The Idiot, Dostoyevsky, and epilepsy.
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Biomedical subjects
Publications and source records attributed to N Senanayake.
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Organophosphorus insecticides (OPI) are the commonest cause of poisoning in Sri Lanka. Being inhibitors of esterases, OPI cause an acute cholinergic crisis as the initial phase of neurotoxicity. The intermediate syndrome (IMS) which develops 24 to 96 hours after poisoning, and the delayed polyneuropathy (OPIDP) which manifests several weeks later, suggest a triphasic effect of OP intoxication. OPI may also cause extrapyramidal manifestations. Chronic neurobehavioural effects of longterm exposure to OPI are also a cause for concern. This paper reviews OPI poisoning in man emphasising the clinical, biochemical, and electrophysiological studies done at Peradeniya over the past two decades.
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The cause of death as recorded in 37125 death certificates (DC) issued in the Kandy District over 20 years at five-year intervals beginning 1967 was analysed to determine the trends in mortality caused by convulsive disorders in the community. Convulsions accounted for 881 (23.7/1000) deaths, the highest number being in infancy (35.8%). A slight male preponderance of 51.5% was observed. Most of the deaths occurred in the periphery (51.6%) and in the tea estates (36.3%) as opposed to town area (12.0%). "Febrile convulsions' was the most common diagnosis in 396 (44.9%) deaths. "Convulsions' which included neonatal and infantile convulsions accounted for 186 (21.1%) deaths. Other causes included chest complications (60, 6.8%), drowning (28, 3.2%), asphyxia (20, 2.3%), status epilepticus (19, 2.2%), burns (7, 0.8%), and poisoning (2, 0.2%). The proportion of deaths due to convulsive disorders showed a decrease from 37.28/1000 in 1967 to 9.55/1000 in 1987, which was most evident in the periphery, from 60.49/1000 to 13.19/1000. This parallelled a drop in the proportion of deaths attributed to "febrile convulsions' and "convulsions'. The study shows the need to educate the public about first-aid and the subsequent management of convulsions, especially in childhood. Health personnel in developing countries should consider it mandatory to make a specific diagnosis in children who present as febrile convulsions. Appropriate antiepileptic medication and compliance can prevent death due to status epilepticus and injuries associated with seizures.
Six patients who developed extrapyramidal manifestations following poisoning with the organophosphorus (OP) insecticide fenthion are reported. The extrapyramidal features, in order of frequency, were dystonia, rest tremor, cog-wheel rigidity, and choreo-athetosis. The delay in onset of these signs, following poisoning, varied from 4 to 40 days, and they disappeared spontaneously in about 1 to 4 weeks in those who survived. The human extrapyramidal system is rich in cholinergic neurons and acetylcholinesterase (AChE). Inhibition of AChE by fenthion, which has ready access to central neurons on account of its lipid solubility, is postulated as the mechanism underlying the extrapyramidal manifestations.
The cause of death as recorded in 37,125 death certificates (DCs) issued in the Kandy District over 20 years at 5-year intervals beginning in 1967 were analysed to determine the trends in mortality caused by poisoning in the community. Poisoning accounted for 718 (19.3 per 1000) deaths, the highest number being in the third decade of life (41.9%). Male:female ratio was 3:1. The agent responsible for 77% of the deaths was pesticides. Acids and chemicals accounted for 6.9% of the deaths. Other poisons each contributing to less than 1% of the deaths were: plant poisons, food items, drugs, kerosine oil and alcohol. Nearly half the deaths had occurred outside the town area, at home or in small hospitals in the periphery. Mortality due to poisoning showed an increasing trend during the 20 years, from 11.8 to 43/1000 deaths, and this increase was most marked in the periphery, from 8/1000 to 70/1000. This increase paralleled the increase in suicide figures in the country. Our findings call for a shift in emphasis in public education towards first-aid management of intoxication. Health services of developing countries should provide appropriate resuscitative equipment, and ensure a regular supply of antidotes and other medication to all rural hospitals. Management of pesticide poisoning should be emphasised in the curricula for medical graduates, nurses, and paramedics.
We report the clinical features of 74 patients with delayed cerebellar ataxia (DCA) following falciparum malaria, who were prospectively followed up at two centres. This unusual complication has an acute onset, with signs suggesting a predominantly midline cerebellar lesion without any evidence of cerebral involvement. There was a delay of a median 13 days between the onset of fever and the onset of ataxia. DCA has a good prognosis, with spontaneous and complete recovery within 3 months. In our opinion, it is an example of a post-infective neurological syndrome possibly mediated via an immune mechanism.
