The chemistry of ethanol is relevant to an understanding of the neurobiology of alcohol addiction. Ethyl alcohol(ethanol) is a small organic molecule consisting of a two-carbon backbone surrounded by hydrogen atoms, with a hydroxyl group attached to one of these carbons. The hydroxyl group provides ethanol with its water soluble properties while the hydrocarbon backbone gives ethanol some of its lipid soluble properties. This composition of ethanol gives it the capacity to interact with and dissolve into both water and lipid. This amphiphilic property of ethanol has been a major impetus for the hypotheses that try to define ethanol's mechanism of action through the perturbation of cell membrane lipids. The small molecular size of ethanol and its lack of isometric carbons supports the theory that ethanol's actions are not expressed through specific recognition sites or receptors for ethanol. The most up to date explanations of ethanol's effects in the central nervous system focus on a nonspecific interaction of ethanol and neuronal membrane lipids. Disorganization of the membrane lipid bilayer is thought to result from this interaction. This perturbation of one of the major structural elements of the neuron is theorized to result in the functional changes seen during alcoholic intoxication.
Knowledge of the nervous system in general and of the brain and human behaviour in particular are of paramount importance to those who are dedicated to a safe and healthy environment. Work conditions, and exposures that directly affect the operations of the brain, influence the mind and behaviour. To evaluate information, to make decisions and to react in a consistent and reasonable manner to perceptions of the world require that the nervous system functions properly and that behaviour not be damaged by dangerous conditions, such as accidents (e.g., a fall from a poorly designed ladder) or exposure to hazardous levels of neurotoxic chemicals.
The clinical examination should include a neurological examination, where attention should be paid to impairment of higher nervous functions, such as memory, cognition, reasoning and emotion; to impaired cerebellar functions, like tremor, gait, station and coordination; and to peripheral nervous functions, especially vibration sensitivity and other tests of sensation. Psychological tests can provide objective measures of higher nervous system functions, including psychomotor, short-term memory, verbal and non-verbal reasoning and perceptual functions. In individual diagnosis the tests should include some tests that give a clue as to the person's premorbid intellectual level. History of school performance and previous job performance as well as possible psychological tests administered previously, for example in connection with military service, can help in the evaluation of the person's normal level of performance.
Assuming that the patient has been exposed to neurotoxic chemicals, the diagnosis of neurotoxic disease starts with symptoms. In 1985, a joint working group of the World Health Organization and the Nordic Council of Ministers discussed the matter of chronic organic solvent intoxication and found a set of core symptoms, which are found in most cases (WHO/Nordic Council 1985). The core symptoms are fatigability, memory loss, difficulties in concentration, and loss of initiative. These symptoms usually start after a basic change in personality, which develops gradually and affects energy, intellect, emotion and motivation. Among other symptoms of chronic toxic encephalopathy are depression, dysphoria, emotional lability, headache, irritability, sleep disturbances and dizziness (vertigo). If there is also involvement of the peripheral nervous system, numbness and possibly muscular weakness develop. Such chronic symptoms last for at least a year after the exposure itself has ended.
Acute neurotoxic syndromes occur mainly in accidental situations, when workers are exposed short-term to very high levels of a chemical or to a mixture of chemicals generally through inhalation. The usual symptoms are vertigo, malaise and possible loss of consciousness as a result of depression of the central nervous system. When the subject is removed from the exposure, the symptoms disappear rather quickly, unless the exposure has been so intense that it is life-threatening, in which case coma and death may follow. In these situations recognition of the hazard must occur at the workplace, and the victim should be taken out into the fresh air immediately.
Electrophysiological techniques include special tests other than the direct conduction velocity, amplitude and latency studies. Somatosensory evoked potentials, auditory evoked potentials, and visual evoked potentials are ways of studying the characteristics of the sensory conducting systems, as well as specific cranial nerves. Afferent-efferent circuitry can be tested by using blink reflex tests involving the 5th cranial nerve to 7th cranial innervated muscle responses; H-reflexes involve segmental motor reflex pathways. Vibration stimulation selects out larger fibres from smaller fibre involvements. Well-controlled electronic techniques are available for measuring the threshold needed to elicit a response, and then to determine the speed of travel of that response, as well as the amplitude of the muscle contraction, or the amplitude and pattern of an evoked sensory action potential. All physiological results must be evaluated in light of the clinical picture and with an understanding of the underlying pathophysiological process.
Most recently, a controversial neurotoxicant syndrome, multiple chemical sensitivity, has been described. Such patients develop a variety of features involving multiple organ systems when they are exposed to even low levels of various chemicals found in the workplace and the environment. Mood disturbances are characterized by depression, fatigue, irritability and poor concentration. These symptoms reoccur on exposure to predictable stimuli, by elicitation by chemicals of diverse structural and toxicological classes, and at levels much lower than those causing adverse responses in the general population. Many of the symptoms of multiple chemical sensitivity are shared by individuals who show only a mild form of mood disturbance, headache, fatigue, irritability and forgetfulness when they are in a building with poor ventilation and with off-gassing of volatile substances from synthetic building materials and carpets. The symptoms disappear when they leave these environments.
Proof that a particular substance has reached a toxicant dose level is usually lacking after symptoms appear. Unless environmental monitoring is ongoing, a high index of suspicion is necessary to recognize cases of neurotoxicologic injury. Identifying symptoms referable to the central and/or the peripheral nervous systems can help the clinician focus on certain substances, which have a greater predilection for one part or another of the nervous system, as possible culprits. Convulsions, weakness, tremor/twitching, anorexia (weight loss), equilibrium disturbance, central nervous system depression, narcosis (a state of stupor or unconsciousness), visual disturbance, sleep disturbance, ataxia (inability to coordinate voluntary muscle movements), fatigue and tactile disorders are commonly reported symptoms following exposure to certain chemicals. Constellations of symptoms form syndromes associated with neurotoxicant exposure.
Neurons (the functional cell unit of the nervous system) have a high metabolic rate and are at greatest risk for neurotoxicant damage, followed by oligodendrocytes, astrocytes, microglia and cells of the capillary endothelium. Changes in cellular membrane structure impair excitability and impede impulse transmission. Toxicant effects alter protein form, fluid content and ionic exchange capability of membranes, leading to swelling of neurons, astrocytes and damage to the delicate cells lining blood capillaries. Disruption of neurotransmitter mechanisms block access to post-synaptic receptors, produce false neurotransmitter effects, and alter the synthesis, storage, release, re-uptake or enzymatic inactivation of natural neurotransmitters. Thus, clinical manifestations of neurotoxicity are determined by a number of different factors: the physical characteristics of the neurotoxicant substance, the dose of exposure to it, the vulnerability of the cellular target, the organism's ability to metabolize and excrete the toxin, and by the reparative abilities of the structures and mechanisms affected. Table 7.11 lists various chemical exposures and their neurotoxic syndromes.
Neurotoxicant syndromes, brought about by substances which adversely affect nervous tissue, constitute one of the ten leading occupational disorders in the United States. Neurotoxicant effects constitute the basis for establishing exposure limit criteria for approximately 40% of agents considered hazardous by the United States National Institute for Occupational Safety and Health (NIOSH).
Engineering controls (e.g., ventilation systems, closed production facilities) are the best means for keeping workers' exposures below permissible exposure limits. Closed chemical processes that keep all toxicants from being released into the workplace environment are the ideal. If this is not possible, closed ventilation systems that exhaust ambient air vapours and are designed so as to pull contaminated air away from workers are useful when well designed, adequately maintained, and properly operated.