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Scaphocephaly and increased intra-cranial pressure in non-operated

adults: a controlled anthropological study on 21 skulls

Maddy-Hélène Delattre , Quentin Hennocq , Sarah Stricker ,

Giovanna Paternoster , Roman Hossein Khonsari

PII: S2468-7855(22)00029-5
DOI: https://doi.org/10.1016/j.jormas.2022.01.012
Reference: JORMAS 1128

To appear in: Journal of Stomatology oral and Maxillofacial Surgery

Received date: 27 January 2022

Accepted date: 30 January 2022

Please cite this article as: Maddy-Hélène Delattre , Quentin Hennocq , Sarah Stricker ,
Giovanna Paternoster , Roman Hossein Khonsari , Scaphocephaly and increased intra-cranial
pressure in non-operated adults: a controlled anthropological study on 21 skulls, Journal of Stomatol-
ogy oral and Maxillofacial Surgery (2022), doi: https://doi.org/10.1016/j.jormas.2022.01.012

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Scaphocephaly and increased intra-cranial pressure in non-operated adults: a controlled

anthropological study on 21 skulls

Running title Raised ICP in adult scaphocephaly

Maddy-Hélène Delattre DDSa, Quentin Hennocq MDa, Sarah Stricker MDb, Giovanna

Paternoster MDc,d, Roman Hossein Khonsari MD, PhDa,d

a
Service de chirurgie maxillo-faciale et chirurgie plastique, Hôpital Necker – Enfants

Malades, Assistance Publique – Hôpitaux de Paris ; Faculté de Médecine, Université de

Paris ; Paris, France

b
Klinik für Neurochirurgie, Universitätsspial Basel ; Basel, Switzerland

c
Service de neurochirurgie, Hôpital Necker – Enfants Malades, Assistance Publique –

Hôpitaux de Paris ; Faculté de Médecine, Université de Paris ; Paris, France

d
Centre de Référence Maladies Rares Craniosténoses et Malformations Craniofaciales

CRANIOST, Filière Maladies Rares TeteCou

Corresponding author

RH Khonsari, Service de chirurgie maxillo-faciale et chirurgie plastique, Hôpital Necker –

Enfants Malades, 149 rue de Sèvres, 75015 Paris, France

Email roman.khonsari@aphp.fr phone +33171396613

ABSTRACT

Aim and scope :

The prevalence of increased intra-cranial pressure (ICP) in patients with scaphocephaly is

controversial. Here, based on anthropological material, we aimed to determine whether adults

with non-operated sagittal synostosis show indirect signs of increased ICP.

Materials and Methods:

Thirty-eight dry skulls (21 skulls with sagittal craniosynostosis and 17 controls) were selected

from the collections of the National Museum of Natural History (Paris, France). All skulls

registered as ‘fused sagittal suture’ or ‘scaphocephaly’ in the registry of the Museum were

included. All had total fusion of the sagittal suture. Controls were selected within skulls of

similar origin (France), without visible craniofacial anomalies. The 38 skulls were CT-

scanned using a standard medical CT-scan with a protocol dedicated to dry bone imaging.

Eight radiological signs associated with raised ICP were assessed: (1) calvaria and (2) skull

base thinning, (3) dorsum sellae erosion, (4) sella turcica lengthening, (5) copper beaten skull,

(6) suture diastasis, (7) persistent metopic suture, and (8) small frontal sinus. Scaphocephaly

was assessed based on head circumference, cranial index, intra-cranial volume, fronto-nasal

angle, and inter-zygomatic distance. Linear and non-linear logistic models were used to

compare groups.

Results:

19/21 skulls with sagittal synostosis were significantly scaphocephalic. None of the criteria

for ICP were significantly different in skulls with scaphocephaly relative to controls.

Nevertheless, 5 individual skulls with scaphocephaly had ≥ 3 signs in favor of a history of

raised ICP.
We do not report the significant prevalence of indirect signs of raised ICP in adults with

scaphocephaly. These results do not allow ruling out a history of early raised ICP or of minor

prolonged raised ICP. Even though our findings support the fact that scaphocephaly is not

significantly associated with prolonged raised ICP, individual cases (5/21) with clear signs in

favor of a history of brain compression indicate that scaphocephaly correction should be

considered as a functional procedure until the production of clear evidence. Cognitive

assessments of non-operated adult patients with scaphocephaly could contribute to tackle this

recurring question in craniofacial surgery.

