Chronic central nervous system effects of acute organophosphate pesticide intoxication

To evaluate the latent neurological effects of organophosphate pesticide poisoning, this epidemiologic study examined 100 matched-pairs of individuals with previous acute organophosphate pesticide poisoning and nonpoisoned controls No significant difference between poisoned subjects and controls was found on audiometric tests, ophthalmic tests, electroencephalograms, or the clinical serum and blood chemistry evaluations Of the more than 50 scores from the neurological examination, abnormalities were demonstrated among the cases only on measures of memory, abstraction, and mood, and on one test of motor reflexes Differences between the two cohorts were much more apparent in the neuropsychological tests The differences occurred on tests of widely varying abilities including intellectual functioning, academic skills, abstraction and flexibility of thinking, and simple motor skills Twice as many cases as controls (24 vs 12) had Halstead-Reitan Battery summary scores in the range characteristic of individuals with cerebral damage or dysfunction Results from the Minnesota Multiphasic Personality Inventory and the Patient's and Relative's Assessment of Patient Functioning Inventories also revealed greater distress and complaints of disability for the poisoned subjects

Chronic neurological sequelae of acute organophosphate pesticide poisoning

Organophosphorus compounds are potent neurotoxic chemicals that are widely used in medicine, industry, and agriculture. The neurotoxicity of these chemicals has been documented in accidental human poisoning, epidemiological studies, and animal models. Organophosphorus compounds have 3 distinct neurotoxic actions. The primary action is the irreversible inhibition of acetylcholinesterase, resulting in the accumulation of acetylcholine and subsequent overstimulation of the nicotinic and muscarinic acetylcholine receptors, resulting in cholinergic effects. Another action of some of these compounds, arising from single or repeated exposure, is a delayed onset of ataxia, accompanied by a Wallerian-type degeneration of the axon and myelin in the most distal portion of the longest tracts in both the central and peripheral nervous systems, and is known as organophosphorus ester-induced delayed neurotoxicity (OPIDN). In addition, since the introduction and extensive use of synthetic organophosphorus compounds in agriculture and industry half a century ago, many studies have reported long-term, persistent, chronic neurotoxicity symptoms in individuals as a result of acute exposure to high doses that cause acute cholinergic toxicity, or from long-term, low-level, subclinical doses of these chemicals. The author attempts to define the neuronal disorder that results from organophosphorus ester-induced chronic neurotoxicity (OPICN), which leads to long-term neurological and neurobehavioral deficits. Although the mechanisms of this neurodegenerative disorder have yet to be established, the sparse available data suggest that large toxic doses of organophosphorus compounds cause acute necrotic neuronal cell death in the brain, whereas sublethal or subclinical doses produce apoptotic neuronal cell death and involve oxidative stress.

Organophosphorus Ester-Induced Chronic Neurotoxicity

Age is probably the single most crucial factor determining how humans sleep Age and level of vigilance significantly influence the electroencephalogram (EEG) and the polysomnogram (PSG) The Pediatric Task Force provide an evidence-based review of the age-related development of the polysomnographic features of sleep in neonates, infants, and children, assessing the reliability and validity of these features, and assessing alternative methods of measurement We used this annotated supporting text to develop rules for scoring sleep and arousals in infants and children A pediatric EEG or PSG can only be determined to be normal by assessing whether the EEG patterns are appropriate for maturational age Sleep in infants at term can be scored as NREM and REM sleep because all the polysomnographic and EEG features of REM sleep are present and quiet sleep, if not NREM sleep, is at least "not REM sleep" The dominant posterior rhythm (DPR) of relaxed wakefulness increases in frequency with age: (1) 35-45 Hz in 75% of normal infants by 3-4 months post-term; (2) 5-6 Hz in most infants 5-6 months post-term; 3) 6 Hz in 70% of normal children by 2 months of age; and 3) 8 Hz (range 75-95 Hz) in 82% of normal children age 3 years, 9 Hz in 65% of 9-year-olds, and 10 Hz in 65% of 15-year-old controls Sleep spindles in children occur independently at two different frequencies and two different scalp locations: 110-1275 Hz over the frontal and 130-1475 Hz over the centroparietal electrodes; these findings are most prominent in children younger than 13 years Centroparietal spikes are often maximal over the vertex (Cz), less often maximal over the left central (C3) or right central (C4) EEG derivation About 50% of sleep spindles within a particular infant's PSG are asynchronous before 6 months of age, 30% at 1 year Based on this, we recommend that: (1) sleep spindles be scored as a polysomnographic signature of NREM stage 2 sleep (N2) at whatever age they are first seen in a PSG, typically present by 2 to 3 months post-term; (2) identify and score sleep spindles from the frontal and centroparietal EEG derivations, especially in infants and children younger than 13 years NREM sleep in an infant or child can be scored if the dominant posterior rhythm occupies 20% of the 30-second epoch contain 05 to 2 Hz >75 microV (usually 100-400 microV) activity as N3 The DPR should be scored in the EEG channel that is best observed, (typically occipital), but DPR reactive to eye opening can be seen in central electrodes Because sleep spindles occur independently over the frontal and central regions in children, they should be scored whether they occur in the frontal or central regions Because sleep spindles are asynchronous before age 2 years, simultaneous recording of left and right frontal and central activity may be warranted in children 1-2 years of age Simultaneous recording of left, right, and midline central electrodes may be appropriate because of the asynchronous nature of sleep spindles before age 2 years, but reliability testing is needed Evidence has shown that the PSG cannot reliably be used to identify neurological deficits or to predict behavior or outcome in infants because of significant diversity of results, even in normal infants Normal sleep EEG patterns and architecture are present in the first year of life, even in infants with severe neurological compromise Increasing evidence suggests that sleep and its disorders play critical roles in the development of healthy children and healthy adults thereafter Reliability studies comparing head-to-head different scoring criteria, recording techniques, and derivations are needed so that future scoring recommendations can be based on evidence rather than consensus opinion We need research comparing clinical outcomes with PSG measures to better inform clinicians and families exactly what meaning a PSG has in evaluating a child's suspected sleep disorder

