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Industrial intoxication by trichloroethylene can produce neurological disturbance of the trigeminal nerve. Therefore, among 105 workers exposed to this toxin, we recorded cortical responses after stimulation of the trigeminal nerve (TSEP) and we compared our results with a control group of 52 subjects. We considered the physical examination exploring, the facial sensitivity and reflexes, the levels of urinary metabolites of trichloroethylene and TSEP. We can describe 4 groups of workers: group A, 13 subjects with perturbations of clinical and evoked responses; group B, 27 subjects with normal physical examination though with disturbed TSEP; group C, 6 subjects had an abnormal examination though evoked responses were normal; group D, 59 subjects had normal clinical examination and TSEP. Disturbed TSEP (particularly delayed responses) are found among the older workers with the longest duration of exposure and higher level of exposure. The alteration of TSEP may appear before clinical disturbance. TSEP could represent a useful test for the supervision of the exposed workers and the clinical diagnosis of the trigeminal impairment.

Animal experiments show that intoxication with hydrocarbon solvents influences the vestibulo-oculomotor reflex arc and indicate that the solvents block the inhibition of the vestibulo-oculomotor reflex presumably exerted by the cerebellum. The blood concentrations necessary to elicit oculomotor disturbances in animals were smaller than those that disturbed the vestibular function. Accordingly, in human experiments styrene and toluene exposure did not elicit any positional nystagmus but caused an increased saccade speed and a diminished visual suppression of vestibular nystagmus. Some cerebellar clinical pathologic process in patients who suffer from a psycho-organic syndrome caused by solvents leads us to believe that the cerebellum might be the most vulnerable part of the brain. Some patients had a positional nystagmus, but the most prominent pathologic signs were elicited by the visual suppression test. Our findings compare well with the increased saccade speed and diminished visual suppression in patients with cerebellar tumors and infarctions.

1. Sudden death is a recognized hazard of volatile substance abuse and may occur during exposure or in the subsequent hours. Intoxication may also lead to indirect deaths due to trauma. 2. Specific post-mortem features have not as yet been identified either macroscopically or microscopically in VSA-related deaths. Toxicological examination for volatile substances of all unnatural teenage deaths is strongly recommended. 3. Four mechanisms for acute, direct VSA-related deaths are discussed, viz anoxia, vagal inhibition, respiratory depression and cardiac arrhythmia. Of these, cardiac arrhythmia due to 'sensitization' of the heart to adrenaline is probably the most common and is well documented in experimental conditions. 4. Deaths from cardiac arrhythmia during or soon after VSA are unpredictable, unpreventable and resuscitation is rarely successful. Previous uneventful sessions of abuse provide no protection from this mode of death.

1. The main neurological disorders associated with chronic VSA are peripheral neuropathy, cerebellar disease, chronic encephalopathy and dementia. Apart from peripheral neuropathy, the clinical features are non-specific, evidence for solvent-related toxicity is in most cases circumstantial and there is no clear dose/response relationship. 2. Peripheral neuropathy is mainly associated with n-hexane and methyl n-butyl ketone. 3. Cerebellar disease is usually associated with toluene exposure; in the more severe cases there is often radiological evidence of irreversible cerebellar atrophy. 4. Chronic encephalopathy and dementia are the most serious consequence of solvent exposure, particularly to toluene in abusers and to mixed solvents in industrial workers. Postmortem studies in some abusers have shown generalized axonal degeneration, demyelination and brain atrophy. 5. Further studies on low level solvent exposure are needed as little is known about the neurological consequences of mild VSA, especially as regards individual susceptibility and possible interactions between solvents and other toxins such as ethanol.

Fast and slow anterograde axonal transport and retrograde axonal transport of proteins were studied in the mainly non-myelinated sensory fibres of the vagus nerve of rabbits fed a diet of 50% galactose over a period of 29 days. Galactose feeding had no effect on the rate or protein composition of slow transport nor on the amount of retrogradely transported proteins. There was a slight retardation of fast transported proteins although their composition was unchanged. The galactose feeding led to a significant increase (p less than 0.005) in nerve water content and nerve galactitol but no significant change in myo-inositol. When 20 mm Hg pressure was applied locally to the cervical vagus nerve, fast transported proteins accumulated proximal to the compression zone in the galactose-fed but not in control rabbits. Administration of the aldose reductase inhibitor Statil (ICI 128436) throughout the experiment prevented the increased susceptibility to pressure and the increase in nerve galactitol and water content. The effects of pressure are similar to those found in the streptozotocin-diabetic rat although the underlying mechanisms may differ.

