Child's Nervous System (2019) 35:1459–1465 https://doi.org/10.1007/s00381-019-04193-1 FOCUS SESSION The growth of the neurocranium: literature review and implications in cranial repair Paolo Frassanito1 & Federico Bianchi1 & Giovanni Pennisi 2 & Luca Massimi2 & Gianpiero Tamburrini2 & Massimo Caldarelli2 Received: 4 April 2019 /Accepted: 1 May 2019 /Published online: 14 May 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Background Postnatal growth of neurocranium is prevalently completed in the first years of life, thus deeply affecting the clinical presentation and surgical management of pediatric neurosurgical conditions involving the skull. This paper aims to review the pertinent literature on the normal growth of neurocranium and critically discuss the surgical implications of this factor in cranial repair. Methods A search of the electronic database of Pubmed was performed, using the key word Bneurocranium growth^,thus obtaining 217 results. Forty-six papers dealing with this topic in humans, limited to the English language, were selected. After excluding a few papers dealing with viscerocranium growth or pathological conditions not related to normal neurocranium growth 18 papers were finally included into the present review. Results and conclusions The skull growth is very rapid in the first 2 years of life and approximates the adult volume by 7 years of age, with minimal further growth later on, which is warranted by the remodeling of the cranial bones. This factor affects the outcome of cranioplasty. Thus, it is essential to consider age in the planning phase of cranial repair, choice of the material, and critical comparison of results of different cranioplasty solutions. Keywords Cranial growth . Cranial repair . Cranioplasty . Neurocranium . Precision medicine . Skull growth Introduction of this factor in cranial repair. On these grounds, the biochem- ical mechanisms involved in cranial growth go beyond the The knowledge of the postnatal growth mechanisms of purpose of this review and would be not discussed. neurocranium started with anatomical studies and significant- ly evolved with the readiness of radiological imaging modal- ities. Although the prevalent growth of the skull in the first Literature review years of life is obviously understood and is confirmed by ex vivo and in vivo radiological data, the clinical and surgical Methods implications are frequently under-recognized or completely disregarded. A search of the electronic database of PubMed using the key The aim of this paper is to thoroughly review the pertinent word Bneurocranium growth^ was performed, thus obtaining literature on the physiological volumetric growth of 217 results. We then applied a series of filters (human, neurocranium and critically discuss the surgical implications English, and childbirth to 18 years) to refine the aforemen- tioned research, thus selecting 46 papers. Papers dealing with viscerocranium growth or pathological conditions not related * Paolo Frassanito to normal neurocranium growth were excluded. Finally, 18 [email protected] papers were included in the present review. 1 Pediatric Neurosurgery, Fondazione Policlinico Universitario A. Cranial growth Gemelli IRCCS, Largo Agostino Gemelli, 8, 00168 Rome, Italy 2 Pediatric Neurosurgery, Fondazione Policlinico Universitario A. The neurocranium can be divided into the cranial base, also Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy known as the chondrocranium, which refers to the cranial base 1460 Childs Nerv Syst (2019) 35:1459–1465 bones that originate from the paraxial mesoderm and undergo These signals stimulate osteoclasts to break down the inte- endochondral ossification, and the cranial vault, which is also rior of the cranial element in order to provide more room for known as the membranous cranium or calvaria [28]. the growing brain. As a direct reaction to the destruction of the The calvarial bones are connected together around their inner surface of the bone, osteoblasts on the ectocranial sur- periphery by sutures that are bands of fibrous connective tis- face activate and begin laying down new bone on the exterior sue that prevent premature bone fusion and are important new surface of the element. This corresponding action of destruc- bone deposition sites that allow for uniform growth of the tion and construction upon the cranial elements, due to the cranium during brain development. pressure exerted by the brain, causes a direct correlation be- As the cerebral and cerebellar hemispheres grow, the tween the size and shape of the brain to the size and shape of calvarial bones are displaced outward, by expanding intracra- the cranial vault, as the skull is essentially formed and molded nial structures. In fact, each