UNIVERSITY OF OULU P .O. Box 8000 F I -90014 UNIVERSITY OF OULU FINLAND
A C T A U N I V E R S I T A T I S O U L U E N S I S
University Lecturer Tuomo Glumoff
University Lecturer Santeri Palviainen
Postdoctoral research fellow Sanna Taskila
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Planning Director Pertti Tikkanen
Professor Jari Juga
University Lecturer Anu Soikkeli
Professor Olli Vuolteenaho
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ISBN 978-952-62-1653-9 (Paperback)ISBN 978-952-62-1654-6 (PDF)ISSN 0355-3221 (Print)ISSN 1796-2234 (Online)
U N I V E R S I TAT I S O U L U E N S I S
MEDICA
ACTAD
D 1428
AC
TAN
iina Salokorpi
OULU 2017
D 1428
Niina Salokorpi
TREATMENT OF CRANIOSYNOSTOSES
UNIVERSITY OF OULU GRADUATE SCHOOL;FACULTY OF MEDICINE;MEDICAL RESEARCH CENTRE OULU;OULU UNIVERSITY HOSPITAL
ACTA UNIVERS ITAT I S OULUENS I SD M e d i c a 1 4 2 8
NIINA SALOKORPI
TREATMENT OF CRANIOSYNOSTOSES
Academic dissertation to be presented with the assentof the Doctoral Training Committee of Health andBiosciences of the University of Oulu for public defencein Auditorium 12 of the Department of Paediatrics, on10 November 2017, at 12 noon
UNIVERSITY OF OULU, OULU 2017
Copyright © 2017Acta Univ. Oul. D 1428, 2017
Supervised byProfessor Willy SerloProfessor Pertti Pirttiniemi
Reviewed byProfessor Federico DiRoccoDocent Arto Immonen
ISBN 978-952-62-1653-9 (Paperback)ISBN 978-952-62-1654-6 (PDF)
ISSN 0355-3221 (Printed)ISSN 1796-2234 (Online)
Cover DesignRaimo Ahonen
JUVENES PRINTTAMPERE 2017
OpponentDocent Junnu Leikola
Salokorpi, Niina, Treatment of craniosynostoses. University of Oulu Graduate School; University of Oulu, Faculty of Medicine; MedicalResearch Centre Oulu; Oulu University HospitalActa Univ. Oul. D 1428, 2017University of Oulu, P.O. Box 8000, FI-90014 University of Oulu, Finland
Abstract
This work evaluated the safety and effectiveness of operative techniques used in cranioplasticsurgery and outcomes of these surgical methods.
In study I the feasibility of endocranial fixation in frontal remodeling surgery for metopic andcoronal synostosis was established. Good to excellent aesthetic results were seen in 96% of casesevaluated by a surgeon at the time of follow-up. Three patients out of 27 had complicationsrequiring revisions. No mortality or permanent morbidity, nor complications related toendocranial placement of the plates were seen. Thus it was verified that placing resorbablematerial intracranially reduces the aesthetic impact without hindering the final result.
Study II found that posterior cranial vault distraction procedures produced a mean increase of25% in intracranial volume. This proved to be an effective technique for treating a variety ofcraniosynostosis with significant shortage of intracranial volume. 3D photogrammetric imagingwas found to be a suitable non-ionizing method for evaluation of cranial volume increasefollowing distraction. In study III a new tool was developed and successfully used for theintraoperative guidance of distractor device placement to ensure congruent vectors and thusreduced complications of these surgical procedures.
In study IV long-term functional and aesthetic outcomes of the surgical treatment for sagittalsynostoses in patients reaching adulthood was examined. The mean follow-up time was 26.5 yearsand the patients were 18 to 41 years old at the time of follow-up. The patients treated for sagittalsynostosis were equally satisfied with their facial appearance as were their age and gendermatched controls. Independent panels found patients’ appearance to be slightly less attractive, butthe difference was less than 10 mm on a 100 mm Visual Analogue Scale, representing a lowclinical significance. Patients’ socioeconomic situation such as education, housing, employmentand marital status equaled controls with similar frequencies of headaches, mental problems orhealth issues as the controls.
Keywords: 3D photogrammetric imaging, cranioplasty, craniosynostosis, distraction,facial aesthetics, intracranial volume, outcome, resorbable plates
Salokorpi, Niina, Kraniosynostoosien hoito. Oulun yliopiston tutkijakoulu; Oulun yliopisto, Lääketieteellinen tiedekunta; Medical ResearchCentre Oulu; Oulun yliopistollinen sairaalaActa Univ. Oul. D 1428, 2017Oulun yliopisto, PL 8000, 90014 Oulun yliopisto
Tiivistelmä
Tässä tutkimuksessa selvitettiin kallon saumojen ennenaikaisen luutumisen (kraniosynostoosi)leikkausmenetelmien tehokkuutta ja turvallisuutta sekä pitkäaikaisia tuloksia.
Leikkausmenetelmä, jossa epämuotoinen kallo uudelleenmuotoillaan ja luiset osat kiinnite-tään toisiinsa kallon sisäpuolelle asennettavilla ja kudokseen hajoavilla levyillä oli tehokas jaluotettava (N=27). Jälkitarkastuksessa tulos arvioitiin erinomaiseksi tai hyväksi 96 %:lla tapauk-sista. Leikkaushoitoa vaativia ongelmia tai komplikaatioita esiintyi kolmella, mutta pysyväähaittaa ei jäänyt. Komplikaatiot eivät johtuneet levyjen sijainnista kallon sisällä.
Saumojen ennenaikaisesta luutumisesta johtuvaa kallon tilavuuden alenemaa hoidettiin veny-tyshoidolla (N=30). Menetelmällä saavutettiin keskimäärin 25 %:n lisääntyminen tilavuudessa,ja se soveltuukin erityisen hyvin potilaille, joilla tarvitaan suuri tilavuuden lisääntyminen. Leik-kaustekniikkaan ei liittynyt isoja komplikaatioita. Tulosta arvioitiin osalla potilaista kolmiulot-teisella valokuvauksella, joka perinteisistä seurantamenetelmistä poiketen ei altista ionisoivallesäteilylle, ja se osoittautui käyttökelpoiseksi seurantamenetelmäksi.
Venytyshoitoa varten kallon pintaan kiinnitettävät pidennyslaitteet tulee asettaa yhdensuun-taisesti, ja se on teknisesti haasteellista. Työssä kehitettiin kirurginen instrumentti, jolla venytti-met voidaan luotettavammin asetella samansuuntaisiksi. Uusi tekniikka ehkäisee mekaanisiaongelmia, joita muuten voisi ilmetä erisuuntaisten venyttimien välillä pidennyksen edetessä.
Lapsuudessa venekallon johdosta leikattujen potilaiden (N=40) pitkäaikaiset hoitotuloksetsekä selviytyminen elämässä 26.5 vuoden seuranta-ajan jälkeen olivat hyviä. Heidän taloudelli-nen ja sosiaalinen tilanne (koulutus, asumismuoto, työllistyminen, siviilisääty ym.) ei eronnutikä- ja sukupuolivakioitujen vertailuhenkilöiden (N=40) tilanteesta. Yleisessä terveydentilassa,päänsärkyjen esiintymisessä ja mielenterveysongelmissa ei ollut eroa. Potilaiden tyytyväisyysomaan ulkonäköönsä oli samankaltainen kuin vertailuhenkilöillä. Ulkopuolisen asiantuntijapa-neelin tekemän arvion perusteella potilaiden kasvojen ulkonäkö oli vähemmän miellyttävä kuinvertailuhenkilöillä, mutta ero oli vähäinen (<10 % ero visual analogue scale, VAS, asteikolla).Asiantuntijapaneeli teki arvionsa tietämättä onko arvioitava henkilö potilas vai vertailuhenkilö.
Asiasanat: 3D valokuvaus, biohajoavat levyt, distraktio, kallonsisäinen tilavuus,kranioplastia, kraniosynostoosi, pitkäaikainen seuranta, ulkonäkö
To my family
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Acknowledgements
This study was carried out at the departments of paediatric surgery and neurosurgery, University of Oulu.
First of all, my deepest gratitude goes to my supervisor, Professor Willy Serlo, M.D., Ph.D., Head of the Department of Paediatric Surgery, Oulu University Hospital, for this opportunity to work and learn under his guidance. He introduced me to this subject and pediatric neurosurgery in general. His endless enthusiasm to acquire and teach new knowledge never ceased to impress me. Thanks also for introducing me to this study group and to the pediatric neurosurgery community as well as for good companionship on the many trips we made. Without his guidance, fatherly support and help this dissertation would not have been possible. My sincere gratitude also goes to my other supervisor, Professor Pertti Pirttiniemi, D.D.S., Ph.D., for all the time and support you gave me. I am truly indebted to Professor György K. Sándor, D.D.S., M.D., Ph.D. who made enormous work with this study including revising the language of the thesis and original publications, and who has always been kind and supportive to me.
I am grateful to docent Juha-Jaakko Sinikumpu, M.D., Ph.D., for his excellent writing skills and valuable comments during the whole process and to Tuula Savolainen, D.D.S., for her friendship and for her great contribution to collecting the data. I am truly thankful to Kaisu Serlo, for her exceptional helpfulness and empathy in the out-patient clinics and for her great work as a research nurse, who made the long-term follow-up study happen. I also want to thank Tarmo Areda, M.D., Ph.D., Heleia Nestal Zibo, M.D., D.D.S., Tarja Iber, M.D. and Leena Ylikontiola, M.D., D.D.S., PhD for helping me to collect the data and write the articles. I am thankful to Leonid Satanin, M.D., C.Sc., and to Anna-Sofia Silvola, D.D.S., Ph.D., for all their support, advices and valuable comments. I am thankful to Pasi Ohtonen, M.Sc., for his patience in teaching me the principles of biostatistics.
I am grateful to Katrin Gross-Paju, M.D., Ph.D. and Professor Toomas Asser, M.D., Ph.D., Head of Neurosurgery Department, Tartu University Hospital, as well as to Professor John Koivukangas, M.D., Ph.D., and Sanna Yrjänä, M.Sc., Ph.D., for introducing the research work to me, for inspiring and supporting me.
I am thankful to Päivi Tapanainen, M.D., Ph.D., Head of the Division of Children and Adolescents, for her support and providing facilities in regard to the study. I owe my gratitude for arranging time for me to work on the thesis project to Susanna Yli-Luukko, M.D., Head of Division of Orthopedics and Neurosurgery and especially to docent Timo Kumpulainen, M.D., Ph.D., Head of the Department
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of Neurosurgery, also for an opportunity to work and learn neurosurgery and pediatric neurosurgery under his guidance. His unbeaten clinical expertise, operative skills, patience and empathy are exemplary.
I want to express my gratitude to the referees of the thesis Professor Federico DiRocco, M.D., Ph.D., and docent Arto Immonen, M.D., Ph.D., for their thorough review of the manuscript and for their constructive criticism and valuable advice, which substantially improved the quality of this manuscript.
I also want to thank my follow-up group: Professor Kyösti Oikarinen, D.D.S., Ph.D., Professor John Koivukangas, M.D., Ph.D., and docent Timo Kumpulainen M.D., Ph.D., for their time and experience.
The support of my present and past co-workers in the Department of Neurosurgery, Maija Lahtinen, M.D., Sami Tetri, M.D., Ph.D., Anna-Leena Heula, M.D., Juho Tuominen, M.D., Tatu Koskelainen, M.D., Mikko Kauppinen, M.D., Matti Heiskari, M.D., Ph.D., Hannu Rönty, M.D., Ph.D. and Professor Esa Heikkinen, M.D., Ph.D., as well as Mirva Nätynki, M.D., Cheng Qian, M.D., Miro Jänkälä, M.D., was invaluable to me during this work. I also express my gratitude to all the paediatric surgeons, paediatric aneasthesiologists and paediatric radiologists with whom I have been involved for their work. I want to express my gratitude to personnel of the paediatric operation department, the paediatric intensive care ward, the paediatric surgery out-patient clinics and the ward who have helped me in multiple ways over the years. Particular thanks go to Kaisa Rahko for her excellent illustrations and for her assistance during the operations.
I want to thank all the patients, lay persons and the dentists who have participated in this study and given their time. It is my hope that this study may help us to understand and help our patients better.
This study has been financially supported by VTR-grant from Oulu University Hospital, The Foundation for Pediatric Research, Finland, Alma and K. A. Snellman Foundation, Oulu, Finland. These grants are gratefully acknowledged.
I am thankful to my parents who not only have loved and encouraged me but also who have taught me to work hard with determination. I want to thank all my friends for being there for me.
This thesis is dedicated to the closest people of my life. I owe my loving thanks to my husband Jyrki, my daughter Emma and my step-daughters Karolina and Kamilla for the love and joy you have given me. Jyrki thanks for your constant love, support and understanding during all these years. I am so privileged to have you in my life.
29th August, 2017 Niina Salokorpi
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Abbreviations
3D three-dimensional
CI cephalic index
CT computer tomography
FGFR fibroblast growth factor receptors
ICP intracranial pressure
ICV intracranial volume
IQ Intelligence Quotient
MCID minimally clinically important difference
MSX2 homeobox containing gene
TWIST a basic helix-loop-helix transcriptor factor
OHIP Oral Health Impact Profile
OHIP-14 14-item Oral Health Impact Profile
MRI magnetic resonance imaging
PCVD posterior cranial vault distraction
PGA Polyglycolic acid
PLA polylactide/polylactic acid
PLLA poly-L-lactic acid
PLDA poly D,L-lactic acid
QOL Quality of Life
SD standard deviation
TMC trimethylene carbonate
VAS Visual Analogue Scale
WHO World Health Organization
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Original publications
This thesis is based on the following publications, which are referred throughout
the text by their Roman numerals:
I Salokorpi, N., Sinikumpu, JJ., Iber, T., Nestal Zibo, H., Areda, T., Ylikontiola, L., Sándor, G.K., Serlo, W. (2015). Frontal cranial modeling using endocranial resorbable plate fixation in 27 consecutive plagiocephaly and trigonocephaly patients. Childs Nerv Syst, 31(7), 1121-8.
II Salokorpi, N., Vuollo, V., Sinikumpu, JJ., Satanin, L., Nestal Zibo, H., Ylikontiola, L., Pirttiniemi, P., Sándor, G.K., Serlo, W. (2016). Increases in cranial volume with posterior cranial vault distraction in 31 consecutive cases. Neurosurgery, EPUB April 2017.
III Salokorpi, N., Sándor, G.K., Sinikumpu, JJ., Ylikontiola, L., Serlo, W. (2013). A new technique to facilitate optimal directions for cranial distractor implantation. Childs Nerv Syst, 29(8), 1359-61.
IV Salokorpi, N., Savolainen, T., Sinikumpu, JJ., Ylikontiola, L., Sándor, G.K., Pirttiniemi, P., Serlo, W. Outcomes of 40 nonsyndromic sagittal craniosynostosis patients as adults: A case-control study with 26.5 years of postoperative follow-up. Manuscript.
