Mast cells in the human dura: effects of age and dural bleeding

Abstract

To the Editor, We read with great interest the manuscript by Varatharaj and colleagues[2] regarding the presence of mast cells in the human dura. The authors should be applauded for their continued efforts to try to bring clarity to an area which remains opaque and complex; timing of subdural haemorrhage (SDH) collections. The central feature of their study is the presence of mast cells in the dura. It is important to note, as the authors indicate, immunologically active cells and angiogenic factors have been identified as part of the reparative reaction to subdural haemorrhage for decades. The authors note Sarkar and colleagues[1] demonstrated the presence of eosinophils the chronic SDH in 2002. Sarkar and colleagues report the finding having been discovered by Yamashima and colleagues[3] demonstrating this finding as early as 1985. The most recent contribution by Varatharaj and colleagues[2], evaluating mast cell density within postmortem dural samples, is quite compelling, but given what is already known about the presence of eosinophils in subdural haemorrhage, some of the conclusions are unsupported by the data presented. The current study was aimed to determine the density of the mast cell population in the dura mater of humans. The authors also wanted to describe changes in the density of the mast cells between fresh and old SDH. It appears that the intention of the investigators, in part, is to assess a “profile” that mast cells may have as related to the age of the subdural collection. What remains unclear from the methods section is if the assessment of the mast cell density was done by an assessor blinded to clinical information. If there were no blinding in the assessment of mast cell density then there is significant opportunity for investigator bias. Varatharaj and colleagues[2] note that the density of mast cells was nearly statistically related to the age of the SDH, although it remains unclear what statistical analysis was being performed. The standard error ranges of the average mast cell density, as shown in Fig. 4, are relatively large. Given the small sample size, it is not surprising the absence of a statistically significant. Despite the lack of statistical significance, a relation between the mast cell density and the age of the SDH would confirm the findings of Yamashima and colleagues. In evaluating dural membrane samples of 50 subjects (10-87 years), Yamashima and colleagues noted that the density of eosinophils was related to the age of the SDH as opposed to the age of the subject. In addition they noted lymphocytes, histiocytes and mast cells in various distributions according to age of the SDH. These authors concluded that eosinopshils were part of a broader cellular inflammatory response to injury and contributed to the healing as well as the angiogenesis associated with “chronic” SDH. We would contend that the findings of Varatharaj and colleagues is quite consistent with these findings, and that any apparent association of mast cell density to age of the subject is confounded by the age of the SDH and small sample size. To help resolve the apparent discrepancy we suggest some clarifications. First, it would be helpful for the authors to present the ages of the subjects and the ages of the SDH collection in tabular form. We would anticipate that the apparent trend of mast cells to the age of the subject is related to the over representation of “old” SDH in younger subjects. Additionally, it is unclear why 200 months (16 years and 8 months) was used as the age cut off. It would be helpful to the reader to have the ages represented in a more standardized fashion (years or developmental stage; i.e. infant, toddler, adolescent, adult...). We anticipate that the apparent age relationship with mast cell density would be readily resolved by a reformatting of the data. Overall, we find the work of Varatharaj and colleagues quite intriguing. We would propose that the relationship of mast cell density is simply a function of inflammatory response to injury as has been reported earlier and that the need for a more complex explanation for these findings (trigemino-cardiac reflex) is unwarranted and remains unsupported.