The findings in the first case may well be due to damage from a combination of volatile solvents in the lacquer thinner (44), and the second case was attributed by the authors themselves to the toxic effects of organic lead in the gasoline (45). In a group of subjects with toluene abuse, brain MRI revealed 1) widespread atrophy (also discernible with CT), 2) loss of differentiation between the gray and white matter throughout the CNS, and 3) increased periventricular white matter signal on T2-weighted images (27). Because nerve damage is often progressive, it is important to consult with a doctor when you first notice symptoms. methylbenzene . The damage to brain white matter appears to become irreversible at some point and no treatment is currently known other than abstinence. The invention relates to a method for producing toluol derivat Some workers have developed reversible disorders of the optic nerves after chronic exposure in the workplace. 2A), and the cerebellar white matter (Fig. In these 20 patients, CT disclosed atrophy of the cerebrum, cerebellum, and brainstem in 8 of 9 who underwent scanning (21). For example, chronic abuse of volatile solvents, such as toluene or naphthalene (the volatile ingredient in mothballs), damages the protective sheath around certain nerve fibers in the brain and peripheral nervous system. He reported wearing latex gloves daily and drinking alcohol occasionally. Nerve damage of this type has been found to While a spectrum of neurobehavioral deficits and white matter damage on MRI can be seen in patients with chronic toluene abuse, severely affected individuals with toluene leukoencephalopathy serve as an excellent example of white matter dementia (7, 10, 25, 26). The clinical syndrome, toluene leukoencephalopathy, can be detected by a combination of characteristic symptoms and signs, detailed neurobehavioral evaluation, and brain magnetic resonance imaging. Please enable it to take advantage of the complete set of features! Prior to the lead phase-out in gasoline, the total amount of lead used in gasoline was over 200,000 tons per year. HHS Nerve damage can make you lose feeling in your feet, so even minor cuts can turn into sores or ulcers without your realizing it. Toluene abuse in pregnancy causes a constellation of teratogenic features known as fetal solvent syndrome, which is similar to the fetal alcohol syndrome. This deficiency could result in higher brain exposure to toluene and a heightened risk of neurotoxicity (6, 49). Although no data exist on long-term outcome in toluene abusers who abstain from inhalant abuse, our experience suggests that individuals may show partial recovery once the toxic effect of toluene is no longer present (21). 2F). Peripheral neuropathy may be caused by a number of different medical conditions, such as diabetes and cancer. Mattia et al reported that, following gavage treatment of rats with toluene, the highest level of induced reactive oxygen species was in the hippocampus; however, they confined their studies to investigating crude synaptosomal fractions from only three sites: the cerebellum, hippocampus, and striatum (52). More than 3 million tons of toluene are produced each year in the United States alone (6), and this solvent is found in many occupational settings and in numerous household products. Tualeka AR(1), Rahmawati P(2), Ahsan A(3), Pathak Y(4), Russeng SS(5), Sukarmin S(6), Wahyu A(7). Other animal studies have raised the possibility that the hippocampus may be damaged by toluene, although the data are inconclusive and this area has not yet been shown to be preferentially affected in humans. He urged quick action in the event of an injury to ensure no lasting damage to the nerve. This extensive destruction of nerve fibers is clinically … More recent studies have also reported Purkinje cell loss and hippocampal neuronal loss in rats with inhalation exposure (55). AIM: This research aimed to calculate the intake of foods rich in CYP2E1 enzyme and glycine to improve toluene detoxification. APF = Assigned Protection Factor. Hippuric acid is the major metabolite of toluene, and up to 75% of inhaled toluene is excreted in the urine as hippuric acid within 12 hours after exposure (9). Our original case also manifested significant reactive astrocytosis, even in areas with ostensibly intact myelin (Fig. In this paper, we consider the impact of toluene abuse on our society, describe the specific neurobehavioral deficits in toluene