Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome.

Apert syndrome is a distinctive human malformation comprising craniosynostosis and severe syndactyly of the hands and feet. We have identified specific missense substitutions involving adjacent amino acids (Ser252Trp and Pro253Arg) in the linker between the second and third extracellular immunoglobulin (Ig) domains of fibroblast growth factor receptor 2 (FGFR2) in all 40 unrelated cases of Apert syndrome studied. Crouzon syndrome, characterized by craniosynostosis but normal limbs, was previously shown to result from allelic mutations of the third Ig domain of FGFR2. The contrasting effects of these mutations provide a genetic resource for dissecting the complex effects of signal transduction through FGFRs in cranial and limb morphogenesis.

Pattern, management and outcome of cervical spine injuries associated with head injuries in paediatric patients.

INTRODUCTION: This study examines the management and outcome of cervical spine injuries in children with head injuries, to assess the need for surgical treatment. MATERIAL AND METHODS: We performed a retrospective analysis (1995-2005) of 445 children admitted intubated and ventilated to the intensive care unit with head injuries. OUTCOME MEASURES: Frankel grade for spinal injuries and Glasgow Outcome Scale (GOS) for head injuries. RESULTS: Cervical spine injuries were detected in 11 patients (incidence 2.5%, mean age: 6.3 years, range: 21 months-15 years). The injuries were: C1/2 distraction: 2; C1/2 subluxation: 2; odontoid peg fracture with C1/2 dislocation and cord transection: 1; disruption of posterior longitudinal ligament at C2: 1; odontoid peg fracture with C2/3 distraction: 1; C2/3 subluxation: 1; C3 lamina fracture: 1; C3/4 facet fracture: 1; C6/7 fracture dislocation with cord transection: 1. One patient was managed operatively, ten patients nonoperatively, two with halo vests and eight with hard collars. There were three deaths (mortality 27%) associated with severe head injuries. At 6 months follow-up, two patients remained quadriplegic (Frankel Grade A), one of them ventilator dependent, one had residual motor function but of no practical use (Frankel Grade C), five had good spinal outcome (Frankel Grade E). Seven patients had good head injury outcomes (GOS 5), one remained disabled (GOS 3). CONCLUSION: Most children with cervical injury can be managed nonoperatively with good outcomes. Surgical management may be necessary in severe unstable injuries.

A new method of occipitocervical fusion using internal fixation.

We describe a method for decompression and fusion of the occipitocervical junction in cases of atlantoaxial subluxation. Use of an implanted steel rectangle provides immediate rigid internal fixation, permitting early mobilization with minimal external support.

Proximal occlusion of the anterior cerebral artery for anterior communicating aneurysm.

Results of proximal anterior cerebral artery occlusion are described in 68 patients with anterior communicating artery aneurysms. The procedure is found useful in the treatment of these aneurysms because of its technical simplicity and the low rates of mortality and morbidity achieved.

Surface ultrastructure of tissues occluding ventricular catheters.

Specimens of material occluding ventricular catheters removed at shunt revision operations were studied by scanning electron microscopy. Immediate fixation allowed examination of human choroid plexus and ependyma which resembled living tissue.

Occipital mesenchymal tumors of infancy. Report of three cases.

Mesenchymal tumors arising from the dura in three newborn babies are described, with discussion of their clinical and pathological significance.

Intracranial volume change in childhood.

OBJECT: The goal of this study was to construct a model of normal changes in intracranial volume occurring throughout childhood from age 7 days to 15 years. METHODS: Using the technique of segmentation on magnetic resonance images obtained in healthy children, intracranial volume was measured and plotted against age. CONCLUSIONS: Intracranial volume in the first few months of life is on average 900 cm3 in males and 600 cm3 in females. By the age of 15 years, it increases up to 1500 cm3 in males and 1300 cm3 in females, increased by factors of 1.6 and 2.1, respectively. By the time the child reaches 2 years of age, intracranial volume has reached 77% (1150 cm3 in males and 1000 cm3 in females) and, by 5 years, 90% (1350 cm3 in males and 1200 cm3 in females) of the volume observed at age 15 years. The change in intracranial volume that occurs with age is not linear, but there seems to be a segmental pattern. Three main periods can be distinguished, each lasting approximately 5 years (0-5, 5-10, and 10-15 years), during which the growth of intracranial volume is linear. Throughout childhood, males have higher intracranial volumes than females, with a similar growth pattern.

