Cytotoxic Lesions of the Corpus Callosum That Show Restricted Diffusion: Mechanisms, Causes, and Manifestations
Abstract
This article describes the imaging spectrum and the causes of cytotoxic lesions of the corpus callosum.
Cytotoxic lesions of the corpus callosum (CLOCCs) are secondary lesions associated with various entities. CLOCCs have been found in association with drug therapy, malignancy, infection, subarachnoid hemorrhage, metabolic disorders, trauma, and other entities. In all of these conditions, cell-cytokine interactions lead to markedly increased levels of cytokines and extracellular glutamate. Ultimately, this cascade can lead to dysfunction of the callosal neurons and microglia. Cytotoxic edema develops as water becomes trapped in these cells. On diffusion-weighted magnetic resonance (MR) images, CLOCCs manifest as areas of low diffusion. CLOCCs lack enhancement on contrast material–enhanced images, tend to be midline, and are relatively symmetric. The involvement of the corpus callosum typically shows one of three patterns: (a) a small round or oval lesion located in the center of the splenium, (b) a lesion centered in the splenium but extending through the callosal fibers laterally into the adjacent white matter, or (c) a lesion centered posteriorly but extending into the anterior corpus callosum. CLOCCs are frequently but not invariably reversible. Their pathologic mechanisms are discussed, the typical MR imaging findings are described, and typical cases of CLOCCs are presented. Although CLOCCs are nonspecific with regard to the underlying cause, additional imaging findings and the clinical findings can aid in making a specific diagnosis. Radiologists should be familiar with the imaging appearance of CLOCCs to avoid a misdiagnosis of ischemia. When CLOCCs are found, the underlying cause of the lesion should be sought and addressed.
©RSNA, 2017
An earlier incorrect version of this article appeared online. This article was corrected on February 13, 2017.
References
- 1. . Cytokine targets in the brain: impact on neurotransmitters and neurocircuits. Depress Anxiety 2013;30(4):297–306. Crossref, Medline, Google Scholar
- 2. Phelps C, Korneva E, eds. Neuroimmune biology. Vol 6, Cytokines and the brain. Amsterdam, the Netherlands: Elsevier, 2008. Google Scholar
- 3. . TNFα-induced AMPA-receptor trafficking in CNS neurons: relevance to excitotoxicity? Neuron Glia Biol 2004;1(3): 263–273. Crossref, Medline, Google Scholar
- 4. . Expression of proinflammatory cytokines tumor necrosis factor-α and interleukin-1β in the brain during experimental group B streptococcal meningitis. Brain Res Mol Brain Res 2004;128(1):95–102. Crossref, Medline, Google Scholar
- 5. . The role of tumor necrosis factor-α in diffuse axonal injury following fluid-percussive brain injury in rats. Int J Legal Med 2000;113(4):221–228. Crossref, Medline, Google Scholar
- 6. . The inflammatory cytokine, interleukin-1 beta, mediates loss of astroglial glutamate transport and drives excitotoxic motor neuron injury in the spinal cord during acute viral encephalomyelitis. J Neurochem 2008;105(4):1276–1286. Crossref, Medline, Google Scholar
- 7. . Into the eye of the cytokine storm. Microbiol Mol Biol Rev 2012;76(1):16–32. Crossref, Medline, Google Scholar
- 8. . Excitotoxic damage to white matter. J Anat 2007;210(6):693–702. Crossref, Medline, Google Scholar
- 9. . Glutamate transport, glutamine synthetase and phosphate-activated glutaminase in rat CNS white matter: a quantitative study. J Neurochem 2003;87(1):230–237. Crossref, Medline, Google Scholar
- 10. . Expression of glutamate transporters in the adult bovine corpus callosum. Brain Res Mol Brain Res 1999;67(2):296–302. Crossref, Medline, Google Scholar
- 11. . Cultured astrocytes derived from corpus callosum or cortical grey matter show distinct glutamate handling properties. J Neurochem 2009;108(6):1442–1452. Crossref, Medline, Google Scholar