leukoencephalopathy, review the spectrum of neuroimaging findings in patients with this disorder, summarize the teratogenic effects of toluene in both humans and animal models, and offer possible explanations for the range of neuropathological damage seen in brains of individuals who chronically abuse toluene. For someone whose livelihood relies on their voice, the situation was confronting. Recent evidence has suggested that defective metabolism of toluene may occur in some individuals because of a deficient gene coding for aldehyde dehydrogenase, one of the hepatic enzymes responsible for metabolizing toluene (6, 8, 49). Indeed, a precise assessment of the extent of exposure to inhalants cannot usually be determined. In a follow-up study of 14 more toluene abusers, detailed neuropsychological testing and magnetic resonance imaging (MRI) scans showed that neuropsychological deficits in patients with toluene-induced white matter damage correlated with the patient's neuroimaging findings (22). Nevertheless, the suggestion was made that duration of exposure was related to the degree of neuropsychological impairment (18). Neurotmesis. However, nerve damage is very serious, and can be permanent. In 1961, Grabski documented chronic cerebellar degeneration in a person who sniffed toluene for an extended period, and this individual was the first published case documenting persistent neurotoxicity from toluene (13). Caldemeyer KS Pascuzzi RM Moran CG Smith RS. Evidence indicated that the toluene originated from bituminous deposits. Toluene abusers with long-term, intense exposure are at risk for toluene leukoencephalopathy, a syndrome characterized by dementia, cerebellar ataxia, corticospinal tract dysfunction, brainstem signs, and cranial neuropathies. It is also found in fuels. Grossly, there was thinning of the corpus callosum but no discernible white matter discoloration or cavitation. The nerve damage made controlling her tongue difficult and some sounds impossible to make correctly. This may in part be due to the fact that brain damage from chronic toluene abuse is probably under-recognized by pathologists. Case 2 differed from Case 1 in that PAS-positive macrophages were considerably fewer, the myelin loss significantly less, and the gliosis was several times more intense than in Case 1. In this disorder, your immune system attacks the myelin sheath or the cells that produce and maintain it. Depending on the degree to which the white matter is affected by the neuropathological insult, changes may be mild, moderate, or severe (7, 10, 25, 26). (Fig. system depression, nerve damage. Central nervous system impairment and visual impairment. However, the absorption of ingested toluene is slower than that of inhaled toluene. Moreover, further analyses showed that cognitive impairment surpassed corticospinal, cerebellar, brainstem, and cranial nerve dysfunction as the most disabling aspect of the chronic neurotoxicity syndrome (21). Another microvascular complication caused by nerve damage is diabetic neuropathy. n-Hexane--Related Peripheral Neuropathy Among Automotive Technicians --- California, 1999--2000. The axon is damaged and the surrounding connective tissue remains intact (Figure 12). At relatively low levels of ambient toluene, just exceeding 200 ppm, fatigue, headache, paresthesias, and slowed reflexes are seen (6). In addition, peripheral nerve dysfunction has been reported, but the peripheral neuropathies may have been due to impurities, such as n-hexane, in the toluene. Nerve damage may cause loss of sensation or numbness in the fingertips, making it harder to do things with your hands. Coronal brain sections from the autopsy case presented by Dr. William Halliday represent the severe end of the spectrum of white matter damage due to toluene abuse, but nevertheless show rather subtle, ill-defined, patchy discoloration of the white matter of the occipital lobe (A), with more obvious involvement of the cerebellar hemisphere (B). C: Axial T2-weighted image showing moderate cerebral white matter hyperintensity. 2C). The idea that toluene may be most damaging when myelin is being formed is corroborated by animal studies demonstrating that rats show a permanent reduction in forebrain myelination after prenatal toluene exposure (50). 