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Contents
Abstract
Tiivistelmä
Acknowledgements 9 Abbreviations 11 Original publications 13 Contents 15 1 Introduction 19 2 Review of the literature 21
2.1 Normal growth of the human skull ......................................................... 21 2.2 Definition and historical aspects of craniosynostoses ............................. 21 2.3 Pathology and genetics of craniosynostoses ........................................... 22 2.4 Epidemiology and classifications of craniosynostoses ........................... 24 2.5 Diagnostics .............................................................................................. 25 2.6 ICP measurement in craniosynostoses .................................................... 26 2.7 Neurodevelopmental aspects ................................................................... 27 2.8 Treatment of craniosynostoses ................................................................ 27
2.8.1 Evolution of surgical methods ...................................................... 28 2.8.2 Operative techniques for sagittal synostosis ................................. 30 2.8.3 Operative technique for metopic synostosis ................................. 30 2.8.4 Operative technique for plagiocephaly ......................................... 30 2.8.5 Fixation materials ......................................................................... 31 2.8.6 Distraction cranioplasties ............................................................. 32 2.8.7 Timing of the surgery ................................................................... 34 2.8.8 Secondary surgery ........................................................................ 34
2.9 Outcome of treatment .............................................................................. 35 2.9.1 Safety of cranioplastic surgery ..................................................... 36 2.9.2 Evaluation of postoperative craniofacial morphology .................. 37 2.9.3 Aesthetic considerations ............................................................... 38 2.9.4 Craniosynostosis patients as adults............................................... 40
3 Aims of the study 43 4 Subjects and methods 45
4.1 Subjects and controls .............................................................................. 45 4.2 Methods ................................................................................................... 48 4.3 Operative procedures (I, II, III, IV) ......................................................... 49 4.4 Distraction protocol (II) .......................................................................... 51
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4.5 Clinical examination (I, II, IV) ................................................................ 52 4.6 Evaluation of the volume gain (II) .......................................................... 52
4.6.1 Using plain cephalograms ............................................................ 52 4.6.2 Using 3D photogrammetric imaging ............................................ 53
4.7 Aesthetic evaluation using photographs (IV) .......................................... 54 4.7.1 The panel groups .......................................................................... 55 4.7.2 Evaluation by craniofacial surgeons ............................................. 56
4.8 Questionnaire (IV) .................................................................................. 56 4.9 Ethical issues ........................................................................................... 56 4.10 Statistical methods .................................................................................. 56
5 Results 59 5.1 Surgical duration and intraoperative blood loss (I, II and IV) ................. 59 5.2 Distraction guides (II, III) ....................................................................... 59 5.3 Distraction results (II) ............................................................................. 60
5.3.1 Volume gain measured from cephalograms (II)............................ 61 5.3.2 Volume gain measured from 3D photographs (II) ........................ 62
5.4 Aesthetic results ...................................................................................... 63 5.4.1 Evaluation by craniofacial surgeons at follow-up visits (I,
IV) ................................................................................................ 63 5.4.2 Evaluation by the craniofacial surgeons from the
photographs (IV) .......................................................................... 64 5.4.3 Evaluation by panels (IV) ............................................................. 65 5.4.4 Patients self-satisfaction with facial aesthetics (IV) ..................... 67 5.4.5 The effect of operative technique on aesthetic outcomes
(IV) ............................................................................................... 68 5.5 Surgical complications (I, II, IV) ............................................................ 69 5.6 Life situation, somatic and mental health at late follow-up (IV) ............. 70
5.6.1 Headaches and migraine ............................................................... 70 5.6.2 General somatic health ................................................................. 70 5.6.3 Mental health ................................................................................ 70 5.6.4 Family, socioeconomic status and education ................................ 71
6 Discussion 73 6.1 Methodological considerations ............................................................... 73 6.2 Surgical duration and bleeding (I, II, IV) ................................................ 75 6.3 Surgeons evaluation of postoperative results .......................................... 75 6.4 Outcomes of operations with endocranial placement of
resorbable plates ...................................................................................... 76
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6.5 Outcomes of posterior cranial vault distraction operations ..................... 77 6.5.1 Volume gain measurements and outcomes (II) ............................. 78
6.6 Complications and unforeseen events ..................................................... 79 6.6.1 Complications of operations with resorbable fixation (I) ............. 80 6.6.2 Complications of distraction operations (II) ................................. 80
6.7 Outcome of surgically treated patients with sagittal synostosis as
adults (IV) ............................................................................................... 81 6.7.1 Results of different operative methods (IV) ................................. 81 6.7.2 Aesthetic evaluation by participants and panels (IV) ................... 82 6.7.3 General life situation and health issues in patients treated
for sagittal synostoses (IV) ........................................................... 84 6.8 Clinical implications and future perspectives ......................................... 85
7 Conclusions 87 List of references 89 Original publications 105
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1 Introduction
Craniosynostosis is a congenital anomaly with premature closure of one or more
sutures between cranial bones, resulting in abnormal head growth and facial
dysmorphism (Flaherty, Singh, & Richtsmeier, 2016). Treatment of
craniosynostoses is surgical, with wide variety of techniques used depending on the
number and the location of prematurely ossified sutures. Suboptimal treatment
may result in cosmetic deformities, psychological, cognitive and developmental
sequelae in the later life (Bellew & Chumas, 2015; Blount, Louis, Tubbs, & Grant,
2007; Kapp-Simon et al., 2012; Speltz, Kapp-Simon, Cunningham, Marsh, &
Dawson, 2004).
In order to improve the quality and effectiveness of surgical treatment it is
important to evaluate the outcomes of surgery, not only from the surgeon’s point of
view, or by performing objective cephalometric measurements, but more
importantly by developing more patient-centered approaches. The present study
was undertaken to evaluate the results of different operative techniques used in
craniosynostosis treatment.
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2 Review of the literature
2.1 Normal growth of the human skull
The human skull is made up of nine bones forming the neocranium and 14 bones
forming facial skeleton. These bones articulate with one another by the means of
fibrous joints or sutures and synchondrosis (Beederman, Farina, & Reid, 2014; Rice,
2008). Sutures are made of two osteogenic fronts and a cellular mass of mitotic
mesenchymal cells, lying between dura mater and the ectoperiostal layer (Flaherty
et al., 2016). Cranial vault bones grow by new bone formation at the sutures and
by remodelling of their inner and outer surfaces to accommodate and fit the
growing brain (Flaherty et al., 2016; Opperman, 2000; Rice, 2008). Bone growth
sites at the sutures of the cranial vault remain dormant until stimulated to make
bone by external signals arising from the growing brain. Animal and in vitro
experiments show that dura mater participates in signalling and thus in determining
fusion or patency of the overlying sutures, especially in newly formed sutures.
More fully developed sutures are able to sustain themselves even in absence of dura
(Opperman, 2000). Signals from dura mater are mediated by different growth- and
transcription factors (transforming growth factor, fibroblast growth factor receptor,
TWIST, and MSX2) (Panchal & Uttchin, 2003). As a result of this tightly regulated
and balanced process of osteogenesis and bone remodelling, the skull grows
intensively to accommodate the growing brain especially during early childhood
with the intracranial volume reaching 77% of adult size by two years and with 90%
of the volume reached by the age of five years (Sgouros, Goldin, Hockley, Wake,
& Natarajan, 1999). While the metopic suture is the first suture to undergo
physiological fusion at approximately nine months of age, other sutures do not fully
close until adolescence or even later (Beederman et al., 2014; Cohen, 2005).
2.2 Definition and historical aspects of craniosynostoses
Craniosynostosis is a condition that involves premature fusion of one or more
cranial vault sutures causing significant alteration in craniofacial morphology and
has the potential for negative neurologic and cognitive effects (Flaherty et al.,
2016).
One of the first scientific descriptions of craniosynostosis was given by von
Sömmering, who published his book “Vom Baue des menschlichen Körpers” in
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1801. He described the structure of the sutures and recognized their primary
importance in skull growth, stating that premature fusion of a suture would
necessarily result in deformity of the head (Laitinen, 1956). Soon, in 1830 another
German anatomist Adolph Wilhelm Otto proposed that when the suture becomes
ossified, the marginal bony growth is arrested and this is compensated by growth
of the skull along another trajectory. Otto was also the first to describe the small
size of the head either by primarily defective brain or by premature fusion of the
sutures (Laitinen, 1956). Virchow further developed and popularised the ideas
proposed by Otto. He published a work were he defined Virchow’s law, stating that
in craniosynostoses skull deformities occur as a result of the cessation of growth
across a prematurely fused suture causing compensatory growth along patent
sutures in a direction parallel to the affected suture (Mehta, Bettegowda, Jallo, &
Ahn, 2010).
In 1866 the first clinical case of craniosynostosis was reported by von Graefe
(Laitinen, 1956). In the early 1900s French physicians Apert and Crouzon gave
their names to the first recognized complex syndromic craniosynostoses with
brachycephalic deformity (Mehta et al., 2010).
With a growing understanding of the role of sutures in skull growth and the
consequences of their premature ossification, the first steps towards the treatment
of craniosynostoses were warranted.
2.3 Pathology and genetics of craniosynostoses
Premature osseous obliteration of sutures leads to fusion of two bones across the
suture site. This prevents further bone formation at this site and redirects growth to
other patent sutures (Opperman, 2000), altering the global shape of the skull in a
predictable way (Fig. 1) (Flaherty et al., 2016). The head shape in craniosynostoses
depends on which sutures are prematurely fused, as well as the order and timing of
their ossification (Cohen, 2005).
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Fig. 1. Variation in cranial vault shape depicted by three-dimensional computed
tomography reconstructions of the infant skulls with different types of single-suture
craniosynostoses.
The fusion of the cranial sutures and maintenance of suture patency are dependent
on the interaction of a large number of cytokines, transcription factors (TWIST,
MSX2), growth factor receptors (FGFR-1, FGFR-2, FGFR-3), as well as molecules
of extracellular matrix. Different types of mutations in genes encoding these factors
have been found to be associated with syndromic forms of craniosynostoses
(Panchal & Uttchin, 2003).
While approximately 85% of craniosynostoses cases are not syndromic, by
August of 2017 the remaining 15% of craniosynostoses cases could be related to
over 200 known syndromes which have been found to be associated with
craniosynostoses. This number is growing continuously (McKusick, 2017). At least
half of the syndromic cases follow a Mendelian pattern of inheritance (Heuze,
Holmes, Peter, Richtsmeier, & Jabs, 2014).
Recently numerous rare gene mutations have been identified in some cases of
nonsyndromic craniosynostoses. They usually have incomplete penetrance, since
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sometimes family members carrying the mutations have been found to be
unaffected or to have craniofacial dysmorphism but not craniosynotosis (Heuze et
al., 2014).
2.4 Epidemiology and classifications of craniosynostoses
Craniosynostoses affects one in 2000-2500 live births worldwide. This estimate is
related to the number of patients that are treated surgically. When considering the
possible undiagnosed cases this number could be much higher (Hunter & Rudd,
1976; Lajeunie, Le Merrer, Bonaiti-Pellie, Marchac, & Renier, 1995; Mehta et al.,
2010; Singer, Bower, Southall, & Goldblatt, 1999). Thus craniosynostoses are the
second most common group of craniofacial anomalies after orofacial clefts
(Flaherty et al., 2016).
Craniosynostoses can be classified in many ways. They can be divided in
syndromic or non-syndromic, single or multiple suture synostoses, primary (caused
by an intrinsic defect in the suture) or secondary synostosis (caused by another
medical condition). Both syndromic and non-syndromic craniosynostoses can
present with a single suture involvement or with complex premature fusion of
multiple sutures.
Single suture involvement is more common, comprising up 85 – 90% of all
craniosynostoses. The most commonly affected suture is the sagittal suture,
followed by the metopic and coronal sutures (Kolar, 2011; Singer et al., 1999).
Isolated premature fusion of the lambdoid suture is very rare (Kolar, 2011; Wilkie,
2000).
Syndromic craniosynostoses comprise approximately 10 – 15% of
craniosynostoses (Heuze et al., 2014). They are generalized disorders of
mesenchymal development that often harbour other anomalies (dysmorphic
features or developmental defects). The occurrence depends on the type of
syndrome. For example, Muenke syndrome, the most common form of syndromic
craniosynostoses, has an incidence of 1 in 30,000 births, while Apert syndrome has
an incidence of 15 in 1,000,000 births (Agochukwu, Solomon, & Muenke, 2012).
Premature fusion of the sagittal suture causes a scaphocephalic head shape due
to diminished skull height and width with compensatory anteroposterior growth
(Fearon, 2014). It is the most common type of craniosynostoses, accounting for 40
to 60% of all synostoses with a birth prevalence ranging from approximately 1.8 to
2.5 in 10,000 live births (Di Rocco, Arnaud, & Renier, 2009; Kimonis, Gold,
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Hoffman, Panchal, & Boyadjiev, 2007; Kolar, 2011; Lajeunie, Le Merrer, Bonaiti-
Pellie, Marchac, & Renier, 1996).
Premature closure of the metopic suture is called trigonocephaly due to lateral
growth restriction of the frontal bones and increased posterior width of the skull
(van der Meulen, 2012). The incidence of trigonocephaly has been reported to
range from 1 in 700 (Alderman et al., 1988) to 1 in 15,000 births (Lajeunie, Le
Merrer, Marchac, & Renier, 1998). Recent reports have noted that its incidence has
increased up to 28% of all non-syndromic craniosynostoses (Kolar, 2011; van der
Meulen et al., 2009).
Plagiocephaly is a term applied to anterior and posterior flattening/bossing of
the skull that can be unilateral or bilateral. Anterior or frontal plagiocephaly is
usually caused by premature occlusion of the coronal sutures and posterior
plagiocephaly is caused by ossification of the lambdoid suture. Asymmetry caused
by outer forces with no premature ossified sutures is called positional
plagiocephaly (Cohen, 2005). Premature ossification of the coronal sutures is seen
in approximately 24% of patients with craniosynostosis (Kolar, 2011).
2.5 Diagnostics
In the majority of cases, an anomalous skull (and face) shape awakens the suspicion
for craniosynostosis. In many syndromic cases and in some single suture synostoses
the presence of some dysmorphic traits and abnormal head shape becomes apparent
immediately after birth (Fearon, 2014; Schweitzer et al., 2012). The diagnosis is
clinical. However, most authors recommend radiographic imaging for further
diagnostics, with 3 dimensional CT imaging being a gold standard for diagnosing
craniosynostoses (Fearon, 2014). Due to the potential negative effects of ionizing
radiation in children, including possible developmental delay and increased risk of
neoplasia in later life, alternative diagnostic protocols have been proposed
(Schweitzer et al., 2012). Physical examination is highly accurate in the diagnosis
of single suture synostoses patients (Fearon, 2014; Schweitzer et al., 2012).
Ultrasound of the sutures can be a useful tool with infants in the hands of
experienced radiologists (Regelsberger et al., 2006; Soboleski et al., 1998). Plain skull X-rays add valuable information on suture condition, typical
secondary deformations of the skull and molding of the inner surface of the skull, with a very low radiation dose and no need of sedation (Schweitzer et al., 2015).
For complex and syndromic synostoses three-dimensional skull CT remains necessary for precise diagnosis and preoperative planning (de Jong et al., 2010).
26
With growing knowledge about possible intracranial pathologies associated with complex synostoses, brain MRI is becoming a part of preoperative screening. It also allows identification of Chiari I malformations if present and whether it needs to be addressed during the surgery (Cinalli et al., 2005). When planning surgery especially involving the posterior cranial vault in syndromic cases, brain MRI and MR-angiography is highly recommended to identify anatomical variations of the venous system (Cinalli et al., 2005; Thompson, Hayward, & Jones, 1995).
Additional functional studies may be warranted in the diagnostic evaluation. They include ICP measurement, polysomnography for cases with complaints suggestive of obstructive sleep apnea, ophthalmological, otolaryngological and audiological evaluations (de Jong et al., 2010).
Genetic testing is a compulsory part of the diagnostic workup in all cases when a syndromic craniosynostosis is suspected (Agochukwu et al., 2012; de Jong et al., 2010).
2.6 ICP measurement in craniosynostoses
Since the growing brain experiences compression when a suture closes prematurely,
children with craniosynostoses, especially multi-suture ones, carry a risk for
developing elevated intracranial pressure (ICP) (Renier, Sainte-Rose, Marchac, &
Hirsch, 1982). Increased ICP is most often found in cases of multi-suture
craniosynostoses (Renier et al., 1982). In patients with craniofacial syndromes like
Apert, Crouzon, Pfeifer and Saethre-Chotzen, the increase in ICP may be found in
33% to 87.5% of patients according to different studies (Bannink et al., 2008; de
Jong et al., 2010; Marucci, Dunaway, Jones, & Hayward, 2008; Tamburrini,
Caldarelli, Massimi, Santini, & Di Rocco, 2005). The long-term consequences of
constantly elevated intracranial pressure may lead to cognitive impairment, visual
impairment, headaches, emesis, irritability, and altered mental status (Blount et al.,
2007). However, the normal range of physiological variations in ICP remains
unclear. Also reduced intracranial volume by itself has not been found to predict
increased ICP (Gault, Renier, Marchac, & Jones, 1992). In addition to the above-
mentioned problems, it is also difficult to compare the results of the different
studies on ICP, due to a wide variety of the methods used to measure ICP
(Tamburrini et al., 2005). Thus the value of ICP recording in craniosynostosis
patients remains unclear (Slater et al., 2008).
27
2.7 Neurodevelopmental aspects
In cases of syndromic craniosynostoses, neurodevelopmental disturbances are
common, especially in individuals with Apert and some types of Pfeiffer syndrome
(Agochukwu et al., 2012).
