Cranial Trepanation: Case Studies between the IV Century BC and VI Century in Southern Italy

Cranial trepanation is among the oldest head surgical procedures, creating a hole through the skull. This procedure is the surgical removal of a portion of the skull as a medical treatment to cure a specific disease or as a religious or magical ritual. Cranial trepanation has been reported from very early times and widespread all over the world. This work is based on data from six trepanned skulls from the Hellenistic Age (IV century BC) to the Late Antiquity (VI century). The samples come from Puglia (Southern Italy), from the northern (the peninsula of Gargano) to the central area: three cases come from Vieste (Foggia), Ischitella (Foggia) and Alberona (Foggia), the others three from Gravina in Puglia (Bari) and Canosa (Barletta, Andria, Trani). All skulls have been evaluated via an anthropological, radiological and odontological approach. This study indicates the value of a methodology, which encompasses anthropology, radiology and imaging, and archeo-forensic investigations, highlighting the need for multidisciplinary teamwork in any assessment of human remains. The study supports the hypothesis of the presence of a long tradition of medical centres in the Mediterranean basin area. hyperdolicocrania, camecrania, acrocrania, hyper-eurimetopic, hyperleptoprosopia, leptorinia, Cranial


Introduction
Cranial trepanation represents one of the earliest forms of head medical surgery [1] performed on the skull to remove a fragment of calvarium using sharp instruments or drill. Trepanation, or trephination, has been used frequently in the past in many cultures over the world [2]. This procedure implicates incision of the scalp, cutting through the soft tissue and removal of the bone [3] without damage to the underlying blood vessels, meninges and brain [4]. According to Verano [5] we use trepanation to describe ancient cranial surgery, supporting the Greek origin of the term trypanon (a drill or a borer), and trephination to the surgery performed with the "trephine", the most widely used tool for this procedure through the end of the 19th century [6].
This surgical procedure was first documented in Neolithic [7][8][9] and widely adopted in later times. The earliest written description is provided by Hippocrates of Cos in the Corpus Hippocraticum in the V centuries BC [10]. The author described scraping, incision and perforation techniques. Then Celso [11], Eliodoro [12] and

Materials and methods
All the crania are undergone anthropological observation to establish a general biological profile. According to the commonly used methodology were determined gender and age [39][40][41] and morphometrical indicators [42]; also periodontal pathologies [2] and caries [2,43], tartar deposits [44] and hypoplastic enamel [45] in order to establish possible nutritional stress and/or previous disease pathologies. The estimation of stature and body mass was carried out according to the methods of Trotter and Gleser [46,47] and Ruff [48]. The investigation concerns the skeletal markers of biomechanical stress through evaluation and interpretation of any syndesmotic pathologies, enthesopathy, supernumerary articulatory facets or degenerative disease of the articulations [49][50][51][52][53]; finally, the criteria of Borgognini Tarli and Repetto [54] was used in order to evaluate any possible alterations to the spinal column. It was applied geometrical techniques concerning the transversal sections of the humerus and the femur [55][56][57][58][59]. The crania were examined by radiological investigation with Computerized Axial Tomography with 3D reconstruction (CAT, Siemens Somatom

The trepanned crania
The findings are six and come from Apulia (South Italy), from the northern to the central area: three cases come from Vieste (Foggia), Ischitella (Foggia) and Alberona (Foggia); the others three from Canosa (Barletta, Andria, Trani) and Gravina in Puglia (Bari) (Figure 1). Three skulls (Gravina, Vieste and Ischitella) are dated to the Greek Classical period (IV-III centuries BC); the other three (Alberona and the two cases from Canosa) between the Late Roman period and the Late Antique period (III-VII centuries).
For each case study we reported: 1) Archeological information (archeological site, the number of the grave and period); 2) biological profile (gender, age at death, height and body mass); 3) presence of anatomical variations; 4) pathologies; Biological Anthropology -Applications and Case Studies 4 5) Cranial characteristics; 6) characteristics of the lesion (location, shape, measurements, type of edges, healing); 7) reference. The findings date span from 1981 up until 2010: some skulls are incomplete and so do not have all the information. We can exclude the possibility that these lesions may be the result of treponematosis, non-specific osteomyelitis or osteoblastoma because the framework of that lesions may be associated with scurvy in adults -as regards periostitis and periodontal disease [47] -and with scurvy in infant -as regards cribra orbitalia, the vascular impressions on the ectocranial surface of frontal bone [63], the diffuse porosity on the large wing of the sphenoid bone, the porosity on the hard palate and severe periodontal disease [45]. Association between periodontal disease and subdural hemorrhages, in particular, indicates scurvy, the sign of avitaminosis C. 6. Characteristics of the lesion: the lesion is located on the left parietal bone, near the parietal eminence. It has an elliptical, irregular shape 18 mm x 15 mm with a major vertical axis. The posterior margins of the lesion are 72 mm from the craniometric point, lambda, while the inferior angle is situated 45.3 mm from the asterion. The margins of the lesion are more irregular along the superior side, and decline inwards, rather like the sides of a volcano, up to the point when they meet a bony layer, which occupies the superior part of the perforation. On the external surface 6 mm from the lower-inferior margin of the lesion, there is a small elliptic perforation 4 mm x 2 mm in size, which obliquely penetrates the cranial cavity. The apposition of the osseous tissue seems to have occurred at a later time than the perforation. The remarkably rounded margins suggest that the subject consequently survived the cranial trepanation, living for a long time, perhaps more than a year (Figure 3). The small perforation near the trepanation was probably done to drain the wound.