1993 Sep-Oct;14(5):1195-9. In a series of toluene leukoencephalopathy patients with white matter dementia (22), the shortest duration of toluene abuse to be associated with toluene leukoencephalopathy by conventional MRI was 168 months (14 years), whereas neuropsychological evidence of impairment could appear as early as 24 months (2 years). Of all the metabolites measured by MRS, N-acetyl aspartate (NAA) is the most important because it is widely considered to be a marker of CNS axons (39). 1997 Jan;72(1):1-7. doi: 10.1006/enrs.1996.3686. Signs of toluene abuse and addiction include the identification of paint stains on the body or clothing, a chemical breath odor, red eyes, nearby discarded spray paint cans or cans of solvent, and a drunken or dazed appearance (1). Low power view of the cerebellum stained with LFB-PAS shows the severe, near-total myelin loss, except for relative preservation in the fleece and hilum of the dentate nucleus (C); this pattern of myelin loss is identical to that described in Case 1 of Kornfeld et al (43). Traductions en contexte de "nerve" en anglais-français avec Reverso Context : nerve cells, have the nerve, optic nerve, nerve gas, nerve stimulation Psychiatr Clin North Am. The level of exposure also depends on the dose, duration, and work done [6]. nom grammaire @Termium. The central nervous system and exposure to toluene: a risk characterization. Although many questions about the toxic effects of inhalants in general are unresolved, the nervous system is clearly vulnerable to toxicity from these substances (4). The chronic encephalopathy associated with long-term toluene abuse is particularly important because it appears to be a permanent and disabling disorder related to white matter damage in the brain. Use of Biodegradable, Chitosan-Based Nanoparticles in the Treatment of Alzheimer's Disease. Perhaps the most significant toxic effect of chronic exposure to inhalants is widespread and long-lasting damage to the brain and other parts of the nervous system. There is no question that the leukoencephalopathy detected by conventional MRI scanning in chronic inhalant abusers represents the severe end of the spectrum of white matter injury, and is usually detected in individuals only after many years of heavy toluene abuse. This is the largest nerve in the human body that extends from the lower back through the hips and the buttocks and down each leg. Over time, nerve damage can also occur in the fingers and hands. The pathogenic action of toluene after localizing in white matter, however, is uncertain. Potential For Nerve Damage. The focus of this review has been on adolescents and adults who have practiced chronic toluene abuse, with some attention to industrial workers who experience much less occupational exposure. Copyright © 2020 American Association of Neuropathologists. Some early reports of presumed toluene neurotoxicity are difficult to interpret because the patients were acknowledged to abuse multiple solvents and may not have represented neurotoxicity from toluene alone. nom grammaire . A serious health concern is that toluene may have an effect on your nervous system (brain and nerves). Overall drug abuse among teenagers has declined in the past several years, but inhalant abuse is on the rise. Concomitant use of several different chemicals of abuse could also potentiate the myelin damage from toluene, a possibility discussed by Kornfeld et al (43). Toluene (methylbenzene) is an aromatic hydrocarbon, and a ubiquitous solvent in societies around the world. Patients with these polymorphisms may develop toxicity with a lower dose of a drug or toxin. Open Access Maced J Med Sci [Internet]. APF = Assigned Protection Factor. Subsequently, an eloquent neuropathological study of two paint sniffers appeared in 1994 in this journal (43). Good animal models of toluene abuse embryopathy have been developed (50, 67). The first description of permanent encephalopathy from toluene dates from 1966, when the same patient reported by Grabski (13) was described as having developed emotional lability and frontal release signs after continued toluene abuse (14). Tualeka AR(1), Rahmawati P(2), Ahsan A(3), Pathak Y(4), Russeng SS(5), Sukarmin S(6), Wahyu A(7). eCollection 2020 Dec. Molecules. The selective damage to white matter caused by chronic toluene abuse has offered an unprecedented opportunity for behavioral neurologists to study the specific effects of cerebral white matter disorders on behavior. Microscopically, diffuse demyelination was found, but there was also significant neuronal loss in the cerebral cortex, basal ganglia, and cerebellum, intense reactive