In spite of previous assumptions, children with single suture non-syndromic
craniosynostoses may also present with mild cognitive, behavioural and speech
disturbances, that are found during tasks that are more challenging, particularly in
children approaching school age (Becker et al., 2005; Kapp-Simon, Speltz,
Cunningham, Patel, & Tomita, 2007). For example, in a Finnish study including 61
children with non-syndromic single suture craniosynostoses or deformational
posterior plagiocephaly, one half of the subjects demonstrated slight or severe
defects in early language acquisition. The prevalence of severe language defects
was three times higher than in the general Finnish population (Korpilahti, Saarinen,
& Hukki, 2012). In another study by Starr and associates, three-year old children
with single suture craniosynostoses gained lower scores on neurodevelopmental
assessments than did a control group of non-synostotic children (Starr et al., 2012).
One explanation for the presence of neurodevelopmental anomalies in non-
syndromic craniosynostoses is that there is a primary anomaly of the brain itself,
which might be specific for each type of craniosynostoses. Aldridge and associates
have shown that the organization of the brain in single suture craniosynostoses is
dysmorphic, with cortical and subcortical dysmorphology (Aldridge, Marsh,
Govier, & Richtsmeier, 2002). They also demonstrated that in spite of restoration
of the shape of the brain as a result of operative treatment, differences in subcortical
morphology remained (Aldridge et al., 2002; Aldridge et al., 2005).
Craniosynostoses have a secondary psychosocial effect. Some patients retain
dysmorphic facies that might attract unfavourable attention from strangers and
peers. Antisocial, withdrawal, or even aggressive behaviour, poor school
performance and difficulty in an educational environment could be responses to
peer rejection (Becker et al., 2005).
2.8 Treatment of craniosynostoses
Since the first operative technique for treatment of craniosynostoses was described
by the French surgeon Lannelongue in 1890 (Bir, Ambekar, Notarianni, & Nanda,
2014), a variety of techniques have been developed.
28
There is little evidence for optimal treatment of craniosynostoses. The choice
of technique depends on the patient age, type of pathology, experience and
philosophy of treatment that rules in the particular institution (Szpalski, Weichman,
Sagebin, & Warren, 2011).
Surgery for craniosynostoses has two major aims: to provide sufficient
intracranial volume for the brain to grow and develop normally and, second, to
normalize head shape and facial appearance (Hankinson, Fontana, Anderson, &
Feldstein, 2010; Szpalski et al., 2011). Operative techniques and their benefits
compared to each other are currently an area of active research.
2.8.1 Evolution of surgical methods
In the beginning of the surgical era, Virchow’s work had a great impact on
development of craniosynostosis surgery since the first attempts to treat
craniosynostoses were based on his theory (Mehta et al., 2010).
The first publication on the technique of craniosynostosis surgery was
published in 1890 by the French surgeon Lannelongue who described a releasing
technique, with cutting craniectomy lines along the margins of the fused sagittal
suture, leaving the suture itself intact (Fig. 2A) (Bir et al., 2014; Clayman, Murad,
Steele, Seagle, & Pincus, 2007). Two years later Lane from San Francisco
described the first strip craniectomy of the fused suture itself (Fig. 2B) (Clayman
et al., 2007).
Success of the first craniectomy procedures was rather questionable due to lack
of distinction between microcephaly caused by incapacity of brain to grow and true
craniostenosis, as well as due to the timing of the operations in the course of the
disease (Mehta et al., 2010). In 1894 Jacobi reviewed a series of 33 children treated
with craniectomy and found a high mortality rate (15 children died). After public
denouncement of these practices at a meeting of the American Academy of
Pediatrics, craniosynostosis surgery was abandoned for nearly 30 years (Mehta et
al., 2010).
29
Fig. 2. Different operative techniques for sagittal synostosis. A. The Lannelongue and
Ingraham “unlocking” suture technique with and without silicone membrane. B. Lane
strip-craniectomy of the suture, C. Modern “H” – technique with and without additional
cuts to the temporal bone. Illustration by Kaisa Rahko.
In 1920th several studies (by Mehner, Faber and Towne) were published, reporting
resection of the ossified suture as a causal treatment for craniosynostoses (Faber,
1962; Laitinen, 1956). Since their results were much better, it inspired further work
on this field. The next technique was proposed by Ingraham who suggested
covering of the craniectomy margins with a plastic film to prevent re-ossification
(Ingraham, Alexander, & Matson, 1948; Laitinen, 1956). Fat tissue was used for
same purpose (Merikanto, Alhopuro, & Ritsila, 1987).
In 1977 van der Werf published a method of dural split with dural outer layer
dissected, turned over the osteotomy edge and sutured over the outer periosteum
done in an attempt to prevent recurrence (van der Werf, 1977).
Meanwhile Moss in 1959 proposed that suturectomy alone did not restore
normal calvarial development, but that a complex calvarial procedure was
necessary to allow proper growth and expansion of the cranium (Pagnoni et al.,
2014). This was followed by the pioneering work of French surgeon Paul Tessier,
who described methods of facial osteotomy in patients with Crouzon syndrome
(Tessier, Guiot, Rougerie, Delbet, & Pastoriza, 1967). Rougerie et al published in
1971 an article about extensive remodelling surgical technique and brought
attention to cosmetic aspects (Rougerie, Derome, & Anquez, 1972). That was the
beginning of the modern era of the surgical treatment of craniosynostoses.
30
2.8.2 Operative techniques for sagittal synostosis
The operative correction of sagittal synostosis, the most frequent type of
craniosynostoses, is generally performed before the age of six months (Pagnoni et
al., 2014). Modern surgical techniques vary from different cranial remodelling
techniques, for example, Renier’s “H” technique (Fig. 2C) (Di Rocco, Knoll et al.,
2012) or pi-procedure (Greene & Winston, 1988) to endoscopic strip craniectomies
with postoperative moulding therapy with helmets (Berry-Candelario, Ridgway,
Grondin, Rogers, & Proctor, 2011; Clayman et al., 2007) or spring-assisted
correction (M. L. van Veelen & Mathijssen, 2012; Windh, Davis, Sanger, Sahlin,
& Lauritzen, 2008).
2.8.3 Operative technique for metopic synostosis
Operative techniques for trigonocephaly developed from the strip craniectomy to
“floating forehead technique” with remodelling of the supra-orbital bandeau (D.
Marchac, Cophignon, Hirsch, & Renier, 1978). Nowadays there exists a variety of
techniques of the frontal bone remodelling with or without releasing of the
supraorbital bar (Aryan et al., 2005; Di Rocco, Arnaud et al., 2012). Also spring-
assisted surgery (Maltese, Tarnow, & Lauritzen, 2007) and endoscopic-assisted
treatment (Hinojosa, 2012) are used.
2.8.4 Operative technique for plagiocephaly
Anterior plagiocephaly and brachycephaly by fusion of one or both coronal sutures
can be treated by fronto-orbital remodelling with bilateral or one-sided frontal
advancement (Matushita, Alonso, Cardeal, & de Andrade, 2012; Mesa, Fang,
Muraszko, & Buchman, 2011). In syndromic cases with severe facial retrusion, the
frontal advancement may be followed by a facial advancement (LeFort III). In
severe cases, if necessary, a frontofacial monobloc advancement can be performed
(A. Marchac & Arnaud, 2012). Posterior plagiocephaly is usually treated with
remodelling cranioplasty (Di Rocco, Marchac et al., 2012; A. Marchac, Arnaud, Di
Rocco, Michienzi, & Renier, 2011) whereas positional posterior plagiocephaly can
be treated with helmets (Lipira et al., 2010).
31
2.8.5 Fixation materials
The majority of the above mentioned operative techniques require fixation of the
reshaped cranial bones. These can be achieved with conventional screws and plates
(Goodrich, Sandler, & Tepper, 2012), biodegradable plates (Arnaud & Renier, 2009)
or resorbable sutures (van der Meulen, 2012).
Successful bone fixation is fundamental in frontal cranial remodelling surgery.
Fixation devices must maintain the new shape of the cranium following surgery
until the new construct is ossified. Historically steel wires, metal plates with screws
were used for this purpose (Goodrich et al., 2012). Though easy to use, malleable
and strong, these materials had several disadvantages. Local skin irritation,
infections, interference with modern imaging technologies, necessity of removal in
a second operation, or the risk of intracranial pseudo-migration into the growing
skull as well as risk of growth restriction if left unremoved, were among the
problems caused by these materials (Arnaud & Renier, 2009; Fearon, Munro, &
Bruce, 1995; Goodrich et al., 2012; Orringer, 1998).
Resorbable sutures are used as additional means to keep the bones fragments
in place (Goodrich et al., 2012; Goodrich, Tepper, & Staffenberg, 2012).
The next advance in craniofacial surgery was the introduction of biodegradable
materials in the beginning of 1990s in order to avoid problems of rigid alloy
fixation (Ahmad, Lyles, Panchal, & Deschamps-Braly, 2008). Postoperative
resorption of the devices after ossification of fixated bony fragments minimized all
potential future device-related complications (Eppley et al., 2004). These resorbable fixation devices are different combinations and formulations
of polymer macromolecules. Mainly polylactic acid in its L-isomer (PLA or PLLA) and polyglycolic acid (PGA) are used. These are the same materials that are used in resorbable sutures, thus having a long history of safe use (Eppley et al., 2004). PLLA is hydrophobic and thus resistant to degradation. PGA is hydrophilic, thus prone to early loosening of the polymer bonds and weakening of implant (Eppley et al., 2004). Early plates, made of monopolymers, tended to cause sterile non-inflammatory granulomas mainly during most active phase of degradation (Goodrich et al., 2012). Copolymers tended to resorb more slowly, thus decreasing the risk of granuloma formation. Blending polymers in different proportions also allowed the building of plates with different strength and resorption profiles (Eppley et al., 2004), as well as with desirable malleability.
Traditionally, the plates fixating the reshaped bones were placed on the outer
surface of the skull bones during remodeling cranioplasties. In some cases these
plates could be palpated through the skin, especially at early postoperative stages,
32
sometimes even for a long period of time thus compromising aesthetic results
(Ashammakhi et al., 2004; Branch et al., 2017; Losken et al., 2001; Wood, Petronio,
Graupman, Shell, & Gear, 2012). Ahmad and associates showed in six patients out
of 146 that the plates were palpable under the skin several days after the operation,
and three of these patients had plates still palpable after six months of follow-up
(Ahmad et al., 2008). Freudlsperger at al. noticed that plates became more visible
with time and palpable with a maximum at 12 months. While visibility resolved by
21 months after surgery, 20% remained palpable (Freudlsperger et al., 2014). In a
study by Woods and associates 31.7% (44 out of 139) of patients had a visible mass
at the site of fixation at some point postoperatively, with 3 patients still having a
visible mass at the latest follow-up visit at 304, 345 and 351 postoperative days
(Wood et al., 2012).
A surgical technique with placement of the resorbable fixation on the inner
surface of the skull for better immediate aesthetic result was reported as a
pioneering surgical technique in 2003 by the Oulu Craniofacial Centre team. In
2007 first follow-up results in ten patients were published (W. Serlo, Ashammakhi,
Lansman, Tormala, & Waris, 2003; W. S. Serlo et al., 2007). This method allowed
for fixating the plate on the inner aspect of the frontal skull and in the outer aspect
of the less visible temporal bone, providing satisfactory aesthetic results (W. S.
Serlo et al., 2007). It was shown previously in animal experiments, that such
placement of the plates did not cause any adverse effects (Peltoniemi et al., 1998).
Another innovation by the team was reinforcement of the fragile bone fragments
with the plates prior to its bending and contouring (W. S. Serlo et al., 2007).
Since then this method has been used in several centres but the reports on the
experience of this method, particularity on its aesthetic outcome, are still scarce
(Konofaos & Wallace, 2014; Konofaos, Goubran, & Wallace, 2016; Sauerhammer
et al., 2014).
2.8.6 Distraction cranioplasties
One of the principal aims of surgery for craniosynostoses is to increase the
intracranial volume. This intracranial volume increase can be achieved with a
traditional cranioplasty procedure or posterior cranial vault distraction (PCVD).
However, the expansion achieved by a one-stage, an all-at once procedure is limited
by the ability of the skin and other soft tissues to stretch over the enlarged and
reshaped skull. An incremental and dynamic expansion overcomes these
limitations by progressive expansion during the postoperative period. This allows
33
time for the soft tissues to adapt. Springs and distractors can be used for these
purposes (Derderian & Bartlett, 2012; Lauritzen, Davis, Ivarsson, Sanger, & Hewitt,
2008) . The use of distractors allows a controlled and gradual shifting of the
osteotomized bone fragment in the desired direction. This allows the skin and soft tissues to gradually stretch and to adapt (Nowinski et al., 2012). During the primary procedure one to four distraction devices are implanted. After a latency period of several days the devices are activated usually at a rate of 1 mm a day. After the desired distraction distance is achieved the devices are left in place for at least one month to allow sufficient time for ossification to take place and provide stability. One more operation is required to remove the distraction devices following this consolidation period. Thus PCVD requires prolonged treatment time, during which regular wound care and follow-up is required (Thomas et al., 2014; White et al., 2009).
Distraction can be done in frontal (Hirabayashi, Sugawara, Sakurai, Harii, &
Park, 1998), lateral (Imai et al., 2002) and posterior directions (White et al., 2009).
Also a multidirectional distraction has been used (Sugawara, Uda, Sarukawa, &
Sunaga, 2010).
Numerous studies have shown that by posterior calvarial expansion a far
greater volumetric increase can be achieved than by frontal advancement. PCVD
can provide better cosmetic results especially in cases with occipital flattening
(Choi, Flores, & Havlik, 2012; Derderian et al., 2015). One more benefit of PCVD
is that in focusing the manipulation to the posterior structures it leaves the anterior
fossa surgically untouched. This means that future surgical procedures (such as
frontal orbital advancement) will not be impeded or compromised (White et al.,
2009). There is also a growing amount of experience with treating syndromic
craniosynostoses using PCVD as a primary procedure. Not only could frontal
remodelling be postponed but in some cases it may also be avoided (Goldstein et
al., 2013). In a pilot study with a small group of patients posterior cranial vault
expansion was calculated to result in as much as a 20% increase in intracranial
volume (W. S. Serlo et al., 2011). Though PCVD is gaining its popularity worldwide, studies are scarce regarding
the long-term results, complications and burden of care of this technique.
34
2.8.7 Timing of the surgery
Timing of the surgery depends on the type of pathology, its severity and clinical
manifestation. It is also a question of finding a balance between benefits and risks
related to the age of the patient at the time of operation. In a child under 6-12
months the calvaria is thin and malleable, ossification is so good that even big bony
defects ossify completely and the brain growing capacity is tremendous (Panchal
& Uttchin, 2003). However, early surgery increases the risk of recurrence of the
condition and the operative risks are higher. Operating in an older child often
requires more extensive procedure and more laborious bone reconstructions
(Pagnoni et al., 2014) due to further worsening of the deformities of cranial base,
facial skeleton and dental malocclusion taking place while the child with unreleased
craniosynostosis grows. Benefits of later surgery include thicker bone for more
stable fixation, less impaired growth going forward after operation and better
tolerance for the perioperative blood loss (Fearon, 2014). Improvements in paediatric anaesthesia and intensive care together with
refinements of surgical techniques and materials mean that one can operate younger patients. For example, centres experienced in endoscopic treatment of craniosynostoses, prefer to operate single suture synostoses as early as three months of age with minimally invasive repair combined with postoperative moulding devices (helmets) (Jimenez, Barone, Cartwright, & Baker, 2002). Also spring assisted surgery is suitable to small infants as well (M. L. van Veelen & Mathijssen, 2012).
Nowadays, in syndromic patients, the calvarial augmentation is usually done before the age of six months aiming to provide sufficient space for the developing brain. The fronto-orbital area is addressed some years later if necessary (Pagnoni et al., 2014).
2.8.8 Secondary surgery
Aproximately 5 to 71% of patients require a re-operation after primary
craniosynostosis surgery either due to suboptimal aesthetic results (recurred or
residual craniofacial deformity) or due to clinically significant recurrence of
craniocerebral disproportion (Foster, Frim, & McKinnon, 2008; Wagner, Cohen,
Maher, Dauser, & Newman, 1995; Wall et al., 1994). Arnaud and associates
estimated that secondary coronal synostoses appeared in 10% of cases following
surgery for scaphocephaly, with 1% requiring cranioplasties due to ICP increase
(Arnaud, Capon-Degardin, Michienzi, Di Rocco, & Renier, 2009). Williams and
35
associates re-operated 6.45% of patients with severe sagittal synostoses initially
treated by total vault remodeling (Williams JK et al., 1997).