Keywords scaphocephaly ; intra-cranial pressure ; intra-cranial volume ;

craniosynostosis ; suture

ABBREVIATIONS :

SC : Sagittal craniosynostosis

CT : computed tomography

MRI : magnetic resonance imaging

ICP : intra-cranial pressure

MSP : median sagittal plane

IQ : intellectual quotient

CSF : cerebrospinal fluid

INTRODUCTION

Sagittal craniosynostosis (SC) causing scaphocephaly has a prevalence of 2-5/10000 births

with a male-to-female ratio of 4:1. SC is the most common form of single-suture

craniosynostosis, accounting for 40-60% of all suture fusions (including syndromic and non-

syndromic cases).1–3 Its origins remain unclear, as multiple mechanisms seem to be involved

including biomechanical, environmental, vascular, hormonal, and genetic factors4. Physical

examination alone is sufficient to diagnose SC in most cases, but suture sonography,

radiography, computed tomography (CT), or magnetic resonance imaging (MRI) with bone-

specific sequences ('black bone') can be of help to assist diagnosis5.

Surgery for scaphocephaly is mostly motivated by aesthetical arguments. Nevertheless,

several authors have reported increased risks of neuropsychological anomalies in non-

operated patients with SC and have advocated surgery in the first year of life for functional

reasons. In fact, children with SC may have increased issues with language acquisition, in

addition to working memory, attention, and planning abilities impairments6. The precise

causes of these moderate cognitive symptoms have not been determined but these may be

related to early-life increases in intra-cranial pressure (ICP)6–8, estimated, according to

different authors, at 4.5% to 24% for non-operated children (at the mean age of 1 year in the

study of Arnaud et al7, mostly before 3 years after Renier et al8, or before 2 years for Bristol et

al9), with peaks at 44% at older ages, as found by Wall and al in patients with a mean age of

56 months10.

However, the problem with ICP assessments in SC lies in the absence of standard scales for

normal values in children, added to the absence of a consensual method for diagnosing raised

ICP11. Moreover, very few studies have assessed the dynamics of ICP in controls and non-

operated adult patients with SC10. For all these reasons, screening for potential signs of raised
ICP in a population of adults with SC could contribute to the debate on morphological vs

functional indications of surgery in scaphocephaly.

Interestingly, the morphometric study of dry skulls is a source of indirect signs of raised ICP

such as, among others, the presence of dorsum sellae erosion, suture diastasis, copper beaten

skull12 and/or calvaria thinning13. Here we assessed 21 CT-scans of adult dry skulls obtained

from a historical anthropological collection (National Museum of Natural History, Paris,

France) with non-operated SC and we performed measurements to screen for a potential

history of raised ICP.

MATERIAL AND METHODS

Study population

A total of 38 adult dry skulls from the anthropological collections of the National Museum of

Natural History (Muséum National d’Histoire Naturelle), Paris, France was considered,

including 21 skulls with SC and 17 controls without malformations or lesions. The 21 skulls

with SC corresponded to all the adult samples labeled ‘scaphocephaly’ and/or ‘sagittal

synostosis’ in the registry of the Museum, all originating from France. SC was confirmed in

all cases by the detection of sagittal synostosis based on visual examination and by the

qualitative presence of anteroposterior elongation of the skull with a bulging forehead. The

controls were selected within skulls originating from France, without visible craniofacial

anomalies. All 38 subjects had a fusion of the spheno-occipital synchondroses and were thus

considered as adults. Information on precise age and sex was not available.