gliosis, and giant axonal degeneration in the long tracts of the spinal cord. Get the latest public health information from CDC:, Get the latest research information from NIH:, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: Long-term toluene abuse has led to neuropsychiatric and neurobehavioral disorders, which in many cases, but not all, were reversible. The myelin loss was milder, more uniform, and the borders between severely depleted and moderately demyelinated areas were ill defined; features identical to those seen in our original case (41). As the damage gets worse, you will likely lose feeling in your toes, feet, and legs. Removal (amputation) of a toe, foot or even the lower leg may be necessary. BACKGROUND: Toluene was an organic compound used in chemical and drug industries, the main source of toluene emissions from fires. The highly lipophilic nature of toluene explains its rapid concentration in the lipid-rich central nervous system (CNS; 1). … effects of toluene include damage to myelin which is essential for the proper functioning of the central and peripheral nervous system. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. Physical Hazards: Flammable Potential Health Effects Inhalation: Irritation, nausea, headache, drowsiness, dizziness, disorientation, sleep disturbances, loss of coordination, dilated pupils, kidney damage and liver damage Skin Contact: Irritation 65 First Street Troy, NY 12180 Phone: 518.273.6266 PbS Core EviDots in Toluene MSDS June … On light microscopy of Case 1, Luxol fast blue-periodic acid-Schiff (LFB-PAS) staining showed severe myelin loss especially around blood vessels. Binswanger's disease: Case presentation and differential diagnosis. These results suggested a primary impact on sustained attention, speed of information processing and visuospatial skills, combined with relative sparing of language (23), a pattern consistent with previous neurobehavioral observations in toluene abuse (21). . MRS provides measures of brain metabolism (39), and can be used to quantitate the chemical environment of brain tissues in the brain without the need for cerebral biopsy. Acute exposure causes fatigue, mild confusion, ataxia, and dizziness. Our original autopsied case was a relatively pure chronic toluene abuser who had sniffed paint on a daily basis for many years up until the time of death (41). Toluene (C₆H₅CH₃) is a colorless liquid with a sweet, pungent odor.  |  Case 2 manifested only slight thinning of the corpus callosum on gross sections, but pale gray discoloration was found in the white matter of the posterior frontal, parietal and temporal lobes, as well as in the cerebellum. Data from 1994 disclosed that 19.9% of eighth graders reported that they had used inhalants, with 5.6% reporting use within the past 30 days (1). Additional acute adverse effects on the kidney (12) and cardiac systems are also recognized (1), and cardiotoxicity with lethal arrhythmia may be the cause of sudden demise in those with acute inebriation (1). The demyelination was interpreted by the authors as being secondary to the neuronal loss. The first report of the fetal solvent syndrome in 1979 (60) described facial dysmorphia, growth retardation, and microcephaly similar to the fetal alcohol syndrome (60, 61). The cerebellar white matter, especially in the vermis, was more affected than cerebral white matter (43). Long-term and intense exposure to toluene vapors in humans who abuse spray paint and related substances has led to the recognition that toluene has a severe impact on central nervous system myelin. E-mail, Sequences of substance use among American Indian adolescents, Clinical neurotoxicology and neurobehavioral toxicology, Clinical environmental health and toxic exposures, The central nervous system and exposure to toluene: A risk characterization, The behavioral neurology of cerebral white matter, Renal tubular acidosis associated with toluene “sniffing.”, Toluene sniffing producing cerebellar degeneration, Permanent encephalopathy from toluene inhalation, Persistent cerebellar ataxia after exposure to toluene, Effects of paint sniffing on neuropsychological test performance, Neuropsychological deficits in chronic inhalant abusers, Multifocal central nervous system damage caused by toluene abuse, Cerebellar, cortical and functional impairment in toluene abusers, Neurologic sequelae of chronic solvent vapor abuse, White matter dementia in chronic toluene abuse, Effects of MRI