Case Report Reversible Cerebral Periventricular White Matter Changes with Corpus Callosum Involvement in Acute Toluene-Poisoning Chih-Ming Lin, MD, MPH, Chi-Kuang Liu, MD From the Department of Neurology, Stroke Center, Chunghua Christian Hospital, Chunghua City, Taiwan (C-ML); and Department of Neuro-imaging, Chunghua Christian Hospital, Chunghua City, Taiwan (C-KL).
ABSTRACT Substance poisoning, such as toluene intoxication, has seldom been reported in the relevant literature. The documented cerebral neuroimaging has mostly described reversible symmetrical white matter changes in both the cerebral and cerebellar hemispheres. This paper presents 2 patients with toluene poisoning, whose brain magnetic resonance imaging studies showed a similar picture that included extra involvement over the corpus callosum; however, such corpus callosum involvement has never been mentioned and is quite rare in the literature. We discussed the underlying neuropathological pathways in this article. Hopefully, these cases will provide first-line clinicians with some valuable information with regard to toluene intoxication and clinical neuroimaging presentations. Keywords: Toluene intoxication, cerebral magnetic resonance imaging, reversible symmetrical white matter change, corpus callosum. Acceptance: Received September 30, 2013, and in revised form June 26, 2014. Accepted for publication July 13, 2014. Correspondence: Address correspondence to Chih-Ming Lin, Department of Neurology, Stroke Center, Chunghua Christian Hospital, 135 Nanxiao Street, Chunghua City 500, Chunghua County, Taiwan. E-mail: [email protected]. Disclosure: We (all of the authors) would like to disclose we did not receive any honoraria, funding or have any connections to any affiliation to subsidize this case report study. J Neuroimaging 2015;25:497-500. DOI: 10.1111/jon.12155
Introduction Symmetrical periventricular white matter change is not uncommon in neuroimaging studies. It can occur in the acute phase and chronic phase of neurological disorders.1–3 The most distinguishable malady with a similar picture in the acute phase is multiple sclerosis, in which the inflammatory plaques can appear with a symmetrical pattern perpendicular to the ventricles.4 Carbon monoxide intoxication is characterized by this neuroimaging picture in the chronic phase of the condition.5,6 It is often characterized by abnormalities in the bilateral basal ganglia, periventricular and cerebellar regions. These periventricular white matter changes can be either reversible or irreversible during the course of the neurological disease; however, there is no definite pathological evidence to delineate the underlying mechanism. Substance poisoning, such as toluene intoxication, can mimic the same picture in cerebral neuroimaging studies.1,2,7–9 A literature review reveals that few reports have focused on this issue. The possible neuropathological mechanism of toluene intoxication is discussed in this report.
Case Reports Case 1 A 31-year-old Taiwanese man was admitted to our emergency department because of refractory convulsions in recent months.
Copyright
His family mentioned he had never had similar symptoms before and recalled of no use of illicit drugs, recent infection, or history of distant travel. He was a factory worker and had been constantly complaining about lack of vitality and general soreness for 5 days before receiving medical attention. A neurological examination was performed based on the suspicion of a central nervous system disorder. Upon examination, it was revealed that he was in a somewhat confused state but still was oriented to time, place, and person name (postictal effect). Other neurological and physical testing results were grossly normal. Cerebral computed tomography disclosed no obvious abnormalities. A cerebral spinal fluid tap was also arranged to rule out possible cerebral infection. The result was unremarkable. Routine biochemistry showed normal results except for mild hypokalemia. He was, therefore, admitted to the neurologic ward for advanced work-up. Review of his occupational history revealed that he was immersed in an unknown chemical environment to paint the ceilings and walls of the factory gateway. The room was not air conditioned and he worked days and nights for 1 week before his symptoms started to emerge. Under a high index of suspicion of substance poisoning, a urine sample was examined. It was later confirmed that he had toluene intoxication. Cerebral magnetic resonance imaging (MRI) showed symmetric brain lesions (Figs 1A–E). Throughout the hospitalization period, he continued to experience several bouts of convulsions. He was hydrated and administered Dilantin by
◦ 2014 by the American Society of Neuroimaging C
497
Fig 1. (A) and (B) Diffusion-weighted images show symmetric, diffusely increased signal intensity in bilateral periventricular white matter, anterior and posterior limbs of the bilateral basal ganglia, thalamus and corpus callosum (Black arrow). (C) ADC map shows low signal intensity in the bilateral internal capsules and corpus callosum (Black arrows). (D) and (E) FLAIR images show symmetrical mild hyperintensities in the bilateral periventricular white matter and corpus callosum, and also low signal intensity in the bilateral basal ganglia and thalamus. (F) Diffusion-weighted images show complete disappearance of abnormal signal intensity in bilateral periventricular white matter, the internal capsules, the thalamus, and the corpus callosum.