The frequency of reoperations is approximately two to three times higher in
syndromic cases (Foster et al., 2008; Wall et al., 1994). In accordance with this,
numerous studies have showed that in syndromic craniosynostoses primarily
elevated intracranial pressure could persist or relapse with delay after surgery (de
Jong et al., 2010; Marucci et al., 2008; Renier, Lajeunie, Arnaud, & Marchac, 2000;
Spruijt et al., 2016; Tamburrini et al., 2005) .
It is also well known that re-do surgery in craniosynostosis patients carry a
much higher risk of complications than primary operations (Czerwinski, Hopper,
Gruss, & Fearon, 2010; Esparza et al., 2008; Sloan, Wells, Raffel, & McComb,
1997).
Tahiri and associates recently reported a new and important finding in several
cases with fusion of preoperatively patent lambdoid sutures after PCVD procedures,
either due to primary condition or as a result of surgery itself (Tahiri, Paliga, Bartlett,
& Taylor, 2015). This requires further investigation.
2.9 Outcome of treatment
The primary objective of any health care intervention is to relieve clinical
symptoms, prolong survival and enhance quality of life along with well-being. It
may include such aspects as life satisfaction, health perceptions and physical,
psychological, social and cognitive well-being (Thoma, Cornacchi, Lovrics,
Goldsmith, & Evidence-Based Surgery Working Group, 2008).
Historically the success of the craniofacial surgery is evaluated by objective
clinical outcome measures such as anatomical measurements, clinical photographs,
radiological images, morbidity, mortality and the necessity for re-do surgery (Tapia
et al., 2016; Thoma & Ignacy, 2012). But none of these measures reflects the
aspects of what patients consider important.
The facial appearance of craniosynostosis patients can differ from what we say
to be “normal”, meaning harmonious, symmetrical, and aesthetically pleasing
facial features. Patients may have physical, mental or developmental disabilities
related to their primary disease (Allam et al., 2011; Kapp-Simon et al., 2007;
Tovetjarn et al., 2012). Suboptimal treatment may result in aesthetic deformities,
psychological, cognitive and developmental sequelae in later life (Joly et al., 2016).
36
2.9.1 Safety of cranioplastic surgery
In the study by Sloan and associates 250 patients who underwent craniosynostosis
surgery were reviewed. The complications were present in 6.8% and the mortality
was low, 0.8% (Sloan et al., 1997). They also found complication rates to be higher
(39%) in syndromic cases than in nonsyndromic cases (3.5%) (Sloan et al., 1997).
In the study by Shastin and associates 103 patients were followed prospectively
and the complication rate was found to be 35.9%, with zero mortality (Shastin et
al., 2017). Both these studies have relatively high numbers of complications due to
inclusion of minor problems often dismissed by other authors.
The use of biodegradable plates has been found to be safe. Losken and
associates reported that complications requiring reoperation occurred in 4.8% of
the patients with single suture craniosynostoses that were operated using
biodegradable plates (Losken et al., 2001). In a study by Branch and associates
unplanned reoperations were required in 5.4% patients, but there was no permanent
morbidity or mortality (Branch et al., 2017).
In a study by Woods the overall complication rate was 2%, delayed foreign
body reaction was noted in 0.7% of patients, but all resolved spontaneously (Wood,
2012). In the studies where the resorbable plates have been placed endocranially,
no plate related complications were reported (Konofaos et al., 2016; Sauerhammer
et al., 2014). PCVD operations are considered safe with low permanent morbidity and
mortality rates. However, much higher frequency of minor complications and unforeseen events, including skin problems and mechanical difficulties with the devices, are reported than with other techniques. This ranges from 12.5% to 80% (Goldstein et al., 2013; Steinbacher, Skirpan, Puchala, & Bartlett, 2011; Thomas et al., 2014; White et al., 2009; Wiberg et al., 2012) (Thomas 2014, White, Steinbacher, Goldstein, Wiberg). In a study by Thomas and associates unplanned operations were required in 19.4% of cases (Thomas et al., 2014). The majority of these unforeseen events were minor and did not hamper the distraction process itself.
Since there is no commonly used classification of complications, unforeseen events are still frequently reported in a descriptive manner using authors’ custom definitions (Shastin et al., 2017). Thus the comparison of numbers presented in different publications has its limitations. The first attempt to standardize the classification of the complications in craniosynostosis surgery was done by Shastin and associates (Shastin et al., 2017).
37
2.9.2 Evaluation of postoperative craniofacial morphology
The evaluation of the outcome of the treatment can also be done objectively, by
evaluating craniofacial morphology based on internal and external landmarks. Such
cephalometric data has been obtained from direct anthropometric caliper
measurements (Farkas, Katic, & Forrest, 2005; Watson, 1971), cephalograms
(Kreiborg, Aduss, & Cohen, 1999), conventional photographs (Farkas & Deutsch,
1996; Mazzoleni et al., 2016) or 3D CT scans (Choi et al., 2012; Fischer et al.,
2016; Goldstein et al., 2013).
Conventional photography is being used on a routine basis to follow-up
changes of the patients appearance during the treatment and follow-up period
(Hilling, Mathijssen, & Vaandrager, 2006; Ozlen, 2011). But the evaluation of
aesthetic outcome is subjective from 2 dimensional pictures made from limited
angles.
There are only a few studies published where results of craniosynostosis
operations were assessed from photographs (Bendon, Johnson, Judge, Wall, &
Johnson, 2014; Hilling et al., 2006; Mazzoleni et al., 2016; Metzler et al., 2014;
Panchal, Marsh, Park, Kaufman, & Pilgram, 1999). Metzler and associates
evaluated outcomes after surgery for metopic synostoses patients a few years after
the operation using a narrow 3 point scale. They used panels of lay persons, medical
students and maxillofacial surgeons evaluating entire facial photographs and
photographs of the smaller sections of the face (Metzler et al., 2014). Probably due
to the narrowness of the scale used, there was significant difference in panel
evaluations only when small section images were used. Bendon and associates used
panels of professionals to evaluate specific morphological findings from pre- and
postoperative photographs using 100-unit VAS scale. The panels were asked to
grade the severity of scaphocephalic shape of skull, frontal bossing, temporal
pinching, occipital bulleting and overall head shape (Bendon et al., 2014). This was
a much more precise measurement of aesthetic outcome but again it represented
only the degree of pathology from the surgeon’s point of view and not the patient’s
attractiveness in general.
Lately non-ionising 3D surface imaging techniques have become available.
There are different systems used for this purpose, including stereo-photogrammetry
and laser scanning (Barbero-Garcia, Lerma, Marques-Mateu, & Miranda, 2017;
Weathers et al., 2014; Wong et al., 2008).
Based on structured light techniques, 3D imaging systems project a random
light pattern onto the subject and capture the image with multiple precisely
38
synchronized digital cameras set at various angles in an optimum configuration.
Three dimensional surface geometry and texture are acquired nearly
simultaneously and a single 3D image is produced (Kau, Richmond, Incrapera,
English, & Xia, 2007). Images captured by this system are highly repeatable,
photo-realistic and 3D anthropometric landmark data is highly reliable (Aldridge,
Boyadjiev, Capone, DeLeon, & Richtsmeier, 2005).
3D photogrammetric imaging is feasible for the evaluation of variety of
craniofacial deformities (Seeberger et al., 2016; M. C. van Veelen et al., 2016;
Wong et al., 2008). Accuracy of 3D photography of the infant head is high, and the
method is rapid, easy to apply, non-invasive, and reliable (Schaaf et al., 2010).
Citing Lipira and associates “contemporary 3D imaging modalities, in
combination with sophisticated shape analysis techniques, are bridging the gap
between aesthetics and mathematics” (Lipira et al., 2010). This method has been
successfully used to measure changes in cranial shape (Lipira et al., 2010) and
intracranial volume in craniosynostosis patients (Seeberger et al., 2016; M. C. van
Veelen et al., 2016).
Thus 3D photography presents a valuable method for craniofacial mapping and
objectification of perioperative changes during craniosynostosis correction. It
facilitates the option of tracing volumetric changes and changes to symmetry
mathematically (Hanis et al., 2010; Wilbrand et al., 2012). Though increasing numbers of publications are available dealing with
volumetric results of posterior cranial vault distraction procedures, they are usually based on evaluations done from highly ionising skull 3D CT scans and the cohorts are small (Derderian et al., 2015; Goldstein et al., 2013; Shimizu, Komuro, Shimoji, Miyajima, & Arai, 2016). There are so far no other series besides our team’s earlier publication (W. S. Serlo et al., 2011), where volumetric analysis is derived from plain cephalograms. There is also a lack of sufficient studies dealing with evaluation of PCVD surgery volumetric results by the means of non-ionising 3D photogrammetric imaging.
2.9.3 Aesthetic considerations
One of the main goals of craniosynostosis surgery is to normalize patients’
appearance (Farkas & Deutsch, 1996). Dysmorphic, asymmetrical face and head
shape can have negative influences on person’s self-esteem, social relationships
and behaviour (Joly et al., 2016).
39
There are numerous studies on outcome of craniosynostoses, where evaluation
is based on presence of postoperative complications and the need for reoperations
(Breik et al., 2016; Joly et al., 2016; Ozlen, 2011; Seruya et al., 2011). Whitaker in
1987 proposed assessing the results of craniosynostoses treatment according to the
need for additional surgery, with category I – no need for refinements, and
categories II to IV reflecting the significance of the further operative correction
required (Table 1) (Whitaker, Bartlett, Schut, & Bruce, 1987). This classification
has been widely used in many published series (Joly et al., 2016; Lloyd et al., 2016;
Mesa et al., 2011; Seruya et al., 2011)). Sloan and associates classified the surgical
results into seven classes (Sloan et al., 1997) and Aryan and associates proposed in
2005 simplified version of this classification (Table 2) (Aryan et al., 2005). The
later has four categories, where only one category infers the need for operative
corrections, while the other three categories correspond to less severe degrees of
deformity (Table 2). This was also used previously in our team’s publication (W. S.
Serlo et al., 2007).
Table 1. Whitaker categorization of surgical results.
Category Description
I No need for surgical revision
II Minor revision needed
III Major alternative bone grafting or osteotomies will be needed
IV A major craniofacial procedure will be necessary
Table 2. 4-point classification of surgical results for craniosynostosis surgery. For
references see text.
Score Description
1 Excellent. No visible or palpable irregularity
2 Good. Palpable or visible irregularity that does not compromise the overall correction.
Deformity observed only by examiner
3 Fair. Compromised correction. Deformity observed by the third persons/parents. Does not
require repeat operation
4 Poor. Recommended repeat operation either for irregularities or compromised correction
While outcome evaluation from a surgeon’s point of view is mainly limited to the
decision making of whether the patient needs additional corrective surgery or not,
other options for aesthetic evaluation of outcome are needed.
There are numerous studies in orthodontics evaluating patients’ self-
satisfaction with pre- and postoperative aesthesis, as well as third persons (panels)
40
quantitative evaluation of aesthetic outcome (Claudino & Traebert, 2013; Silvola
et al., 2014).
One of the first attempts to determine a correlation between appearance and
quality of life (QOL), thus evaluating aesthetic results of the surgery from patient’s
point of view was published by Lloyd and associates in 2016 (Lloyd et al., 2016).
However, the facial aesthetics was evaluated using the above mentioned Whithaker
classification, which is surgeon-oriented. Kluba and associates asked parents how
satisfied they were with the results of treatment using a 5-point rating scale (Kluba
et al., 2016). Joly and associates evaluated the results after suturectomy for metopic
and coronal synostoses by asking children and parents if the head shape was normal
in their opinion. They also used the Withacker scale to evaluate the surgeons’ point
of view of the result (Joly et al., 2016). The studies by Metzler and Bendon intended
to evaluate surgical results from photographs, but instead of evaluating the
attractiveness of patients’ faces the grading was directed to deformity and
evaluation of necessity for reoperations (Bendon et al., 2014; Metzler et al., 2014).
Neither of these studies reflects sufficiently the results of the surgery from the
aesthetical, patient oriented point of view. Another problem of all of the above
mentioned studies is that different scales and questions are used. Thus comparison
between the studies is challenging. The heterogeneity of the deformities, the wide
variety of operative techniques and consequently a small number of patients in each
series, makes the comparison even more obscure.
There are so far no publications describing the aesthetic results of frontal
remodelling operations with endocranial placement of plates. There are no studies
reporting the aesthetic outcome of patients treated for sagittal synostoses with
follow-up reaching adulthood.
2.9.4 Craniosynostosis patients as adults
During the last years only a few studies were published evaluating the impact of
craniostynostoses on health related quality of life (HRQOL) (Bannink, Maliepaard,
Raat, Joosten, & Mathijssen, 2010; de Jong, Maliepaard, Bannink, Raat, &
Mathijssen, 2012; Lloyd et al., 2016). However, to date there is no condition-
specific Health related Quality of life questionnaire for patients with
craniosynostoses. Neither is there a validated instrument to measure the impact of
craniofacial dysmorphology on a patient’s psychosocial function (Szpalski et al.,
2011).
41
In the previous studies it was found that the overall quality of life is lower than
average in patients with syndromic and complex craniosynostoses (Bannink et al.,
2010; de Jong et al., 2012).
In a study of 28 adults with Apert syndrome it was found that the patients
managed relatively well in terms of education and employment, although the
highest level of education was lower than with controls. The social relations
(marriage, number of friends) of these patients appeared to require improvement
(Tovetjarn et al., 2012). More optimistic results were reported by Allam and
associates who followed up eight Apert syndrome patients for over 15 years and
assessed their social and educational progress. It was demonstrated that these
patients can function quite well in society, can achieve a high level of education,
hold full-time employment, and integrate well socially (Allam et al., 2011).
42
43
3 Aims of the study
The goal of this study was to evaluate the safety and effectiveness of operative
techniques used in cranioplastic surgery and to evaluate outcomes of different
operative methods used for treatment of patients with craniosynostoses.
In order to answer these questions the specific research objectives were set as
follows:
1. Is it feasible to use endocranial fixation with resorbable material in
craniosynostosis surgery? What are the aesthetic results after surgery for
metopic and coronal suture craniosynostoses using this method? What are the
typical complications and their frequency? (I)
2. What magnitude of increase in the intracranial volume can be achieved by
posterior cranial vault distraction using internal distractors? Is 3D
photogrammetric imaging an applicable method for evaluation of cranial
volume increase compared with estimations from conventional cephalograms?
(II)
3. What kind of tool can facilitate congruent positioning of the distraction devices?
(III).
4. What are the long-term aesthetic results in patients operated for sagittal suture
craniosynostoses? Is there an association between the patient’s self-satisfaction
with their facial appearance in relation to aesthetic evaluations by independent
panels?
What socioeconomic situation, somatic health, mental health and self-
satisfaction with facial appearance do such patients experience compared with
controls? (IV)
44
45
4 Subjects and methods
4.1 Subjects and controls
The basic patient cohort of this study consisted of 250 consecutive patients with
craniosynostoses that were treated at the Oulu University Hospital between 1977
and 2015. The demographic data of the final study population and follow-up times
are presented in the Table 3.
Table 3. Demographic characteristics of the study groups.
Subjects
Study I Study II Study IV
Number of patients 27 30 40
Gender
Females 12 12 15
Males 15 18 25
Age at follow-up
Mean 5.7 y 5.9 y 27.4 y
Range 9 mo –18 y 4 mo – 12 y 18 y – 41 y
Follow-up time
Mean 4.2 y 2.9 y 26.5 y
Range 2 mo – 12 y 1 mo – 6 y 17 – 37 y
Diagnosis Metopic and coronal
synostosis
Syndromic and non-
syndromic craniostenosis
Sagittal synostosis
Operative Procedures Frontal remodeling
surgery with endocranial
placement of the
resorbable plates
Posterior cranial vault
distraction
Craniotomia
parasagittalis,
suturectomy or H-plasty
y = years, mo= months
The study dealing with endocranial resorbable fixation comprised of 27 cases
operated between 2009 and 2013 for metopic (n=10) or coronal (n=17) synostoses
at the Oulu Craniofacial Centre (I). The mean age of the patients at surgery was
13.4 months (range 7.6 – 55.2 months). Male-female ratio was 1.25. Particularly,
there was a dominance of male patients in metopic synostosis group with only one
patient being female.
