Title: New insights into the palaeopathological diagnosis of tuberculous meningitis

Authors: Olga Spekker^1,2, David R. Hunt³, Erika Molnár¹, György Pálfi¹, Michael Schultz⁴

Affiliations: ¹Department of Biological Anthropology, Institute of Biology, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary; ²Institute of Archaeological Sciences, Eötvös Loránd University, Múzeum körút 4/B, H-1088 Budapest, Hungary; ³Department of Anthropology, National Museum of Natural History, Smithsonian Institution, 10^th Street and Constitution Avenue, Washington, DC 20013-7012, USA; ⁴Institute of Anatomy and Embryology, Center of Anatomy, University of Göttingen, Kreuzbergring 36, D-37075 Göttingen, Germany

Abstract: Based on findings of previous palaeopathological studies, endocranial granular impressions (GIs), abnormal blood vessel impressions (ABVIs), periosteal appositions (PAs), and abnormally pronounced digital impressions (APDIs) have been considered as diagnostic criteria for tuberculous meningitis (TBM). However, their diagnostic value has been questioned, as most of the previous studies were not performed on identified skeletal collections but on osteoarchaeological materials, and did not include statistical data analysis. To fill the aforementioned research gap, a combined macroscopic and statistical evaluation of 427 identified pre-antibiotic era skeletons from the Terry Collection (Washington, DC, USA) was conducted. A sample set of 234 individuals who died of TB (TB group) and 193 individuals who died of non-tuberculous causes (NTB group) were examined, and the investigations focused on the macromorphological characteristics and frequency of GIs, ABVIs, PAs, and APDIs in the TB group and NTB group. Based on our results, there is a positive association between TBM and the four evaluated endocranial alteration types; and thus, all of them can be used as diagnostic criteria for the disease in the palaeopathological practice. Nonetheless, it is also obvious that GIs, ABVIs, PAs, and APDIs do not have the same diagnostic value. Our findings imply that GIs can be considered as specific signs of TBM; and thus, are sufficient enough on their own to make a definitive diagnosis of the disease. On the other hand, our results strengthen those of previous studies that ABVIs, PAs, and APDIs are not specific to TBM but can be of tuberculous origin, and the chance of them being tuberculous in origin is higher when they concomitantly occur with each other. Although the palaeopathological diagnosis of TBM cannot be established based only on the presence of ABVIs, PAs, and/or APDIs without the simultaneous presence of GIs, if ABVIs, PAs, and/or APDIs are concurrently present with GIs, their tuberculous origin is very likely. In summary, with suitable circumspection, the utilization of GIs, ABVIs, PAs, and APDIs provides palaeopathologists with a stronger basis for identifying TB and consequently, with a more sensitive means of assessing TB frequency in past human populations.

Funding: The support provided by the Hungarian State Eötvös Fellowship 2016 (grant agreement n° 77466) of the Tempus Public Foundation, the NTP-NFTÖ-16 (grant agreement n° 1116) of the Hungarian Ministry of Human Capacities & Human Capacities Grant Management Office, and the National Research, Development and Innovation Office, Hungary (grant agreement n° K 125561) is greatly acknowledged.