Data extraction

All the skulls were scanned using a standard medical CT-scan at Centre Hospitalier National

d'Ophtalmologie des Quinze-Vingts (Service d’Imagerie Médicale, Pr. Emmanuel-Alain

Cabanis) with the following parameters: detector row channels = 16; effective detector row

thickness = 1.25 mm; acquisition mode = 0.562:1 ; speed = 5.62 mm / rotation; detector

configuration = 16 x 0.625; beam collimation = 10.0 mm; image count = 136; Scan Field Of

View (SFOV) = small; tension = 120 kV; intensity= 300 mA; and Display Field Of View

(DFOV) = 23 cm. Visualization and measurements on DICOM files were performed using

Blue Sky Plan (Blue Sky Bio, Libertyville, IL, USA) and the computation of the intra-cranial

volumes with Slicer14, by a single observer (MHD) (Figure 1).

In order to quantify the extent of skull deformation, the cranial index, the fronto-nasal angle

and the head circumference were measured on each skull. The inter-zygomatic distance was

also measured as the distance on a coronal slice between the farthest points located on the

bodies of the zygoma. Intra-cranial volume was computed by segmenting the intra-cranial

cavity.

As described by Du Boulay13, the following signs in favor of raised ICP were assessed: (1)

calvaria and skull base thinning; (2) copper beaten skull, (3) suture diastasis, (4) dorsum

sellae erosion, and (5) sella turcica lengthening. Small frontal sinuses and persistent metopic

suture were also screening as they are listed by several authors as indirect raised ICP signs15.

The skulls were oriented according to the Frankfurt plane. The median sagittal plane (MSP)

was defined by three landmarks: nasion, bregma and basion. Calvaria thickness was measured

following a previously published method16 at four points: (1) metopion, (2) at the highest

point between lambda and inion on the MSP, (3) at the vertex on a coronal section, and (4) on

the parietal bones on a coronal section. Parietal bone thickness was assessed at the most

convex point of the bones on each side located on a superior view and then measured on a

coronal section. Skull base thickness was obtained following the method of Rabbani et al.17

by measuring the bone above the internal auditory canal at the level of the labyrinthine

segment of the facial nerve as it enters the fallopian canal on the coronal plane (Figure 2).

Sellar length was measured on the MSP; dorsum sellae erosion was also noted (Figure 3).

Copper beaten skull (localized or diffuse, moderate or severe) was defined by Tuite et al.12 as

markings of the inner table of the cranial vault that had indistinct margins and variable (Figure

4). Persistent metopic suture and suture diastasis were screened on three-dimensional

reconstructions.
Statistical analysis

Linear logistic models for quantitative variables and non-linear logistic models for qualitative

variables were used to compare the two groups (SC vs. controls). For lateralized variables,

hierarchical models were used in order to account for repeated measurements in a single

patient and thus non-independent data. The model coefficients were compared to 0 using

Student tests. The significance threshold was defined as p < 0.05; a significant parameter (SC

yes/no) influenced the relevant variables for each model. Assumptions of normality and

homoscedasticity of errors were tested. The statistical analyses were performed on R 3.6.21

using the nlme2 and ggplot3 packages.

RESULTS

Adult SC patients did not have significant signs in favour of history of raised ICP (Tables 1-2,

Figure 5). Copper beaten skull was present in 9/21 (43%) of SC vs 4/17 (24%) in controls,

with diffuse forms in 4/21 (19%) of SC vs 0/17 in controls – this sign was not significantly

more prevalent in SC than in controls. Dorsum sellae erosion occurred in 9/21 (43%) of SC vs

4/17 (24%) of controls, again without significant difference. Only 1/38 from the control group

had a persistent metopic suture; 21% of skulls both in SC (9/42) and controls (7/34) had no

frontal sinuses. At least one suture diastasis was found in three skulls with SC (two skulls

presented a diastasis of the squamous suture and one skull of the lambdoid suture); no suture

diastasis was found in controls. 3/21 skulls with SC showed 3/6 raised ICP signs, and 2/21 SC

skulls showed 4/6 raised ICP signs. Sella turcica lengthening and dorsum sellae erosion were

constantly reported in these 5/21 skulls with multiple raised ICP signs (Table 3).

All SC skulls were significantly scaphocephalic based on the head circumference, cranial

index, and inter-zygomatic distance (Table 1). The intra-cranial volume (p=0,590) and the

fronto-nasal angle (p=0,015) were similar in SC and controls.

DISCUSSION

Cognition in scaphocephaly

It has been repeatedly suggested that raised ICP in patients with craniosynostosis leads to

insufficient blood supply in the regions below the fused sutures, potentially interfering with

brain development, causing subsequent lesions and various levels of cognitive impairement8.