In study II 30 patients were treated with the posterior cranial vault distraction
(PCVD) at the Oulu Craniofacial Centre between January 2009 and December
2015. One of the patients with Apert syndrome had been operated twice using
46
posterior distraction, first at the age of 3 months and then at the age of 2 years. The
follow-up time for the first operation in that case was determined to be the time
interval between the first and second procedures. Data regarding on both operations
is presented, thus the number of operations analyzed was 31. The mean age of
patients at the time of distraction surgery was 2.9 years (3 months to 9 years). The
male-female ratio was 1.5. All patients with bicoronal craniosynostoses underwent
a genetic analysis for Muenke syndrome. There were 14 patients with syndromic
craniosynostoses: Muenke syndrome (n=4), Apert syndrome (n=3), Crouzon
syndrome (n=3), Saethre-Chotzen syndrome (n=2) and other syndromes (n=2).
Restenosis was an indication for a distraction procedure in eight patients who were
treated previously for scaphocephaly. Two patients had bicoronal synostoses but
testing showed no Muenke syndrome. Two patients had bilambdoid synostoses.
One patient had a Mercedes-Benz type synostosis with premature ossification of
both lambdoid and sagittal sutures. One more patient had bicoronal synostosis
combined with premature ossification of sagittal suture. One patient had
craniocerebral disproportion as a complication of overdrainage of
ventriculoperitoneal shunt. One patient had a Chiari I malformation.
47
Fig. 3. Flow chart of the subjects through each stage of study IV.
The long term follow up study (IV) consisted of 40 patients operated for non-
syndromic sagittal synostoses between 1977 and 1998. A total of 171 operations
for craniosynostoses during this period were identified from the database of the
Oulu University Hospital (Fig. 3). Since the aim was to study long-term outcomes
in adulthood, only patients over the age of 18 years at the time of the follow-up
examination were included. Only isolated disorders were included and patients
with any associated disease such as hydrocephalus or other neurological disease
were excluded. A total of 115 patients met the inclusion criteria and were contacted
by mail or telephone by a study nurse. Of these, 61 patients were reached and
agreed to participate in the study. From 61 patients, one appeared to have slight
form of Crouzon. Eight had metopic synostoses while one had isolated unliateral
synostosis of the lambdoid suture. Six had one-sided and 3 bilateral coronal
synostoses. One patient with sagittal synostosis had hydrocephalus and one patient
was re-operated due to the prominent frontal area persisting after primary sagittal
synostosis operation and a fusion of coronal sutures was found during surgery. The
remaining 40 patients had been surgically treated for sagittal synostoses and thus
48
were included in study IV. The same amount (40) of age and gender matched
controls were randomly selected from the Finnish Population Register Centre. For
logistical reasons the controls were recruited from the area of Oulu and its
surroundings. The patients’ mean age at a time of surgery was 5.7 months (range 9
days to 45 months). The male-female ratio was 1.7 (Table 3).
4.2 Methods
For the study on the endocranial use of biodegradable plates (I) data on preoperative
diagnosis, operations, follow-up visits, results of different imaging modalities and
postoperative complications were collected from the patients’ medical records. The
follow-up schedule included visits at 1-3, 6 and 12 months after surgery. Thereafter,
follow-up continued biannually until the patient reached seven years of age. During
follow-up visits, the patients underwent clinical evaluation and parents were
interviewed. Also plain radiographs of the skull, photographs and occasionally 3D
computer tomography were taken.
For the study on distraction procedures (II) data on preoperative diagnosis,
operations, hospital stay, distraction details were recorded. After distractor devices
were removed follow-up continued with annual visits until the patient reached
seven years of age. During follow-up visits, the patients underwent clinical
examination, parents were interviewed, plain radiographs of the skull and
photographs were taken. 3D computer tomographs were performed if necessary. In
the last five patients 3D photogrammetric images were taken before and after the
procedure.
For study III a surgical guide device (Fig. 7) to facilitate the implantation of
distractor devices in correct position was developed in collaboration with Mectalent
Oy (I).
Both patients and controls included in the late follow-up study IV were invited
to the out-patient clinic and had completed their questionaries’ prior to the visit.
During the follow-up visit a clinical evaluation was done. The examination of the
patients included evaluation of facial appearance, skull shape, the scar, and
palpation of the head. Standard photographs and 3D photogrammetric images were
taken.
Information regarding patients’ preoperative diagnosis and surgeries was
extracted from the medical records.
49
4.3 Operative procedures (I, II, III, IV)
The operative techniques used in this study, are described in historical order.
In the 1970-s craniosynostoses were operated in the Oulu University Hospital
using the suture release technique by Lannelongue. For that purpose two parallel
strip craniotomies were done on both sides of prematurely ossified suture with bone
over the ossified suture preserved intact. In case of sagittal synostoses these
craniotomies reached over the unfused coronal and lambdoid sutures. Silicone
membranes were placed to cover bone edges at osteotomies in order to prevent re-
ossification (Fig. 2). Nine patients from study group IV were operated using this
technique. Since the early 1980-s the technique was replaced by strip suturectomy,
with removal of the ossified suture. Out of seven patients (study group IV) operated
using this surgical technique in four patients the suturectomy was supplemented
with dural split to wrap the bony edges. Since 1985 these methods were
subsequently replaced by the “H”-technique. In this technique the ossified sagittal
suture was removed with additional bone strips removed behind coronal sutures
and in front of the lambdoid sutures on both sides with the final osteotomy defect
having a shape of the letter “H”. Then a sub-fracture of temporal bone was done to
allow further reshaping of the skull. Rather soon the technique was enriched by
adding barrel stave osteotomies to the temporal bone. The later 24 cases from study
group IV had surgery performed using this technique.
From 40 sagittal synostosis patients in study group IV two patients were re-
operated due to residual scaphocephalic head shapes. One of these patients was
operated with linear craniotomy by the Lannelongue technique twice. Another one
was operated using this technique at the age of nine days, and 10 months later this
patient was operated with strip suturectomy technique in another hospital.
Since the 1980-s craniosynostoses with frontal deformities were operated in
Oulu University Hospital using frontal remodelling cranioplasties. Resorbable
plates came to use in the early 1990-s. In study I two different operative techniques
for treatment of such cases were used depending on the diagnosis of the patient. In
both techniques after bicoronal skin incision frontal bone from the anterior fontanel
down to approximately 1 cm from above the orbital upper rim was removed in one
piece.
In patients with coronal synostoses a supraorbital bandeau was removed and
thinned. A resorbable plate was then fixed on the inner surface of the bandeau.
Frontal bone was cut into suitable fragments and thinned if necessary. The
50
fragments were fixed to the bandeau-plate construct with the plate placed on the
endocranial surface of the bones.
In metopic synostosis patients, a supraorbital bandeau was not removed, but
the prominent interorbital ridge was removed and the fused metopic suture was
removed down to the nasofrontal suture. The frontal bone was then also cut into
fragments and assembled in a manner improving forehead convexity with
resorbable plates placed endocranially. Thus the orbits were left untouched but a
suturectomy of the fused metopic suture between the orbits was performed.
In both techniques the operation was finalized by fixing the newly formed
bone-plate construct to the outer aspect of the temporal bones on both sides. Final
stabilization was achieved by placing resorbable plates on the top of the vertex of
the skull in a conventional way. All bone dust and bone chips were collected using
a suction trap bone collector and used to fill the bony defects. Fibrin glue was
spread on top of the bone dust material filling just prior to covering the bony
fragments with periosteum. The major part of the osteotomies by the end of the
procedure was covered with resorbable plates or filled with the bone dust.
Posterior cranial vault distraction procedures (PCVD) came to use in 2009
(study II). For PCVD after a bicoronal skin incision, a posterior osteotomy was
performed. The occipital osteotomy was intended to extend as low posteriorly as
feasible, reaching the torcula or extending even lower in 24 out of 31 cases. The
osteotomized bone was detached from the dura in all but one case. After checking
for haemosthasis, the bone was fixed with initial distraction of few millimeters
using two to four distraction devices in accordance with preoperative plan. In order
to ensure parallelism of distractors, the new distraction vector guides, described in
study III, were used in the last 14 cases. The distraction devices (Biomet
Microfixation 1.5 mm CMF Quick-Disconnect Distractors, Biomet Microfixation,
Jacksonville, Florida, USA or Mectalent Oy, Oulu, Finland) were fixed to the bone
with self-drilling titanium screws (Fig. 4). The number of distractor devices used
per patient was: four devices in 18 cases, three devices in six cases and two devices
in seven cases.
51
Fig. 4. Distraction devices and their placement on the skull. The distractor devices are
shown both with and without the external activation rods attached.
Along with gained experience and evolution of surgical methods the skin incision
was gradually changed to be cosmetically more favorable. Initially when the
Lannelongue technique was used, a straight midsagittal incision was preferred.
Later straight bicoronal incision was used. In the late 1990-s straight incision was
replaced by the zig-zag shaped incision.
4.4 Distraction protocol (II)
After a latency period of several days (mean 6 days, range 4 – 9 days), the distractor
devices were activated at a rate of 1 – 2 mm once a day. Each time, prior to
activation of the devices, the skin around the activation rods was cleaned and
lubricated with antibacterial ointment. After the first few days, the activation was
usually continued at home by parents. During this distraction period the patients
were followed in the outpatient clinics weekly. The plain lateral view cephalograms
were taken at weekly follow-up visits to monitor the distraction process and screen
for device failures. At these visits the status of the wounds and skin in the area of
the distractors was monitored closely.
When the posterior vault was advanced to its planned position, the activation
rods were removed under general anaesthesia. The average time from primary
surgery to removal of devices was 27.3 days (range 13 – 43 days). The distractors
were left under the skin to keep the distracted bone block in achieved position until
the ossification of the bony gap was sufficient. Then the devices were removed
52
under general anaesthesia usually from a new short incision done just above the
body of distractor. Removal of devices was performed at a mean of 5.2 months
(range 3 – 9 months) after the primary operation. Thus each patient had
approximately three to four lateral cephalograms taken postoperatively, but no CT
scans were taken on routine basis.
4.5 Clinical examination (I, II, IV)
The clinical examination by the staff surgeon (study I and II) or by the author (study
IV) included evaluation of facial appearance, skull shape, the scar, palpation of the
head for irregularities and ossification defects, signs of infection, instability in the
operated area and for possible failure of the device. In study group I plate visibility,
palpability, and signs of delayed foreign body reaction were assessed.
The subjective evaluation of surgical outcome was done using the previously
described 4-point classification scale (Table 2) (Aryan et al., 2005; W. S. Serlo et
al., 2007) and the Whitaker classification (Table 1) (Whitaker et al., 1987).
4.6 Evaluation of the volume gain (II)
4.6.1 Using plain cephalograms
The cephalograms were used to calculate the volume gain after the distraction was
completed in patients undergoing PCVD (W. S. Serlo et al., 2011).
The upper part of the skull that includes majority of intracranial space was
assumed to have a shape of half ellipsoid. Thus volume and volume change after
distraction of the half of an ellipsoid was calculated. The length and half the height
of the skull were measured on the preoperative radiographs.
The preoperative volume V of the skull (half-ellipsoid) was then calculated
using the formula:
V = (1)
Half of the length of skull was named as a and its heights was b. C was a half
of the width of the skull. In the first several cases c was measured from frontal view
of plain x-rays. There was no significant difference between b and the c. Also
calculation of the skull width from the anterior view appeared to be rather unprecise
since its results depended on the angle under which the image was taken. For this
53
reason further calculations were done assuming that the half-height of the skull was
equal to its half-width. Thus the final formula for preoperative skull volume
calculation was as follows:
V = (2)
The amount of distraction (the linear shift of the bone block) d was calculated
from the radiographs taken after the distraction was completed. The measurements
were done close to distraction devices in three different points and the mean of
these three measurements was used.
The volume gained by distraction VΔ was then calculated using the formula:
VΔ = (3)
The increase of the skull volume was calculated then using the formula:
X = VΔ ∗ V %. (4)
All measurements were performed by the author using commercially available
software (NeaView Radiology, Neagen OY, Finland).
4.6.2 Using 3D photogrammetric imaging
3D photogrammetric images were taken from five patients before the PCVD
operation and several months (mean 4.8 months, range 3 – 7 months) afterwards.
The 3D images were taken in the Natural Head Posture using the 3dMD system
(3dMD Cranial, Atlanta, GA, USA) by the author.
54
Fig. 5. Volumetric analysis using 3D imaging. The postoperative image (gray) is overlaid
on the preoperative image (pink).
The change in the individual head volume was then calculated for each patient
separately using previously described method (Aarnivala et al., 2015).
Postoperative images were overlaid on the preoperative images by superimposing
the facial areas (Fig. 5). The commercial software Rapidform2006 (INUS
Technology Inc., Seoul, Korea) was used to process and analyse these images.
4.7 Aesthetic evaluation using photographs (IV)
Facial aesthetic appearance was objectively determined by two independent panels
and by two experienced craniofacial surgeons. A series of slides with photographs
of the patients and their controls were shown in a random order. Neither panels nor
craniofacial surgeons were informed regarding whether a slide contained control
person or craniosynostosis patient. Each slide included four images in standard
projection of every subject including: anterior view with and without smile, lateral
and oblique views (Fig. 6). The slide show included all 62 patients with their
controls who came for the follow-up visits. This was done in order to make the
range of deformities wider. Each slide was shown for a standard ten seconds during
the slide show, to obtain the initial immediate evaluator impression.
55
Fig. 6. An example of the slide with standard position photographs used for the
evaluation of aesthetic result of the surgery in study group IV. An image of a healthy
person not included in the study is present with his consent.
4.7.1 The panel groups
The first panel consisted of consultants or residents in orthodontics (one male and
three females) and one orthognathic surgeon (female). This panel was referred as
the “dentists’ panel”. Another panel consisted of three female and one male, all
members of the lay public, having no health care education. They were referred to
as the “lay panel”. The members of the panels were not involved in the original
treatment of the patients.
The aesthetic outcomes were determined using a 100 mm VAS scale with 0
mm as the least attractive and 100 mm being the most attractive. The following
instructions were presented to the panelists: “Please place a cross on the continuous
line in a place which best depicts your opinion about the attractiveness of the face
on the photographs.”
56
4.7.2 Evaluation by craniofacial surgeons
In addition to the evaluation by panels, the aesthetic results were also evaluated by
two experienced male craniofacial surgeons, involved in some original operations.
The same slide show and the scales presented in the tables 1 and 2 were used for
these purposes.
4.8 Questionnaire (IV)
The self-reported questionnaire used in the long follow-up study part IV included
questions regarding education, housing, marital status, employment, general health,
presence of headaches, history of mental disturbances and the need for orthodontic
treatment. Participants’ relationship status was recorded as either “single” or “in a
permanent relationship” which included those who were married or cohabiting. The
participants’ education level was classified into three groups: no professional
education (e.g. primary school only), secondary professional education and tertiary
professional education (including university education).
The questionnaire also included question: “is there something that bothers you
about your facial appearance?” Those who responded positively were asked to
clarify. The patients were also asked whether their scar was bothersome.
The participants were also asked to determine their subjective satisfaction
regarding facial appearance by using a 100 mm VAS. The question was: “How
satisfied are you with your current facial appearance?” In the VAS, 0 mm referred
to “very unsatisfied” and 100 mm to “very satisfied”.
4.9 Ethical issues
The study was performed in accordance with the declaration of Helsinki on ethical
principles for medical research. The study was approved by Ethics Review
Committee of the Northern Ostrobothnia Hospital District (No. 86/2013). Patients
and controls filled in informed consent for study IV.
4.10 Statistical methods
In study I and II frequencies and other descriptive details were reported with means and deviations, if needed. Spearman rank correlation test was used for calculating correlations between parameters. T-test was used to compare means between the
57
diagnostic groups (plagiocephaly versus trigonocephaly). Two-tailed p values were presented.
Nominal variables were analyzed with crosstabs and Pearson Chi-square tests,
in cases with small group size Fisher test was used.
To compare means between two groups the Levene’s test for equality of variances
and t-test for equality of means was used.
To compare linear variables between patients and controls in study IV Pared
Samples T-test was used. For nominal variables McNemar test in crosstabs was
applied.
To evaluate reliability of the panels the inter-observer reliability was analyzed
using intraclass correlation coefficient between the panels and inside the panels
between the panel members. The reliability for both panels members was moderate
with p = 0.573 for the dentists panel and p = 0.555 for the lay panel. Reliability
between the panels was almost perfect p = 0.840.