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intravenous drip to control the convulsions. His condition stabilized and he was allowed to be discharged. Another cerebral MRI study was performed 1 month after his discharge and it showed improvement of cerebral abnormalities (Fig 1F). He continued to be followed up at regular neurologic out-patient clinic visits.
Case 2 A 61-year-old Taiwanese man was admitted to our emergency department because of deteriorating mental status and unsteady gait for 2 months. His son stated that his father was a blue-collar worker and worked in a material-processing factory. His physical condition was quite well until 2 months previously, when he started to exhibit bizarre behaviors. He would become lost in the park if he walked by himself and could not remember what he had done a few minutes earlier. He was cheated by food vendors as he paid 35 US dollars for two apples. In addition, his gait seemed to be waddling and tilted sideways. One week before he received medical attention, he was barely able to stand up and, even if he did, he complained of whirling sensation and general weakness that kept him in a sitting position. His son mentioned that his father did not have an apparent major medical history of using herbal medication, a recent upper respiratory infection or emotional stress. Neurological evaluation was carried out. It revealed he had a low score on the Mini-Mental State Examination. He had a wide-based gait, indicating likely cerebellar abnormality. Routine biochemistry showed mild hypokalemia. Electroencephalography disclosed diffuse cortical dysfunction of variable cause. A cerebral spinal tap was also arranged to rule out central infection. The result showed insignificant findings. Cerebral MRI showed bilateral periventricular white matter change with corpus callosum involvement (Figs 2A-C). His boss recalled that the patient had helped his coworkers paint and decorate the factory office for 5 days. The room was poorly air conditioned and he spent long hours working in that environment. Material poisoning was, therefore, suspected and his urine sample was sent to the toxicology laboratory. Toluene intoxication was confirmed. He was administered hydration therapy and a rehabilitation program was also arranged for his gait problem. He stayed in the hospital for more than 1 month. He had improved mental status throughout the course of his hospitalization though his gait was still waddling. He had regular neurological follow-up evaluations after discharge.
Discussion Although several case reports1,2,7–9 relating to cerebral imaging changes in patients afflicted with toluene intoxication had been published, there has been little focus on the diffusion-weighted sequences of cerebral magnetic resonance studies. Our patient in Case 1 presented with refractory convulsions. Epilepsy has never been reported in the literature as the first manifestation of toluene intoxication. Since the cerebral lesions observed in our Case 1 were diffuse, we can only speculate that the epilepsy this patient had suffered might be due to a deranged cortical-subcortical pathway and/or an unstable cerebral condition superimposed with a hypokalemic state.
Fig 2. (A) and (B) Cerebral MRI shows symmetrically increased signal intensities on diffusion-weighted, involving the posterior limbs of the basal ganglia, centrum semiovale, and corpus callosum (Black arrows). (C) Brain MRI ADC mapping shows decreased signal intensity over the corpus callosum (Black arrows).