- 12. . Diffusion-weighted imaging of acute excitotoxic brain injury. AJNR Am J Neuroradiol 2005;26(2):216–228. Medline, Google Scholar
- 13. . Reversible cytotoxic edema in the splenium of the corpus callosum related to antiepileptic treatment: report of two cases and literature review. Epilepsia 2005;46(10):1633–1636. Crossref, Medline, Google Scholar
- 14. . Diffusion-weighted imaging demonstrates transient cytotoxic edema involving the corpus callosum in a patient with diffuse brain injury. Clin Neurol Neurosurg 2000;102(3):135–139. Crossref, Medline, Google Scholar
- 15. . Transient focal lesion in the splenium of the corpus callosum: MR imaging with an attempt to clinical-physiopathological explanation and review of the literature. Radiol Med (Torino) 2007;112(6):921–935. Crossref, Medline, Google Scholar
- 16. . Reversible splenial lesion in the corpus callosum on MRI after ingestion of a herbicide containing glufosinate ammonium: a case report. J Korean Soc Radiol 2014;70(6):399–402. https://doi.org/10.3348/jksr.2014.70.6.399. Published online June 3, 2014. Crossref, Google Scholar
- 17. . A case of clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with anti-glutamate receptor antibody [in Japanese]. Rinsho Shinkeigaku 2011;51(7):510–513. Crossref, Medline, Google Scholar
- 18. . Widening spectrum of a reversible splenial lesion with transiently reduced diffusion. AJNR Am J Neuroradiol 2006;27(4):836–838. Medline, Google Scholar
- 19. . Transient splenial lesion of the corpus callosum in clinically mild influenza-associated encephalitis/encephalopathy. AJNR Am J Neuroradiol 2006;27(9):1983–1986. Medline, Google Scholar
- 20. . Reversible splenial lesion with restricted diffusion in a wide spectrum of diseases and conditions. J Neuroradiol 2006;33(4):229–236. Crossref, Medline, Google Scholar
- 21. . Influenza-associated encephalitis/encephalopathy with a reversible lesion in the splenium of the corpus callosum: a case report and literature review. AJNR Am J Neuroradiol 2004;25(5):798–802. Medline, Google Scholar
- 22. . Hypothetical pathophysiology of acute encephalopathy and encephalitis related to influenza virus infection and hypothermia therapy. Pediatr Int 2000;42(2):197–203. Crossref, Medline, Google Scholar
- 23. . Diffusion-weighted magnetic resonance imaging in early stage of 5-fluorouracil-induced leukoencephalopathy. Acta Neurol Scand 2002;106(6):379–386. Crossref, Medline, Google Scholar
- 24. . Clinically mild encephalitis/encephalopathy with a reversible splenial lesion. Neurology 2004;63(10):1854–1858. Crossref, Medline, Google Scholar
- 25. . Clinically mild encephalitis with a reversible splenial lesion (MERS) after mumps vaccination. J Neurol Sci 2015;349(1-2):226–228. Crossref, Medline, Google Scholar
- 26. . Reversible splenial lesion syndrome (RESLES): what’s in a name? J Neuroimaging 2011;21(2):e1–e14. Crossref, Medline, Google Scholar
- 27. . Lesions in the splenium of the corpus callosum: clinical and radiological implications. Neurol Asia 2014;19(1):79–88. http://www.neurology-asia.org/articles/neuroasia-2014-19(1)-079.pdf. Google Scholar
- 28. . Clinical implications of splenium magnetic resonance imaging signal changes. Arch Neurol 2005;62(3):433–437. Crossref, Medline, Google Scholar
- 29. . MRI evaluation of pathologies affecting the corpus callosum: a pictorial essay. Indian J Radiol Imaging 2013;23(4):321–332. Crossref, Medline, Google Scholar
- 30. . Localized reversible reduction of apparent diffusion coefficient in transient hypoglycemia-induced hemiparesis. Stroke 2005;36(3): e20–e22. Crossref, Medline, Google Scholar
- 31. . Magnetic resonance imaging evidence of cytotoxic cerebral edema in acute mountain sickness. J Cereb Blood Flow Metab 2007;27(5):1064–1071. Crossref, Medline, Google Scholar
- 32. . Cytokines, epilepsy and epileptic drugs: is there a mutual influence? Pharmacol Rep 2007;59(2):129–138. Medline, Google Scholar
