Cytotoxic lesions of the corpus callosum (CLOCCs)

Changed by Arlene Campos, 7 May 2024
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Cytotoxic lesions of the corpus callosum (CLOCCs) represent a collection of disparate conditions that can cause signal change in the corpus callosum, usually involving the splenium. 

Terminology

The term cytotoxic lesions of the corpus callosum (CLOCCs) has been proposed recently 12 as a more precise description of this phenomenon which has previously been known by a variety of terms including transient lesions of the splenium of the corpus callosum, mild encephalitis/encephalopathy with a reversible isolated SCC lesion (MERS), reversible splenial lesions and reversible splenial lesion syndrome (RESLES). CLOCCs not only better reflects currentreflect understanding of the underlying pathophysiology of these lesions but also doesdo not explicitly imply that these lesions are confined to the splenium. As such it is probably a better term to use. 

Clinical presentation

Clinical presentation relates to the underlying pathology (see below) rather than to the callosal lesion itself. Unlike many other lesions of the corpus callosum, CLOCCs do not demonstrate convincing signs or symptoms of hemispheric disconnection, such as pseudoneglect, alien hand syndrome, apraxia of the left hand, agraphia, alexia, and visual apraxias 4. 

Pathology

Although numerous underlying aetiologies have been identified, these lesions appear to result from a stereotyped cascade of cytokines and stimulated cells. An initial insult results in macrophages releasing inflammatory cytokines (IL-1 and IL-6) which in turn leads to a cascade of changes including recruitment of T-cells, break-down of the blood-brain barrier, production of TNF-α, and activation of astrocytes. The end result is a massive increase in glutamate in the extracellular fluid which, via interactions with a number of cell membrane receptors, results in an influx of water into both astrocytes and neurones which manifests macroscopically as cytotoxic oedema 12. 

It appears that the reason the splenium of the corpus callosum is preferentially affected is the presence of a high density of oligodendrocytes expressing large numbers of glutamate affected receptors 12. 

Aetiology

Cytotoxic lesions of the corpus callosum are seen in a wide variety of clinical settings, although exactly which conditions are listed in any one publication varies. Classically CLOCCs are seen in patients with seizures or metabolic disturbances, although many other aetiologies are recognised. Reported aetiologies include 1-5,12: 

Radiographic features

Transient lesions of the splenium are only really appreciable on MRI where they have three distinct patterns 4,12: 

  1. well-circumscribed, small, oval lesions in the midline within the substance of the splenium (most common)

  2. more extensive less well-defined irregular lesions extending throughout the splenium and into the adjacent hemispheres (boomerang sign) 

  3. more extensive extension anteriorly into the body of the corpus callosum

The smaller well-circumscribed lesions are the typical lesion seen in the setting of seizures/cessation of antiseizure medications, whereas the larger lesion is more typical of other aetiologies.  

MRI

These lesions demonstrate the expected features of cytotoxic oedema 4,12: 

  • T1: hypointense

  • T2: hyperintense

  • DWI/ADC: restricted diffusion (ADC typically 300–500 x 10-6 mm2/s)

  • T1 C+ (Gd): no enhancement

Some studies have shown that patients generally recover completely on MRI studies within 1 month, mostly within 1 week following the neurological recovery 7.

Treatment and prognosis

The prognosis generally depends on the underlying cause, but in the setting of epilepsy or antiseizure medication-related lesions, it is very good. 

Differential diagnosis

Depending on the publication, some of the differentials to contemplate are included in the list of aetiologies of CLOCCs. In any case, when confronted with a splenial lesion consider:

