Cytotoxic lesions of the corpus callosum (CLOCCs)

Authors: J. Mračková 1;  R. Tupý 2;  V. Rohan 1;  J. Mraček 3;  P. Ševčík 1
Authors‘ workplace: Neurologická klinika LF UK a FN Plzeň 1;  Klinika zobrazovacích metod LF UK a FN Plzeň 2;  Neurochirurgická klinika LF UK a FN Plzeň 3
Published in: Cesk Slov Neurol N 2020; 83/116(4): 347-352
Category: Review Article
doi: 10.14735/amcsnn2020347


Cytotoxic lesions of the corpus callosum (CLOCCs) represent a group of conditions that cause MRI signal intensity changes in the corpus callosum. Etiology of this phenomenon is very heterogenous. CLOCCs are associated with a spectrum of metabolic disorders, drug therapy, infections, epileptic seizures and many other causes. It appears that these lesions result from a stereotyped inflammatory cascade which leads to a massive increase in levels of extracellular glutamate. The final result is development of cytotoxic edema. The range of clinical features is very wide. Neurological symptoms include motor and/or sensory involvement, cognitive decline, behavioral changes, dizziness, loss of consciousness and others. The main dia­gnostic tool is MRI, especially diffusion-weighted images, where CLOCCs manifest as regions of restricted diffusion. CLOCCs are reversible in most cases. Prognosis and treatment generally depend on the etiology, but clinical outcome is usually favorable. Physicians should be familiar with this recently named dia­gnosis, primarily because most of the underlying causes are treatable. In this article, we summarize the current knowledge and describe five cases of CLOCCs.


corpus callosum – reversible lesions – cytotoxic edema – magnetic resonance imaging – restricted diff usion


1. Starkey J, Kobayashi N, Numaguchi Y et al. Cytotoxic lesions of the corpus callosum that show restricted diffusion: mechanisms, causes, and manifestations. Radiographics 2017; 37 (2): 562–576. doi: 10.1148/rg.2017160085.

2. Conti M, Salis A, Urigo C et al. 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 2007; 112 (6): 921–935. doi: 10.1007/s11547-007-0197-9.

3. Fujiki Y, Nakajima H, Ito T et al. 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. doi: 10.5692/clinicalneurol.51.510.

4. Böttcher J, Kunze A, Kurrat C et al. Localized reversible reduction of apparent diffusion coefficient in transient hypoglycemia-induced hemiparesis. Stroke 2005; 36 (3): e20–e22. doi: 10.1161/01.STR.0000155733.65215.c2.

5. Kazi AZ, Joshi PC, Kelkar AB et al. MRI evaluation of pathologies affecting the corpus callosum: a pictorial essay. Indian J Radiol Imaging 2013; 23 (4): 321–332. doi: 10.4103/0971-3026.125604.

6. Doherty MJ, Jayadev S, Watson NF et al. Clinical implications of splenium magnetic resonance imaging signal changes. Arch Neurol 2005; 62 (3): 433–437. doi: 10.1001/archneur.62.3.433.

7. Garcia-Monco JC, Cortina IE, Ferreira E et al. Reversible splenial lesion syndrome (RESLES): What‘s in a name? J Neuroimaging 2011; 21 (2): e1–e14. doi: 10.1111/j.1552-6569.2008.00279.x.

8. Galnares-Olalde JA, Vázquez-Mézquita AJ, Gómez-Garza G et al. Cytotoxic lesions of the corpus callosum caused by thermogenic dietary supplements. AJNR Am J Neuroradiol 2019; 40 (8): 1304–1308. doi: 10.3174/ajnr.A6116.

9. Bagatti D, Messina G. Cytotoxic lesion in the splenium of corpus callosum associated with intracranial infection after deep brain stimulation. World Neurosurg 2020; 135: 306–307. doi: 10.1016/j.wneu.2019.12.114.

10. Le Bras A, Proisy M, Kuchenbuch M et al. Reversible lesions of the corpus callosum with initially restricted diffusion in a series of Caucasian children. Pediatr Radiol 2018; 48 (7): 999–1007. doi: 10.1007/s00247-018-4124-x.

11. Knyazeva MG. Splenium of corpus callosum: Patterns of interhemispheric interaction in children and adults. Neural Plasticity 2013; 2013: 639430. doi: 10.1155/2013/639430.

12. Rakic P, Yakovlev PI. Development of the corpus callosum and cavum septi in man. J Comp Neurol 1968; 132 (1): 45–72. doi: 10.1002/cne.901320103.

13. Deoni SC, Mercure E, Blasi A et al. Mapping infant brain myelination with magnetic resonance imaging. J Neurosci 2011; 31 (2): 784–791. doi: 10.1523/JNEUROSCI.2106-10.2011.

