LATE NEUROLOGICAL SEQUELS AFTER ACUTE POISONING WITH DIMETHOATE Niko Bekarovski, B. Pavlovski, N.Popovski, I.Jurukov Clinic of Toxicology and Urgent Internal Medicine Clinic Center - Skopje, Republic of Macedonia

INTRODUCTION There are large number of studies describing acute neurological effects after acute organophosphate poisoning, but there are only a limited number of studies describing the chronic neurological effects, after acute organophosphate poisoning.

AIM OF THE STUDY is to show a case with late neurological sequels, develop one year after acute poisoning with organophosphate pesticide Dimethoate Aim of this study is to show a case with late neurological sequels, develop one year after acute poisoning with organophosphate pesticide Dimethoate ( Sistemin 40). ( Sistemin 40).

CASE REPORT 63 year old male patient was admitted to the Clinic of Toxicology in Clinic Center Skopje, Republic of Macedonia, six hours after ingesting an unknown dose of the organophosphate Dimethoate in a suicide attempt. In the next few days developed bilateral hyporreflexia, positive Babinski, rigidity of all limbs, akinesia, tremor, that persisted even after total cardiopulmonary recovery (8th day) and normalization of plasma cholinesterase range (12th day).

Bradyphrenia, tremor and rigidity remained after two weeks of poisoning and therefore the diagnosis of Parkinsonism was suspected by neurologist, and treatment with Biperiden lactate (Akinetone) 2x5 mg. started I.V. After second injection, there was great improvement of all symptoms, especially on consciousness, mobility and speech. Four weeks latter, at 43rd day of poisoning, all signs disappeared and patient was discharge from the Clinic completely free of Parkinsonism. CT, EEG and EMG were normal.

One year later the patient was called to hospital and matched controls. We found a serious deficit in memory, decrease in vibrotactile sensitivity, as indicator for peripheral neuropathy, tremor and bilateral patellar hiporreflexia. EEG didn't show any pathological changes and EMG wasn't made because the patient didn't allow to make it.

DISCUSSION Three large epidemiological studies have examined the chronic effects among patients poisoned by organophosphates. Savage et al studied 100 patients, an average of nine years after poisoning. They found significant deficits among the cases on several cognitive tests of memory and abstraction but no differences on electroencephalography or neurological examination. Cases had worse reading ability than controls, and educational differences may have accounted for the results.

Rosenstock et al. and McConnell et al. studied 36 men poisoned by organophosphates (mostly methamidaphos) who had been admitted two years earlier, as well as matched controls. They found several cognitive deficits in the poisoned subjects and a significant decrease in vibrotactile sensitivity, an indicator of peripheral neuropathy.

Finally, Steenland et al studied 128 men poisoned a mean of seven years earlier and 90 controls. Vibrotactile sensitivity and one cognitive test (sustained attention) were significantly worse in the poisoned men, and several tests showed deficits which increased with the severity of the poisoning. Nerve conduction tests and clinical neurological examination showed no differences

In summary, therefore, well-designed studies have shown chronic sub clinical damage to the central and peripheral nervous system among those previously poisoned by organophosphates. Studies of subjects with long-term low level exposures have been less consistent, but some have also shown sub clinical effects on the central and peripheral nervous system. Low response rates and possible selection biases have affected almost all studies but are unlikely to explain the observed effects; indeed loss to follow up of more severely affected individuals may have caused some bias towards showing no effect

Differences between studies may be due to the different organophosphates. The observed peripheral effects are consistent with persistent delayed neuropathy induced by organophosphate. The mechanism by which chronic central nervous system effects might occur is unknown; Duffy et al has observed persistent changes on electroencephalograms after high level exposure.

Clinical neurological examinations have given negative results in the subjects studied epidemiologically. The importance of the observed sub clinical effects on quality of life or day to day functioning may be minimal. The study subjects generally were not followed for long periods, and we do not know whether the observed sub clinical effects will diminish, persist, or get worse. This question is important in the light of the large number of people exposed and in the light of some case reports that suggest that more severe long term effects are possible.

CONCLUSSION This case shown that all patients with acute organophosphate intoxication have to be monitoring few years after the poisoning, especially if there are any signs of neurological sequels during the acute phase.