Genetic and imaging features of cerebellar abnormalities in tuberous sclerosis complex: more insights into their pathogenesis

Le résumé fourni par la source

We read with great interest the study by Boronat et al.1 which focused on frequency rate, magnetic resonance imaging (MRI) features, and the genetics of cerebellar lesions in tuberous sclerosis complex (TSC). Beside confirming in a large series that cerebellar lesions are common in TSC (about 26% of patients), the authors nicely showed that cerebellar lesions are: found in specific lobules of the posterior lobes (namely Crus-I, Crus-II, and lobule VIIB), often present folial retraction, and are almost exclusively linked to TSC2 gene mutations. The authors also pointed out several ancillary features such as rate of contrast enhancement or calcification and reviewed the relatively scarce literature on the topic. As cerebellar lesions obtain an increasing clinical role in TSC, especially for cognitive aspects and autism spectrum disorders, we would like to add our experience with another large series (Table 1) which aims to improve cerebellar lesion characterization and gain more insights into their pathogenesis. First of all, our centralized retrospective magnetic resonance evaluation confirmed four major findings: (1) the cerebellar lesions frequency-rate is close to 30% (44 cerebellar lesions affecting 34/112 patients with TSC); (2) the strict relationship with TSC2 gene mutations (91% of cerebellar lesions harbored TSC2 mutations; 32/69 [46%] patients with TSC2 had cerebellar lesions); (3) the specific vulnerability of the above mentioned posterior lobe cerebellar lobules; (4) and the dystrophic appearance of cerebellar lesions with folial retraction in almost all patients with TSC (33/34). In contrast, right-side prevalence was not confirmed, as cerebellar lesions were found equally on both sides (21/44 cerebellar lesions on the right; 23/44 on the left). In addition, looking more precisely into cerebellar lesion topography, our sample showed an intriguing intralobular regional vulnerability (Fig. 1) unveiling lesion clusters within the involved cerebellar lobules, thus providing possible hints about TSC-related cerebellar lesion pathogenesis. Most authors refer to cerebellar lesions as if they are purely dysplastic in nature, resembling those that appear in the supratentorial structures. Indeed, abnormal neurons and cortical/subcortical calcification are detected in both cortical tubers and cerebellar lesions.2 Nonetheless, some striking differences can be noted between supratentorial and infratentorial lesions. Cortical tubers, for example, are randomly distributed among the gyri so that virtually the whole cerebral cortex may be involved (tubers have even been detected in the olfactory bulbs).3 In contrast, infratentorial lesions typically spare large portions of the cerebellum; not only the anterior and posterior-lateral lobes and the vermis, but also the medial part of the posterior lobes. From a pathologic and imaging point of view, calcification seems to ensue earlier in cerebellar than in cerebral lesions, and supratentorial tubers usually result in enlargement of the affected gyri,4 while cerebellar lesions present with folial retraction with dystrophic rather than dysplastic appearance. Furthermore, unlike cortical tubers, cerebellar lesions are usually wedge-shaped and cluster in nearly side-to-side symmetric regions that resemble the watershed territories of the posterior inferior cerebellar artery.5 This peculiar topographic vulnerability is difficult to explain as the cerebellar cortex does not differ regionally in terms of structure or TSC2 expression,6 thus suggesting that other metabolic, vascular, or genetic factors likely concur in the pathogenesis of infratentorial TSC-related lesions. Recently, a pathological/MRI study2 investigated cerebellar lesions in a 32-year-old man with a TSC2 mutation, reporting prominent astrogliosis with few giant dysmorphic cells but no tuber-like foci. The extensive neuron loss with reactive changes was consistent with degenerative processes rather than developmental or hamartomatous alterations. Taken together, pathological and topographical findings strongly suggest a metabolic/vascular tissue vulnerability as a pivotal cofactor of cerebellar lesion pathogenesis. As cerebellar arteries show high interindividual variability, prospective MRI/magnetic resonance-angiography studies evaluating TSC-related cerebellar lesions and the concomitant anatomical pattern of posterior cranial fossa arteries could help to disentangle the role of regional vascularization in the pathogenesis of cerebellar lesions.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.