Vajira S. Weerasinghe

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.

Long-term event-related potential changes following organophosphorus insecticide poisoning

OBJECTIVE To determine prolonged effects of organophosphorus (OP) insecticide poisoning on cognitive event-related potentials (ERPs). METHODS ERPs of a group of 32 patients recovered from cholinergic phase of OP insecticide poisoning were compared with those of two matched control groups: 32 healthy volunteers and nine patients hospitalised with paracetamol overdose. A follow-up assessment was done in 21 patients (66% of the initial sample) 6 months after OP intoxication and the findings were compared with their initial ERP data. RESULTS Patients showed highly significant prolongation of P300 latency, compared to healthy controls (p=0.003) and the controls with paracetamol overdose (p=0.016). Follow-up ERP findings of the patients revealed that this impairment remained unchanged even 6 months after OP poisoning (p=0.790). There was no significant difference in N100, P200 and N200 latencies or P300 amplitude either among the groups or between the two assessments of the patients with OP poisoning. CONCLUSIONS Our results suggest that acute OP poisoning causes a delay in cognitive processes involved in stimulus classification, lasting at least for 6 months. SIGNIFICANCE These findings highlight the possibility of development of long-lasting cognitive deficits following OP insecticide poisoning, and warrant longer-term prospective studies to determine whether this impairment is permanent.

Cognitive processing of visual stimuli in patients with organophosphate insecticide poisoning

Objective: To determine the effect of organophosphate (OP) insecticide poisoning on cognitive processing time of visual stimuli. Methods: We compared 33 patients who recovered from the cholinergic phase (on average, 15 days after poisoning) with an age- and sex-matched control group. The tests used were simple visual reaction time (SVRT), recognition visual reaction time (RVRT), visual evoked potentials (VEP), and motor evoked potentials (MEP). The term cognitive processing time (CPT) was used to denote the time taken from the initial cortical perception of a stimulus to initiation of the descending motor impulse. CPT of each type of visual reaction was calculated by subtracting the sum of the visual impulse duration and the motor impulse duration from reaction time (CPT = reaction time − [P100 latency + total motor conduction time]). Results: Both the SVRT and RVRT were significantly prolonged in patients. There was no significant difference in P100 latency or total motor conduction time (TMCT) between patients and the controls. However, CPT of simple visual reactions (CPTSVR) and the CPT of recognition visual reactions (CPTRVR) were significantly prolonged in patients. Conclusions: Acute organophosphate poisoning may slow higher-order cognitive processing involved in visual stimulus detection and visual stimulus discrimination, even after clinical recovery from the cholinergic phase.

Effect of manipulation and fractionated finger movements on subcortical sensory activity in man

Previous studies have shown that the somatosensory evoked potentials (SEPs) recorded from the scalp are modified or gated during motor activity in man. Animal studies show corticospinal tract terminals in afferent relays, viz. dorsal horn of spinal cord, dorsal column nuclei and thalamus. Is the attenuation of the SEP during movement the result of gating in subcortical nuclei? This study has investigated the effect of manipulation and fractionated finger movements of the hand on the subcortically generated short latency SEPs in 9 healthy subjects. Left median nerve SEPs were recorded with electrodes optimally placed to record subcortical activity with the least degree of contamination. There was no statistically significant change in amplitude or latency of the P9, N11, N13, P14, N18 and N20 potentials during rest or voluntary movement of the fingers of the left hand or manipulation of objects placed in the hand. The shape of the N13 wave form was not modified during these 3 conditions. It is concluded that in man attenuation of cortical waves during manipulation is not due to an effect of gating in the subcortical sensory relay nuclei.

Auditory event-related potential changes in chronic occupational exposure to organophosphate pesticides

OBJECTIVE To determine whether chronic occupational exposure to organophosphates (OP) pesticides leads to cognitive impairment using event-related potentials (ERPs). METHODS ERPs of 38 vegetable farmers applying OP pesticides and 35 controls were recorded using an auditory oddball paradigm. The N1, P2, N2 and P300 ERP components and the number of counting errors were compared between the groups. RESULTS The farmers made significantly more counting errors than controls in the oddball task. The mixed model ANOVA of component latencies revealed a significant componentxgroup interaction, suggesting farmers had a greater delay in later ERP components. Intergroup comparisons of individual components showed significant delays in N2 and P300 latencies. Subsequent ANCOVA showed significant P300 delay even after adjusting for the latency of the preceding component, N2. Intergroup differences of P300 amplitudes were not significant, although there was limited evidence of a difference in scalp topography. CONCLUSION Our findings indicate that chronic low-level occupational exposure to OP pesticides is associated with progressively increasing delay in successive ERP components, particularly P300. SIGNIFICANCE Chronic exposure to OP pesticides may delay the neurophysiological processes underlying early stages of selective attention and late stages of sensory information processing that include stimulus evaluation and updating of working memory.