P values < 0.05 were considered as significant.
All statistical analysis was performed using commercially available SPSS for
Windows 14.0 software.
58
59
5 Results
5.1 Surgical duration and intraoperative blood loss (I, II and IV)
When frontal remodeling surgery was performed with endocranial placement of
resorbable plates, the mean operative time was 210 minutes (range 95 – 315
minutes, SD 54.3, 95% CI=188.9 – 231.8). The metopic synostosis group required
less operative time (average 170 minutes) than operations for the coronal synostosis
group (average 234 minutes). The difference in operation time between the two
groups was statistically significant (p = 0.001). In one patient who was operated
due to sagittal synostosis in the 1970-s the data concerning blood loss and surgical
duration was missing. The data on operative details is presented in Table 4.
Table 4. Data regarding details of different operative methods.
Operative
procedure
Old techniques
for sagittal
craniosynostosis
(N15)
H-cranioplasty
for sagittal
craniosynostosis
(N24)
Frontal
remodelling for
metopic
synostosis
(N10)
Frontal
remodelling for
coronal
synostosis
(N17)
Posterior
cranial vault
distraction
(N31)
Duration (min)
Mean 130.2 60.5 169 234 149
Range 65 – 182 35 – 128 95 – 295 170 – 315 89 – 217
Bleeding (ml)
Mean 196 89 289 449 310
Range 28 – 380 15 – 260 90 – 600 150 – 1700 70 – 1300
Age at operation
(months)
Mean 9.1 3.4 12.9 20.6 35.8
Range 0.3 – 45.3 1.3 – 9.9 7.6 – 22.5 8.9 – 55.2 3 – 109.4
5.2 Distraction guides (II, III)
In order to avoid distractor vector incongruities and conflicts when placing
distractor devices during the surgery, a new method to ensure that the distractors
are implanted in coherent directions was developed. The method was based on the
guides that can easily and temporarily be fitted to the distractors during the
implantation of the distractor devices. These guides (Fig. 7A) fit over the
60
distractor’s body. When the guides are attached to the distractors, their relative
directions can easily be checked visually by comparing orientation of the guides.
Fig. 7. The distraction guides. A. The guides are attached to two distractors on a dry
skull model to check distractor vector parallelism. B. Guide application during the
surgery.
After final fixation of the distractors to the cranial bones, the guides are removed
(Fig. 7B). The guides were manufactured to specification by Mectalent Oy (Oulu,
Finland). It is possible to fix one or two guides to each distractor in either or both
the anterior or posterior directions relative to the distractors activation rods. Fixing
two guides to the distractors makes longer lines to be compared visually thus
increasing the probability that even smaller angulation errors are detected to
prevent excessive convergence or divergence of the vectors of distraction.
After introduction of the guides (study III) facilitating placement of distraction
devices in a parallel position, they were used in 14 consecutive cases from study
group II. None of these patients had problems with incongruence of the devices’
vectors unlike one case from the previous 17 cases.
5.3 Distraction results (II)
In the PCVD study group (II) the patients were followed on a routine basis with
mean follow-up time of 35 months. All turribrachycephalic cases achieved the
desired improvement in head shape. In cases with increased ICP, resolution of
symptoms was achieved in all cases.
The results of the distraction procedures are presented in Table 5. The mean
distraction distance was 2.8 cm (95% CI 27 – 30) ranging from 2.1 cm up to 4.3
cm.
61
Table 5. Cranial volume increase: patients’ age at the time of operation, distraction
distance achieved; and relative volume change (%) calculated from cephalograms.
Data Age at operation (months) Distraction distance (cm) Volume change (%)
Mean 34.7 2.8 25.7
Range 3.4 – 109.4 2.1 – 4.3 16.9 – 39.4
5.3.1 Volume gain measured from cephalograms (II)
Results of the cephalometric measurements are presented in Table 5. The mean
volume gain by PCVD in this study population was 275.4 cm3 (95% CI 252.5 –
298.3). Thus the mean achieved increase in cranial volume was of 25% (95% CI
23.0 – 27.0; range 16.9 – 39.4%). The calculated volume increase for each
centimeter of distraction was therefore 8.8% of the cranial volume (95% CI 8.4 –
9.3). There were no significant differences in volumetric increases attained between
genders.
The absolute volume gain did increase with increase in the age of the patient at the
time of the operation (p = 0.002). However, the age did not correlate with the
relative increase in cranial volume (p = 0.296) or with the achieved distraction
distance (p = 0.828).
The extension of the osteotomy line occipitally below the torcula did not
increase the gained volume. Achieved volumetric results were not dependent on
whether the distraction was a primary operation or a re-do surgery. Neither did these
results correlate with patient’s diagnosis when comparing syndromic cases with the
non-syndromic cases or doing estimations for each syndrome separately compared
to non-syndromic patients.
62
5.3.2 Volume gain measured from 3D photographs (II)
Fig. 8. Cranial volume increase (%) in 5 patients after posterior cranial vault distraction
as calculated from the 3D photogrammetric images (V% 3D) and plain cephalograms (V%
X-ray).
In five cases the pre- and postoperative 3D photographs were taken and the change
of volume was calculated from these images. The volume calculations for these
cases were compared with results of volumetric calculations from cephalograms
(Fig. 8). The increase in volume calculated from the 3D images was a mean of
17.4% (range 14.5 – 23.2%) whereas the volumes calculated from cephalograms
for same patients gave a mean of 20.8% (range 19.3 – 21.9%).
Thus mean volume gain was 8.1% per centimeter of distracted distance when
calculated from cephalograms and 6.7% when calculated from 3D photographs.
The statistical significance of this difference could not be evaluated due to the small
size of this subgroup.
23,2
14,5
16,3
16,7
16,1
21,9
20,2
21,9
19,3
20,6
0 5 10 15 20 25
1
2
3
4
5
Cranial volume increase (%)
Pati
ent
num
ber
V% X-ray
V% 3D
63
5.4 Aesthetic results
5.4.1 Evaluation by craniofacial surgeons at follow-up visits (I, IV)
All but one patient’s aesthetic outcome after frontal remodeling procedures with
endocranial placement of plates (study I) was judged to be good (N=16) or excellent
(N=10) at the follow-up visits using 4-point grading (Tables 2 and 6). In the metopic
synostosis group, excellent results dominated, in six out of 10 patients. In the
coronal synostosis group excellent results were noted in four patients, and 12
patients were rated as having good results (Table 6). The only patient that was
judged as having an unsatisfactory aesthetic result after the first surgery belonged
to coronal synostosis group and had craniofrontonasal dysplasia. The patient had
significant fronto-orbital dysmorphia with major asymmetry of the skull base. At
the time of the first surgery only a partial correction was possible. This was also
only patient to be classified as category IV by Whitaker classification (Table 3),
with the rest of patients falling into the category I.
From the sagittal synostosis group (study IV) four patients were judged as
having fair results, and none was judged as poor. Three out of these four patients
were male who had very short hair and were becoming bald. Thus unevenness in
the shape of the skull was not masked by their hair style.
Table 6. Aesthetic results of surgery by 4-point grading at follow-up visits according to
the type of craniosynostosis.
Diagnosis Aesthetic results (number of patients) Mean follow-
up time (years) Excellent Good Fair Poor
Metopic synostosis 6 4 0 0 6.9
Coronal synostosis 4 12 0 1 6.4
Sagittal synostosis 26 10 4 0 26.5
Total 36 26 4 1
The majority of the patients in both study groups (93%, 62 out of 67) achieved good
or excellent aesthetic outcome, according to the evaluation by the surgeon on the
follow-up visit. When applying the Whitaker categorization all but one case was
classified as category 1.
64
5.4.2 Evaluation by the craniofacial surgeons from the photographs
(IV)
The following results were not included in the original publications.
The majority of the patients, who were operated for single suture sagittal
synostoses achieved good or excellent aesthetic outcomes, according to the
evaluations done by the senior craniofacial surgeons from the images taken during
the visit (93%, N=37). No cases were rated as having poor (grade 4) results. Also,
none was rated as having fair results by both surgeons. The majority of patients (22
and 20 patients) were scored as having excellent results, 15 and 19 as good and
accordingly only three and one as fair. None of the patients was rated as having bad
results. When calculating the mean score from the evaluation by both surgeons
using a 4-point scale, four patients had a mean of 2.5, eight had a mean of 2.0 and
the rest had 1.5 or 1.0. Table 7 presents the data regarding these four patients who
had a mean score of 2.5. Out of these four patients three were scored as fair as well
on personal encounter during the follow-up visit. But one was scored as excellent
at personal encounter (Table 7, patient 1). When applying the Whitaker
categorization all cases were classified as category 1.
Table 7. The data on patients with average score of 2.5 from the 4 point-scale when
evaluated by senior craniofacial surgeons from the photographs.
Patient Gender Age
(years)
4-point
grade at
follow-up
visit
Self-
evaluation,
mm VAS
Lay
panel,
mm VAS
Dentists
panel,
mm VAS
Hair Operative
technique used
1 male 39.2 1 93 47 50 short Craniotomia
linearis from
sagittal incision
2 male 34.5 3 78 49 52 bald Craniotomia
linearis from
sagittal incision
3 male 27.6 3 89 51 49 bald H-plasty from
coronal incision
4 male 26.0 3 51 50 58 bald H-plasty from
coronal incision
65
5.4.3 Evaluation by panels (IV)
In the long-term follow-up study IV, regarding the results of appearance evaluation
by the dentists panel, the cases achieved lower results than the controls (VAS 62 vs.
69, p = 0.002). The similar difference in facial appearance was found by the lay
panel (VAS 60 vs. 66, p = 0.011) (Table 8, Fig. 9). Age did not correlate with the
rating of the facial appearance. However, both the lay and dentists panels tended to
give higher scorings for female persons. The dentists panel gave a mean score of
68 mm for females and of 64 mm for males (p = 0.116) and the lay panels
accordingly scored females as 67 mm and males 61 mm (p = 0.009). Six patients
and one control received a score less than 50 mm by the lay panel. The dentists
panel graded seven patients and one control under 50 mm in the VAS scale.
Table 8. Facial aesthetic evaluation on 100 mm VAS, mean and range. Panels ratings
and patients self-satisfaction.
Variable Patients Controls ρ
Self-satisfaction with
appearance, mm VAS
75 (29 – 100) 76 (29 – 98) 0.662
Dentists panel, mm VAS 62 (36 – 79) 69 (50 – 82) 0.002
Lay panel, mm VAS 60 (43 – 82) 66 (45 – 85) 0.011
66
Fig. 9. Ratings of facial appearance as evaluated on the 100 mm VAS scale by the panels
and self-satisfaction with own facial appearance in study IV.
When comparing the panels evaluation from the photographs with the evaluation
by a surgeon at a personal encounter, there was certain congruency in the results;
the panels tended to rate those patients with a lower score who had worse aesthetic
results also from the surgeons point of view (Table 9). However, since the fair
results group included only four patients, statistical analysis was unreliable.
Table 9. Summary of the results according to 4-point evaluation at follow-up visit for
patients operated due to sagittal synostosis. There were no cases with the score of 4
(poor).
4-point scoring results 1 – excellent 2 – good 3 – fair
Number of cases 26 10 4
Dentists panel, mean mm VAS 64 63 50
Lay panel, mean mm VAS 62 61 50
Self-evaluation, mean mm VAS 76 76 63
67
5.4.4 Patients self-satisfaction with facial aesthetics (IV)
There was no statistically significant difference in subjective evaluation of one’s
own facial appearance between the patients and their controls (p = 0.662) in the
long follow-up study (IV). The VAS mean was 75 mm among the patients and 76
mm among the controls, while the higher result referred to a higher rating of self-
satisfaction (Table 8, Fig. 9).
The patients’ own, subjective satisfaction with their facial appearance did not
correlate with the results by the panels (p = 0.775 for the dentists panel and p =
0.396 for the lay panel). The controls satisfaction with their facial appearance also
did not correlate with the results by the panels (p = 0.239 for the dentists panel and
p = 0.222 for the lay panel).
Though both patients and controls were on average satisfied with their
appearance to same extent, there were six patients and two controls who rated their
self-satisfaction with their facial appearance to be less than 50 mm on the 100 mm
VAS scale. There was some tendency to give to these subjects slightly worse scores
than for the rest of the groups by the independent panels, though the difference did
not attain statistical significance probably due to its small sample size. Lay persons
panels points were 57 vs 61 (p = 0.385) and dentists panels points were 60 vs 63 (p
= 0.596) for patients, and the same numbers for controls were accordingly 57 vs 66
(p = 0.119) by the lay persons panel and 60 vs 70 by the dentists panel (p = 0.101).
However, on personal encounter on the follow-up visit only one of these six patients
was graded as having fair results, with the rest graded as having good or excellent
result. Two of these six patients were operated using old methods and four were
operated using “H”-cranioplasty. Thus, proportion of the less satisfied patients
according to the operative technique was 12.5% (2 out of 16) and 16.7% (4 out of
24), respectively.
There were four patients who were bothered by the scar. All of them had a
bicoronal direction of the scar. They all also belonged to the abovementioned group
of six patients whose satisfaction was below average.
On the other hand from all the patients whose scar was visible even on photos
(N 6), only one was bothered by the scar. Thus the visibility of the scar seemed not
to be the main reason for more critical grading of the patients’ own appearance.
Thirteen patients (32.5%) and 11 controls (27.5%) answered “Yes” to the
question: “Is there something that bothers you in your facial appearance (except the
scar)?” (McNemar p = 0.804). These groups of patients and their controls did not
differ from the rest of the study persons neither in self-evaluation nor in the
68
attractiveness as evaluated by panels (for patients p = 0.308, p = 0.271 and p =
0.659, for controls p = 0.069, p = 0.306 and p = 0.194 accordingly). Factors
mentioned to bother study persons in own facial appearance are summarized in the
Table 10.
Table 10. Factors that were mentioned to bother study persons regarding facial
appearance, study IV. Number of subjects presented for each group.
Subjects Head and
face shape
(except
nose)
Dental
appearance
Nose
shape
Skin Hair Eyelids total Missing
answer
Patients 6 4 1 1 1 0 13 2
Controls 5 2 1 2 0 1 11 0
The postoperative scar
Postoperative scars, either bicoronal or sagittal in direction, were straight in all
patients, not with a zig-zag pattern. The scar was visible in one female patient (6.7%)
and in five male patients (20%). All patients who considered the postoperative scar
as an aesthetic burden (N = 4), had been operated with H-cranioplasty via a
bicoronal skin incision. One patient, who was re-operated, experienced pain in the
area of the scar on palpation.
5.4.5 The effect of operative technique on aesthetic outcomes (IV)
In order to evaluate the influence of operative technique on the results of the surgery
in the study on long-term follow-up after cranioplastic surgery for sagittal
synostosis (IV), each technique was analyzed separately. Further, old surgical
techniques (16 cases) were compared with the modern technique of H-cranioplasty
(24 cases). There were significant (p < 0.001) differences between the old and new
techniques regarding patient age at operation (9.1 vs. 3.4 months) and age at follow-
up visit (32.8 vs. 23.9 years). However, no association between different operative
techniques and subjective, patient’s own satisfaction with appearance (p = 0.801)
or panels’ evaluation of aesthetic results (p = 0.671 and p = 0.922) were found
(Table 11). To confirm these findings the analysis was repeated leaving out three
patients from the old operation technique group, who were operated at the age of
two years or later. This had no effect on the significance of the result.
69
Table 11. Comparison between the results of the old and new operative techniques.
Operative technique Self-satisfaction, mm VAS Dentists panel, mm VAS Lay panel, mm VAS
Old techniques (N16)
Mean 75 61 60
Range 29 – 100 36 – 79 43 – 81
H-cranioplasty (N24)
Mean 73 63 61
Range 30 – 96 40 – 78 43 – 82
5.5 Surgical complications (I, II, IV)
In study I after frontal remodeling with endocranial placement of resorbable plates,
three patients (11%) had complications severe enough to require reoperation. One
developed minor detachment of the skin with exposure of the plate, and a plate
underlying this part of the wound was removed without later problems. A second
patient was found to have unsatisfactory position of the frontal bandeau on routine
postoperative imaging. Repositioning of the frontal bandeau was performed a few
days after the primary operation, during the same hospitalization. Two other
patients developed a postoperative pseudomeningocele, one resolved
spontaneously but the other required revision six months after the initial
cranioplasty.