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Immunological mechanisms have been implicated in the pathogenesis of delayed cerebellar ataxia following falciparum malaria (DCA). We tested serum and CSF samples obtained from 39 Sri Lankan patients with DCA for the presence of antibodies (Ab) directed against cerebellar Purkinje cells by an immunofluorescence (IF) technique and Western blot analysis. For the IF test 7 mu thick frozen sections of histologically normal cerebellum obtained at post mortem were used. Proteins obtained from crude preparations of Purkinje cells isolated from the cerebellum were used for Western blot analysis. Sera obtained from patients known to have antineuronal antibodies associated with cerebellar degenerations and paraneoplastic disorders (anti-Hu and anti-Yo Ab) and sera from normal blood donors served as positive and negative controls, respectively. All serum and CSF samples obtained from patients with DCA were negative for Ab directed against cerebellar Purkinje cells. Humoral mechanisms are, therefore, unlikely to be important in the pathogenesis of this delayed complication of falciparum malaria.
We describe 14 Sinhalese male patients with hypokalaemic periodic paralysis (HPP). The age at onset was between 10 and 32 years. Each paralytic episode lasted from 6 to 48 hours (except in one patient who had an attack lasting 5 days). The frequency of attacks varied from 8 to 10 per month in one patient to only 2 attacks over a period of 16 years in another. Four patients (28.6%) had a family history of the disease. Hypokalaemia (serum potassium 1.5 to 3 mmol/l) was documented during an attack in 11 patients. No cause for hypokalaemia was evident in any of them. Investigations including EMG, thyroid hormone level and skeletal muscle histology were within normal limits between episodes. All the patients responded well to treatment with potassium supplementation, alone or with acetazolamide.
Reflex epilepsy (RE) is characterised by seizures that are regularly elicited by some specific stimulus or event mediated by neural pathways. In a prospective study of 1287 epileptic patients seen at Peradeniya, 223 (17.3%) were found to have RE, eating being the commonest stimulus (191 patients, 85.7%). Photosensitive epilepsy (PSE) was relatively rare. Intermittent photic stimulation on 874 unselected epileptic patients produced a positive photoconvulsive response in 60 (6.9%). None had photosensitive seizures, but 3 had a higher frequency of seizures while watching television. Eating epilepsy (EE) had the highest prevalence at Peradeniya (148/1000 epileptic patients). This group was male predominant, and the onset of epilepsy in most cases was in the second decade. The majority experienced partial complex seizures. Repetitive and chronic stimulation of the amygdala during eating is suggested as the mechanism underlying EE. Twenty-one patients had seizures evoked by calculation, problem solving or spatial tasks. Juvenile myoclonic epilepsy was the commonest form of seizure disorder in them. Although PSE itself is rare, self-induced epilepsy (SIE) was common. There were 8 patients who self-induced seizures. The majority were photosensitive and they induced seizures by gazing at the sun and waving a hand in front of the eyes. In the management of REs, clobazam produced impressive results. As for possible seizure-inhibitory mechanisms, our studies on a "Sathi" mediator showed definite EEG changes during mediation. Can mediation increase the seizure-threshold and abort or prevent the propagation of the epileptic discharge? The answer, apart from its possible therapeutic applications, may provide insight into the mechanisms of seizure generation.
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Pulmonary function tests (FVC, FEV1, FEV1/FVC%, TLCO, single breath CO diffusion), chest x ray film, renal function (serum creatinine and blood urea nitrogen), liver function (serum alanine aminotransferase, aspartate transferase, and alkaline phosphatase, bilirubin, total protein, and albumin), a haematological screen (haemoglobin and packed cell volume), and a general clinical examination were performed on 85 paraquat spraymen (mean spraying time 12 years) and on two control groups (76 factory workers and 79 general workers) frequency matched for age and years of occupational service. All the subjects were men. There were no clinically important differences in any of the measurements made between the study group and the two control groups. In particular the results of the lung function tests, appropriate for paraquat toxicity of the study group, were similar to those of the control groups. The same was true of blood tests for liver and kidney function. The incidence of skin damage, nose bleeds, and nail damage in the study group was slightly higher than in the control groups but lower than the incidence reported for paraquat workers in previous studies. The results of this study confirmed that long term spraying of paraquat, at the concentrations used, produced no adverse health effects, in particular no lung damage, attributable to the occupational use of the herbicide.
We have developed a clinical scale to assess severity or organophosphorus (OP) intoxication. Five common clinical manifestations of OP poisoning have been selected as parameters, each to be assessed on a 3 point scale varying from 0-2. Poisoning can then be graded as mild (score 0-3), moderate (score 4-7) or severe (score 8-11) when the patient first presents. The scale was validated using two consecutive series of 173 patients with OP poisoning. Correlations between the scores obtained on admission and three outcome variables, namely, death, the need for ventilatory support and the dose of atropine required in the first 24 hours after admission were significant. We believe that this scale would assist in grading severity of OP intoxication at first contact and help in predicting possible outcome.