This hypothesis has been widely publicized and used as an argument for early corrective

surgery. The topic is nevertheless highly controversial. Arnaud et al.7 did not find significant

correlation between raised ICP in non-operated SC children and cognitive impairment;

nevertheless, these authors reported a trend for the presence of cognitive symptoms in

children non-operated children assessed after 1 year of age, associated with a higher rate of

raised ICP in these ‘older’ patients (20% vs 2% for patients seen before 1 year). However,

Arnaud et al.7 did not find any significant difference in intellectual quotient (IQ) between

operated and non-operated patients for all age groups. The systematic literature reviews of

Speltz et al.18 and of Thiele-Nygaard et al.19 found no difference in cognitive functions

between operated and non-operated SC patients. The authors, however, temper their results

due to the small number of articles included, the variety of techniques for quantifying

cognition, and the diversity of surgical procedures. Interestingly, in the retrospective survey of

Patel et al20, SC patients who underwent surgery before 6 months of age demonstrated

significantly higher full-squale IQ and verbal IQ than those operated after 6 months of life.

This surprising diversity of cognitive outcomes underlines the fact that the neurodevelopment

of SC patients is still a poorly understood phenomenon: ICP alone cannot account for

neurocognitive defects, and the possible roles of (1) potential intrinsic morphological and

functional brain anomalies, and (2) the variety of surgical corrections in terms of technique

and protocol, and their respective morbidity. Of note, there is currently no data solid available
on the long-term cognition of non-operated patients, and thus no control group to evaluate the

long-term cognitive effects of surgery in SC21.

Brain and skull anomalies in scaphocephaly

Morphological changes in cranial and endocranial structures have been described in

scaphocephaly. The typical appearance of the skull in SC is the shape of an inverted boat,

since it is elongated in the antero-posterior direction and narrow medio-laterally. The cranial

index is reduced to an average of 60-65%, with bone thinning adjacent to the fused suture

and thickening of the sagittal suture22,23. According to Ghosh and al24, the unoperated regions

of the calvaria in SC children are thicker than controls.

In non-operated SC children, Lee and al25 report that brain tissue volume and intracranial

cavity volume are significantly smaller compared to control children. These volumes tend to

normalize after surgery25. These results are supported by Aldridge et al26 and Brooks et al27,

who found no difference in the overall brain size and lobe size between patients with operated

single-suture craniosynostosis and controls. However more localized differences were found

in the brain of both operated and non-operated single-suture craniosynostosis in comparison

to controls: ventricular volume was greater, the total corpus callosum area was reduced

(particularly in segment 5)26–28, regions of the midline cerebellar vermis were significantly

smaller (lobules VI-VII)26, and Chiari malformation was occasionally reported27–29. The

increased ventricular volume was explained by some authors as a consequence of abnormal

venous flow26,30. In addition, enlargement of the subarachnoid space has been repeatedly

reported in single-suture craniosynostosis 23,28,30,31. The causality between craniosynostosis

and these intracranial structural characteristics remains questionable, for instance for findings

such as Chiari malformations. Furthermore, their clinical implications remain unclear26.

Nevertheless, several anatomo-clinical correlations have been proposed in the literature: (1)

size reduction of the corpus callosum could induce a deficit in bimanual dexterity32-34, (2)
abnormalities in cerebellar lobules VI-VII have been associated with learning35, reading36, and

language37 impairements.6,7,19,21,38–40, and (3) white matter anomalies in the left fronto-parietal

region (Brodmann area 22) was been related to language and speech processing anomalies.19

Despite these numerous hypotheses on the origins of cognitive symptoms in patients with

single-suture craniosynostoses, correlations between and cognitive abilities will remain

speculative without further functional assessments of brain activity in SC patients.

The skull as a marker of raised ICP

Du Boulay together with other authors12,13,17,41,42 indicate that calvaria and skull base

thinning, erosion of the dorsum sellae, suture diastasis, and copper beaten skull can be indirect

signs in adults of a history of raised ICP.

