CURRENT DIAGNOSIS AND TREATMENT IN CRANIOSYNOSTOSES

Crouzon disease is difficult to predict. According to the series described by Arseni et al., (1985) [4] Crouzon disease represents 3.4% of all craniosynostoses.

Apert Syndrome (acrocephalosyndactilia)

The French paediatrician Dr. Eugene Charles Apert (1868-1940) described nine cases of syndactilia in 1906 associated with acrobrahicephaly. Known today as Apert syndrome, this entity is characterized by coronary craniosynostosis, syndactyly, symphalangism, (fusion of the phalanges of a finger), the merger of radius and ulna, with varying degrees of mental retardation (Figure 11). It is considered to have a very well delimited phenotype, proved on a wide range of cases with craniofacial changes and cognitive impairment [9].

Figure 11. Apert syndrome including: turibrahicephaly, ex-ophthalmos, maxillary hypoplasia and syndactyly. The compromised airways due to maxillary hypoplasia required tracheostomy (Reproduced with permission from Cunningham et al. [10])

The incidence of Apert disease is estimated by Arseni et all at 3% of all craniosynostoses. In Apert syndrome an autosomal dominant transmission has been demonstrated in association with advanced paternal age. Apert syndrome treatment consists of surgical correction of the craniosynostosis, the facial hypoplasia and of sydactilia.

Trilobate skull (Kleeblattschadel, Cloverleaf skull)

At birth or in utero period, the child has got a “clover leaf ” shaped skull, marked exophthalmos, flattened thumb and the thumb of the foot medially deviated. Associated malformations may also be present, such as atresia or stenosis quantum, laryngo-tracheal abnormalities, elbow ankylosis or its synostosis, hydrocephalus, seizures and intellectual deficit (Figure 12).

Figure 12. Trilobate skull

The incidence of this craniosynostosis is extremely rare, Arseni et all (1985) in the studied series notes 1.7% of total craniosynostoses [4].

Pfeiffer Syndrome

In 1964, Rudolf Arthur Pfeiffer geneticist at the University of Münster described a syndrome which now bears his name as “Dominant erbliche akroceph-alosyndaktylie (hereditary dominant acrocephalosyn-dactilia) [23]. The main features of this craniosynostosis are raniosynostoza, hypertelorism, hypopalsia of the middle level of the face with its exaggerated widening, short polices and haluces and various forms of brachidactyly [8].

Carpenter’s syndrome

Carpenter syndrome is an autosomal recessive transmitted craniosynostosis associated with obesity, heart malformations, polydactyly, foot brachidactyly, syndactyly and middle phalanx hypoplasia of the fingers. Mental retardation is not found in all cases.

IV. CRANIOSYNOSTOSIS ACCOMPANYING SYNDROMS

When besides craniosynostoses, there are other abnormalities or developmental delays present, one must take into consideration the possibility of a malformative syndrome. Today there are over 180 described syndromes associated with craniosynostosis and significant progress has been made in understanding their clinical and molecular aspects [7].

Mutations in genes encoding fi broblast growth factor receptor 1, 2 and 3 (FGFR1, FGFR2, FGFR3),TWIST1 and MSX2 (muscle segment home box 2) determine the most common and well characterized syndromes. In 85% cases of non syndromic craniosynostosis,no genetic mutations have been identified.

Primary evaluation of abnormal skull shapes

Primary assessment of patients with craniosynostoses raises many issues for paediatric neurosurgeons.As symptom, the abnormal shape of the skullmay have multiple aetiologies and it creates different problems both in terms of surgical and non surgicaltreatment [27].

Perinatal examination, the development of the curve occipito-frontal circumference (cranial perimeter)and the newborn physical examination, including palpation of fontanels, of bones and sutures will givean initial impression on the conditions which generated the pathological changes in skull shape.

When it is proved that changes in skull shape aredetermined by anomalies of the bones and/or sutures,the neurosurgeon has to answer three questions [7]:

1. If they produce a focal compression on a certain portion of the brain.
2. If they induce intracranial hypertension.
3. If not only do they have the potential to producean inaesthetic deformity but are significant enough tocause a delay in psychosomatic development [27].

Any showing signs of intracranial hypertension syndrome require emergency surgery. If the changesare just inaesthetic, they do not require emergency surgery. But, for a good result, it is desirable that certain corrective procedures should be performed when the child is still young (during the first six months oflife).

