The clinical severity of toluene leukoencephalopathy parallels the degree of white matter injury in the brain as seen by neuroimaging studies, and accordingly, toluene has become a prototypical brain white matter neurotoxin (7). In contrast, Ikeuchi and Hirai investigated the effects of toluene on guinea pig hippocampal slices and found inhibition of synaptic transmission but no morphological abnormalities (56). 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 caused by diabetes is one of the most common forms of neuropathy. In the 1980s, modern neuroimaging began to be regularly applied to the study of chronic toluene abusers. 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. The highly lipophilic nature of toluene explains its rapid concentration in the lipid-rich central nervous system (CNS; 1). 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). Please enable it to take advantage of the complete set of features! Although similar to the neurobehavioral changes of benzene-induced toxic effects, those of toluene toxicity are more severe. Nevertheless, the suggestion was made that duration of exposure was related to the degree of neuropsychological impairment (18). For someone whose livelihood relies on their voice, the situation was confronting. As with DTI, it is anticipated that MTI will prove useful in quantitating white matter damage in areas of NAWM. Copyright © 2020 American Association of Neuropathologists. Deficits in executive function and working memory were the most prominent abnormalities in the solvent abusers, and again language was spared (24), paralleling results of previous investigations (21–23). Princeton researchers — led by Jeffrey Schwartz, professor of chemistry, and Jean Schwarzbauer, the Eugene Higgins Professor of Molecular Biology — have developed a technique for adhering and aligning cells on a soft and flexible material, known as hydrogel, with the goal of creating … Visual function was not detailed in their report, and toluene is not known to affect the optic nerves [ 3 ] . In addition, the degree of myelination that exists in the individual when inhalant abuse begins may play a role in host susceptibility to toluene leukoencephalopathy. This brake cleaner contained 50%--60% hexane (composed of 20%--80% n-hexane), 20%--30% toluene, and 1%--10% each of methyl ethyl ketone (MEK), acetone, isopropanol, methanol, and mixed xylenes. Building on these observations, standardized neurobehavioral testing was undertaken in another cohort of toluene abusers and a characteristic clinical profile emerged (21). Toluene leukoencephalopathy has become a prototypical example of white matter dementia, and, more generally, underscores the importance of cerebral white matter in neurobehavioral function. (Fig. The primary target of toluene is thought to be the CNS (6, 8), and both acute and chronic effects are recognized. It is also found in fuels. Exposure through inhalation is much more common. ketone cause damage to the peripheral nerves, particularly of the feet and hands and this results in disturbances of sensation (numbness and tingling) and muscle weakness. Sciatic Nerve Conditions . Although many patients manifest less severe impairment than do patients with disorders of cortical gray matter, a significant percentage are sufficiently affected that they fulfill clinical criteria for dementia (10, 26). 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. … Neuropsychological deficits in chronic inhalant abusers were first documented in the same year (16, 17), although the possible confounding effects of multiple substance abuse (17) and the acute effects of abused inhalants were acknowledged as methodological issues (18). 2A), and the cerebellar white matter (Fig. Exposure to inhalants occurs primarily via pulmonary absorption, and significantly less absorption takes place through the skin or gastrointestinal tract (1). 2019 Dec;179(Pt B):108834. doi: 10.1016/j.envres.2019.108834. 2G). The optic nerve can be damaged by toluene (causing demyelination) and hexachlorophene (causing myelin deformation). Chronic solvent-induced encephalopathy (CSE) is a condition induced by long-term exposure to organic solvents, often but not always in the workplace, that lead to a wide variety of persisting sensorimotor polyneuropathies and neurobehavioral deficits even after solvent exposure has been removed. This is another medical condition that develops slowly and may begin years before a person is finally diagnosed with diabetes. 