Dorsum sellae erosion can be explained by a herniation of the arachnoid and subarachnoid

spaces through the infundibular hiatus of the sellar diaphragm due to the pulsatile pressure of

the cerebrospinal fluid (CSF), leading on the long term to sellar remodeling. This remodeling

leads to an ‘empty’ sellar appearance as the cavity is filled with CSF due to the herniation,

with the pituitary gland being squeezed on the sellar floor41.

Copper beaten skull is a more debated sign of raised ICP. The imprints on the internal table of

the calvaria could be the impressions of the gyri caused by to raised ICP, with bony bridges

between the imprints corresponding to the sulci43. Tuite et al.12 found in his study on 123

children with craniosynostosis that ICP was significatively higher when a diffuse copper

beaten skull was present in comparison with no marking or localized copper beaten aspect.

Agrawal et al.5, in his study on 48 patients, found a significantly higher frequency of clinical

signs of raised ICP in patients with copper beaten skull patients relative to controls.

Nevertheless, a series of 13 children with raised ICP reported by Sulong et al.43 had no cases

with copper beaten aspect.

Rabbani et al.17 assessed CT-scans of 58 patients with increased intra-cranial pressure in a

controlled study by computing the average bone thickness on a rectangular region of interest

on the temporal bone and reported a correlation between calvaria thinning and raised ICP.

Finally, Nikolova et al.15 highlighted the links between raised ICP, persistence of the metopic

suture and small frontal sinuses.

Raised ICP in scaphocephaly

The assessment of 21 adult skulls with scaphocephaly did not show significant signs in favor

of a history of raised ICP. Nevertheless, 5/21 in the SC group had 3-6 indirect signs of raised

ICP, showing that individual cases with sagittal synostosis may have raised ICP relative to

controls (of which 0/17 showed 3-6 indirect signs of raised ICP).

It is difficult to draw any definitive or straightforward clinically relevant conclusion from

these results, especially knowing that raised ICP is most probably an early phenomenon in

scaphocephaly, occurring before the age of 6 according to most authors7,8. Furthermore, it is

not known if bone stigma of early raised ICP persist in time or are progressively erased by

bone remodeling when intra-cranial pressure normalizes. However, 5/21 SC skulls in our

study showed signs in favor of a history of raised ICP at some – undetermined - point of their

clinical evolution. Dorsum sellae erosion and sella turcica lengthening were constant findings

in these 5/21 cases, and 4/5 of these cases had copper beaten skulls. Calvaria and skull base

thinning were only found in 2/5 cases. Even though our statistically negative results in a large

series of skulls with adult scaphocephaly tend to indicate that raised ICP is not a major

concern in this condition in formal terms, at least as a continuous phenomenon in adulthood,

the presence of individual cases (5/21) with reliable signs in favor of a phenomenon

potentially causing brain suffering support the functional conception of surgery in

scaphocephaly as long as definitive data on long-term cognition in this condition are not

available.
ACKNOWLEDGEMENT AND DISCLOSURES

Special thanks for Martin Friess and Philippe Mennecier for providing access to the

anthropological collections of the National Museum of Natural History (Paris, France). The

authors declare that they have no conflict of interest and no financial interest in relation to the

content of this article.

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Figure legends

Figure 1. 21 skulls with scaphocephaly from the anthropological collections of the National

Museum of Natural History (Paris, France).

Figure 2. Measurement of bone thickness above the left internal auditory canal on a coronal

CT-scan section. Yellow star: internal auditory canal; arrows: fallopian canal.
Figure 3. Sella turcica length measured on the mid-sagittal plane of a CT scan. Presence of

dorsum sellae erosion.

Figure 4. Copper beaten skull (arrows) on the inner aspect of the vault. A: horizontal section;

B: coronal section.

Figure 5. Average cortical and skull thickness values for scaphocephaly and controls.
Table legends

Table 1. Morphological characteristics of skulls with sagittal craniosynostosis and controls.

SC: Sagittal Craniosynostosis; FNA: Fronto-Nasal Angle; CB: Copper Beaten skull.