DIAGNOSIS

Many of the cases diagnosed as craniosynostosis are actually flattened bones due to the baby’s head position.It is well known the so-called “lazy lambdoid“craniosynostosis, determined by the extended position of the child face-up, the pressure of the cushion being exerted on the lambdoid suture [7]. If such a situationis suspected, parents should be instructed to positionthe baby’s head so as to prevent compression and the head shape will return to normal in 6-8 weeks [14].

Diagnosis of craniosynostoses is based on:

I. Physical examination consisting of palpationof the bony prominence of the suture synostosis. Occipito-frontal circumference measurements (cranial perimeter) may be normal, even in the presence of skull deformation.

II. Simple skull X-rays show that:

a) lack of normal transparency of the suture. Insome cases, however, despite the normal appearance of cranial suture on plain radiography (even on CT),there may be a focal formation of bone spicules [14].

b) Calvary with closed sutures, diastatic suture anderosion of the Turkish saddle where intracranial pressureis increased.

III. Brain CT scan with ‘bone windows’

a) clearly shows the outline of the head.

b) may reveal thickening and / or a ridge in thesynostosis area.

c) demonstrates the presence of hydrocephalus.

d) may show frontal expansion of subarachnoidspace.

CT scans with three dimensional reconstruction(3D) allow easy, overall viewing of skull anomalies (Figure 13).

Figure 13. CT scan with tridimensional (3D) reconstruction:Scaphocephaly

IV. Technetium bone scan may be performed indoubtful cases [14]. It is now completely abandonedas for of investigation.

V. MRI investigation is usually reserved for cases with associated intracranial malformations having no value in craniosynostosis,

VI. Ophthalmologic examination reveals phenomena of papilledema.

VII. Neuropsychological examination reveals irritability in the first phase followed gradually by psychomotor retardation [14].

Differential diagnosis of craniosynostoses

The main diagnostic problem is to distinguish between the skull shape changes in the newborn and true craniosynostoses. The skull of the newborn has aparticular form which determines its great flexibility during birth. The newborn’s changes in head shape are the result of forces acting on it in the uterus during child birth and then during the early postnatal period.Typical round shape of the newborn’s head results from the symmetrical action of these forces at the level of the skull [27].

Given the inherent flexibility of the skull during its development a variety of craniofacial anomalies may occur due to compression of the skull ‘in utero’. [11,12, 13, 16]. Obstetrical factors predisposing to craniofacial anomalies are: first pregnancy, early descentin maternal pelvis, anomalous positions of the foetus,uterine anomalies (bicornuate uterus), the presenceof twins or triplets [27]. Most of these abnormalities resolve spontaneously within the first months after birth, due to remodelling forces and the rapid growthof the brain [6].

The main Differential diagnosis is with microcephaly-growth anomaly of the whole encephalon that causes cranial size reduction. Under these conditionsthe brain expansion is minimal leading to the emergenceof a small skull with harmonic aspect without phenomena such as exophthalmia or papilledema. Ofcourse, CT and MRI are relevant for diagnosis.

TREATMENT

The only treatment capable to prevent or suppress the syndrome of intracranial hypertension and to ensurenormal brain development is surgery.

The general principle of surgical decompression should be a physiological decompressive craniectomy to loosen the synostosed suture and to delay or suppress reossification until the age of normal sutureclosure [3]. Neurosurgical intervention types have been perfected over time and today the following are known:

— simple linear craniectomy removing the synostosed suture.

— extensive craniectomy recommended in completeand complex craniosynostoses,

— extensive craniectomies with bone reconstructionsbased on 3D CT data – which constitutethe current procedures due to possibilities to use the craniotome and high speed drills (portions of bone are reshaped and set up to achieve a skull with normal appearance).

The optimal time for surgical correction is before the occurrence of suture fusion. Early surgery benefits from the plasticity of the child’s skull a quality that suffers a significant loss by the end of the first year of life. This plasticity can be reconfigured using the method of radial and / or linear osteotomies combined with controlled fractures [17]. Early correctionhas also the advantage of normal brain growth andremodelling of the skull contour and of preventing compensatory skull growth. Without surgery, skull deformation deteriorates in time [1]. Most authors recommended surgical treatment within the first 3 months [7].

After the normal contour was restored by surgery,brain growth will keep this shape. When surgeryis practiced early, it is preferable to use absorbable plates, so as not to influence remodelling due to brain growth. When the correction takes place later,after the merger of the sutures and after brain growthis largely completed, a rigid fixation is preferable.Current methods allow remodelling processes based on preoperative 3D CT assessment and based on current modern instrumentation for osteotomy and fixation.