Case
7. Reference: [38].  6. Characteristics of the lesion: there is a smooth margined, trapezoidal shaped lesion present on the occipital squama of the cranium, along the right occipitotemporal suture and in correspondence to the mastoid process. The lesion is regular in shape and size. The perforation reveals, at an ectocranial level, that the greatest diameter, antero-posteriorly situated, measures 17 mm while the shorter side measures 8.6 mm. The radiological observation confirm that the lesions appear irregular contours and not rounded as to no bone remodeling postintervention: the absence of apposition of osseous tissue suggests that either the subject did not survive trepanation or that the procedure was, in fact, carried out post mortem since the lesion did not undergo cicatrisation (Figure 4). 7. Reference: none.    2. Biological profile: male; generically adult. We cannot provide more detailed information because it's impossible to attribute its post-cranial skeleton.
3. Anatomical variations: none.   osseous tissue and not evident thickening marginal bone remodeling suggests that the subject did not survive trepanation as the lesion did not undergo cicatrisation (Figure 7).

Discussion
About distribution of this evidence by gender and age on the sample, five subjects are male (CSP 2; SST 25; ISCH 3.2.; ALB 1; VIE r.s.18) and just one probably female (the "Bologna skull"). All the crania are from adult subjects as most found in the anthropological literature, except for rare cases [32,64,65]. Mariani-Costantini and colleagues ( [32], analyzed the skull of a child from Imperial Rome, that showed evidence of hydrocephaly. The authors argue against hydrocephaly as the need for trepanation, performed to alleviate symptoms of this disease. The most common hypothesis surrounding trepanation is that it was performed as a surgical treatment in cases of severe disease, including scurvy [64], meningiomas and bone tumors [66], chronic ear infections [67], headaches and seizures [33]. In Roman time individuals were trepanned to alleviate intracranial pressure due to trauma or disease, treat possible cranial fractures [68]. In a case of cranial trepanation found in a Roman necropolis (Cassino, Italy, 3rd century BC) the surgical procedure seems to be referred to a treatment of a sword wound [31]. Five skulls have just one lesion (SST 25; ISCH 3.2.; ALB 1; VIE r.s.18; the "Bologna skull"); in one case (CSP 2) the result of the trepanation is a double hole. As also seen in a number of cases, the skull can be poly-trephined by two or more holes [8].
The site of cranial intervention is systematic: in four of the cases (CSP 2; SST 25; ALB 1; "Bologna skull") involves the parietal bone (two holes on the right side, three on the left); in three cases (ISCH 3.2.; ALB 1; VIE r.s.18) involves the occipital bone; finally in only one skull (ISCH 3.2.) the temporal bone, on the right. The shape of the lesion is regular and attributable to geometric shapes (triangle, trapezium, quadrilateral, piriform, semicircular) in five cases (CSP 2; ISCH 3.2.; ALB 1; VIE r.s.18; the "Bologna skull"), except one case (SST 25). Measures ranging from a minimum of 8.6 mm to a maximum of 31 mm. The edges of the lesions are rounded and sloping inward where the operation has been successful and the patient survived; otherwise, where the intervention did not have healing or was made post mortem, the edges are irregular and the diploe is visible on all sides of the perforation. Analysis of skeletal features shows in four cases (CSP 2; SST 25; ALB 1; VIE r.s.18), convincing evidence that the cranial trepanations were carried out ante mortem: the hypothesis is confirmed both by radiographic and tomographic examination, which revealed evidence of remodeling of the cranial tables, indicative of the subjects having survived the procedures. Bone regrowth is representative of the individual's extended postoperative survival and his rehabilitation.
However, in two cases (ISCH 3.2.; the "Bologna skull"), are absent signs of osseous remodeling, suggesting that the subjects did not survive the trepanation or alternatively that the procedure was made post mortem on the corpse. As documented in both ancient and present times, trephination has also been reported to be adopted as a magic-ritual practice. In post-mortem symbolic trephinations, cranial bones were being used as religious objects that have curative powers in Medieval Europe and bone roundels were worn as ornaments or amulets [69,70].
Different techniques of drilling are attested. In three cases (CSP 2; SST 25; ALB 1) the morphology of the trepanned apertures -especially the broad shallow bevel of the edges -indicates that was probably used the scraping technique, when a sharpedged tool is repeatedly scraped over a designated portion of the bone until the vault was away and oval or round-shaped perforation is complete: the edges, in fact, are of this type -a broad shallow bevel, smooth and remodeled -while the diploe is not visible.
A double well healed skull trephination associated with a post-cranial traumatic event occurring intra vitam to a young male from the Early Chalcolithic cemetery of Pontecagnano (South Italy, ca. 4900-4500 cal BP). X-ray and 3D-CT scan skull-cap evaluation revealed that an orifice was probably produced by scraping with a sharp stone tool, obtained by clockwise rotation motion of a right-handed surgeon facing the patient [71]. A second trephination instead seems carried out by drilling with a stone point as a tool, which produced a round, cone-shaped hole, involving only the external cortical layer.