Abnormal parameters of magnetically evoked motor-evoked potentials in patients with cervical spondylotic myelopathy

BACKGROUND CONTEXT Magnetic stimulation (MS), which is used to evaluate motor pathways, is helpful in evaluating cervical spinal cord compression (cervical myelopathy [CM]). Previous studies have shown that the central motor conduction time (CMCT), which is the time taken for the nerve impulses to reach the cervical spinal roots after the stimulation of the motor cortex, is prolonged in CM. However, the duration of motor-evoked potentials (MEPs) in CM has not been studied in detail. PURPOSE To compare the duration, CMCT and amplitude of MEPs by MS between patients with clinical and magnetic resonance imaging (MRI) features of CM and a control group. STUDY DESIGN/SETTING A cross-sectional study done at Teaching Hospital, Peradeniya, Sri Lanka. PATIENT SAMPLE Consecutive patients with clinical features of cervical spondylotic myelopathy, without coexisting neurological abnormality. METHODS Transcranial and cervical spinal magnetic stimulation were performed on 21 patients with clinical and MRI features of spondylotic CM (mean age, 43.5years; range, 36-63 years; 9 men) and 17 healthy volunteers (mean age, 39.05 years; range, 23-54yrs; 6 males) using a circular coil with a Magstim 200 stimulator. MEPs were recorded over abductor digiti minimi muscle on both hands. RESULTS Seventeen patients had upper motor neuron (UMN) features in all four limbs; in the others, both lower limbs and one upper limb were affected. The upper limbs with UMN features had shorter duration MEPs compared with the control group. The CMCT and the total motor conduction time were also delayed in the CM group. All three differences were very highly significant (t=5.75, -3.76, 5.27; p<.001). The amplitudes showed no significant difference between the two groups (t=1.27, p=.208). CONCLUSION This study shows that in addition to the CMCT, the duration of MEPs is also useful in evaluating patients with CM using MS.

Acute effects of theanine, caffeine and theanine–caffeine combination on attention

Objective: l-theanine is a constituent of tea which is claimed to enhance cognitive functions. We aimed to determine whether theanine and theanine–caffeine combination have acute positive effects on cognitive and neurophysiological measures of attention, compared to caffeine (a positive control) and a placebo in healthy individuals. Design: In a placebo-controlled, five-way crossover trial in 20 healthy male volunteers, we compared the effects of l-theanine (200 mg), caffeine (160 mg), their combination, black tea (one cup) and a placebo (distilled water) on cognitive (simple [SVRT] and recognition visual reaction time [RVRT]) and neurophysiological (event-related potentials [ERPs]) measures of attention. We also recorded visual (VEPs) and motor evoked potentials (MEPs) to examine any effects of treatments on peripheral visual and motor conduction, respectively. Results: Mean RVRT was significantly improved by theanine (P = 0.019), caffeine (P = 0.043), and theanine–caffeine combination (P = 0.001), but not by tea (P = 0.429) or placebo (P = 0.822). VEP or MEP latencies or SVRT did not show significant inter-treatment differences. Theanine (P = 0.001) and caffeine (P = 0.001) elicited significantly larger mean peak-to-peak N2-P300 ERP amplitudes than the placebo, whereas theanine–caffeine combination elicited a significantly larger mean N2-P300 amplitude than placebo (P < 0.001), theanine (P = 0.029) or caffeine (P = 0.005). No significant theanine × caffeine interaction was observed for RVRT or N2-P300 amplitude. Discussion: A dose of theanine equivalent of eight cups of back tea improves cognitive and neurophysiological measures of selective attention, to a degree that is comparable with that of caffeine. Theanine and caffeine seem to have additive effects on attention in high doses.

P337: Stimulated single fibre electromyography using concentric needle electrode in organophosphate insecticide poisoning in Sri Lanka

form two conditions (standard, creature category). They were asked to immediately say a word starting with the last character of the written Japanese word shown in front of them, and this procedure was repeated 20 times. During control condition, they repeated the vowels “A, I, U, E, O”. Grand mean waveforms of the 20 responses were produced and changes in oxygenated hemoglobin (oxy-Hb changes) from the control state were converted to numeric values every 100 ms. The approximated value of area, peak amplitude and latency after performance were determined as data. Left channel 11 and right channel 12 in midfrontal area, left channel 19 and right channel 22 in frontopolar area were selected as the regions of interest (ROIs) and oxy-Hb changes in the ROIs was evaluated. This study was performed with the approval of the Ethical Committee, Kurume University and informed consent obtained from all subjects after a written explanation of the contents of the examination. Results: In ROIs, Patients showed decreased oxy-Hb changes compared with healthy subjects in both tasks. In addition, the peak amplitude was larger and latency was earlier in healthy subjects than those in patients during creature category shiritori task. There was significant correlation between the negative syndrome scales of the PANSS and oxy-Hb changes. Conclusion: These results suggest the usefulness of NIRS using shiritori tasks for evaluating psychophysiological indices.

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.

Task-specific kinetic finger tremor affects the performance of carrom players.

Abstract We aimed to determine the effect of task-specific kinetic finger tremor, as indexed by surface electromyography (EMG), on the accuracy of a carrom stroke. Surface EMG of extensor digitorum communis muscle of the playing arm was recorded during rest, isometric contraction and stroke execution in 17 male carrom players with clinically observed finger tremor and 18 skill- and age-matched controls. Log-transformed power spectral densities (LogPSDs) of surface EMG activity (signifying tremor severity) at a 1-s pre-execution period correlated with angular error of the stroke. LogPSDs in 4–10 Hz range were higher in players with tremor than controls during pre-execution (P < 0.001), but not during the resting state (P = 0.067). Pre-execution tremor amplitude correlated with angular deviation (r = 0.45, P = 0.007). For the first time, we document a task-specific kinetic finger tremor in carrom players. This finger tremor during the immediate pre-execution phase appears to be a significant determinant of stroke accuracy.