Lin and Liu: Corpus Callosum Lesion in Toluene Intoxication
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In Case 2, in contrast to Case 1, the patient presented with relative conventional symptoms—decreased mental status and unsteady gait. In case reports it has been reported that toluene exposure can lead to reversible multifocal cerebral injuries, including cerebral focal neurological defects, cerebellar signs/symptoms, decline in consciousness, and decline in mental status, depending on the lesion site.3,8–10 The commonly affected areas where signal intensity is observed on brain MRI of toluene-intoxicated patients include periventricular white matter, the internal capsule, the brain stem, and the cerebellar hemispheres.8,9 Both of our cases demonstrated extra involvement over the corpus callosum. The increased signal intensity over the corpus callosum was clearly observed on the initial brain MRI. Throughout the hospitalization course and aggressive treatment, abnormalities disappeared on the follow-up MRI scans. Although corpus callosum atrophy has been reported,1 both of our cases were the first to show reversible signal intensity change in this region. In the scenarios of patients like chronic toluene abusers, it is not surprising to observe atrophic change and widespread white matter abnormalities on cerebral MRI. In the T2 sequences of cerebral MRI, it was also common to observe symmetric hyposignal intensity over the basal ganglia and hypersignal intensities restricted to cerebral, cerebellar, and upper spinal cord regions.1 It was hypothesized that the apparent hyposignal intensities observed over the bilateral basal ganglia and/or thalamus were due to iron deposition or the iron extravasations on the cerebral parenchyma leading to partitioning of cellular lipid membranes.2 Postmortem studies echo the abovementioned findings. The pathological findings from acute toluene abusers reveal myelin pallor, and mild astrogliosis without demyelinization.1 In contrast, in long-term toluene users, irreversible cerebral atrophy has been found, especially with regard to Purkinje cells of the cerebellum.3 Elevations of signal intensities on diffusion-weighted sequences could be derived from restricted water mobility or the T2 shine-through effect on MRI. The apparent diffusion coefficient (ADC) sequences could be used to confirm whether this was a water restriction phenomenon.5–7 Though the diffusionweighted image was sensitive in detecting the water restriction phenomenon, it was by no means specific for disease differentiation—we could observe similar pictures in acute ischemic stroke, head trauma, perinatal hypoxic-ischemic brain injury,7 pyogenic abscess, herpes encephalitis, CreutzfeldtJakob disease,5 and multiple sclerosis,4 to name just a few. The mobility of water is greater in extracellular than intracellular spaces. When cytotoxic edema occurs, shifting of water into intracellular spaces causes decreased signal intensities in both diffusion-weighted and ADC sequences. Based on pathological findings, also noted have been diffuse and symmetrical hypersignal intensities on diffusion-weighted imaging in substance intoxication cases.1,7,11 In Creutzfeldt-Jakob disease,5 pathology examination showed nerve cell loss, spongiform change, and astrocytic gliosis. It was postulated that in spongiform degeneration and vacuole formation causing diffusion restriction, the high signal intensity subsided months after disease onset, probably due to
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tissue damage and subsequent increased extracellular space.5 In carbon monoxide intoxication, there was tissue injury combined with cytotoxic edema. This was probably due to the direct toxic effect of carbon monoxide immersion.6 Other toxic metallic substance, like 5-FU, may directly injure the microvasculature causing cytotoxic edema whereas immunosuppressive medication might cause capillary endothelial injury and blood-brain barrier dysfunction.11,12 Although we did not provide pathological evidence in our report, reversible hypersignal intensities observed on diffusionweighted images probably resulted from a similar mechanism. That is to say, toluene might give rise to direct cell injury and/or inhibition of neurotransmitters in the cerebral parenchyma that subsequently leads to an indirect toxic effect. We hope our cases provide first-line doctors with some valuable clinical information when they encounter scenarios like toluene poisoning. Our cases demonstrate that brain MRI can show symmetrical periventricular white matter changes with additional corpus callosum involvement in conditions like toluene poisoning.
We received no funding to support this report.