In two cases (the "Bologna skull"; VIE r.s.18) the trepanned apertures indicate that was probably used the incision/chiseling technique: edges are steeply beveled and the diploe is visible. The latter case (ISCH 3.2) is an unusual trepanation for anatomical location and it's difficult to recognize the precise technique. A metal or a hard instrument was employed, maybe drills and chisels.
Cranial trepanation is the most valid explanation for the presence of these holes on the skulls, excluding the possibility that they are anatomical variations, matches of trauma, secondary breaks after the deposition or diagenetic events of the soil. Concerning CSP 2, based on differential diagnosis cranial trepanation is the most valid hypothesis. For this study, we reconsidered the possibility that it can be caused by a pathology. Enlarged parietal foramina or "Catlin marks" are symmetrical, normally oval defects in the parietal bone situated on each side of the sagittal and involve the lack of ossification of the posterior membranous parietals suture. In the past, enlarged parietal foramina were confused with trepanations [72]. Concerning this finding, we do not totally exclude the possibility that the holes were caused by this pathology. But, based on the data obtained from the CT image, there appears to be a re-apposition of the bone after the trepanation. This further supports the hypothesis of medical intervention. In this case, it would be an operation performed by a person with in-depth anatomical knowledge.
From contemporaneous perspective, the motivation of trepanation events in the past can only be conjectured. Although in literature various motives are debated, grouped into two wide-ranging categories: therapeutic and ritual [73].
Explanations for ritual trepanations are the hardest to interpret, as their motive is culturally based [74]. Motivations for therapeutic trepanations are mainly  [75,76]. In our case studies there are no specific evidences which can highlight the motives behind the trepanation. We cannot motivate the procedure, if for therapeutic, magic/ritual or both reason, based on the location, the technique, the shape, the success of the surgery or other cultural or archeological evidence. In one case (CSP 2) it's possible that the drilling is therapeutic, to rid the tissues of the head from subperiosteal hemorrhage, one of the main symptoms of scurvy, of which he was ill the subject [64]; in another case (SST 25) we hypothesize that the hole, caused by a pointed weapon, maybe an arrow, produced a penetrating wound with the formation of an epidural or subdural hematoma, which necessitated the surgical operation. The absence of signs of healing in two cases (ISCH 3.2.; the "Bologna skull") suggests two possible interpretations: therapeutic if the surgical operation is not successful and the patient died during or shortly after; ritual if these drillings have been made after the death of the subject. Table 1 shows a summary view of the data.
However, only a scarce numbers of studies have underline the role of anesthesia [77] to minimize pain during operations performed. Mednikova [78] suggests that immersion in altered states of consciousness may have been a necessary part of the process of trepanation, along with shamanic practices, such as consumption of psychotropic substances or ecstatic dance. Inserting these elements in the Mediterranean and southern Italian context, it is possible to mention how Tarantism in Puglia has been known since ancient times as an ecstatic and therapeutic dance for other kinds of pathology. We have no direct evidence about the use of drugs or different methods of altering consciousness used. We can only speculate about the consumption of fungi [79] or the use of smoke from the burning leaves, such as the use of juniper (Juniperus sibirica) and thyme (Thymus vulgaris) in shamanic practices in some Siberia population [80], as reported in ethnographic materials collected worldwide. John Moyle in his work "Chirurgus marinus or the Sea surgeon" suggests administering alcohol, in specific Cordial, a liqueur obtained from various plants, before head surgery [81].
In some tombs in the vicinity of some of the findings analyzed, in Daunia, some anthropomorphic stone funerary monuments (VIII -VI century BC) were found at the end of the last century. Studying the figurative scenes drawings, Leone [82] hypothesized the use of Papaverum somniferum in medical practice.

Conclusion
The approach of this work is global, both in terms of geographic and chronological point of view. First, the burials are representative of the territory of Apulia, from the northern to the central area of the region. The findings also cover a long period (nine centuries) from the Greek Classical (IV-III centuries BC) (SST 25; ISCH 3.2.; VIE r.s. 18) to the Late Antique period (III-VII centuries for CSP 2; ALB 1; the "Bologna skull"). Therefore, the chronological and geographical distribution and some common characteristics of the trepanation, as described in the chapter of "Discussion", allow us to draw some historical considerations. First of all, it's attested a great number of scraping, the oldest trepanning technique [22] that provides the greatest control over the process and involves the lowest risk of damaging the brain, using, especially before the widespread use of metals, a sharp-edged oval stone but more advanced instruments such as metal scrapers (raspatories) [83]. Also the large geographical distribution and chronology of the