- 33. . Focal lesion in the splenium of the corpus callosum in epileptic patients: antiepileptic drug toxicity? AJNR Am J Neuroradiol 1999;20(1): 125–129. Medline, Google Scholar
- 34. . Focal transient lesion in the splenium of the corpus callosum in three non-epileptic patients. Neuroradiology 2006;48(10):731–735. Crossref, Medline, Google Scholar
- 35. . Transient lesion in the splenium of the corpus callosum in an epileptic patient. Neurology 2003;60(11):1838–1841. Crossref, Medline, Google Scholar
- 36. . Transient lesion in the splenium of the corpus callosum: three further cases in epileptic patients and a pathophysiological hypothesis. J Neurol Neurosurg Psychiatry 2001;70(4):459–463. Crossref, Medline, Google Scholar
- 37. . Transient lesion in the splenium related to antiepileptic drug: case report and new pathophysiological insights. Seizure 2008;17(7):654–657. Crossref, Medline, Google Scholar
- 38. . Transient postictal magnetic resonance imaging abnormality of the corpus callosum in a patient with epilepsy: case report and review of the literature. J Neurosurg 2002;97(3):714–717. Crossref, Medline, Google Scholar
- 39. . Transient splenial lesion of the corpus callosum associated with antiepileptic drugs: evaluation by diffusion-weighted MR imaging. Eur Radiol 2003;13(8):1902–1906. Crossref, Medline, Google Scholar
- 40. . Effect of anticonvulsant drugs on interleukins-1, -2 and -6 and monocyte chemoattractant protein-1. Clin Exp Med 2001;1(3):133–136. Crossref, Medline, Google Scholar
- 41. . Transient lesion in the splenium of the corpus callosum after oral corticoid therapy. Eur J Neurol 2007;14(8):e19–e20. Crossref, Medline, Google Scholar
- 42. . Reversible MR imaging and MR spectroscopy abnormalities in association with metronidazole therapy. J Comput Assist Tomogr 2002;26(6):948–951. Crossref, Medline, Google Scholar
- 43. . MR imaging of metronidazole-induced encephalopathy: lesion distribution and diffusion-weighted imaging findings. AJNR Am J Neuroradiol 2007;28(9):1652–1658. Crossref, Medline, Google Scholar
- 44. . Immunopathogenesis of cerebral malaria. Int J Parasitol 2006;36(5): 569–582. Crossref, Medline, Google Scholar
- 45. Moritani T, Ekholm S, Westesson PL, eds. Diffusion-weighted MR imaging of the brain. 2nd ed. Berlin, Germany: Springer, 2009. Crossref, Google Scholar
- 46. . MRI of CNS fungal infections: review of aspergillosis to histoplasmosis and everything in between. Clin Neuroradiol 2014;24(3):217–230. Crossref, Medline, Google Scholar
- 47. . Cerebral malaria: role of microparticles and platelets in alterations of the blood-brain barrier. Int J Parasitol 2006;36(5):541–546. Crossref, Medline, Google Scholar
- 48. . The systemic pathology of cerebral malaria in African children. Front Cell Infect Microbiol 2014;4:104. doi:10.3389/fcimb.2014.00104. Published online August 21, 2014. Crossref, Medline, Google Scholar
- 49. . Transient MR signal changes in the splenium of the corpus callosum in rotavirus encephalopathy: value of diffusion-weighted imaging. J Comput Assist Tomogr 2002;26(5):825–828. Crossref, Medline, Google Scholar
- 50. . Transient widespread cortical and splenial lesions in acute encephalitis/encephalopathy associated with primary Epstein-Barr virus infection. Int J Infect Dis 2016;42:7–10. Crossref, Medline, Google Scholar
- 51. . Clinical features and treatment strategies of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Crit Rev Oncol Hematol 2002;44(3):259–272. Crossref, Medline, Google Scholar
- 52. . Cerebrospinal fluid interleukin-1 receptor antagonist and tumor necrosis factor-α following subarachnoid hemorrhage. J Neurosurg 1997;87(2):215–220. Crossref, Medline, Google Scholar
- 53. . Cisternal CSF levels of cytokines after subarachnoid hemorrhage. Neurol Res 1998;20(4):337–342. Crossref, Medline, Google Scholar
- 54. . Inflammation, vasospasm, and brain injury after subarachnoid hemorrhage. Biomed Res Int 2014;(2014):384342. doi:10.1155/2014/384342. Published online July 3, 2014. Crossref, Medline, Google Scholar