References 1. Gupta SR, Palmer CA, Cure´ JK, et al. Toluene optic neurotoxicity: magnetic resonance imaging and pathologic features. Hum Pathol 2011;42(2):295-298. 2. Unger E, Alexander A, Fritz T, et al. Toluene abuse: physical basis for hypointensity of the basal ganglia on T2-weighted MR images. Radiology 1994;193:473-476. 3. Geibprasert S, Gallucci M, Krings T. Addictive illegal drugs: structural neuroimaging. Am J Neuroradiol 2010;31:803-808. 4. Moore GR, Laule C. Neuropathologic correlates of magnetic resonance imaging in multiple sclerosis. J Neuropathol Exp Neurol 2012;71:762-778. 5. Tschampa HJ, Murtz P, Flacke S, et al. Thalamic involvement in ¨ sporadic Creutzfeldt-Jakob disease: a diffusion-weighted MR imaging study. Am J Neuroradiol 2003;24:908-915. 6. Kim JH, Chang KH, Song IC, et al. Delayed encephalopathy of acute carbon monoxide intoxication: diffusivity of cerebral white matter lesions. Am J Neuroradiol 2003;24:1592-1597. 7. Matsuoka M. Neurotoxicity of organic solvents–recent findings. Brain Nerve 2007;59:591-596. 8. Suzuki K, Wakayama Y, Takada H, et al. A case of chronic toluene intoxication with abnormal MRI findings: abnormal intensity areas in cerebral white matter, basal ganglia, internal capsule, brain stem and middle cerebellar peduncle. Rinsho Shinkeigaku 1992;32:84-87. 9. Fujita K, Koga Y, Takemasa K, et al. A case of chronic toluene intoxication with atrophy of cerebrum, cerebellum and brainstem on CT and MRI. Rinsho Shinkeigaku 1992;32:421-425. 10. Filley CM. Toluene abuse and white matter: a model of toxic leukoencephalopathy. Psychiatr Clin North Am 2013;36:293302. 11. Matsuda M, Yamamoto T, Ishikawa E, et al. A prognostic factors in glioblastoma multiforme patients receiving high-dose particle radiotherapy or conventional radiotherapy. Br J Radiol 2011;84:S54S60. 12. Quinn CT, Griener JC, Bottiglieri T, et al. Effects of intraventricular methotrexate on folate, adenosine, and homocysteine metabolism in cerebrospinal fluid. J Pediatr Hematol Oncol 2004;26:386-388.
ABSTRACT Substance poisoning, such as toluene intoxication, has seldom been reported in the relevant literature. The documented cerebral neuroimaging has mostly described reversible symmetrical white matter changes in both the cerebral and cerebellar hemispheres. This paper presents 2 patients with toluene poisoning, whose brain magnetic resonance imaging studies showed a similar picture that included extra involvement over the corpus callosum; however, such corpus callosum involvement has never been mentioned and is quite rare in the literature. We discussed the underlying neuropathological pathways in this article. Hopefully, these cases will provide first-line clinicians with some valuable information with regard to toluene intoxication and clinical neuroimaging presentations. Keywords: Toluene intoxication, cerebral magnetic resonance imaging, reversible symmetrical white matter change, corpus callosum. Acceptance: Received September 30, 2013, and in revised form June 26, 2014. Accepted for publication July 13, 2014. Correspondence: Address correspondence to Chih-Ming Lin, Department of Neurology, Stroke Center, Chunghua Christian Hospital, 135 Nanxiao Street, Chunghua City 500, Chunghua County, Taiwan. E-mail: [email protected]. Disclosure: We (all of the authors) would like to disclose we did not receive any honoraria, funding or have any connections to any affiliation to subsidize this case report study. J Neuroimaging 2015;25:497-500. DOI: 10.1111/jon.12155
Introduction Symmetrical periventricular white matter change is not uncommon in neuroimaging studies. It can occur in the acute phase and chronic phase of neurological disorders.1–3 The most distinguishable malady with a similar picture in the acute phase is multiple sclerosis, in which the inflammatory plaques can appear with a symmetrical pattern perpendicular to the ventricles.4 Carbon monoxide intoxication is characterized by this neuroimaging picture in the chronic phase of the condition.5,6 It is often characterized by abnormalities in the bilateral basal ganglia, periventricular and cerebellar regions. These periventricular white matter changes can be either reversible or irreversible during the course of the neurological disease; however, there is no definite pathological evidence to delineate the underlying mechanism. Substance poisoning, such as toluene intoxication, can mimic the same picture in cerebral neuroimaging studies.1,2,7–9 A literature review reveals that few reports have focused on this issue. The possible neuropathological mechanism of toluene intoxication is discussed in this report.