  • -<p><strong>Cytotoxic lesions of the corpus callosum (CLOCCs) </strong>represent a collection of disparate conditions that can cause signal change in the <a href="/articles/corpus-callosum">corpus callosum</a>, usually involving the splenium.&nbsp;</p><h4>Terminology</h4><p>The term cytotoxic lesions of the corpus callosum (CLOCCs) has been proposed recently <sup>12</sup>&nbsp;as a more precise description of this phenomenon which has previously been known by a variety of terms including<strong> transient lesions of the splenium of the corpus callosum</strong>,<strong>&nbsp;mild encephalitis/encephalopathy with a reversible isolated SCC lesion (MERS)</strong>, <strong>reversible splenial lesions</strong> and <strong>reversible splenial lesion syndrome (RESLES)</strong>.&nbsp;CLOCCs not only better reflects current understanding of the underlying pathophysiology of these lesions but also does not explicitly imply that these lesions are confined to the splenium. As such it is probably a better term to use.&nbsp;</p><h4>Clinical presentation</h4><p>Clinical presentation relates to the underlying pathology (see below) rather than to the callosal lesion itself. Unlike many other <a href="/articles/lesions-of-the-corpus-callosum-1">lesions of the corpus callosum</a>, CLOCCs do not demonstrate convincing signs or symptoms of hemispheric disconnection, such as <a href="/articles/pseudo-neglect">pseudoneglect</a>, <a href="/articles/alien-hand-syndrome">alien hand syndrome</a>,&nbsp;<a href="/articles/apraxia-1">apraxia</a> of the left hand, <a href="/articles/agraphia">agraphia</a>, <a href="/articles/alexia">alexia</a>, and visual apraxias <sup>4</sup>.&nbsp;</p><h4>Pathology</h4><p>Although numerous underlying aetiologies have been identified, these lesions appear to result from a stereotyped cascade of cytokines and stimulated cells. An initial insult results in macrophages releasing inflammatory cytokines (IL-1 and IL-6) which in turn leads to a cascade of changes including recruitment of T-cells, break-down of the blood-brain barrier, production of TNF-α, and activation of astrocytes. The end result is a massive increase in glutamate in the extracellular fluid which, via interactions with a number of cell membrane receptors, results in an influx of water into both astrocytes and neurones which manifests macroscopically as <a href="/articles/cytotoxic-cerebral-oedema">cytotoxic oedema</a> <sup>12</sup>.&nbsp;</p><p>It appears that the reason the splenium of the corpus callosum is preferentially affected is the presence of a high density of oligodendrocytes expressing large numbers of glutamate affected receptors <sup>12</sup>.&nbsp;</p><h5>Aetiology</h5><p>Cytotoxic lesions of the corpus callosum are seen in a wide variety of clinical settings, although exactly which conditions are listed in any one publication varies. Classically CLOCCs are seen in patients with seizures or metabolic disturbances, although many other aetiologies are recognised. Reported aetiologies include <sup>1-5,12</sup>:&nbsp;</p><ul>
  • +<p><strong>Cytotoxic lesions of the corpus callosum (CLOCCs) </strong>represent a collection of disparate conditions that can cause signal change in the <a href="/articles/corpus-callosum">corpus callosum</a>, usually involving the splenium.&nbsp;</p><h4>Terminology</h4><p>The term cytotoxic lesions of the corpus callosum (CLOCCs) has been proposed <sup>12</sup>&nbsp;as a more precise description of this phenomenon which has previously been known by a variety of terms including<strong> transient lesions of the splenium of the corpus callosum</strong>,<strong>&nbsp;mild encephalitis/encephalopathy with a reversible isolated SCC lesion (MERS)</strong>, <strong>reversible splenial lesions</strong> and <strong>reversible splenial lesion syndrome (RESLES)</strong>.&nbsp;CLOCCs not only better reflect understanding of the underlying pathophysiology of these lesions but also do not explicitly imply that these lesions are confined to the splenium. As such it is probably a better term to use.&nbsp;</p><h4>Clinical presentation</h4><p>Clinical presentation relates to the underlying pathology (see below) rather than to the callosal lesion itself. Unlike many other <a href="/articles/lesions-of-the-corpus-callosum-1">lesions of the corpus callosum</a>, CLOCCs do not demonstrate convincing signs or symptoms of hemispheric disconnection, such as <a href="/articles/pseudo-neglect">pseudoneglect</a>, <a href="/articles/alien-hand-syndrome">alien hand syndrome</a>,&nbsp;<a href="/articles/apraxia-1">apraxia</a> of the left hand, <a href="/articles/agraphia">agraphia</a>, <a href="/articles/alexia">alexia</a>, and visual apraxias <sup>4</sup>.&nbsp;</p><h4>Pathology</h4><p>Although numerous underlying aetiologies have been identified, these lesions appear to result from a stereotyped cascade of cytokines and stimulated cells. An initial insult results in macrophages releasing inflammatory cytokines (IL-1 and IL-6) which in turn leads to a cascade of changes including recruitment of T-cells, break-down of the blood-brain barrier, production of TNF-α, and activation of astrocytes. The end result is a massive increase in glutamate in the extracellular fluid which, via interactions with a number of cell membrane receptors, results in an influx of water into both astrocytes and neurones which manifests macroscopically as <a href="/articles/cytotoxic-cerebral-oedema">cytotoxic oedema</a> <sup>12</sup>.&nbsp;</p><p>It appears that the reason the splenium of the corpus callosum is preferentially affected is the presence of a high density of oligodendrocytes expressing large numbers of glutamate affected receptors <sup>12</sup>.&nbsp;</p><h5>Aetiology</h5><p>Cytotoxic lesions of the corpus callosum are seen in a wide variety of clinical settings, although exactly which conditions are listed in any one publication varies. Classically CLOCCs are seen in patients with seizures or metabolic disturbances, although many other aetiologies are recognised. Reported aetiologies include <sup>1-5,12</sup>:&nbsp;</p><ul>