The visual scoring of sleep and arousal in infants and children.

Pesticides, rice productivity, and farmers' health: an economic assessment.

In the early 195O’s, the University of Colorado Medical Center conducted a multidisciplinary investigation of industrial and agricultural workers acutely exposed to a variety of pesticides. The focus of this program was a special project involving the intensive study of workers engaged in the manufacture of several organophosphorus (OP) anticholinesterase compoh,. ’.,. Because of the acute confusional states induced by O P exposure and because of the need for more information regarding the central effects of OP exposure in humans, an effort was made to examine certain psychological, neurological, and clinical-neurophysiological variables; additionally, a number of biochemical parameters were investigated. Since January, 1965, a group of men from this same industrial population has been studied; many of the current subjects have been continuously employed in the same capacity since 1950. This report is concerned primarily with some of the psychological, neurological, and clinical-neurophysiological results of these studies. In the 1952 program, psychological testing involved a large battery of measures designed to search for classic evidences of brain damage. Data analysis revealed no formal evidences of organic brain damage in psychological test terms. Testing done within 72 hours of exposure almost always showed erratic and slowed functioning, interpreted as indicating the presence of clinical delirium for many individuals within three days of a symptomatic exposure. The one differentiating test in the original study was the Rotary-Pursuit task, a test of hand-eye coordination. Recently exposed men had worse performance than controls, but we have since found that this type of test is unreliable because of technical limitations. Neurological examinations revealed multiple minor signs such as generalized weakness and confusion shortly after exposure; hard neurological signs were absent after treatment and clinical recovery. In the 1952 study, electroencephalograms were done as close to time of exposure as possible and, in many cases, repeated after treatment and recovery. Typical slow-wave bursts after activation by overbreathing were observed if EEGs were done soon after untreated exposure (FIGURE 1 ). These findings were similar to those reported by Grob (1953). A t this time, it was believed that adequate treatment normalized the EEG. These old EEGs have been reevaluated in light of findings from our current investigations and modern knowledge of the neurophysiology of drowsiness and sleep. Upon reevaluation, we find an increase in medium-voltage, irregular theta activity, OCcurring in bursts of one to five seconds’ duration, most often seen during light drowsiness. Special characteristics of the drowsy EEG-there is a normal increase in slow activity-made it easy to overlook this change. In the 1952 study, psychiatric interviews were done o n 78 men: 56 with histories

Eeg, psychological, and neurological alterations in humans with organophosphorus exposure*

The “spontaneous” K-complex, an EEG phenomenon, was studied with an explicit rating system The spontaneous K-complex can first be identified at age 6 months Maturation of the K-complex progresses rapidly for about the first 2 years after birth, then slows, albeit, with increased variability until age 5 years, progressing again until a relative plateau in K-complex development is reached at about age 12 Four parameters are used in the rating system: individuation, vertex focus, repetition, and spread of the K-complex It is hypothesized that neurofunctional development underlying K-complex ontogenesis may have referents observable in terms of a number of information-processing parameters such as behavioral-developmental, and cognitive-perceptual levels of functioning during early childhood It is speculated that the neurofunctional change implied by the early ontogenesis of K-complexes indexes the approximate age of onset of the infant's capacity to experience dreams

Ontogenesis of spontaneous K-complexes.

A method is described for identifying and scoring average evoked response (AER) components. The method uses background EEG activity as a guide for visual identification of AER components. This procedure provides an advantage in objectivity and precision over most other methods, thus producing an increase in reliability and greater likelihood for interlaboratory agreement in experiments employing measures based upon the AER components.

/pdf/an-objective-procedure-for-the-hand-scoring-of-scalp-average-fo0ks9k1vl.pdf

David R. Metcalf

Papers

Eeg, psychological, and neurological alterations in humans with organophosphorus exposure*

Ontogenesis of spontaneous K-complexes.

An objective procedure for the hand scoring of scalp average evoked potentials

A flexible IBM system for collating EEG and clinical data