Response from Dr. Martinez‐Anton, et al. to Dr. Foster letter to editor regarding Investigation of the role of Campylobacter infection in suspected acute polyradiculoneuritis (APN) in dogs

Dear Editor, Thank you for the opportunity to respond to the letter from Dr. Foster regarding our recent publication “Investigation of the role of Campylobacter infection in suspected acute polyradiculoneuritis (APN) in dogs.” Dr Foster's main concern about the paper was the inclusion criteria. Our inclusion criteria were similar to previously published papers about acute polyradiculoneuritis (APN) in dogs. There is no definitive diagnostic test available for dogs with APN. It is a diagnosis made on the basis of clinical signs and clinical course. Further testing such as electrodiagnostic investigation and cerebrospinal fluid (CSF) analysis provides further supporting evidence but these tests do not provide a definitive diagnosis; and negative or positive results are not diagnostic. This is the reason why we have used the term “suspected APN” in this investigation. Other diagnostic tests such as biochemistry and serology are performed to rule out other diseases; however, considering the main differential diagnoses in acute LMN diseases, we do not believe these tests are mandatory for the inclusion criteria. The main differential diagnoses for acute onset of LMN disease in dogs are myasthenia gravis, botulism, tick paralysis (in some Australian states and North America), and death from adder envenomation (in Australia). All were considered very unlikely in our cases considering their history, clinical course, and neurological examination, including the lack of autonomic signs and mild cranial nerves involvement. Moreover, as explained in the paper, a thorough tick search was performed and found to be negative in all the APN dogs. In Australia, this is routine in dogs presenting with acute onset of LMN signs. Based on these, we respectfully disagree with the statement that our inclusion criteria were insufficient for a diagnosis of APN or the suggestion of tick search being required as part of the inclusion criteria. Regarding Dr Foster’s comment about the inclusion criteria of “ascending LMN”: four cases had descending tetraparesis and four cases had all limbs affected. Thus, 30% of the APN cases in this study did not appear to meet the inclusion criteria of the study, we agree that using the term “ascending” may cause confusion as with APN, all forms should be considered; ascending, descending, and all limbs at the same time. Therefore, it would be more appropriate to use “rapid development of LMN” to avoid confusion. Dr Foster cited that snake envenomation is another common cause for lower motor neuron signs in Australian dogs. We agree that paralysis and weakness have been reported in snake envenomation in Australia; however, the clinical presentation tends to be very different from dogs with APN. Ataxia is more common than progressive LMN tetraparesis, and these dogs are usually systemically affected including mydriasis, acute collapse, vomiting, ptyalism, dyspnea, reduced gag reflex, and pigmenturia. The most common snake species in the geographic area described are eastern brown snakes, mainland tiger snakes, Red bellied black snakes, and death adders. Brown snake envenomation is associated with a very rapid onset of neurologic signs and coagulopathy not evident in any cases included. Black snake and tiger snake envenomation causes significant rhabdomyolysis and pigmenturia also not evident in any of the cases. Death adder envenomation is very rare in urban areas and is characterized by rapid onset of LMN signs, which is rapid involvement of the cranial nerves and often respiratory failure. This was not observed in any of our cases. Dr Foster cited that with each case of APN enrolled, the study design was such that two case controls were to be recruited from staff and client dogs yet only 47 control dogs were included not 54 as there should have been for 27 APN cases; that is there were 13% fewer controls than specified in the study design. There was no mention of why this deviation from the study design occurred. We would like to clarify this from the statistical point of view. A priori sample size calculations were undertaken based on best available evidence. As the study progressed, it became clear that a very strong magnitude association was present and many fewer dogs than the prior estimates would be required. Post hoc sample size re-estimation suggests that the power to detect the reported odds ratio of 9.4 may be achieved with only 14 cases and 28 controls. Given the extreme magnitude of the detected association, the minor discrepancy focused on by Dr Foster between what was intended and what was undertaken is completely irrelevant. Dr Foster also presented a few concerns that we would like to address individually as follows: