Case report: Moderate therapeutic response to Bevacizumab in late-onset Labrune syndrome

Abstract

Labrune syndrome (LS) is caused by SNORD118 gene mutations with a particular neuroimaging of white matter disease, intracranial calcification, and cysts. There was no effective treatment until now. An 18-year-old man with infancy-onset LS was first treated with vascular endothelial growth factor (VEGF) inhibitor Bevacizumab for 1 year, resulting in significant clinical and radiological improvements. We adopted a similar regimen in a patient with late-onset LS and demonstrated moderate cognitive improvements but without changes in imaging. As such, Bevacizumab could potentially be clinically effective in adult-onset LS with great safety.

Case report: Clinical and neuroradiological longitudinal follow-up in Leukoencephalopathy with Calcifications and Cysts during treatment with bevacizumab

“…We consider the following as important points of discussion. Firstly, previous reports described a single 12-month period of treatment ( 10–12 ), associated with apparent clinical improvement in two patients ( 10 , 12 ), even if only moderate in one ( 12 ). Of note, clinical improvement in these two cases appeared to plateau after 6 months of therapy.…”

“…Secondly, evidence of a neuroradiological response to bevacizumab is currently difficult to determine from the cases published to date, with an absence of regression of brain lesions in the single-reported adult patient ( 12 ) compared to the two younger subjects ( 10 , 11 ). Indeed, the age of the treated patients in these reports ranged from 19 months to 53 years, and it can be speculated upon that the initiation of therapy at a younger age might be associated with a better clinical outcome.…”

Expanding the Natural History of SNORD118-Related Ribosomopathy: Hints from an Early-Diagnosed Patient with Leukoencephalopathy with Calcifications and Cysts and Overview of the Literature

“…Bevacizumab, a recombinant humanized monoclonal antibody already employed in treating specific cancer types [ 36 ], exerts its anti-angiogenic effects by inhibiting the binding of vascular endothelial growth factor (VEGF) to its receptor. Subsequently, two more LCC patients received bevacizumab, resulting in mixed outcomes: a pediatric patient showed neuroradiological improvement without a concomitant enhancement in clinical status [ 24 ], while an adult patient experienced clinical improvement with no evident neuroradiological changes [ 14 ]. To date, the timing and necessity for the administration of bevacizumab therapy have been topics of debate due to conflicting data available and the possible side effects associated with its use.…”

“…U8 snoRNA is involved in the maturation of the 60S ribosome subunit [ 10 ]. Microangiopathic changes manifest as heightened tortuosity and calcification in small blood vessels, resulting in augmented focal edema and increased water content in the white matter [ 9 , 11 , 12 , 13 , 14 ]. Nevertheless, even though U8 snoRNA plays a pivotal role in ribosomal biology, the pathophysiological connection between a potentially global disturbance in ribosomal function and the development of cerebral microangiopathy with highly stereotyped radiological characteristics remains unclear [ 1 ].…”

Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions

“…Variable clinical and radiological therapeutic response to Bevacizumab has been described in the literature ( 90 ). Surgical decompression for progressive compressive symptoms due to enlarging cysts needs to be carefully considered on a case-to-case basis ( 87 , 90 ).…”