Intracranial volume change in craniosynostosis.

OBJECT: There is still controversy regarding the optimum time to perform surgery for craniosynostosis. Some recommend surgery soon after birth and others delay until the age of 12 months. Intracranial pressure has been measured in an attempt to provide a scientific rationale, but many questions remain unanswered. To date, little attention has been given to intracranial volume and its changes during the first few years of life in children with craniosynostosis. The authors' goal was to focus on intracranial volume during this period and to compare measurements obtained in patients with craniosynostosis with measurements obtained in healthy individuals. METHODS: Using the technique of segmentation, the intracranial volume of 84 children with various forms of craniosynostosis was measured on preoperative computerized tomography scans. The change in average volume that occurs with increasing age was calculated and compared with a model of normal intracranial volume growth. The age at presentation for children with craniosynostosis was 1 to 39 months; 76% of the patients were younger than 12 months. In eight patients in whom only one cranial expansion procedure was performed, postoperative intracranial volumes were measured as well. Several interesting observations emerged. 1) There was little difference in head growth between boys and girls with craniosynostosis during the first few months of life. After the age of 12 months, however, the difference in intracranial volume normally seen between the two genders was observed in the craniosynostosis group as well. 2) Excluding children with complex pansynostosis, who have smaller heads, children with all other types of craniosynostosis have similar head growth after the 1st year of life, with no difference between the number of and type of suture affected. Children with Apert's syndrome develop greater than normal intracranial volumes after the 1st year of life. 3) Although children with craniosynostosis are born with a smaller intracranial volume, by the age of 6 months volume has reached normal levels, and from that point on volume follows the pattern of normal head growth. 4) Children who presented after the age of 6 months and later developed recurrent craniosynostosis after initial successful treatment had a small intracranial volume at their initial presentation. 5) Of the patients whose postoperative intracranial volumes were measured, all but one had preoperative volumes at or above normal values, and their postoperative volumes were considerably higher than normal for their age. These children all followed a growth curve parallel to that of healthy children but at higher volume value. One patient with a smaller-than-normal initial intracranial volume was surgically treated at a very young age and, despite cranial expansion surgery, postoperative volume did not reach normal levels. It is postulated that this was due to the fact that the operation was performed at a time when craniosynostosis was still active. CONCLUSIONS: The results of this study indicate that the underlying mechanism leading to craniosynostosis and constriction of head volume "exhausts" its effect during the first few months of life. Measurement of intracranial volume in clinical practice could be used to "fine tune" the optimum time for surgery. In late-presenting children, this may be useful in predicting possible recurrence.

Management of intracerebral hemorrhage in idiopathic thrombocytopenic purpura. Report of four cases.

There has been little comment on the specific management of intracerebral bleeding occurring in patients suffering idiopathic thrombocytopenic purpura. The authors present the cases of four children with intracerebral hemorrhage due to this coagulation disturbance. A plan of management is described based on this experience; it includes immediate control of cerebral edema, emergency splenectomy, supportive care with platelet transfusions and corticosteroids, cerebral angiogtaphy, and a definitive neurosurgical procedure. If necessary, the radiological investigation and surgical therapy can be performed with a single general anesthetic. Three of the patients have survived without major neurological sequelae.

Unilateral proptosis and intracranial schwannoma.

Two cases of unilateral proptosis associated with intracranial schwannomas in children are described. In both cases, tumour occupied both the orbit and middle cranial fossa, where in one case the intracranial component was extradural and in the other intracerebral. Possible sites of tumour origin are discussed.

A distinct autosomal dominant craniosynostosis-brachydactyly syndrome.

We report a family with an autosomal dominantly inherited craniosynostosis. Five affected individuals have been identified with a variable clinical picture of premature coronal sutural synostosis accompanied by a mild midfacial hypoplasia and hypertelorism, downslanting external palpebral fissures, beaking of the nose and brachydactyly. This pedigree appears to represent a distinct craniosynostosis entity.

