Author Response: Teaching NeuroImage: Partially Reversible Widespread Leukoencephalopathy Associated With Atypical Hemolytic Uremic Syndrome

We greatly appreciated the comment by Dr. Graber on our case.1 To date, kidney involvement associated with TREX1 sequence variations has been sparsely reported in the context of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S). Specifically, different subtypes of kidney involvement have been described in RVCL-S, including thrombotic microangiopathy (TMA) and glomerulosclerosis.2-4 As for our case, unfortunately, TREX1 analysis was not included in the genetic panel. However, a diagnosis of RVCL-S was unlikely, given the optimal response to eculizumab. Indeed, TREX1-related TMA and leukoencephalopathy have been suggested to be driven by dysregulated type-1 interferon pathways.5 Therefore, the pathophysiologic association between TREX1 sequence variations and endothelial damage is supposed to be independent of complement and should not improve after anticomplement treatment. In addition, after 14 months from onset, no other episodes of leukoencephalopathy occurred in our patient, and she was totally weaned from hemodialysis. To sum up, even if in our case RVCL-S was a remote possibility, we agree with Dr. Graber's suggestion to consider TREX-1 analysis in patients presenting with acute leukoencephalopathy and small vessel kidney disease. Close collaboration between neurologists and nephrologists remains the key point to promptly recognize such a critical condition.