover with washout, to five boys (8-15 years) with ADHD. Functional magnetic resonance imaging (fMRI) was performed during a Go/NoGo task and a Stop-signal task ~ 1 h post-dose. NIH Cognition Toolbox was administered ~ 2 h post-dose. Treatment vs. placebo effects were examined in multi-level mixed-effects models. L-Theanine improved total cognition composite in NIH Cognition Toolbox (p = 0.040) vs. placebo. Caffeine worsened and L-theanine had a trend of worsening inhibitory control (i.e. increased Stop-signal reaction time; p = 0.031 and p = 0.053 respectively). L-Theanine-caffeine combination improved total cognition composite (p = 0.041), d-prime in the Go/NoGo task (p = 0.033) and showed a trend of improvement of inhibitory control (p = 0.080). L-Theanine-caffeine combination was associated with decreased task-related reactivity of a brain network associated with mind wandering (i.e. default mode network). L-Theanine-caffeine combination may be a potential therapeutic option for ADHD-associated impairments in sustained attention, inhibitory control and overall cognitive performance.

Electro-oculography in bilateral optic neuropathy.

OBJECTIVE: Effect of bilateral, optic neuropathy on the function of retinal pigment epithelium has not been investigated extensively to date. This study aimed to determine the effect of bilateral, optic neuropathy on light peak:dark trough ratio, light peak and dark trough values of electro-oculography. Thirty-seven patients with a clinical diagnosis of bilateral optic neuropathy and 40 control subjects were recruited in this observational, cross-sectional study, carried out at the Neurophysiology unit, Teaching Hospital, Peradeniya, Sri Lanka. Pattern reversal visual evoked potentials, pattern electroretinography and electro-oculography were recorded in all of them. RESULTS: Twenty-four patients (64.9%) had reduced light peak:dark trough ratio values. The median light peak:dark trough ratio ± inter quartile range of the patient group (1.50 ± 0.4) was significantly lower than that of the controls (1.80 ± 0.2), (p < 0.001). Median dark trough value was significantly higher in patients compared to the control value. These changes may be due to higher conductance of ion channels in the retinal pigment epithelium, sub retinal space creation, changes in choroidal circulation or secondary to photoreceptor abnormalities in the macular region. These results indicate that retinal pigment epithelium might be affected in bilateral optic neuropathy.

Differences between organophosphates in respiratory failure and lethality with poisoning post the 2011 bans in Sri Lanka.

Introduction: Self-poisoning with organophosphorus pesticides (OPs) has high morbidity and mortality. The most toxic OP formulations have been progressively banned in Sri Lanka over the past three decades. However, respiratory failure (RF) requiring ventilation remains a major contributor to fatalities. Therefore, this study was conducted to examine the frequency of RF and death after poisoning with the currently available OPs to determine if further bans might be warranted to reduce the burden of OP poisoning in Sri Lanka.Methods: Five hundred and forty patients with confirmed OP self-poisoning were prospectively observed throughout their hospital stay following admission to Peradeniya hospital in the Central Province of Sri Lanka. Clinical data including the time and duration of intubation were documented prospectively in structured datasheets.Results: One hundred and forty-nine patients required ventilation (27%), and 34 (23%) of those died. Males with alcohol co-ingestion were more likely to develop RF. Compared to other OPs, profenofos (Odds Ratio [OR] = 2.5, 95% CI: 1.5-3.9), and quinalphos (OR = 4.5, 95% CI: 1.6-12.6) were more likely to, and chlorpyrifos (OR = 0.2, 95% CI: 0.1-0.4) less likely to lead to RF than other OPs. Profenofos was also associated with higher mortality (OR = 2.3, 95% CI: 1.1-4.6) than other OPs. The median time to intubation was longer for profenofos, but the duration of intubation was similar for all OP formulations.Conclusion: RF and deaths following OP ingestion continue to be a major problem in Sri Lanka, with profenofos being the major current agent of concern. Strategies to replace profenofos and quinalphos use with less toxic insecticides should be explored. Doctors should be alert to the high probability of delayed and prolonged RF after profenofos poisoning.

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.