There were no other significant unforeseen events or ossification problems in
this series. Neither there were any complications related to the endocranial
placement of the plates.
In the PCVD study (II) unforeseen events requiring minor interventions
occurred in 12 cases. They were either due to skin problems in the area of distractor
or due to fractures of distraction devices activating arms. There was one case with
postoperative CSF leakage that resolved after the placement of a lumbar drain for
five days. Unplanned surgery was required in four patients. Re-alignment of one of
the distraction devices was performed in one patient due to conflicting vectors. In
three cases all devices were removed and replaced with resorbable fixation plates
after the planned distraction endpoint was reached. This was done due to skin
problems caused by distractors to avoid further exacerbation of the skin condition.
One of these three patients developed a sterile fluid collection of the plate site six
month later and required minor wound revision due to it. There were no
complications which resulted in permanent morbidity in this series. Neither were
there problems with resorption or non-ossification of the bone fragments. In spite
70
of unforeseen events the distraction was successfully performed to planned extend
in all cases.
Two patients out of 40 in the sagittal synostosis study (IV) required re-
operations due to the residual scaphocephalic shape of the head. One of these
patients experienced pain on palpation in the former suturectomy area revealing
defect of ossification. The majority of patients (32 out of 35, in five cases the data
was missing) had unevenness of the calvarial bone in the former craniectomy area
on palpation, but only in one an ossification defect was suspected. Since no
radiological studies were made at the follow-up visits these findings were not
confirmed radiologically.
5.6 Life situation, somatic and mental health at late follow-up (IV)
The following data was collected from the questionnaires filled by the adult patients
who were operated due to sagittal synostosis and their controls (study IV). Thus all
information on medical conditions presented was based on the participant’s own
reports.
5.6.1 Headaches and migraine
Having migraine was mentioned by nine (22.5%) patients and 15 (37.5%) controls.
Migraine was diagnosed by a doctor in four (10.8%) patients and in ten (27%)
controls. Other types of occasional headaches were reported by 23 (57.5%) patients
and 22 (55%) controls. There was no significant difference between either of these
results (McNemar p > 0.05).
5.6.2 General somatic health
A total of 32 (82.1%) patients and 28 (71.8%) of controls reported having no
medical concerns or taking routine medications (McNemar p = 0.424). No epilepsy
was reported in either group.
5.6.3 Mental health
Eleven (27.5%) patients mentioned at the time of their follow-up evaluation that
they have or have had mental health problems. Their mean age was 26.3 years.
There was also a history of mental problems in eight (20%) of the controls and their
71
mean age was 30 years. This group of patients and controls was as satisfied with
own appearance as those who did not mention having any mental problems.
5.6.4 Family, socioeconomic status and education
There was no statistically significant difference between the patients and controls
in education, housing, marital status or employment.
Half of the patients (N=21) and controls (N=20) were either being married or
cohabiting (Table 12).
The same number of patients and controls had children (McNemar test p = 1.00)
with average of 1.7 and 2 children per family. Also the same number of patients
and controls were not renting their apartments but lived in privately owned
apartments (Table 12).
The educational level of the participants, who were still studying, was
considered according to their existing degree (Table 13).
Table 12. Socioeconomic status for patients and controls in study IV. Number of
subjects in each group presented, McNemar p > 0.05 for all variables.
Subjects Living with
parents
In permanent
relation
Having
children
Working Unemployed Owning real
estate
Patients 5 20 12 25 5 17
Controls 2 21 12 29 3 17
Table 13. Education level for patients and controls in study IV. Number of subjects in
each group presented, McNemar p > 0.05 for all variables.
Subjects No professional
education
Professional
secondary
Professional tertiary Students
Patients 9 19 12 10
Controls 11 16 13 8
72
73
6 Discussion
The present study was conducted on the one hand to analyse the effectiveness and
safety of surgical tools used in craniosynostosis surgery and on the other hand to
assess the outcome of the surgeries performed using these tools. Among these were
resorbable plates and their endocranial use, distractor devices and their application
for PCVD and guides facilitating placement of the distraction devices.
The author studied the outcomes of metopic and coronal synostosis surgery,
posterior cranial vault distraction surgery and long-term results of sagittal
synostosis correction surgery.
Such evaluation tools as four point scoring, Whitaker categorization, aesthetic
evaluation from conventional photographs by independent panels using VAS score,
patients’ self-satisfaction using VAS score, cephalometric measurements from
cephalograms and finally 3D photogrammetric imaging were used and compared.
6.1 Methodological considerations
Outcome studies can be broadly divided into three categories: clinical efficacy
outcomes, patient-reported outcomes, and financial outcomes (Luce, 1999).
While study I and II belong to the group of clinical outcome evaluation from
the surgeons point of view, study IV aimed to evaluate outcome using tools from
all three categories of studies to collect data meaningful for both patients and
surgeons.
When performing studies on outcomes of surgical treatment the length of
follow-up is crucial. As Goodrich states, a child operated due to craniosynostosis
undergoes dramatic growth changes up to teenage years with the last point for
relapse at the beginning of the teenage years. Thus studies on follow-up of at least
12 to 15 years are required for adequate evaluation of surgical results (Goodrich,
2017). The strength of the present study was the length of follow-up for the sagittal
synostosis group and its patient-oriented design. So far this is the only study with
such long follow-up of patients with isolated sagittal synostoses.
Convincing proof of the superiority of one surgical method over the others
requires prospective randomized trials with follow-up times reaching at least in to
adolescence. The weakness of the study was the small number of patients.
The best study design for testing the reliability of the 3D photogrammetric
method as a tool for evaluation of volumetric changes would include 3D skull CT
imaging. However, CT is an ionising imaging method, and it is not used routinely
74
in the follow-up at the Oulu Craniofacial Centre. To use it only for the study
purposes was found to be unjustified.
One major weakness in all long-term follow up studies on craniosynostoses is
the lack of knowledge of the natural course of the disorder if no surgery was
performed. Thus it is not known what would have been the aesthetic appearance,
stigma of the malformation, somatic and mental health as well as general life
situation of the persons with craniosynostoses without treatment.
There can be a bias in case selection for the long-term follow-up study IV.
Since not all patients agreed to come, it is not known if the patients who agreed to
participate represent sufficiently well the whole cohort. However, this is a minor
bias that has to be accepted in studies like this. It is possible that both in the case of
patients and controls, the persons with higher level of education are prone to accept
the invitations to participate due to better understanding the significance of the
studies for the scientific research.
Neuropsychological tests are often included in the follow-up evaluation. Based
on the previous reports it was assumed that the patients were doing rather well even
if having minor defects in their neurocognitive performance. Thus it was found
unjustified to perform such tests to adult patients. Especially, when the findings
would not influence on the treatment, rehabilitation, education nor career planning.
On the contrary, knowledge of abnormal neurocognitive functions can have
negative effects on their self-esteem. The results of the follow up study IV
confirmed this assumption. The patients were doing as well as controls in many
aspects of their wellbeing.
Limitation of the present study IV was the lack of preoperative images. It was
not possible to evaluate how much the deformity was improved as a result of the
surgery.
Unlike many centres (Shah et al., 2011; Wilbrand et al., 2012) at the Oulu
University Craniofacial Centre no routine measurement of cephalic index (CI) is
done in craniosynostosis patients. Both CI and head circumferences are neither
reliable nor informative enough in the follow-up of these patients. This was in
accordance with a finding by Leikola and associates who found that CI correlated
poorly with intracranial volume in non-syndromic scaphocephalic patients (Leikola,
Koljonen, Heliovaara, Hukki, & Koivikko, 2014).
Attention should be drawn to the fact that the results of the long follow-up
study IV are applicable only to patients with nonsyndromic sagittal synostosis.
75
6.2 Surgical duration and bleeding (I, II, IV)
Analysis of operative time and blood loss was not a primary aim of the study. They
are presented more for descriptive purposes and no significant conclusion should
be done from these data. This data was not included in the original publications.
In all cases, except one, the osteotomized bone was detached from the dura
when performing PCVD. The perioperative bleeding was equal to those reported
in the literature when the bone block was left attached to the dura (Imai et al., 2002;
Steinbacher et al., 2011). While there were no major complications with detaching
the bone, there seemed to be no benefits from this. In general, leaving the bone
attached to dura is considered less invasive. We have adopted the approach and we
are in process of collecting results to analyse the influence of this change.
6.3 Surgeons evaluation of postoperative results
In both studies number I and IV, the same simplified 4-point classification (Table
2) was used to evaluate the postoperative aesthetic results from the clinicians’ point
of view. According to this classification (Table 6) the results of frontal remodelling
(study I) and scaphocephaly surgery (study IV) were either good or excellent in
over 90% of patients.
In study group I the only unsatisfactory result was due to the underlying
condition (craniofrontonasal dysplasia).
In sagittal synostoses the unsatisfactory outcome was related to failure of the
surgery to normalize the skull shape despite the use of the same remodeling surgery
in all these cases. Thus outcome was also probably related to the gravity of the
underlying pathology and the tendency to develop some degree of re-synostosis
after the primary operation. This finding highlights the variability and the
unpredictability of the long term results of the surgery for sagittal synostosis in a
small (10%) proportion of patients. Unfortunately the study design did not allow
reliable estimation of the re-operations rate after primary sagittal synostosis surgery
neither was there data available on preoperative severity of the pathology.
In the long follow-up study (study IV) the 4-point classification results were
compared with the panels’ evaluation of facial appearance using a VAS scale. There
was some congruency of the results. There were four cases from study IV, where
the surgeon evaluation during personal encounter showed the adult patients’
appearance to be fair. In these four cases, all panels and patients themselves also
evaluated their appearance to be worse when compared with the other cases.
76
However, the correlation between these two rating systems could not be properly
tested due to the small numbers of the group with fair outcome.
When grading the same patients according to the Whitaker classification, all
cases in the sagittal synostosis group with very long follow-up times (study IV) and
all but one case in the frontal remodelling group with short follow-up times (study
I) fell into the same class. This is because in the 4-point classification only one
grade corresponds to the necessity of re-do surgery. The Whitaker classification has
three out of the four classes dedicated to grade cases that require reoperations.
While evaluating the necessity for re-do surgery, which is crucial during the first
years of follow-up, the Whitaker classification was not sensitive enough to evaluate
the degree of residual dysmorphia later in life.
The 4-point scale is more specific to the questions of aesthetic outcomes. The
4-point scale is easily applicable to the evaluation of outcomes whether on personal
encounter, from the photographs or on the basis of the medical records.
6.4 Outcomes of operations with endocranial placement of
resorbable plates
Bone fixation is particularly challenging in coronal suture and metopic suture
synostosis. In the Oulu Craniofacial Centre these cases are treated by one-stage
fronto-orbital remodelling operations which, as mentioned earlier, require fixation
of the reshaped cranial bones. The region of operative interest includes the frontal
bone and the orbital rim, which comprise the upper part of the face and thus are
crucial for facial appearance. This sets a high standard for symmetry and shape.
The thin overlying soft tissues and skin in frontal area makes fixation even more
demanding since any unevenness of the bone-plate construct can be not only
palpable but may even be visible after operation (Freudlsperger et al., 2015; Wood,
2012). When placing the plates on the inner surface of the frontal bone, the
aesthetic result is better immediately after surgery. It also allows using plates in
very young patients with thin skin. These endocranial plates have been in use since
1998 and the description of the technique was first published in 2003 (W. Serlo et
al., 2003). Later the technique has been proven to be safe also by other groups
(Konofaos et al., 2016; Sauerhammer et al., 2014).
When placed endocranially the resorbable plates leave no “traces” in the form
of impressions or unevenness of the bone after the plate is resorbed which is a usual
finding in cases of superficial plate location. This phenomena of “traces” was
noticed earlier and named “bone memory” by Goodrich (Goodrich et al., 2012).
77
This can possibly be explained by a fact that osteoclastic activity dominates
endocranially and osteoblasts are more active at the outer surface of calvarial bone
where new bone formation is taking place. Thus the foreign material placed on the
outer surface interacts with new bone formation. This process explains intracranial
pseudo-migration of metal fixation material. The resorbable plates slow down or
prevent the new bone formation at their location until they are resorbed (Goodrich
et al., 2012; Sauerhammer et al., 2014).
Insufficient stabilization and difficulties while handling resorbable plates have
been reported earlier (Landes & Kriener, 2003). Choosing plates consisting of three
different polymers helps to avoid these inconveniences. During the operation the
plates made from several polymers were flexible enough to tolerate bending to
certain extent at room temperature. After warming in hot water the plates were
easily mouldable and rapidly solidifying when cooling, also sustaining repeated
warmings, if required. This property can be used when operating on children with
very thin and fragile bone. The bone was first reinforced with the plate fixed to its
inner surface and a newly created bone-plate construct was heated and moulded to
desired extent. This way breaking of the bone was less probable and had no
negative influence on the final result.
The plates cannot be placed endocranially in all parts of the skull. This method
has been applied mainly to the frontal area, where extracranial plates would cause
the most visible harm.
6.5 Outcomes of posterior cranial vault distraction operations
In study II the extent of the distraction was achieved as planned in all cases. In one
case completion of distraction required re-operation to resolve conflicts of the
device vectors. After the invention and application of the distractor guides (study
III) there were no such vector conflicts any longer.
PCVD allowed the attainment of a sufficient increase in intracranial volume
and in all patients the preoperative symptoms of raised ICP resolved after operation.
From an aesthetic point of view the results were acceptable also in cases with an
already scaphocephalic shape of the head. PCVD has less adverse effect from the
aesthetic point of view, which is important especially in patients whose shape of
the head was normal before operation (W. S. Serlo et al., 2011). In previous studies
(Goldstein et al., 2013; White et al., 2009) it was noted that PCVD has a positive
influence on frontal cranial morphology. There is a relief in frontal bossing
subsequent to posterior distraction in study group II. So far only three out of 14
78
syndromic cases from this series had to undergo fronto-orbital remodeling surgery
later in life. None of two patients with non-syndromic bilateral coronal synostosis
required additional cranioplastic surgery (by now 2.5 and 5.5 years of follow-up).
But since the protocol of the current study does not include routine CT scans, and
since 3D photogrammetry has been used only during the last year of the study
period, there is not enough data to objectively prove positive changes in the frontal
morphology. Thus there is only subjective data available to support this. The
analysis of remodeling of the frontal cranium after PCVD would be an interesting
topic for future studies.
The strength of the present study was that this technique was applied to patients
with variety of indications. While PCVD is an established method for patients with
syndromic craniosynostoses, it has been used also for shunt induced craniocerebral
disproportion and for other indications. The present study included eight patients
who had been operated earlier due to scaphocephaly and later presented with
symptoms craniocerebral disproportion confirmed by ICP measurement and thus
requiring re-operation. When performing PCVD in patients with recurrent
scaphocephaly the head shape became more scaphocephalic. In all these cases one
stage cranial vault remodeling, though being a better choice from aesthetic point of
view, was considered to provide insufficient increase in intracranial volume. Thus
a decision was made in favor of PCVD. The patients got relief of their symptoms
and the aesthetic outcome did not bother neither the patients nor their families.
One interesting indication for PCVD might be cranial expansion in treating a
primary Chiari type I malformation. It has been shown by Leikola and associates
that cranial expansion procedures reduce the extent of tonsil herniation in patients
with craniosynostoses (Leikola, Hukki, Karppinen, Valanne, & Koljonen, 2012). In
the present series one patient was diagnosed with Chiari I malformation. This
patient remained symptomatic after foramen magnum decompression and
duraplasty and the degree of tonsil herniation increased after this procedure. A
decision to perform PCVD was done. After the surgery the tonsils elevated 5 mm,
and the patient got relief of her symptoms. Although this indication for PCVD is
discussed by paediatric neurosurgeons, there is so far no published evidence
proving the feasibility of PCVD as a treatment option for primary Chiari type I.
6.5.1 Volume gain measurements and outcomes (II)
Volumetric changes were analyzed on the basis of plain cephalograms. This is a
mathematical approximation and not an exact volumetric calculation based on 3D
79
data. In spite of this the results correlate well with results of the studies performed
using 3D CT scans. The present study showed that an average increase in cranial
volume was 25% after PCVD. This is in line with previous studies reporting a 21-
29% volume gains with this surgical technique when calculated from 3D CT scans
(Goldstein et al., 2013; Nowinski et al., 2011).