References changed:

  • 2. Bulakbasi N, Kocaoglu M, Tayfun C, Ucoz T. Transient Splenial Lesion of the Corpus Callosum in Clinically Mild Influenza-Associated Encephalitis/Encephalopathy. AJNR Am J Neuroradiol. 2006;27(9):1983-6. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977886">PMC7977886</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/17032879">Pubmed</a>
  • 5. Cho J, Ha S, Han Y et al. Mild Encephalopathy with Reversible Lesion in the Splenium of the Corpus Callosum and Bilateral Frontal White Matter. J Clin Neurol. 2007;3(1):53-6. <a href="https://doi.org/10.3988/jcn.2007.3.1.53">doi:10.3988/jcn.2007.3.1.53</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/19513344">Pubmed</a>
  • 6. Kimura. Mumps-Virus-Associated Clinically Mild Encephalopathy With a Reversible Splenial Lesion. Int J Clin Pediatr. 2012;1(4-5):124-8. <a href="https://doi.org/10.4021/ijcp51w">doi:10.4021/ijcp51w</a>
  • 7. Tada H, Takanashi J, Barkovich A et al. Clinically Mild Encephalitis/Encephalopathy with a Reversible Splenial Lesion. Neurology. 2004;63(10):1854-8. <a href="https://doi.org/10.1212/01.wnl.0000144274.12174.cb">doi:10.1212/01.wnl.0000144274.12174.cb</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/15557501">Pubmed</a>
  • 8. Loh Y, Watson W, Verma A, Krapiva P. Restricted Diffusion of the Splenium in Acute Wernicke's Encephalopathy. J Neuroimaging. 2005;15(4):373-5. <a href="https://doi.org/10.1177/1051228405279037">doi:10.1177/1051228405279037</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/16254404">Pubmed</a>
  • 2. Bulakbasi N, Kocaoglu M, Tayfun C et-al. Transient splenial lesion of the corpus callosum in clinically mild influenza-associated encephalitis/encephalopathy. AJNR Am J Neuroradiol. 2006;27 (9): 1983-6. <a href="http://www.ajnr.org/content/27/9/1983.full">AJNR Am J Neuroradiol (full text)</a> - <a href="http://www.ncbi.nlm.nih.gov/pubmed/17032879">Pubmed citation</a><span class="auto"></span>
  • 5. Cho JS, Ha SW, Han YS et-al. Mild encephalopathy with reversible lesion in the splenium of the corpus callosum and bilateral frontal white matter. J Clin Neurol. 2007;3 (1): 53-6. <a href="http://dx.doi.org/10.3988/jcn.2007.3.1.53">doi:10.3988/jcn.2007.3.1.53</a> - <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686937">Free text at pubmed</a> - <a href="http://www.ncbi.nlm.nih.gov/pubmed/19513344">Pubmed citation</a><span class="auto"></span>
  • 6. Kimura. International Journal of Clinical Pediatrics. 2012; . <a href="http://dx.doi.org/10.4021/ijcp51w">doi:10.4021/ijcp51w</a><span class="auto"></span>
  • 7. Tada H, Takanashi J, Barkovich A et-al. Neurology. 2004;63 (10): . <a href="http://dx.doi.org/10.1212/01.WNL.0000144274.12174.CB">doi:10.1212/01.WNL.0000144274.12174.CB</a><span class="auto"></span>
  • 8. Loh Y, Watson WD, Verma A, Krapiva P. Restricted diffusion of the splenium in acute Wernicke's encephalopathy. J Neuroimaging. 2005 Oct;15(4):373-5. <a href="https://www.ncbi.nlm.nih.gov/pubmed/16254404">https://www.ncbi.nlm.nih.gov/pubmed/16254404</a>

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