Craniosynostosis, defined as the untimely and premature closure of a calvarial suture in an infant, leads to well-defined and described phenotypic deformational changes of the neocranium, endocranium, or both. The first recorded description in modern times is ascribed to Otto in 1830. Twenty-one years later, Rudolf Virchow, a German pathologist, developed a classification system for the phenotypes of deformities associated with craniosynostosis. The underlying principle in his theory is that bone growth takes place perpendicular to the suture, and premature closure leads to defined skull shapes based on compensatory brain growth in other areas of the skull. Dr. Odilon Marc Lannelongue, a French surgeon, was the first to report a surgical correction for craniosynostosis in 1890. His procedure consisted of two parallel strip craniectomies lateral to the midline, leaving a strip of bone over the sagittal sinus. Lannelongue performed this operation on 59 patients and reported only one death. This work was quickly adopted by other surgeons, including Dr. L.C. Lane of San Francisco in 1892. Since the introduction of the original surgery in 1890, a multitude of surgeries and procedures have been developed and instituted throughout the world. In 1967, French surgeon Paul Tessier performed the first “craniofacial” operation and thus instituted and pioneered the discipline of craniofacial surgery. Subsequently, craniofacial techniques championed by Tessier were used for the treatment of craniosynostosis. Many different types of extensive reconstruction procedures are now classified under the term “calvarial vault remodeling” (CVR) and have become the standard of care for managing this condition.
Epidemiology and Other General Facts
It has been generally estimated that craniosynostosis develops in about 1 in 2500 births worldwide. The incidence varies according to the affected suture. Prevalence is approximately 3.1 to 6.4 in 10,000 live births and reportedly rising. A 2016 study in the Netherlands found a prevalence of 7.2 per 10,000 live births. This study also showed an annual increase prevalence for total craniosynostosis of 12.5%, sagittal (+11.7%), and metopic (+20.5%) from 1997 to 2013. Another study in Australia indicated the prevalence there to be 3.1 per 10,000 live births and an overall increase in incidence on nonsyndromic craniosynostosis of 2.5% per year. Metopic synostosis was found to have increased by 7.1% over a 25-year period. It has been our experience over the last 25 years that there has indeed been an increase in the overall incidence of metopic synostosis, with this suture accounting for the second highest number of cases after sagittal synostosis. It is also estimated that up to 20% of the cases are caused by specific single gene mutations or chromosomal abnormalities. The most commonly mutated genes include FGFR2, FGFR3, TWIST 1, and EFNB1. Most genetically determined craniosynostosis is characterized with an autosomal dominant inheritance pattern, with half of the cases being new mutations and most commonly present in syndromic patients. Craniosynostosis has been described in more than 150 syndromes but most frequently, it has been associated with Apert, Crouzon, Pfeiffer and Saethre-Chotzen syndromes. ,
In a 10-year prospective study, a genetic diagnosis was achieved in 21% of cases, with 86% being single gene disorders and 15% being chromosome abnormalities. FGFR2 accounted for 32% of all genetic cases, FGFR3 for 25%, TWIST for 19%, and EFNB1 for 7%. Other associations found included the following genes with the corresponding syndromes: FGFR1 (Pfeiffer syndrome), POR (Antley-Bixler syndrome), RAB23 (Carpenter syndrome), ESC02 (Roberts syndrome), GL13 (Greig syndrome), JAG1 (Alagille syndrome), KRAS (Noonan syndrome), FGFR2 (Apert syndrome), and FRFR3 (Muenke and Crouzon syndromes).
A persistent debate in the literature has been whether single suture craniosynostosis causes decreased intracranial volume and elevations in intracranial pressure (ICP). Several studies have found little difference in the intracranial volume among the different types of craniosynostosis , ; as such, craniosynostosis has not been found to be associated with low or lower intracranial volumes. This is most likely due to compensatory brain growth in other areas secondary to other patent sutures. Likewise, hydrocephalus has not been found to have a higher incidence in patients with craniosynostosis, with an estimated incidence of 0.28% in infants with nonsyndromic synostosis. This is the same incidence of hydrocephalus and shunting seen in the general population. However, even though craniosynostosis has not been shown to be associated with decreases in intracranial volumes, multiple studies have shown a positive correlation with increased intracranial pressure. A study which defined elevated ICP as greater than 15 mmHg, found an incidence of intracranial hypertension of 20%, with a large number being found in syndromic cases. Another study found an incidence of intracranial hypertension in 30% of the affected children and included a 14% incidence in infants with single suture synostosis. Thompson also found an incidence of increased ICP in 15% of single suture synostosis and 24% in nonsyndromic craniosynostosis. These findings raise the question of the need for early rather than delayed surgery in these patients. It has been our experience with the use of minimally invasive early surgery to find that most of our parents consistently report improvement in the child’s behavior and development soon after surgery. Anecdotally, we are told that the baby is no longer irritable and fuzzy, that the child sleeps and eats better. Motor function has also repeatedly been found to improve. We have also found this to be the case on many postoperative follow-up clinic visits. We did (unpublished) a prospective study looking at irritability and fuzziness of our endoscopically treated patients, assessing frequency and severity on a scale from 0 to 5. Parents were asked to rate their children before and at 1 and 2 months after surgery. Our results indicated a significant decrease in both parameters as related to frequency and severity ( P < .001). These findings seem to indicate that the cause of the patient’s irritability immediately subsided after surgery. That would not be as evident with the much more invasive and traumatic CVR surgery.