Quantitative variates SC group Control group

Volume (cm3) 1362 +/- 145 1337 +/- 141
Skull length (cm) 19.4 +/- 1.3 16.9 +/- 0.6
Skull width (cm) 11.8 +/- 0.8 14.0 +/- 0.8
Cranial index 1.7 +/- 0.2 1.2 +/- 0.1
Head circumference (cm) 52.5 +/- 2.5 49.4 +/- 2.0
Interzygomatic distance (cm) 10.3 +/- 0.8 11.2 +/- 0.6
Thnikness at the lambda-inion highpoint (mm) 7.7 +/- 2.3 6.4 +/- 1.7
Thickness at metopion (mm) 9.8 +/- 3.0 8.4 +/- 2.5
Thickness at vertex (mm) 6.3 +/- 1.8 6.5 +/- 1.1
Thickness in the center of the parietal bone (mm) 3.8 +/- 1.3 4.8 +/- 1.2
Skullbase thickness (mm) 3.4 +/- 1.3 4.3 +/- 1.1
Sellar length (mm) 14.3 +/- 3.9 12.3 +/- 1.6
FNA (°) 115.4 +/- 19.4 129.3 +/- 12.4
Qualitative variates SC group Control group
Frontal sinus 33/42 (79%) 27/34 (79%)
Dorsum sellar erosion 9/21 (43%) 4/17 (24%)
Suture diastasis 3/21 (14%) 0/17 (0%)
Open metopic 0/21 (0%) 1/17 (6%)
CB pattern 9/21 (43%) 4/17 (24%)
CB frontal 2/21 (10%) 2/17 (12%)
CB parietal 2/21 (10%) 1/17 (6%)
CB temporal 1/21 (5%) 1/17 (6%)
CB diffuse 4/21 (19%) 0/17 (0%)
Table 2. Multivariate assessment of the prevalence of indirect signs of raised intra-cranial
pressure in adult skull with sagittal craniosynostosis relative to controls. For instance, head
circumference was on average 3.167 +/- 0.734 cm greater in patients with scaphocephaly, and
this difference was statistically significant (p<0.001). Patients with scaphocephaly had a 2.438
[0.617; 11.00] increased risk of dorsum sellae erosion compared to control patients, but this
difference was not significant (p = 0.217). Sd: Standard Deviation; FNA: Fronto-Nasal Angle;
CB: Copper Beaten skull; NC: Non-Conclusive.

Quantitative variates Estimate Sd p value

Volume (cm3) + 25.41 46.70 0.590
Skull length (cm) + 2.658 0.346 < 0.001
Skull width (cm) - 2.249 0.258 < 0.001
Cranial index + 0.458 0.042 < 0.001
Head circumference (cm) + 3.167 0.734 < 0.001
Interzygomatic distance (cm) - 0.919 0.232 < 0.001
Thnikness at the lambda-inion highpoint (mm) + 1.289 0.671 0.062
Thickness at metopion (mm) + 1.328 0.911 0.154
Thickness at vertex (mm) - 0.256 0.501 0.613
Thickness in the center of the parietal bone (mm) - 0.287 0.470 0.545
Skullbase thickness (mm) - 0.886 0.371 0.022
Sellar length (mm) + 1.940 1.021 0.066
FNA (°) - 13.94 5.441 0.015
Qualitative variates OR IC 95 % p value
Frontal sinus 0.789 [0.128; 4.875] 0.806
Dorsum sellar erosion 2.438 [0.617; 11.00] 0.217
Suture diastasis NC NC NC
Open metopic NC NC NC
CB pattern 2.438 [0.617; 11.00] 0.217
CB frontal 1.684 [0.148; 38.23] 0.682
CB parietal 1.684 [0.148; 38.23] 0.682
CB temporal 0.800 [0.030; 21.30] 0.878
CB diffuse NC NC NC
Table 3. Assessment of raised intra-cranial pressure in individual skulls with scaphocephaly
with more than 3 co-occurring indirect signs.
Skull SC Skull SC Skull SC Skull SC Skull SC
№1 №2 №3 №4 №5
Calvaria and skull base thinning - X - - X
Copper beaten skull X - X X X
Suture diastasis - - - - -
Dorsum sellae erosion X X X X X
Sella turcica lengthening X X X X X
Small frontal sinuses and persistent X X - - -
metopic suture