Case Reports Case 1 A 31-year-old Taiwanese man was admitted to our emergency department because of refractory convulsions in recent months.
Copyright
His family mentioned he had never had similar symptoms before and recalled of no use of illicit drugs, recent infection, or history of distant travel. He was a factory worker and had been constantly complaining about lack of vitality and general soreness for 5 days before receiving medical attention. A neurological examination was performed based on the suspicion of a central nervous system disorder. Upon examination, it was revealed that he was in a somewhat confused state but still was oriented to time, place, and person name (postictal effect). Other neurological and physical testing results were grossly normal. Cerebral computed tomography disclosed no obvious abnormalities. A cerebral spinal fluid tap was also arranged to rule out possible cerebral infection. The result was unremarkable. Routine biochemistry showed normal results except for mild hypokalemia. He was, therefore, admitted to the neurologic ward for advanced work-up. Review of his occupational history revealed that he was immersed in an unknown chemical environment to paint the ceilings and walls of the factory gateway. The room was not air conditioned and he worked days and nights for 1 week before his symptoms started to emerge. Under a high index of suspicion of substance poisoning, a urine sample was examined. It was later confirmed that he had toluene intoxication. Cerebral magnetic resonance imaging (MRI) showed symmetric brain lesions (Figs 1A–E). Throughout the hospitalization period, he continued to experience several bouts of convulsions. He was hydrated and administered Dilantin by
◦ 2014 by the American Society of Neuroimaging C
497
Fig 1. (A) and (B) Diffusion-weighted images show symmetric, diffusely increased signal intensity in bilateral periventricular white matter, anterior and posterior limbs of the bilateral basal ganglia, thalamus and corpus callosum (Black arrow). (C) ADC map shows low signal intensity in the bilateral internal capsules and corpus callosum (Black arrows). (D) and (E) FLAIR images show symmetrical mild hyperintensities in the bilateral periventricular white matter and corpus callosum, and also low signal intensity in the bilateral basal ganglia and thalamus. (F) Diffusion-weighted images show complete disappearance of abnormal signal intensity in bilateral periventricular white matter, the internal capsules, the thalamus, and the corpus callosum.
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intravenous drip to control the convulsions. His condition stabilized and he was allowed to be discharged. Another cerebral MRI study was performed 1 month after his discharge and it showed improvement of cerebral abnormalities (Fig 1F). He continued to be followed up at regular neurologic out-patient clinic visits.
Case 2 A 61-year-old Taiwanese man was admitted to our emergency department because of deteriorating mental status and unsteady gait for 2 months. His son stated that his father was a blue-collar worker and worked in a material-processing factory. His physical condition was quite well until 2 months previously, when he started to exhibit bizarre behaviors. He would become lost in the park if he walked by himself and could not remember what he had done a few minutes earlier. He was cheated by food vendors as he paid 35 US dollars for two apples. In addition, his gait seemed to be waddling and tilted sideways. One week before he received medical attention, he was barely able to stand up and, even if he did, he complained of whirling sensation and general weakness that kept him in a sitting position. His son mentioned that his father did not have an apparent major medical history of using herbal medication, a recent upper respiratory infection or emotional stress. Neurological evaluation was carried out. It revealed he had a low score on the Mini-Mental State Examination. He had a wide-based gait, indicating likely cerebellar abnormality. Routine biochemistry showed mild hypokalemia. Electroencephalography disclosed diffuse cortical dysfunction of variable cause. A cerebral spinal tap was also arranged to rule out central infection. The result showed insignificant findings. Cerebral MRI showed bilateral periventricular white matter change with corpus callosum involvement (Figs 2A-C). His boss recalled that the patient had helped his coworkers paint and decorate the factory office for 5 days. The room was poorly air conditioned and he spent long hours working in that environment. Material poisoning was, therefore, suspected and his urine sample was sent to the toxicology laboratory. Toluene intoxication was confirmed. He was administered hydration therapy and a rehabilitation program was also arranged for his gait problem. He stayed in the hospital for more than 1 month. He had improved mental status throughout the course of his hospitalization though his gait was still waddling. He had regular neurological follow-up evaluations after discharge.
