Cerebellar Progressive Multifocal Leukoencephalopathy Mimicking Anti-Yo-Antibody-Associated Rapidly Progressive Cerebellar Syndrome
Round 1
Reviewer 1 Report
The manuscript by Akimbo, et al., is a case report that describe an unusual presentation of Progressive Multifocal Leukoencephalopathy in a patient being treated with immunosuppressants for Lupus, and whose original diagnosis was incorrectly classified as anti-Yo antibody associate, rapidly progressive cerebellar syndrome.
This is a very interesting case, with some degree of uniqueness, and it is worth to be presented. However, the manuscript is poorly written and requires significant improvements to be suitable.
For example, the introduction is extremely small and simple. Only 1 paragraph with 11 lines!!! There is no description of what Progressive Multifocal Leukoencephalopathy is (perhaps the sentence in the discussion could be moved to the introduction, but that would not be sufficient, it would need to be expanded). There is no mention of what the frequency of PML is the cerebellum is (some references should be cited showing cerebellar PML). There is no mention of the human neurotropic polyomavirus JCPyV in the introduction either, including the different strains and what mutations constitute what strains. Under what clinical conditions is PML seen? There is no mention of AIDS, nor the new immunotherapies (all the "-zumabs"). Since the final diagnosis of the patient was PML, there should be a well developed, longer introduction of the demyelinating disease, including the clinical differential diagnoses.
In contrast to the very short introduction, the clinical presentation is very long and contains only the lab results and clinical presentation, without a connotation of their significance. What values were important for the diagnosis of cerebellar ataxia and anti-Yo syndrome? It may be advisable to remove irrelevant clinical information (such as serum creatinine, proteinuria or hematuria just to mention some examples).
Next, the authors mention that JCPyV was found, but they don't mention how? Since they are presenting copy number, one can assume Real Time PCR? This need to be clearly specified. The authors also mention that the strain is "prototype" which does not exist. Do they mean "archetype"? Also, what is a "defective" regulatory region? Do they meant that the regulatory region contains mutations? Since this is stated, the sequencing of the control region needs to be presented in the paper.
And in the Discussion section, the authors present facts about the different conditions in the paper, but they don't make any thoughtful discussion. For example, how common or rare is a cerebellar presentation of PML? What was the cause of this demyelinating disease in this person? Also to be discussed, how often is PML presented in the cerebellum? Most importantly, this patient PML went into remission once the immunosuppressants were discontinued, and that is again, a very rare occurrence in PML, which is usually fatal. That is another fact that makes this a very interesting case and that requires a more in depth discussion.
English grammar needs to be thoroughly revised and edited. For example:
"The pictures showed the Purkinje cell layer and granule cell layer of rat’s cerebellar. Sections reacted with patient serum showed no staining to Purkinje cells, as did negative controls (yellow allow head). If anti-Yo antibody was present in the patient’ serum the Purkinje cells were stained"
The pictures show... of rat cerebellum.
Immunohistochemistry is not a "staining", despite the term being widely used. Change to labeling or immunolabeling.
If anti-Yo antibody would be present in the patient's serum, the Purkinje cells would be labeled (or positive).
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
I felt a bit puzzled that the authors concluded that the positive testing result of serum anti-Yo antibody was incorrect, based on the negative result on their rat brain tissue samples. Negative results generally do not mean anything, because negative data can be caused by anything (for instance, due to any misuse unuse of appropriate reagents). Furthermore, you cannot deny the positive testing results of immunoblot by showing negative immunohistochemistry results. There are numerous antibodies that work only for immunoblot but not for immunohistochemistry. If the authors want to deny the positive line blot testing data, they need to show other data showing inaccuracy of the commercially available anti-Yo antibody line blot.
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Round 2
Reviewer 2 Report
I have no more comments.