- 55. . Ammonia: key factor in the pathogenesis of hepatic encephalopathy. Neurochem Pathol 1987;6(1-2):1–12. Crossref, Medline, Google Scholar
- 56. . Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure. J Clin Exp Hepatol 2015;5(suppl 1):S96–S103. Crossref, Medline, Google Scholar
- 57. . Cerebral cortical and white matter lesions in chronic hepatic encephalopathy: MR-pathologic correlations. AJNR Am J Neuroradiol 2005;26(2):347–351. Medline, Google Scholar
- 58. . Molecular mechanism of acute ammonia toxicity: role of NMDA receptors. Neurochem Int 2002;41(2-3):95–102. Crossref, Medline, Google Scholar
- 59. . Molecular neurobiology of acute liver failure. Semin Liver Dis 2003;23(3):251–258. Crossref, Medline, Google Scholar
- 60. . Neuroinflammation in hepatic encephalopathy: mechanistic aspects. J Clin Exp Hepatol 2015;5(suppl 1):S21–S28. Crossref, Medline, Google Scholar
- 61. . MR imaging findings in hepatic encephalopathy. AJNR Am J Neuroradiol 2008;29(9):1612–1621. Crossref, Medline, Google Scholar
- 62. . Reversible reduction of apparent diffusion coefficient values in bilateral internal capsules in transient hypoglycemia-induced hemiparesis. AJNR Am J Neuroradiol 2006;27(8):1760–1762. Medline, Google Scholar
- 63. . Reversible splenial abnormality in hypoglycemic encephalopathy. Neuroradiology 2007;49(3):217–222. Crossref, Medline, Google Scholar
- 64. . Osmotic myelinolysis: does extrapontine myelinolysis precede central pontine myelinolysis? report of two cases and review of literature. Indian J Radiol Imaging 2015;25(2):177–183. Crossref, Medline, Google Scholar
- 65. . Role of microglia in the pathogenesis of osmotic-induced demyelination. Exp Neurol 2007;204(1):88–94. Crossref, Medline, Google Scholar
- 66. . Diffusion-weighted magnetic resonance imaging in Marchiafava-Bignami disease: follow-up studies. Neuroradiology 2005;47(7):520–524. Crossref, Medline, Google Scholar
- 67. . Reversible restricted-diffusion lesion representing transient intramyelinic cytotoxic edema in a patient with traumatic brain injury. Neuroradiol J 2015;28(4):409–412. Crossref, Medline, Google Scholar
- 68. . Imaging for the diagnosis and management of traumatic brain injury. Neurotherapeutics 2011;8(1):39–53. Crossref, Medline, Google Scholar
- 69. . Reversible abnormalities of DWI in high-altitude cerebral edema. Neurology 2004;62(2):335–336. Crossref, Medline, Google Scholar
- 70. . Teaching neuroimages: reversible splenial cytotoxic edema in acute mountain sickness [comment]. Neurology 2012;78(12):932. Crossref, Medline, Google Scholar
- 71. . Transient splenial lesion after recovery of cerebral vasoconstriction and posterior reversible encephalopathy syndrome: a case report of eclampsia. Intern Med 2012;51(11):1407–1411. Crossref, Medline, Google Scholar
- 72. . Association of reversible splenial lesion syndrome (RESLES) with anti-VGKC autoantibody syndrome: a case report. Neurol Sci 2016;37(5):817–819. Crossref, Medline, Google Scholar
- 73. . Reversible MR findings of hemolytic uremic syndrome with mild encephalopathy. AJNR Am J Neuroradiol 1998;19(6):1144–1145. Medline, Google Scholar
- 74. . Kawasaki disease complicated by mild encephalopathy with a reversible splenial lesion (MERS). J Neurol Sci 2012;315(1-2):167–169. Crossref, Medline, Google Scholar
- 75. . Reversible splenial lesion in postpartum cerebral angiopathy: a case report. J Neuroimaging 2014;24(3):292–294. Crossref, Medline, Google Scholar
- 76. . Viral infections and white matter lesions . Radiol Clin North Am 2014;52(2):355–382. Crossref, Medline, Google Scholar
- 77. . Callosal and diffuse white matter lesions with restricted water diffusion in hemophagocytic syndrome . Magn Reson Med Sci 2010;9(2):91–94. Crossref, Medline, Google Scholar
Article History
Received: Apr 3 2016Revision requested: Sept 1 2016
Revision received: Sept 22 2016
Accepted: Nov 1 2016
Published online: Feb 06 2017
Published in print: Mar 2017