Discussion Although several case reports1,2,7–9 relating to cerebral imaging changes in patients afflicted with toluene intoxication had been published, there has been little focus on the diffusion-weighted sequences of cerebral magnetic resonance studies. Our patient in Case 1 presented with refractory convulsions. Epilepsy has never been reported in the literature as the first manifestation of toluene intoxication. Since the cerebral lesions observed in our Case 1 were diffuse, we can only speculate that the epilepsy this patient had suffered might be due to a deranged cortical-subcortical pathway and/or an unstable cerebral condition superimposed with a hypokalemic state.
Fig 2. (A) and (B) Cerebral MRI shows symmetrically increased signal intensities on diffusion-weighted, involving the posterior limbs of the basal ganglia, centrum semiovale, and corpus callosum (Black arrows). (C) Brain MRI ADC mapping shows decreased signal intensity over the corpus callosum (Black arrows).
Lin and Liu: Corpus Callosum Lesion in Toluene Intoxication
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In Case 2, in contrast to Case 1, the patient presented with relative conventional symptoms—decreased mental status and unsteady gait. In case reports it has been reported that toluene exposure can lead to reversible multifocal cerebral injuries, including cerebral focal neurological defects, cerebellar signs/symptoms, decline in consciousness, and decline in mental status, depending on the lesion site.3,8–10 The commonly affected areas where signal intensity is observed on brain MRI of toluene-intoxicated patients include periventricular white matter, the internal capsule, the brain stem, and the cerebellar hemispheres.8,9 Both of our cases demonstrated extra involvement over the corpus callosum. The increased signal intensity over the corpus callosum was clearly observed on the initial brain MRI. Throughout the hospitalization course and aggressive treatment, abnormalities disappeared on the follow-up MRI scans. Although corpus callosum atrophy has been reported,1 both of our cases were the first to show reversible signal intensity change in this region. In the scenarios of patients like chronic toluene abusers, it is not surprising to observe atrophic change and widespread white matter abnormalities on cerebral MRI. In the T2 sequences of cerebral MRI, it was also common to observe symmetric hyposignal intensity over the basal ganglia and hypersignal intensities restricted to cerebral, cerebellar, and upper spinal cord regions.1 It was hypothesized that the apparent hyposignal intensities observed over the bilateral basal ganglia and/or thalamus were due to iron deposition or the iron extravasations on the cerebral parenchyma leading to partitioning of cellular lipid membranes.2 Postmortem studies echo the abovementioned findings. The pathological findings from acute toluene abusers reveal myelin pallor, and mild astrogliosis without demyelinization.1 In contrast, in long-term toluene users, irreversible cerebral atrophy has been found, especially with regard to Purkinje cells of the cerebellum.3 Elevations of signal intensities on diffusion-weighted sequences could be derived from restricted water mobility or the T2 shine-through effect on MRI. The apparent diffusion coefficient (ADC) sequences could be used to confirm whether this was a water restriction phenomenon.5–7 Though the diffusionweighted image was sensitive in detecting the water restriction phenomenon, it was by no means specific for disease differentiation—we could observe similar pictures in acute ischemic stroke, head trauma, perinatal hypoxic-ischemic brain injury,7 pyogenic abscess, herpes encephalitis, CreutzfeldtJakob disease,5 and multiple sclerosis,4 to name just a few. The mobility of water is greater in extracellular than intracellular spaces. When