The preservation of the venous sinuses during the surgical procedures is of particular importance, as there is an increased risk of intercepting them during remodelling processes. Performing angio CT andangio MRI exams in the venous phase is compulsory.The excessive loss of blood has to be prevented due to young age of patients exposed to hemorrhagic shock [17, 22].

We will present some guiding surgical elementsfor different types of craniosynostoses.

In case of premature closure of metopic suture surgery must reshape normal contour of the forehead,bringing orbital arches in the normal position, widening the skull in the temporal region and correcting hypotelorism.

When the coronary suture is unilaterally synostosed,it causes clogging of frontal region unilaterally and of parietal bones. To restore the normal contour of the frontal region the surgeon must place the frontal bones and the supraorbital rim further forwards bring orbit to the front and to rebulge the frontal-parietal ipsilateral region. At the same time, the surgeon must flatten the controlateral part. Bifrontal craniotomy is a practiced,including coronary suture and remodelling is done usingradial osteotomy and controlled fractures [22].

Moving the orbital arch forward is made using orbitosteotomy as that described above for the metopicsynostosis (Figure 14 d). If the ipsilateral temporal region increased in excess, a temporal craniotomy and bone reconstruction may be practiced using radial osteotomies[17].

Figure 14. Unilateral coronary synostosis: a. Primary pathologicaland compensatory modifications. b. Bifrontal craniotomywith remodelling. c. Superior orbital fissure drilling d. Movingforward of orbital arch. e. Moving forward the temporal muscle.Reproduced with permission from Jane JA, Dumont A, Lin andJohn A. Jane K: Craniosynostosis, p. 445-460, in Anne J. Moore,David W. Newell ‘neurosurgery Principles and Practice’, SpringerLondon, 2005 [ 17].

Bilateral synostosis of coronal suture restricts anterior-posterior growth of the skull, compensatory growthoccurring in the metopic, sagittal and squamous suturesdetermining increases in height of the skull, producingturibrachicephaly. (Figure 15). Surgery shouldreduce the height of the skull and widen the narrowedfrontal-orbital region. To reduce the height of the skulland increase the anterior-posterior diameter, a calvariectomyof approach is needed. (Figure 15b) A bifrontalcraniotomy together with a parieto-occipital craniotomyis practiced, uplifting the bone flap in one piece,between the two remaining only the sagittal suture and the two parietal bones. The anterior and posterior flapsare remodelled using radial osteotomies and controlled fractures. The remainder occipital bone is fractured andreshaped so that the skull is re-expanded backward.(Figure 15 d, e) [17].

Figure 15. Bilateral coronal synostosis: a. Primary and compensatory pathologic modifications b. Bifrontal-parietal and parietal-occipital craniotomies. c.Reconstruction of orbital ridged, e. Reconstruction of cranial vault .Reproduced with permission from: Jane JA, Dumont A, Lin Kand John A. Jane SA: Craniosynostosis, p. 445-460, in Anne J.Moore, David W. Newel ‘Neurosurgery Principles and Practice’,Springer London, 2005 [17].

Sagittal suture synostosis causes several distinct clinical presentations that require different surgical interventions. The most important abnormality associated with premature closure of this suture is narrowingof the skull. Compensatory growth occurs in the coronary and lambdoid sutures and determines the increase of anterior-posterior diameter.

Complete synostosis of the sagittal suture determined anterior and posterior deformation of the skull,producing dolicocephaly or scaphocephaly and surgical correction involves the whole the skull, reshaping both scaphocephaly frontal bulging and occipital projection.We present below the synostosis of anterior sagittal suture and the method of osteotomy (Figure16) and posterior sagittal suture synostosis using the adapted osteotomy procedure (Figure 17), aiming atexpanding the brain and at shaping the skull.

Figure 16. Synostosis of anterior sagittal suture: a Primarypathological and compensatory modifications and craniotomylines. b. Bone remodelling. c. Bone fixation. d. Principles of correction.Reproduced with permission from Jane JA, Dumont A,Lin and John A. Jane K: Craniosynostosis, p. 445-460, in Anne J.Moore, David W. Newell ‘neurosurgery Principles and Practice’,Springer London, 2005 [ 17].