abnormalities on WAIS-R performance in solvent abusers, Neuropsychologic impairment and MRI abnormalities associated with chronic solvent abuse, White matter dementiaClinical disorders and implications. Long term exposure to low levels of toluene has been speculated to cause neurobehavioral dysfunction, but the threshold of exposure above which leukoencephalopathy occurs is debated. Epub 2013 Apr 15. Solvent vapor leukodystrophy demonstrated less lymphocytic inflammation, no lipid-laden macrophages in areas of myelin breakdown, and more patchy, incomplete, and ill-defined myelin loss than ALD (43). A comparison of fetal alcohol syndrome, toluene embryopathy, and maternal phenylketonuria, Toluene embryopathy: Clinical delineation and developmental follow-up, Toluene embryopathy: Delineation of the phenotype and comparison with fetal alcohol syndrome, Solvent abuse in pregnancy: A perinatal perspective, Prenatal exposure to toluene results in abnormal neurogenesis and migration in rat somatosensory cortex. Animal studies suggest that astrocytes are activated by toluene, paralleling the reactive gliosis seen in human cases with lesser degrees of myelin damage. Rosenberg NL Kleinschmidt-DeMasters BK Davis KAet al. Disorders of the muscles, cardiovascular effects, renal tubular damage, and sudden death have occurred in chronic abusers of toluene. Environ Res. A decrease in NAA concentration, expressed as the ratio of NAA to creatine (NAA/Cr), may thus serve as an indicator of axonal damage, an important variable in considering the potential reversibility of an insult such as toluene leukoencephalopathy. Craniofacial features of the fetal solvent syndrome include micrognathia, low set ears, flat nasal bridge, abnormal scalp hair patterning, down-turned corners of the mouth, and a large anterior fontanelle (62–65). Thus the correlation between the effects of a given inhalant such as toluene and its clinical and neuroradiological findings can be difficult in some patients. If the damage is severe, paralysis may result; this paralysis is rarely permanent but recovery is slow. This is another medical condition that develops slowly and may begin years before a person is finally diagnosed with diabetes. Toluene abusers generally employ one of two methods to achieve a “high” with this substance: “huffing,” in which a rag is soaked with toluene and the fumes are directly inhaled, and “bagging,” in which the fumes are inhaled as they arise from the solvent placed in a plastic bag. In addition, the ALD-like EM changes were confined to brain and no such inclusions were found in the adrenal cortical cells (Cases 1 and 2) or Leydig cells of the testis (Case 1). B: Sagittal T1-weighted image of the same patient shown in (A), demonstrating thinning of the corpus callosum and cerebellar atrophy. Exposure to toluene can cause eye and nose irritation, tiredness, confusion, euphoria, dizziness, headache, dilated pupils, tears, anxiety, muscle fatigue, insomnia, nerve damage, inflammation of the skin, and liver and kidney damage. Chronic toluene abuse produces a devastating neurological disorder, of which dementia is the most disabling component. Toluene leukoencephalopathy has become a prototypical example of white matter dementia, and, more generally, underscores the importance of cerebral white matter in neurobehavioral function. Toluene generates reactive oxygen species (ROS) and the toxic effects relating to these reactants. Gross brain abnormalities were more readily detectable in Case 1, which showed thinning of the corpus callosum and gray, patchy discoloration and mottling of the cerebral white matter with sparing of the U-fibers. Figure 1 displays MRI scans from several different chronic toluene abusers and illustrates the range of atrophy and white matter abnormalities that can be detected. As the damage gets worse, you will likely lose feeling in your toes, feet, and legs. Exactly when in the clinical course the damage becomes irreversible, an issue of paramount importance for prognostic counseling is unknown. Many abusers attain the desired effects of inhalants by simply removing the lid of a can or tube and sniffing the fumes, or spraying the aerosolized mists into the mouth. Graph theory analysis of the dopamine D2 receptor network in Parkinson's disease patients with cognitive decline. The understanding of the chronic effects of toluene on the brain has evolved over the last four decades. The mechanism of brain white matter