cytotoxic edema occurs, shifting of water into intracellular spaces causes decreased signal intensities in both diffusion-weighted and ADC sequences. Based on pathological findings, also noted have been diffuse and symmetrical hypersignal intensities on diffusion-weighted imaging in substance intoxication cases.1,7,11 In Creutzfeldt-Jakob disease,5 pathology examination showed nerve cell loss, spongiform change, and astrocytic gliosis. It was postulated that in spongiform degeneration and vacuole formation causing diffusion restriction, the high signal intensity subsided months after disease onset, probably due to
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tissue damage and subsequent increased extracellular space.5 In carbon monoxide intoxication, there was tissue injury combined with cytotoxic edema. This was probably due to the direct toxic effect of carbon monoxide immersion.6 Other toxic metallic substance, like 5-FU, may directly injure the microvasculature causing cytotoxic edema whereas immunosuppressive medication might cause capillary endothelial injury and blood-brain barrier dysfunction.11,12 Although we did not provide pathological evidence in our report, reversible hypersignal intensities observed on diffusionweighted images probably resulted from a similar mechanism. That is to say, toluene might give rise to direct cell injury and/or inhibition of neurotransmitters in the cerebral parenchyma that subsequently leads to an indirect toxic effect. We hope our cases provide first-line doctors with some valuable clinical information when they encounter scenarios like toluene poisoning. Our cases demonstrate that brain MRI can show symmetrical periventricular white matter changes with additional corpus callosum involvement in conditions like toluene poisoning.
We received no funding to support this report.
References 1. Gupta SR, Palmer CA, Cure´ JK, et al. Toluene optic neurotoxicity: magnetic resonance imaging and pathologic features. Hum Pathol 2011;42(2):295-298. 2. Unger E, Alexander A, Fritz T, et al. Toluene abuse: physical basis for hypointensity of the basal ganglia on T2-weighted MR images. Radiology 1994;193:473-476. 3. Geibprasert S, Gallucci M, Krings T. Addictive illegal drugs: structural neuroimaging. Am J Neuroradiol 2010;31:803-808. 4. Moore GR, Laule C. Neuropathologic correlates of magnetic resonance imaging in multiple sclerosis. J Neuropathol Exp Neurol 2012;71:762-778. 5. Tschampa HJ, Murtz P, Flacke S, et al. Thalamic involvement in ¨ sporadic Creutzfeldt-Jakob disease: a diffusion-weighted MR imaging study. Am J Neuroradiol 2003;24:908-915. 6. Kim JH, Chang KH, Song IC, et al. Delayed encephalopathy of acute carbon monoxide intoxication: diffusivity of cerebral white matter lesions. Am J Neuroradiol 2003;24:1592-1597. 7. Matsuoka M. Neurotoxicity of organic solvents–recent findings. Brain Nerve 2007;59:591-596. 8. Suzuki K, Wakayama Y, Takada H, et al. A case of chronic toluene intoxication with abnormal MRI findings: abnormal intensity areas in cerebral white matter, basal ganglia, internal capsule, brain stem and middle cerebellar peduncle. Rinsho Shinkeigaku 1992;32:84-87. 9. Fujita K, Koga Y, Takemasa K, et al. A case of chronic toluene intoxication with atrophy of cerebrum, cerebellum and brainstem on CT and MRI. Rinsho Shinkeigaku 1992;32:421-425. 10. Filley CM. Toluene abuse and white matter: a model of toxic leukoencephalopathy. Psychiatr Clin North Am 2013;36:293302. 11. Matsuda M, Yamamoto T, Ishikawa E, et al. A prognostic factors in glioblastoma multiforme patients receiving high-dose particle radiotherapy or conventional radiotherapy. Br J Radiol 2011;84:S54S60. 12. Quinn CT, Griener JC, Bottiglieri T, et al. Effects of intraventricular methotrexate on folate, adenosine, and homocysteine metabolism in cerebrospinal fluid. J Pediatr Hematol Oncol 2004;26:386-388.