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). MRI demonstrates cerebral and cerebellar atrophy, and the severity of cognitive dysfunction correlates with the degree of cerebral white matter hyperintensity on T2-weighted images. +1 définitions @en.wiktionary.org. Most of the available toxicity studies relate to exposure via inhalation. The level of exposure also depends on the dose, duration, and work done [6]. D: Axial T2-weighted image demonstrating severe, diffuse cerebral white matter hyperintensity and marked ventricular enlargement. Although many inhalant abusers expose themselves to a wide variety of solvents, a subset of abusers confines themselves largely or exclusively to the inhalation of paint fumes. Văcăraș V, Cordoș AM, Rahovan I, Frunze S, Mureșanu DF. Your skin will also become numb. 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). The myelin loss was near-total in the cerebellum, except for relative sparing of the hilum and fleece of the dentate nucleus, findings identical to those described in Case 1 of Kornfeld et al (43) (Fig. After inhalation, toluene is rapidly absorbed through the lungs and then widely distributed throughout the body (8). Our original autopsy case presents the milder end of the spectrum; although myelin pallor was best seen in the cerebellum, as illustrated in our original paper (41), in the cerebral white matter illustrated here (G) the myelin loss was more subtle and associated with only scattered PAS-positive macrophages, seen here near a small blood vessel. Nervous system effects can be temporary, such as headaches, dizziness, or unconsciousness. Recent improvements in MRI technology that promise to rectify this include diffusion tensor MRI (DTI), magnetization transfer imaging (MTI), and magnetic resonance spectroscopy (MRS). 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. Some workers have developed reversible disorders of the optic nerves after chronic exposure in the workplace. Recommendations apply only to National Institute for Occupational Safety and Health (NIOSH) approved respirators. The mechanism of brain white matter injury from toluene is unknown. Nerve damage may cause loss of sensation or numbness in the fingertips, making it harder to do things with your hands. Toluene (C₆H₅CH₃) is a colorless liquid with a sweet, pungent odor. In recent years it has been recognized that disorders of the cortical gray matter (e.g. Formal evaluation of neurobehavioral function in one group of such patients documented widespread cognitive dysfunction with neuropsychological measures, including the Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Memory Scale (20). Prior to the lead phase-out in gasoline, the total amount of lead used in gasoline was over 200,000 tons per year. Epub 2018 Jul 26. Caldemeyer KS Pascuzzi RM Moran CG Smith RS. Animal and human research shows that most inhalants are extremely toxic. 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. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Campos-Ordonez T, Zarate-Lopez D, Ibarra-Castaneda N, Buritica J, Gonzalez-Perez O. Neurotmesis. A 1977 report of neurologic findings in two individuals with toluene exposure suggested that the toxic effects of the solvent were confined to the CNS (15). A combination of sensory and motor neuropathy is particularly common (sensorimotor polyneuropathy). Ann Neurol. 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). A new recipe for patterning cells on a surface holds promise for the repair of damaged nerve tissue. 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. Urinary tract infections and urinary incontinence. All of the patients who were well-studied at autopsy abused toluene, but the spectrum of severity of myelin damage between them is striking and parallels the range of white matter damage in toluene abusers seen by MRI in multiple studies (22–24, 27–30). The spectrum of leukoencephalopathy in toluene abuse as demonstrated by brain MRI. | Disorders of the muscles, cardiovascular effects, renal tubular damage, and sudden death have occurred in chronic abusers of toluene. Because cerebral and cerebellar neurons were intact and axons were preserved in areas of myelin pallor, toluene was hypothesized to be a pure myelin toxin (41). Exactly when in the clinical course the damage becomes irreversible, an issue of paramount importance for prognostic counseling is unknown. n-Hexane is an isomer of hexane and was identified as a peripheral neurotoxin in 1964 (1). Both acute and chronic encephalopathies are common (1). The understanding of the chronic effects of toluene on the brain has evolved over the last four decades. In contrast to neurotoxic agents that disrupt neurotransmitter or receptor function and elicit no structural changes, damage to brain myelin has been well documented with chronic toluene abuse, although a surprisingly small number of autopsy cases have been reported (40–43). Beyond this generalization, however, animal studies have not been particularly helpful in elucidating the specific mechanisms of myelin damage noted in humans. CAS Number: 15833-63-3. This will help in the speedy recovery of the damaged nerve. Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. Direct damage to the retina, though associated with some therapeutic agents, is rarely associated with neurotoxin exposure. The level of exposure also depends on the dose, duration, and work done [ 6 ]. In these 20 patients, CT disclosed atrophy of the cerebrum, cerebellum, and brainstem in 8 of 9 who underwent scanning (21). Many of the symptoms resemble ethanol intoxication and abusers utilize toluene to achieve a “quick drunk” effect. These individuals displayed a pattern of neurobehavioral deficits consisting of inattention, apathy, memory dysfunction, visuospatial impairment, and preserved language (21). Other investigators have focused more on alterations in astrocytes than on neuronal populations (57, 58). Over time, nerve damage can also occur in the fingers and hands. In other cases, direct damage to a nerve may occur during an addict’s attempt to gain access to a vein, and the median nerve in the antecubital fossa and femoral nerve in the groin are particularly prone. People “huff” or “sniff” paint, paint thinner, or glue in order … Workers may be harmed from exposure to toluene. 2017 Sep 18;9(9):457. doi: 10.3390/polym9090457. Deepwater Horizon oil spill exposures and neurobehavioral function in GuLF study participants. 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. To reduce and even eliminate toluene toxins in chemical component could be using detoxification by foods. However, the effects of toluene on the fetuses of chronically abusing mothers also deserve mention. Repeated exposure to toluene can cause permanent central nervous system effects, and can damage the liver, kidney, and upper respiratory system. In rat brain, toluene inhalation appears to activate astrocytes, with enhancement of GFAP immunoreactivity (59). Left untreated, nerve damage may worsen over time. Genetic and Pathological Characteristic Patterns of a Family With Neuronal Intranuclear Inclusion Disease. These observations support the notion that myelin, which contains 70% lipid, is targeted for damage. In an autopsy study of a patient who inhaled toluene … 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. Christopher M. Filley, MD, William Halliday, MD, B. K. Kleinschmidt-Demasters, MD, The Effects of Toluene on the Central Nervous System, Journal of Neuropathology & Experimental Neurology, Volume 63, Issue 1, January 2004, Pages 1–12, https://doi.org/10.1093/jnen/63.1.1. Our original case also manifested significant reactive astrocytosis, even in areas with ostensibly intact myelin (Fig. Pathophysiology of Toluene Brain Damage. . Traductions en contexte de "nerve" en anglais-français avec Reverso Context : nerve cells, have the nerve, optic nerve, nerve gas, nerve stimulation Cyclohexane Inhalation Produces Long-Lasting Alterations in the Hippocampal Integrity and Reward-Seeking Behavior in the Adult Mouse. Tualeka AR(1), Rahmawati P(2), Ahsan A(3), Pathak Y(4), Russeng SS(5), Sukarmin S(6), Wahyu A(7). Neuropathological examination shows cerebral and especially cerebellar myelin loss, perivascular macrophages stuffed with coarse or linear PAS-positive debris, and trilaminar inclusions by EM. Since results of laboratory tests are usually not rapidly available, diagnosis of acute toxicity is usually made based on the clinical history, coupled with the onset of a constellation of neurological symptoms and signs consistent with inebriation (1). Toluene, a common organic solvent that for some individuals is a substance of abuse, has been recognized as a neurotoxin that damages cerebral white matter. 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). Indeed, the signature pathological feature, and perhaps the earliest morphological evidence of toluene leukoencephalopathy, seems to be the presence of astrocytosis and these perivascular PAS-positive macrophages containing coarse or laminar myelin debris, which can be found even in areas devoid of recognizable myelin damage (Fig. Overall drug abuse among teenagers has declined in the past several years, but inhalant abuse is on the rise. Neuropsychiatry Neuropsychol Behav Neurol. 1C and 1D courtesy of James N. Dreisbach, MD). On light microscopy of Case 1, Luxol fast blue-periodic acid-Schiff (LFB-PAS) staining showed severe myelin loss especially around blood vessels. Evidence indicated that the toluene originated from bituminous deposits. 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. As the primary solvent in spray paints, thinners, lacquers, and glues, toluene is inhaled for its capacity to cause euphoria. 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. As experience with all of these disorders increased, it became apparent that a relatively specific neurobehavioral profile is associated with diffuse involvement of the brain white matter (10, 26). 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