14. Blaauw J, Meiners LC. The splenium of the corpus callosum: embryology, anatomy, function and imaging with pathophysiological hypothesis. Neuroradiology 2020; 62 (5): 563–585. doi: 10.1007/s00234-019-02357-z.

15. Seidl Z, Vaněčková M. Dia­gnostická radiologie: neuroradiologie. 1. vyd. Praha: Grada Publishing 2014:  12–15.

16. Kakou M, Velut S, Destrieux C. Arterial and venous vascularization of the corpus callosum. Neurochirurgie 1998; 44 (1 Suppl): 31–37.

17. Kaminski JA, Prüss H. N-methyl-d-aspartate receptor encephalitis with a reversible splenial lesion. Eur J Neurol 2019; 26 (6): e68–e69. doi: 10.1111/ene.13900.

18. Miyata R, Tanuma N, Hayashi M et al. Oxidative stress in patients with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). Brain Dev 2012; 34 (2): 124–127. doi: 10.1016/j.braindev.2011.04.004.

19. Takanashi J, Tada H, Maeda M et al. Encephalopathy with a reversible splenial lesion is associated with hyponatremia. Brain Dev 2009; 31 (3): 217–220. doi: 10.1016/j.braindev.2008.04.002.

20. Phelps C, Korneva E (eds). Neuroimmune bio­logy. Vol 6, Cytokines and the brain. Amsterdam, Netherlands:  Elsevier 2008.

21. Leonoudakis D, Braithwaite SP, Beattie MS et al. TNFa-induced AMPA-receptor trafficking in CNS neurons: relevance to excitotoxicity? Neuron Glia Biol 2004; 1 (3): 263–273. doi: 10.1017/S1740925X05000608.

22. Kim YS, Honkaniemi J, Sharp FR et al. Expression of  proinflammatory cytokines tumor necrosis factor-a and interleukin-1b in the brain during experimental group B streptococcal meningitis. Brain Res Mol Brain Res 2004; 128 (1): 95–102. doi: 10.1016/j.molbrainres.2004. 06.009.

23. Kita T, Tanaka T, Tanaka N et al. The role of tumor necrosis factor-a in diffuse axonal injury following fluid-percussive brain injury in rats. Int J Legal Med 2000; 113 (4): 221–228. doi: 10.1007/s004149900095.

24. Prow NA, Irani DN. 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. doi: 10.1111/j.1471-4159.2008.05230.x.

25. Takanashi J, Barkovich AJ, Shiihara T et al. Widening spectrum of a reversible splenial lesion with transiently reduced diffusion. Am J Neuroradiol 2006; 27 (4): 836–838.

26. Yuan ZF, Shen, J, Mao SS et al. Clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with Mycoplasma pneumoniae infection. BMC Infect Dis 2016; 26 (16): 230. doi: 10.1186/s12879-016-1690-0.

27. Li S, Sun X, Bai YM et al. Infarction of the corpus callosum: a retrospective clinical investigation. PLoS ONE; 10 (3): e0120409. doi: 10.1371/journal.pone.0120409

28. Tsuji M, Yoshida T, Miyakoshi C et al. Is a reversible splenial lesion a sign of encephalopathy? Pediatr Neurol 2009; 41 (2): 143–145. doi: 10.1016/j.pediatrneurol. 2009.02.019.

29. Malhotra HS, Garg RK, Vidhate MR et al. Boomerang sign: clinical significance of transient lesion in splenium of corpus callosum. Ann Indian Acad Neurol 2012; 15 (2): 151–157. doi: 10.4103/0972-2327.95005.

30. Tada H, Takanashi J, Barkovich AJ et al. Clinically mild encephalitis/encephalopathy with a reversible splenial lesion. Neurology 2004; 63 (10): 1854–1858. doi: 10.1212/01.wnl.0000144274.12174.cb.

31. Hoshino A, Saitoh M, Oka A et al. Epidemiology of acute encephalopathy in Japan, with emphasis on the association of viruses and syndromes. Brain Dev 2012; 34 (5): 337–343. doi: 10.1016/j.braindev.2011.07.012.

32. Maeda M, Tsukahara H, Terada H et al. Reversible splenial lesion with restricted diffusion in a wide spectrum of diseases and conditions. J Neuroradiol 2006; 33 (4): 229–236. doi: 10.1016/s0150-9861 (06) 77268-6.

33. Sedláčková Z, Dorňák T, Čecháková E et al. Přehled onemocnění s obrazem restrikce difuze na magnetické rezonanci mozku. Cesk Slov Neurol N 2018; 81/114 (5): 539–545. doi: 10.14735/amcsnn2018539.

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