Commonly used antibacterial agents may be associated with various neurotoxic reactions. Central nervous system toxicities include seizure disorders, encephalopathy, bulging fontanelles, and neuropsychiatric symptoms. These abnormalities have been associated with the use of the penicillins, cephalosporins, sulfonamides, tetracyclines, chloramphenicol, colistin, aminoglycosides, metronidazole, isoniazid, rifampin, ethionamide, cycloserine, and dapsone. Cranial nerve toxicities, such as myopia, optic neuritis, deafness, vertigo, and tinnitus, have been associated with the use of erythromycin, sulfonamides, tetracyclines, chloramphenicol, colistin, aminoglycosides, vancomycin, isoniazid, and ethambutol. Peripheral nerve symptoms consisting of paresthesias, motor weakness, or sensory impairment have been associated with the use of the penicillins, sulfonamides, chloramphenicol, colistin, metronidazole, isoniazid, ethionamide, and dapsone. Neuromuscular blockade has been associated with the use of the tetracyclines, polymyxins, lincomycin, clindamycin, and aminoglycosides. Management generally consists of supportive therapy and immediate discontinuation of therapy with the offending drug.

Dizziness, headaches, and weakness occurred among three men after short-term hydrocarbon exposure during improper welding procedures in a closed container. Symptoms were related to objective evidence of vestibular and cognitive dysfunction. Symptoms and abnormal test results persisted for 6 to 18 months. Simulation of the accident failed to demonstrate likely exposures except aliphatic hydrocarbons, well within the permissible exposure levels. Short-term exposures to neurotoxins may lead to long-term central nervous system abnormalities.

Trigeminal nerve impairment is frequently seen in chronic trichlorethylene intoxication (TRI). A total of 104 occupationally exposed subjects were selected for study because they were employed at a highly exposed workplace. They were studied by clinical examination and by trigeminal somatosensory evoked potentials (TSEP). Normal values for TSEP were obtained from the study of 52 healthy nonexposed subjects. Facial hypoesthesia, when present, was global and predominant in the mandibular and maxillary nerve areas, associated or not with absent reflexes. A disturbed TSEP was found in 40 subjects which was predictable from their clinical symptoms. Correlation with exposure parameters (duration of exposure, trichlorethanol, and trichloracetic acid urinary rates) was mainly observed in subjects presenting both clinical and electrical alterations. Electrical alterations alone were less predictive. An abnormal TSEP may thus provide objective determination of risk assessment in the absence of clinical signs.

The mechanism of the cranial neuropathy associated with heavy exposure to trichloroethylene (or dichloroethylene) is unknown. In severe cases there is destructive spread of the neuropathic process from the Vth cranial nerve nuclei up and down the brain stem in a manner that is difficult to explain on accepted neurotoxicological principles. However, there is a close association reported of this form of trigeminal neuropathy with reactivation of orofacial herpes simplex that suggests the possibility that the chemical, which readily gains entrance into the nervous system, may be responsible for reactivating the latent virus. This novel hypothesis is discussed in the light of current understanding of latency in herpes simplex infection in nervous tissue.

Neurologic abnormalities were seen in 13 of 20 patients with a history of chronic solvent vapor (primarily toluene) abuse for 2 or more years. The patients were evaluated after an abstinence period of at least 4 weeks, to avoid neurologic effects of acute intoxication. Neurologic signs included cognitive (60%), pyramidal (50%), cerebellar (45%), and brainstem/cranial nerve (25%) findings. Eight of nine CTs revealed diffuse atrophy of cerebral hemispheres, cerebellum, and brainstem. BAERs were abnormal in three of four patients, and EEG abnormalities were seen in three of seven patients. Chronic exposure to solvent vapor may cause persistent neurologic impairment.

We report the clinical and neuropathologic findings of a 63-year-old woman who died following an accidental lithium overdose that produced coma, respiratory depression, horizontal gaze palsy, and downbeating nystagmus. She also had mild hypomagnesemia. The pathology was cytotoxicity, predominantly in the regions of the nuclei prepositus hypoglossi and medial vestibular nucleus. Damage to this area with kainate and ibotenate in rhesus monkeys has produced horizontal gaze palsy and downbeating nystagmus. In addition, we report our clinical experience during the past 6 years with other examples of downbeating nystagmus in patients receiving lithium.

Neurotoxicity after intra-arterial administration of cisplatin, alone or in combination with other chemotherapeutic agents, is not yet well-documented. In our experience with 63 previously untreated patients with head and neck cancer, we observed four patients with cranial nerve impairment ipsilateral to the cannulated artery. The first patient has already been reported, whereas the other three are the subject of the present report. Overall, all three patients developed cranial peripheral palsy a few days after the end of intra-arterial cisplatin and after a median total dose of 200 mg (range, 160-250). The nerves involved were the 12th in the first patient, the seventh in the second, and the ninth, tenth, 11th, and 12th in the third patient. Complete recovery of the palsy was noted only in the first patient. The patient reported previously had developed a cranial nerve palsy involving the ninth, tenth, 11th, and 12th nerves of the right side. The low incidence of this toxicity (6.3% in our experience) and the very high objective remission rate achieved by the intra-arterial administration of cisplatin justify the continuation of such an approach to obtain the maximum tumor regression and to research the individual predisposing factors.