Frontonasal dysplasia with optic disc anomalies and other midline craniofacial defects: a report of six cases.

The association of optic disc abnormalities with basal encephaloceles, specifically of the sphenoethmoidal type, and midline facial clefts has rarely been reported, although the association of midline facial clefts with encephaloceles is well described. We now report six cases of children, three males and three females, presenting with a sphenoethmoidal encephalocele, optic disc anomalies, midline facial clefting, hypertelorism, complete or partial agenesis of the corpus callosum, and endocrinological disturbances, including diabetes insipidus and pituitary dysfunction. This report underlines the importance of careful ophthalmic and endocrinological investigation of children with midline clefts associated with basal encephaloceles. These cases may represent a distinct entity within the spectrum of frontonasal dysplasia.

The median cleft face syndrome with associated cleft mandible, bifid odontoid peg and agenesis of the anterior arch of atlas.

A case is reported of median cleft face syndrome with bifid tongue and odontoid peg and failure of formation of the anterior arch of the atlas. These are features which have not been reported previously. The preoperative CT demonstrated its potential to enhance our understanding of complex and rare craniofacial deformities.

Treatment for children with brain tumours.

The overall survival for children with malignant brain tumours has not greatly improved in recent years, so that apparently innovative treatments may seem attractive, especially in cases with a poor prognosis. Problems associated with treating such children include balancing the need to provide optimum treatment for individual patients with the need to properly evaluate advances in treatment in clinical trials and determining who should be responsible for decisions about funding such treatments. Treatment abroad is rarely justified when judged on the basis of whether the treatment is available in Britain (or European Community) and whether there is accepted evidence for its clinical benefit. However, referral to specialist paediatric centres is essential. The range of daily experience in such centres allows an educated choice between established and new treatments. Close collaboration between these centres is essential for clinical trials.

Diastematomyelia in children: treatment outcome and natural history of associated syringomyelia.

OBJECTIVE: To quantify the long-term outcome of children with diastematomyelia and the implication of syringomyelia in the natural history. MATERIALS: Retrospective study of 17 children (nine girls and eight boys) with diastematomyelia operated during 1989-2004. Mean age at diagnosis was 3.4 years (range 5 days-12 years), mean follow-up was 5 years; 14 had excision of spur and cord untethering, 3 had excision of spur alone. RESULTS: The bony spur was in the lumbar region in 12 and thoracic in 5 patients. Syringomyelia was present in eight (47%), associated with bony spur between L1 and 4 (p=0.088), spina bifida occulta in ten (58.8%), and spinal lipoma in one (6%). Preoperative Necker Enfants Malades (NEM) scores were 17 in eight patients, 16 in four, 15 in three, 13 in one, and 12 in one patient. Presenting neurological deficits were motor in eight, sensory deficits in three, and anal incontinence in one patient. There was improvement of NEM scores postoperatively in five patients only, but still with residual deficit. Repeat spur excision and cord untethering was performed in three patients for neurological deterioration 1-4 years after first operation. On postoperative MRI scans syringomyelia remained unchanged in all eight patients. There were one skin infection, one transient motor deterioration, and one patient with sensory deficit after surgery. CONCLUSION: Prophylactic operations were associated with the best clinical outcome. Despite improvement, all patients with established preoperative deficit still had residual neurological deficits at their last follow-up. The associated syringomyelia remained unchanged after surgery, indicating that it does not contribute to the neurological syndrome.

Incidence of vascular malformations in spontaneous intra-cerebral haemorrhage in children.