Figure 17. Posterior sagittal suture synostosis: a. Occipital pathologicalprojection (left) and its correction (right). b. Pathologicaldent (left) and its correction (right). c. Batrocephaly correction.Reproduced with permission from Jane JA, Dumont A, Linand John A. Jane K: Craniosynostosis, p. 445-4602005 [ 17]., inAnne J. Moore, David W. Newell ‘neurosurgery Principles andPractice’, Springer London,

For complete scaphocephaly, approach calvariectomie should be performed, practicing a bifrontal flap, a bioccipital one and two parietal ones (Figure18). The flaps are remodelled using radial osteotomies and then are repositioned, resulting in a shorteningand rounding of the skull [17, 18, 22].

Figure 18. Complete synostosis of sagittal suture: a. primarypathological and compensatory modifications. b. Craniotomyand remodelling. c. Fixing the remodelled bone. Reproduced with permission from Jane JA, Dumont A, Lin and John A. JaneK: Craniosynostosis, p. 445-460, in Anne J. Moore, David W.Newell ‘neurosurgery Principles and Practice’, Springer London,2005 [ 17].

Unilateral synostosis of lambdoid suture results inaflattening of the ipsilateral parieto-occipital region(Figure 19). Compensatory growth occurs in the sagittal suture plasne and of the controlaterale lambdoid suture causing an increase of the controlateral parietal bone and at the level of the squamous suture causing a temporal bulge anterior and anterior – inferior displacement of the pinna. A biparieto-occipitalcraniotomy is performed, using g radial osteotomiesand controlled fractures for remodelling [17].

Figure 19. Synostosis of the lambdoid suture and positional plagiocephaly a. Pathological modifications of the synostosis of the lambdoid suture. b. Lambdoid synostosis correction. c.Plagiocephaly position. d. Plagiocephaly position correction.Reproduced with permission from Jane JA, Dumont A, Lin andJohn A. Jane K: Craniosynostosis, p. 445-460, in Anne J. Moore,David W. Newell ‘neurosurgery Principles and Practice’, SpringerLondon, 2005. [17].

Endoscopic procedures in craniosynostoses

Endoscopic procedures have been tried in craniosynostoses,too. Endoscope was used in conducting anosteotomy of the sagittal suture in scaphocephaly at 4-6 weeks after birth.. Osteotomy was done through an anterior and posterior opening of the sagittal suture following subcutaneous osteotomy assisted by endoscope.The procedure is minimally invasive but it maylead to the injury superior longitudinal sinus [19].

CONCLUSIONS

Abnormal skull shapes have interested medicine since ancient times. Craniosynostoses result from premature closure of one or more sutures and havea complex ethiopathogeny explained in recentyears due to progress in genetics and molecularbiology. Premature closure of sutures producesmajor cranio-facial modifications with disordersat the level of the brain and of cranial nerves. They can be diagnosed accurately and the diagnosis of the forms of craniosynostosis is not a difficult issue based on current neuroimagery. Because each form of synostosis is subject to certain growth compensatory rules, surgeons are cautioned to avoid use of preestablished surgical procedures. The aim of surgery should be to restore the normal and aesthetic form of the skull [17].

We insist on early diagnosis of craniosynostoses,during the first three months, with intervention of decompression surgery and skull remodelling ofthe.

GENETIC COUNSELLING

Most craniosynostoses are autosomal dominant.Because of variable expressivity, mutation identificationin affected individuals should be found throughgenetic testing of parents. In the most severe typesof craniosynostoses the rate of mutations occurred‘de novo’ is high. In autosomal-dominant types ofcraniosynostoses, mutation carriers have a 50% riskof transmitting the aff ected gene to their off spring. Anegative genetic test in parents leaves a risk smallerthan 1%, explained by gonadal mosaicism [21].

Figure 20. Appearance before and after surgery ina case of scaphocephaly, a personal case

Prenatal testing strategies include chorionic villusbiopsy (usually at 10-14 weeks of gestation) or amniocentesis(usually at 16-18 weeks of gestation). In case of in vitro fertilization, testing the product of conception before implantation is an option available in orderto prevent the birth children carrying the mutation[21]. In the last century, medicine has advanced since the first description of the complex craniosynostoses to the identification of mutations FGFR, TWIST, andMSX2. The research in fundamental sciences leadingto the revolutionary discoveries of the last 15 years willc ontinue to enrich our knowledge in understanding the molecular causes of these diseases. In future, attention should be directed to research that will impact on the treatment of these genetic disorders.

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