Brain Growth and Timing of Surgery
Brain growth and development is a complex and dynamic process in the first years of life. Total brain volume increases by 101% in the first year of life and is followed by a 15% increase in the second year ; grey matter growth increases by 149% in the first year and accounts for the majority of cerebral growth. The cerebellar volume increases by 240% during the first year. As such, premature sutural closure can have significant effects on a rapidly growing brain, particularly in the first year of life. The ultimate effects of craniosynostosis on overall cognition and neurodevelopment are not well known. A number of studies have been done looking at this issue, yet no clear consensus can be had. Some studies have looked at maldevelopment of speech, behavior, and cognition. One study showed a 47% rate of neurocognitive developmental abnormalities in children aged 5 years or older who had undergone corrective surgery. Another study found a 37% rate of speech delay, language, and cognitive impairment in children with nontreated sagittal synostosis. Thus, it has been difficult to discern if the neurodevelopmental problems arise from the craniosynostosis itself or the surgery used to correct the condition.
Although our team performed a number of open procedures over the years to treat craniosynostosis, we became particularly disillusioned with the lack of consistency of the short- and long-term results. Whether similar procedures such as pi or reverse pi procedures were done, or more extensive calvarial vault expansions and reconstruction such as the Marchac transpositions, the results were consistently suboptimal and inconsistent. The use of distractors did not help improve the poor results of single isolated craniosynostosis. It was this lack of reliable and consistent results that led us to rethink and reevaluate our surgical approach. Hence, relying on the concept of extreme brain growth during the first year of life, coupled with the belief that the brain is the primary driver of head and facial growth, we conceptualized, in the mid-1990s, that ultra-early release of the closed suture should allow the brain to develop normally and reshape the misshapen face and cranium. Contrary to Moss’ theory, which in essence states that the skull base plays the primary role in the pathophysiology of craniosynostosis, we believe that the skull base changes are only secondary to calvarial sutural stenosis. Furthermore, early release of the suture should solve the primary problem in isolated, nonsyndromic synostosis. The problem remained how to do surgery safely in very young children only several weeks of age. Utilizing concepts learned from endoscopic neurosurgical procedures, we decided to apply these concepts to treating craniosynostosis infants. Our original goals included minimizing the following factors: (1) surgical exposure; (2) surgical time; (3) intraoperative blood loss; (4) blood transfusion rates; (5) length of hospitalization; and (6) complications; and most importantly, to improve outcome consistency and better long-term results. The techniques described in this book are the work done by our team over the last 25 years using these principles and techniques. The results, we believe, speak for themselves.
Our current treatment protocol calls for treating affected infants as soon as the diagnosis is made and surgery can be arranged. The most ideal time is 8 weeks of age. This is an ideal time for a number of reasons, including the fact that the calvarial bone is very thin, malleable, and easy to cut. The diploë is almost nonexistent or very small and as such, bone bleeding is minimal when the osteotomies are performed. Because of the rapid brain growth that occurs during this period, the correction of the deformity happens rather quickly. This is of particular importance in a coronal synostosis in which the face, orbit, forehead, nose, and skull base are all affected. Early release allows the brain to correct all these deformities, as can be seen in the outcomes shown in that Chapter 9 . In patients with metopic synostosis and significant trigonocephaly and hypotelorism, both of these deformities are completely corrected when infants are operated on at an early age. In the cases of bicoronal synostosis, the forehead and facial advancement can be seen by the end of the first year of life. Even in cases of syndromic bicoronal synostosis, early bilateral coronal sutural release negates the need for a fronto-orbital advancement. Our original recommendation for timing of surgery was 3 months of age or younger. Subsequent experience allowed us to recommend surgery up to 6 months of age. In efforts to set an upper limit, we continued to expand our timeline, and in selected cases, we operate on children of 9 or 10 months of age and still achieve superior results to those obtained in patients operated with CVR techniques.
Postoperative Orthosis Therapy
For thousands of years, indigenous people have used a number of contraptions and apparatuses to mold the head of infants in their belief that certain head shapes lead to increased beauty and power. In intentional cranial deformation as a “process of dynamic distortion of the normal vectors of infantile neurocranial growth through the agency of externally applied forces” a number of constrictive devices have been utilized and include wooden boards and planks, cloth ties, bands, manual molding, stones and rocks placed on cribs. Other appliances have also been tried and successfully used. The reason for these practices includes the goals of creating class and tribal distinction, enhancing sexual prowess or intellect, and, in others, intimidating opponents in battle. The rationale then exists that if a normal head can be misshaped, can a misshaped head be similarly corrected? During the treatment of our craniosynostosis patients with CVR procedures, we began to successfully use molding helmets in efforts to minimize relapse and the development of postoperative deformity. Our results definitely improved with the use of postoperative orthoses. When we began to release stenosed sutures endoscopically, we immediately began to use these molding orthoses soon after surgery with great success and have continued to do so until current days. Notwithstanding this, the use of helmets has generated a significant amount of controversy and angst amongst craniofacial surgeons treating these patients. Although these helmets provide the patients with superb results and minimal problems or complications, a lot of resistance is still present from many surgeons treating these children. It is our strong belief that these orthoses should be an integral part of the therapy. We have carefully studied all of our patients and no brain growth restriction has been found in any of them ( Fig. 3.1 ). Careful follow up on head circumferences indicate no deviation from expected isocurves for the individual patient. Complete neuropsychologic testing has not shown any negative effect of cranial molding.