flat bone is suspended, with the by the increase of brain tissue. With the human brain having existent traction forces, within a widespread sling of the col- such a close developmental correlation to the cranial vault, it lagenous fibers of the enlarging inner (meningeal) and outer has been shown that the inverse relationship between the cra- (cutaneous) periosteal layers. As these membranes grow in an nial vault and the brain is comparable. This parallel growth ectocranial direction ahead of the expanding brain, the bones allows for the possibility to measure the external dimensions are carried with them and thus displaced (Fig. 1). of the cranium and extrapolate the interior volume of the brain It is widely accepted that various genetic and epigenetic in physiological conditions. factors regulate bone formation at the sutures, with one of During the early years of life, human brain volume in- the key driving factors for skull growth being provided by creases rapidly and the cranium undergoes rapid morpholog- the rapidly expanding brain, through the mechanical tension ical changes in both size and shape, with the neurocranium in exerted on the immature dura mater. Indeed, the dura mater is particular required to expand to provide protection for the considered the main regulator of osteogenesis, by producing brain. signaling and growing factors [9]. Fig. 1 The complex osteodural structure of the neurocranium with large When brain growth is completed, the tension on the dura mater stops, and patent sutures and fontanelles in the first months of life (left), thus resulting in closure of the fontanelles and sutures (right). See text for accounting for growth of the calvarium with outward displacement of further details the cranial bones and progressive bone deposition at the suture site. Childs Nerv Syst (2019) 35:1459–1465 1461 Indeed, the neurocranium is normally estimated to be 25% Technological evolution has allowed assessing these pa- of its adult size by birth, 50% by 6 months, 65% by 1 year, and rameters more easily and accurately by means of sophisticated 90% by 7 years, with minimal further growth after 10 years measurement instruments, such as optical scanners and [15]. Variability of volume estimation at birth, ranging from stereophotography. 23 to 40%, has been reported through the literature. This may On the other hand, the introduction of CT scan and MRI be partly due to the deformation and compression of the head offered the possibility to evaluate in vivo the intracranial com- related to the delivery, though this picture is estimated to solve partment and calculate the intracranial volume by cross- spontaneously within a few days after birth. Indeed, over- sectional methods, such as the less accurate point-counting riding of cranial sutures after delivery is a common finding method and the more evolved planimetry method [19, 24]. in daily clinical practice as well as the possibility of significant difference in head circumference between the mea- Craniometric data surement at birth and at discharge, due to the rapid resolution of this picture. In one of the first craniometric studies, assessing the growth of On the other side, variability at elder age may be observed the skull in the pediatric age, Lichtenberg measured widths, through the literature studies according to the different methods lengths, and heights from plain radiographs of the head of 226 used to estimate the volume (anthropometric or cephalometric French children aged up to 8 years. He used MacKinnon’s versus more modern cross-sectional radiological methods). formula to calculate the intracranial volume. Mean intracranial However, the trend of growth observed by different studies seems volume stops its growth by the seventh year of age [1]. constant. The postnatal growth of the calvarium proceeds very Another study assessed skull growth beyond pediatric age, rapidly during the first 2 years, particularly in the first year of age, including 1058 Caucasian subjects, 555 males and 503 fe- and is followed by a much slower growth rate until approximately males in 20 consecutive age groups from 7 days to 20 years the seventh year when the skull approaches adult size. of age. They were evaluated by measuring linear craniometric The rapid cranial growth in the first years of life is well parameters using manual instrumentation (the measuring in- represented by the Center for Disease Control and Prevention struments consisted of a metric linen spring tape graduated in (CDC) growth charts [27]. Indeed, the growth of occipito- millimeters, the spreading and sliding calipers of Hrdlitka, and frontal circumference (OFC) parallels the growth of the cal- a Western Reserve scepter) and calculating the cranial volume varium. In