Recurrent Intracerebral Haematomas Due to Amyloid Angyopathy after Lyodura Transplantation in Childhood

Round 1

Reviewer 1 Report

The authors present a case report of iatrogenic-Cerebral Amyloid Angiopathy (i-CAA) potentially from LYODURA. These cases have been recently identified and reported. As such this case is consistent with those cases already reported. Nevertheless these are rare cases, especially those fulfilling the criteria of being "probable" rather than "possible" i-CAA. As mentioned by the authors there is still merit in publishing these cases not just for clinical awareness but also to gather data to enhance the knowledge regarding the pathophysiology of this condition. 

Although the content of the manuscript is sound, however there are parts including repetition (for example the summary of the case with details in the introduction and in the first paragraph of the discussion section in addition to what is already presented in the case report. As a result the manuscript is excessively lengthy and perhaps revision with the use more succinct language and avoidance of unnecessary repetition would enhance its readability.  

Author Response

Thank you very much for your opinion and a remark regarding shortening some parts of the manuscript due to repetition. As requested, we shortened the text in the last paragraph of the Introduction section regarding the summary of the case with details (page 2, lines 70-72), in the first paragraph of the Discussion section (page 5, lines 149-151), in the second paragraph of the Discussion section (page 5, line 159) and in the Conclusions section (page 6, lines 199 and 201). 

Reviewer 2 Report

The authors present a complex case of recurrent intracerebral haemorrhages in a middle aged patient operated in his childhood and exposed to lodura transplantation. The focus is on the possible relation of amiloid angiopathy to the use of lyodura in man. The paper is well presented, the case accurately described, the conclusions seem pertinent. My only doubt is that the number of patients treated with lyodura now approximates zero and that the largest  part of patients treated with this implant have not been known to develop ICH haemorrhages. ALthough dr Pjika collected 27 cases, it is very difficult to demonstrate a correlation. Also, there really is no way of preventing amiloid from developing if really it is dependent on lyodura implant. We might know more in the next future. Nonetheless, since the case is well explained and it induces to consider what a terrile result might be seen in similar patients, it might have predictive value and help clinicians to decide to stop treatment before worse things happen.

Author Response

Thank you very much for your opinion. We completely agree with you and already appropriately wrote the same concern/issues in the last paragraph of the Discussion part “Clinicians should consider iCAA in patients presenting with ICHs suggestive of CAA aetiology and be more aware of taking patients’ medical history regarding CNS neurosurgical procedures done in early childhood. Brain biopsy or autopsy should be performed in order to establish a definite diagnosis of CAA. Importantly, even larger multinational registries are mandatory for further exploration of this novel rare disease. Using QSC as standardized criteria for iCAA will help clinicians in wider recognition of the disease.” (page 6, lines 191-196)