Also these findings seemed to be in accordance with the first results of 3D
photogrammetric analysis. Five patients were imaged with this method both before
and after PCVD surgery. For these patients the average increase in ICV was 17.4%
as estimated from 3D photographs compared to 20.8% as calculated from
cephalograms.
Although, 3D CT is a gold standard when evaluating results of cranioplastic
surgery (Fearon, 2014), in the Oulu Craniofacial Centre 3D CT scans are not done
on routine basis but are reserved for cases with strict indications thus avoiding
ionizing studies whenever possible. Plain cephalograms expose patients to less
ionization and sedation is not required while taking these images. In the future 3D
photography will be applied more frequently in this field, thus further decreasing
need for ionizing studies. This method has already been applied to follow-up
outcomes in patients with sagittal synostosis and positional plagiocephaly
(Aarnivala et al., 2015; Le et al., 2014).
6.6 Complications and unforeseen events
Neither study I nor II revealed any complications causing permanent morbidity or
mortality. This is a very positive finding, because in general, surgery for
craniosynostosis is considered to be high risk procedure.
One of the usual intraoperative risks of any craniosynostosis surgery is a dural
tear during osteotomy phase. Even if all dural tears are detected and sutured
properly, later there can be CSF leakage from the wound or CSF collection under
the skin. Sometimes CSF leaks after operation can appear even without
intraoperative damage to the dura but as a result of screws “scratching” the dura
during distraction process (Goldstein et al., 2013). Two patients in the frontal
remodelling group (study I), and one patient in distraction group (study II) had such
CSF leak related complications. One patient had a dural tear detected and sutured
during PCVD surgery, but postoperatively the patient had CSF leak from the wound
and required lumbar drainage for several days. In the other two patients who had
frontal remodelling surgery there was no information on intraoperative dural tears.
One of the patients had a postoperative pseudomeningocele persisting for several
80
months after the primary surgery and required minor revision. Another patient was
diagnosed with a pseudomeningocele several months after surgery, but this
resolved spontaneously. None of these three patients developed meningitis, nor had
any other signs of infection. There was no compromise in ossification. Avoiding
and managing dural tears during surgery for craniosynostosis remains challenging.
6.6.1 Complications of operations with resorbable fixation (I)
Complications requiring re-operations were observed in three (11%) patients. This
was in accordance with previous publications where the same method was used
(Konofaos et al., 2016; Sauerhammer et al., 2014). None of these complications
was related to the resorbable fixation material itself.
It is reported that resorbable plates can cause sterile inflammatory reactions in
some patients (Wood, 2012). No cases with such reactions were observed in this
series, which was in accordance with findings in the studies by Konofaus and
Sauerhammer (Konofaos et al., 2016; Sauerhammer et al., 2014). One of the
patients diagnosed with a small spontaneously resolved pseudomeningocele several
months following surgery, possibly had a fluid collection caused by plate resorption
rather than CSF collection. But the finding was minor, with no skin changes nor
any signs of infection or other complaints. It is possible that sterile inflammation
could take place intracranially without any external signs. In the above mentioned
studies there was not a single case with intracranial inflammation among the
patients who had the postoperative CT scans done. One possible reason for decrease
in such inflammatory reactions may be explained by the currently used plate
materials. In the Oulu Craniofacial Centre the plates made from three different
polymers, poly-L-lactide (LPLA), polyglycolide (PGA) and trimethylene
carbonate (TMC), are used. There were no complications related to the plates
themselves independent of plate location. Therefore, resorbable plates made from
copolymers may be recommended.
6.6.2 Complications of distraction operations (II)
The detailed data on complications of distractions in study group II was not
included in the original publications. There were unforeseen events in more than
half of the cases in this study group. They mainly consisted of minor skin and
mechanical problems of the distractor devices during the immediate postoperative
and distraction periods. There were no cases of permanent morbidity or bone flap
81
resorption. Although distraction was performed to the planned extent in all cases,
according to our experience informed commitment of the parents is important when
planning a distraction procedure.
The number of distractors to use is a topic of debate. Some authors intend to
place just one to two devices in order to avoid mechanical complications related to
the devices (Goldstein et al., 2013; Thomas et al., 2014; White et al., 2009; Wiberg
et al., 2012). In the Oulu Craniofacial Centre it is preferred to use four distractors
whenever feasible, as it not only allows better stability but also deals with the
possibility of distractor failure allowing the distraction to continue to completion
with the remaining two or three devices. This occurred in two out of 31 cases in
study group II.
In spite of the fear of infections due to external rods and thus open skin wounds
that could serve as a portal of entry for infections, there was not a single case of
systemic infection requiring antibiotics in this study population.
Routine preoperative CT or MR angiograms were not performed to evaluate
the vasculature of the region of surgical interest at the time when this series of cases
was operated. Since then the authors have become aware of potential abnormal
cerebral venous drainage through the planned bone flap and have added MR
angiogram when necessary in the preoperative evaluation protocol.
The subject of complications and unforeseen events related to distraction
operations will be further analyzed in the next publication.
6.7 Outcome of surgically treated patients with sagittal synostosis
as adults (IV)
The aim of study IV was to fill the gap in knowledge on outcomes from patients’
and third persons’ point of view, to find out how the patients are really managing
in adulthood when compared to co-eves or controls.
6.7.1 Results of different operative methods (IV)
In the present study there was no difference in outcomes regarding different
operative techniques for sagittal synostosis. However, the aim of this study was not
to compare different surgical techniques, and it would even be impossible in such
retrospective series.
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6.7.2 Aesthetic evaluation by participants and panels (IV)
To the author’s knowledge, study IV was the first study where adult
craniosynostosis patients were asked to evaluate their own satisfaction with a 100
mm VAS scale with a lay panel evaluating postoperative aesthetic outcome with
the same scale.
One very important finding of the present study was that adults who were
treated for sagittal craniosynostosis were equally satisfied with their appearance
compared to controls independently of age or gender.
Both panels of independent evaluators did rate patients’ appearance to be
slightly less attractive when compared to controls. The difference was statistically
significant. However, it was less than 10% out of 100 mm VAS scale (7 mm in case
of the dentists panel and 6 mm in case of the lay panel’s evaluation). This was in
accordance with a previous study by Panchal et al, where assessment of the head
shape from photographs was performed by panels of lay and professional observers
in the children operated due to sagittal synostosis in the early infancy. In this study
controls also tended to receive slightly higher rankings, but the difference was not
significant (Panchal et al., 1999).
The difference between controls and patients group in panel evaluation was
less than 10 mm. The small difference between the groups raised the question of
clinical significance of that difference. Responsiveness of the magnitude of change
of any outcome measurement instruments is to be clinically correlated and is open
to interpretability (Rhee & McMullin, 2008). In 100-point scales like HRQOL
scales a 10-point gain is used as an Minimum Clinically Important Difference
(MCID) (Thoma & Ignacy, 2012). In Medline no standard method was found for
measuring MCID in VAS scales used for evaluation of aesthetic results of surgery
neither earlier (Beaton, Boers, & Wells, 2002) nor currently when the search was
performed by the author.
It was previously found that when assessing certain traits in facial shape from
photographs by panel evaluators, the reliability was likely to be improved by
additional training and further exposure of panel members to the spectrum of
possible deformities (Asher-McDade, Roberts, Shaw, & Gallager, 1991; Bendon et
al., 2014). This can explain why in the studies evaluating results of orthodontic
treatment by panels of lay persons and dentists, the panels of dentists have been
stricter in their evaluations (Kokich, Kokich, & Kiyak, 2006). Since in this study
facial attractiveness was evaluated in general, not specifically seeking for certain
traits neither comparing pre- and postoperative images, it was found unnecessary
83
to educate the panels. Thus panels were shown in advance before the slide show
only one slide of a healthy person not included into the study group itself (Fig. 6).
Asher-McDade and associates have shown that with increasing the number of
panelists from three to six the reliability was increased from 0.82 to 0.90, thus
allowing a decreased influence of variation between individual evaluators that is to
be expected when the facial appearance is scored (Asher-McDade et al., 1991). In
this study interobserver reliability was for individual members of panels moderate
with p = 0.573 for the dentists panel and p = 0.555 for the lay panel. When
increasing the number of observers in the dentists panel from four to five, the
reliability increased up to p = 0.840.
When a person is asked to judge “attractiveness” of someone’s face these
judgements appear to reflect sexual attractiveness. According to Rhodes, contrary
to the popular assumption that beauty is in the eye of the beholder, there appears to
be an agreement between men and woman independently of cultural background in
the question about what traits make the face attractive. These biologically based
preferences are averageness, symmetry and sexual dimorphism (Rhodes, 2006).
Thus surgery should aim at restoring facial symmetry and make the shape of the
face and head as close to average as possible.
There was no correlation between third persons evaluation of facial appearance
and satisfaction with own facial appearance neither in patients, nor in the control
group. In contrast with these findings, in cases of patients seeking treatment for
malocclusion or aesthetic reasons there was usually some correlation found
(Badran, 2010; Silvola et al., 2014).
A lack of such correlation in the present study was probably due to its design.
The patients were invited to participate in the study, and they were not seeking
treatment.
This finding was also in accordance with the studies on body image. Research
done on a number of conditions (e.g. craniofacial anomalies, amputations or burns)
found that objective severity of a disfigurement does not predict extent of distress
or negative body image (Tiggemann, 2015). This probably explains why visibility
of the scar seemed to have no influence on satisfaction with own appearance in the
study IV patients.
Though there was no statistical difference between patients and controls in the
matter of self-satisfaction with facial appearance, there were slightly more patients
than controls among those who graded their satisfaction below general. However,
none of these patients during the interview appeared to be significantly dissatisfied
with their appearance. For example, none of them showed any interest in further
84
correction of facial shape or the scar. Though all four of the patients who admitted
that the scar bothered them belonged to this group of less satisfied patients, the scar
did not seem to be the only or main reason for such dissatisfaction. Also one
interesting finding was that none of the patients with parasagittal direction of the
wound complained about the scar. Because of the small size of these subgroups
only limited conclusions can be drawn.
6.7.3 General life situation and health issues in patients treated for
sagittal synostoses (IV)
It is essential to assess the impact of the disease and its treatment process on the
adult patients when compared with co-eves. It is also essential to assess the degree
of psychosocial impact of the disease and its treatment process on patients and their
families.
One positive finding was that being operated on sagittal synostosis did not
influence patients’ somatic health, education level, employment status or finding a
partner. There was no significant difference between the patients and controls in
any of these aspects.
According to the Eurostat regional book 2016, 4% of young people aged 25 –
34 live with their parents in Finland (Kotzeva, Brandmüller, & Önnerfors, 2016).
That was the case in the control group where two persons were living with parents.
In the patient group 5 (12.5%) lived with their parents. This difference was not
significant, and can be explained by small study sample. Also this study included
younger persons than the above mentioned Eurostat data.
According to the same Eurostat year book, in general in Finland 42.7% of
persons aged 30 – 34 years have tertiary education (Kotzeva et al., 2016). Among
patients 30% and controls 32.5% had tertiary education. This was less than the
average in the population, but the study IV participants were younger and
approximately 23% were still studying in order to get higher education. For the
analysis students’ education was graded according to their highest accomplished
education level. Thus for comparison, in the case of medical students for example,
even if they were in their last year of studies, their education level was still
classified as primary, not as professional tertiary education.
The general unemployment level in Northern Finland in 2015 was 10 – 15%
among persons aged 15 – 74. It was much higher (over 20%) in the age group
between 15 – 24 years (Kotzeva et al., 2016). In this study population, only five
patients (12.5%) and three controls (7.5%) were unemployed and not studying.
85
According to the present study IV, regarding patients with isolated sagittal
synostosis, there was no difference in somatic health compared to controls. Also no
correlation between treated sagittal synostosis and prevalence of headaches or
migraine was found. Both, patients and controls, had same frequency of mental
problems. A history of mental problems surprisingly did not influence the study
persons satisfaction with their own appearance.
6.8 Clinical implications and future perspectives
The study has shown that it is possible to use nonionizing 3D photogrammetric
imaging to evaluate volume gain after cranioplastic surgery. Further studies will
focus on validating the method comparing to cephalograms and CT scan methods.
While, the 3D-camera is expensive, once the investment is made, the use of the
camera requires no additional expenses, it is neither time consuming nor technically
demanding. Application of this method for follow-up of results of other treatment
modalities should be studied, including frontal remodeling, sagittal synostosis
surgery and conservative treatment of positional plagiocephaly. This method could
also be included in the diagnostic and treatment protocols of the patients with
craniosynostoses once validated. It provides an easy and precise method of routine
clinical documentation of the changes in patients’ appearance during the treatment
and follow-up.
Another application of 3D photogrammetric imaging will be to study the effect
on the frontal cranial shape and volume after PCVD.
A standardization of methods for the evaluation of the aesthetic outcomes will
facilitate the evaluation of the results between various surgical methods. However,
this will remain very challenging. As stated by Goodrich (Goodrich, 2017) an
estimation of the aesthetic results with a follow-up of less than 12 to 15 years is of
minor value.
Application of PCVD as a treatment modality when dealing with primary
Chiari type I malformations might be revolutionary. However, future prospective
and randomized studies will show the suitability of this method.
Regarding the skull growth after PCVD the concern arose about timing of
device removal after the surgery. Maintaining metal constructs fixed to a rapidly
growing young child’s skull can at certain time periods after surgery, when the brain
had already occupied the space “won” by the surgery, may start restricting further
skull growth (Di Rocco, personal communication, December 2016). Also the
86
resorbable plates positioned over the patent sutures can have the same growth
restricting influence. This topic should be addressed by future research.
87
7 Conclusions
Generally patients treated for craniosynostoses managed in life as well as controls
with equally good aesthetic outcomes. The operative techniques including
resorbable plates or distractors were found to be effective.
In answer to the specific questions the following may be concluded:
1. The feasibility of endocranial fixation in craniosynostosis surgery was
established. Good or excellent aesthetic results were seen in 96% of cases as
evaluated by a surgeon at follow-up. Only three patients out of 27 had
complications that required revisions. No mortality or permanent morbidity,
nor complications related to endocranial placement of the plates were seen. (I)
2. Posterior cranial vault distraction allowed a mean increase of 25% in
intracranial volume. It proved to be an effective technique for treatment of a
variety of craniosynostotic conditions with significant shortage of intracranial
volume. 3D photogrammetric imaging is a suitable non-ionizing method for
evaluation of cranial volume increase following distraction. (II)
3. A new tool was developed and successfully used for the intraoperative
guidance of distractor device placement with congruent vectors (III, II).
4. Patients treated for sagittal synostosis were equally satisfied with their facial
appearance as their age and gender matched controls. Independent panels
found patients appearance to be slightly less attractive, but the difference was
only 6-7 mm on a 100 mm Visual Analogue Scale, representing a low clinical
significance. Patients’ socioeconomic situation such as education, housing,
employment and marital status equaled controls. They had similar frequencies
of headaches, mental problems or health issues as the controls. (IV)
88
89
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Original publications
I Salokorpi, N., Sinikumpu, JJ., Iber, T., Nestal Zibo, H., Areda, T., Ylikontiola, L., Sándor, G.K., Serlo, W. (2015). Frontal cranial modeling using endocranial resorbable plate fixation in 27 consecutive plagiocephaly and trigonocephaly patients. Childs Nerv Syst, 31(7), 1121-8.
II Salokorpi, N., Vuollo, V., Sinikumpu, JJ., Satanin, L., Nestal Zibo, H., Ylikontiola, L., Pirttiniemi, P., Sándor, G.K., Serlo, W. (2016). Increases in cranial volume with posterior cranial vault distraction in 31 consecutive cases. Neurosurgery, EPUB April 2017.
III Salokorpi, N., Sándor, G.K., Sinikumpu, JJ., Ylikontiola, L., Serlo, W. (2013). A new technique to facilitate optimal directions for cranial distractor implantation. Childs Nerv Syst, 29(8), 1359-61.
IV Salokorpi, N., Savolainen, T., Sinikumpu, JJ., Ylikontiola, L., Sándor, G.K., Pirttiniemi, P., Serlo, W. Outcomes of 40 nonsyndromic sagittal craniosynostosis patients as adults: A case-control study with 26.5 years of postoperative follow-up. Manuscript.
Reprinted with permission from Springer (I, III) and Oxford University Press (II).
Original publications are not included in the electronic version of the dissertation.
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