Prediction of organophosphorus insecticide-induced intermediate syndrome with stimulated concentric needle single fibre electromyography.

BACKGROUND: Deliberate self-poisoning (DSP) using organophosphorus (OP) insecticides are a common clinical problem in Asia. OPs inhibit acetylcholine esterase (AChE), leading to over-activity of muscarinic and nicotinic cholinergic circuits. Intermediate syndrome (IMS) is mediated via prolonged nicotinic receptor stimulation at the neuromuscular junction and its onset is between 24-96 hours post ingestion. The aims of the present study were 1) to investigate whether neuromuscular junction dysfunction within the first 24 hours following exposure, quantified by jitter in single fibre electromyography (SfEMG), can predict IMS, and 2) to compare the changes in SfEMG jitter over the course of the illness among patients who developed IMS (IMS+) and those who did not (IMS-). METHODS AND FINDINGS: We conducted a prospective cohort study in a tertiary care hospital in Sri Lanka on 120 patients admitted between September 2014 and August 2016 following DSP by OP insecticides viz., profenofos 53, phenthoate 17, diazinon 13, chlorpyrifos 5, others 12, unknown 20. SfEMG was performed every second day during hospitalization. Exposure was confirmed based on the history and red blood cell AChE assays. IMS was diagnosed in patients who demonstrated at least three out of four of the standard IMS criteria: proximal muscle weakness, bulbar muscle weakness, neck muscle weakness, respiratory paralysis between 24-96 hours post ingestion. Respiratory failure requiring intubation occurred in 73 out of 120 patients; 64 of these were clinically diagnosed with IMS. Of the 120 patients, 96 had repeated SfEMG testing, 67 of them being tested within the first 24 hours. Prolonged jitter (>33.4µs) within the first 24 hours was associated with greatly increased risk of IMS (odds ratio = 8.9, 95% confidence intervals = 2.4-29.6, p = 0.0003; sensitivity 86%, specificity 58%). The differences in jitter between IMS+ and IMS- patients remained significant for 72 hours and increased jitter was observed in some patients for up to 216 hours. For intubated patients, the median time for jitter to normalize and median time to extubate were similar, and the two variables had a moderate positive correlation (r = 0.49, P = 0.001). CONCLUSIONS: Prolonged jitter recorded with SfEMG <24 hours of ingestion of an OP strongly correlates with subsequent occurrence of IMS. The time course of electrophysiological recovery of the NMJ was similar to the time course of respiratory recovery in IMS patients.

l-Theanine and caffeine improve target-specific attention to visual stimuli by decreasing mind wandering: a human functional magnetic resonance imaging study.

Oral intake of l-theanine and caffeine supplements is known to be associated with faster stimulus discrimination, possibly via improving attention to stimuli. We hypothesized that l-theanine and caffeine may be bringing about this beneficial effect by increasing attention-related neural resource allocation to target stimuli and decreasing deviation of neural resources to distractors. We used functional magnetic resonance imaging (fMRI) to test this hypothesis. Solutions of 200mg of l-theanine, 160mg of caffeine, their combination, or the vehicle (distilled water; placebo) were administered in a randomized 4-way crossover design to 9 healthy adult men. Sixty minutes after administration, a 20-minute fMRI scan was performed while the subjects performed a visual color stimulus discrimination task. l-Theanine and l-theanine-caffeine combination resulted in faster responses to targets compared with placebo (∆=27.8milliseconds, P=.018 and ∆=26.7milliseconds, P=.037, respectively). l-Theanine was associated with decreased fMRI responses to distractor stimuli in brain regions that regulate visual attention, suggesting that l-theanine may be decreasing neural resource allocation to process distractors, thus allowing to attend to targets more efficiently. l-Theanine-caffeine combination was associated with decreased fMRI responses to target stimuli as compared with distractors in several brain regions that typically show increased activation during mind wandering. Factorial analysis suggested that l-theanine and caffeine seem to have a synergistic action in decreasing mind wandering. Therefore, our hypothesis is that l-theanine and caffeine may be decreasing deviation of attention to distractors (including mind wandering); thus, enhancing attention to target stimuli was confirmed.

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.