AIM: To assess the incidence of vascular malformations in children presenting with non-traumatic intra-cerebral haemorrhage and outline the need for radiological investigations. MATERIALS AND METHODS: Between 1993 and 2002, 26 children presented with spontaneous intra-cerebral haemorrhage at a mean age of 26 months (range 1-192 months). RESULTS: Twenty-two children had, as first treatment, surgical removal of the haematoma and any malformation found. One patient with no evidence of vascular malformation had conservative treatment, two had embolisation and one had stereotactic radiosurgery of arteriovenous malformations (AVMs). The diagnosis of vascular malformation was confirmed histologically and/or radiologically in 16 (61%) patients. Of these 16 patients, 7 were AVMs, 1 thrombosed middle cerebral artery (MCA) aneurysm, 1 cavernous angioma, 6 aggregates of abnormal vessels, 1 vein of Galen aneurysm. Pre-operatively, 12 patients had magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) and 7 were positive for vascular malformation (1 false positive) with no false negatives. Digital subtraction angiography (DSA) was performed pre-operatively in 7 patients, 4 were positive with no false negatives. There were no re-bleeds at the follow-up period. Five (19%) patients died from the haemorrhage, 7 (27%) had severe neurological deficit and 14 (54%) had no neurological deficit. Residual malformation after surgery requiring additional treatment was found in 3 (16%) patients. All patients with confirmed malformations were followed-up with DSA. CONCLUSION: MRI/MRA has high sensitivity and specificity in identifying vascular malformations in children presenting acutely with spontaneous intra-cerebral haemorrhage. This may prove useful when pre-operative DSA is not promptly available. After acute clot evacuation, there is high incidence of residual malformation and such patients should be followed-up with DSA.

Outcome of children with posterior fossa medulloblastoma: a single institution experience over the decade 1994-2003.

AIM: While the impact of radiotherapy in the management of medulloblastoma was recognised, the introduction of chemotherapy was investigated in clinical trials and shown to confer an additional advantage. We reviewed the outcome of a series of consecutive patients to assess the impact in a population-based clinical establishment. MATERIALS AND METHODS: A series of 38 children treated for medulloblastoma at Birmingham Children's Hospital between 1994 and 2003 was analysed. The effect of surgery, radiotherapy, chemotherapy and metastasis on survival was analysed. RESULTS: The overall 5-year survival rate was 61.4% for the 36 patients who had resective surgery, while 2 patients had biopsy only and died within a few months. There was no operative mortality. The incidence of hydrocephalus needing permanent shunting was higher in the first 3 years of life (p = 0.007, chi-square). The 5-year survival rate of patients with total and sub-total excision of medulloblastoma was 61.1% and 61.8%, respectively. The 5-year survival rate of patients older than 3 years was 73.4% and for patients under 3 years was 36.3% (p = 0.007, log rank). Metastases at presentation did not influence survival. All deaths occurred in the first 32 months. CONCLUSION: The contribution of chemotherapy in the improvement of the overall survival appears more evident in children younger than 3 years or presenting with metastases. The absence of significant difference in survival between patients with total or sub-total excision of medulloblastoma supports the view that total excision of medulloblastoma can be avoided when the risk for potential intra-operative damage and consequent neurological deficits is high.

Cranioplasty in children.

OBJECTIVE: The objective was to assess the outcome and complications associated with different cranioplasty implant materials in children. MATERIALS AND METHODS: A retrospective review was conducted of 28 consecutive cranioplasties carried out on 24 children between 1994 and 2001 (age range, 9 months to 15 years; minimum follow-up 18 months). The indications were: defect from previous craniectomy for trauma, tumour, infection or evacuation of haematoma (n=21), intradiploic dermoid cysts (n=2), growing fractures (n=4) and residual bony defect following craniofacial reconstruction (n=1). The materials used were: patient's craniectomised bone flap (n=16), split calvarial graft (n=8), acrylic (n=3) and titanium (n=1). All patients were assessed for bony fixation, cosmesis, wound healing and flap infection. RESULTS: There was no mortality and 18% morbidity (n=5: 3 infected flaps, 1 sterile wound dehiscence and 1 sterile wound discharge; overall infection rate 10%). Out of the 14 patients who had their own craniectomised bone flaps implanted initially, 3 became infected (2 in patients with bilateral defects) necessitating flap removal. Two of these were successfully re-implanted. No donor or recipient bone flap complications were seen in the 8 split calvarial grafts, wound discharge was seen in 1, requiring wound toilet. No complications were seen with acrylic or titanium cranioplasties. CONCLUSION: In this series, the use of the patients' own craniectomised flap had a low infection rate, and was mainly seen in patients who had bilateral flaps re-implanted soon after removal. There were no complications arising from the use of split calvarial and allograft material. Use of autologous implant material should be preferred whenever possible due to obvious resource and biological advantages, and can even be re-implanted if infected.