injury from toluene is unknown. As mentioned, this solvent, like many others, is highly lipophilic (1), and in laboratory animals toluene is preferentially distributed in lipid-rich regions of the brain (51). The optic nerve can be damaged by toluene (causing demyelination) and hexachlorophene (causing myelin deformation). Although similar to the neurobehavioral changes of benzene-induced toxic effects, those of toluene toxicity are more severe. Despite the severity of white matter damage in this case, autopsy brain sections demonstrated relatively subtle, patchy, ill-defined discoloration of cerebral white matter, especially in the occipital lobes (Fig. Despite these changes in astrocytic function, little has been described in the way of white matter changes in these models, save for the study by Gotohda et al that mentions “thinning” of the cerebellar white matter in toluene-exposed rats (55). Other investigators have focused more on alterations in astrocytes than on neuronal populations (57, 58). Solvents, glues, spray paints, coatings, silicones, and other products contain normal (n-) hexane, a petroleum distillate and simple aliphatic hydrocarbon. Parkinson disease), and the cerebral white matter each manifest a distinctive constellation of cognitive and emotional disturbances. This will help in the speedy recovery of the damaged nerve. This study was important because it identified abnormalities in the brains of individuals who abused toluene and were not acutely intoxicated when tested, but it was apparent from the early days of CT that this technique could not provide detailed information on the brain white matter (26). The reader is directed to the facility's website at for specifics regarding the variety of tests available, types of tubes in which specimens should be collected, and methods of analyses. In contrast, Case 2 of Kornfeld et al (43) and our original case (41) were both described as “paint sniffers” only and showed significantly less myelin loss. This leads to numbness, pain, and a loss of sensation in the extremities. These individuals have been studied by investigators in several countries, and enabled the collection of a substantial amount of clinical, neuroimaging, and neuropathological information on the neurotoxic effects of toluene (1, 4, 5, 7). Clipboard, Search History, and several other advanced features are temporarily unavailable. cranial nerve dysfunction as the most disabling aspect of. Recovery from an injured or damaged nerve may take long time, but again it depends on the degree or severity of the nerve injury. Toluene is also used in the production of polymers used to make nylon, plastic soda bottles, and polyurethanes and for pharmaceuticals, dyes, cosmetic nail products, and the synthesis of organic chemicals. There will be no recovery with neurotmesis. Copyright © 2004 by the American Association of Neuropathologists, Inc. Glioma-Derived TSP2 Promotes Excitatory Synapse Formation and Results in Hyperexcitability in the Peritumoral Cortex of Glioma, PTEN Blocking Stimulates Corticospinal and Raphespinal Axonal Regeneration and Promotes Functional Recovery After Spinal Cord Injury, Early Selective Vulnerability of the CA2 Hippocampal Subfield in Primary Age-Related Tauopathy, PCBP2 Is Downregulated in Degenerating Neurons and Rarely Observed in TDP-43-Positive Inclusions in Sporadic Amyotrophic Lateral Sclerosis, About Journal of Neuropathology & Experimental Neurology, The Public Health Impact of Inhalant Abuse, General Effects of Inhalants on the Brain, Acute Encephalopathy after Toluene Ingestion, Toluene Leukoencephalopathy due to Chronic Abuse, Neurobehavioral Deficits in Chronic Toluene Abuse, Toluene Leukoencephalopathy as an Example of White Matter Dementia, Neuroimaging Studies of White Matter Damage in Chronic Toluene Abuse, The Promise of Advanced Neuroimaging Techniques, Experimental Adult Animal Models of Chronic Toluene Abuse, Toluene as a Teratogen: The Fetal Solvent Syndrome, Receive exclusive offers and updates from Oxford Academic, Multifocal Necrotizing Leukoencephalopathy: Expanding the Clinicopathologic Spectrum, Pathologic Correlation of Paramagnetic White Matter Lesions in Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia, Histopathologic Analysis of Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CARASIL): A Report of a New Genetically Confirmed Case and Comparison to 2 Previous Cases. 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