Faculty Bibliography

The etiology of craniosynostosis remains unknown. The beta group of transforming growth factors (TGF-beta) and insulin-like growth factors (IGF-I and IGF-II) are known to induce new bone formation and, when added exogenously, cause accelerated closure of calvarial defects. The possible roles of these bone growth factors in premature cranial suture fusion in humans have not been explored. We analyzed a total of 20 cranial suture biopsy samples (10 synostotic and 10 normal) from 10 infants with single-suture craniosynostosis undergoing cranial vault remodeling. Using isoform-specific antibodies for TGF-beta 1, -beta 2, and -beta 3 and IGF-I, we demonstrated immunoreactivity of these growth factors were present in human cranial sutures; the TGF-beta 2 isoform was the most intensely immunoreactive. Most importantly, the TGF-beta isoforms and IGF-I showed more intense immunoreactivity in the actively fusing craniosynostotic sutures compared with the control patent sutures. Specifically, the TGF-beta isoforms and IGF-I were intensely localized in the osteoblasts synthesizing new bone at the suture margin. It is noteworthy that although the patent sutures were less immunoreactive for TGF-beta isoforms than fused sutures, there was a distinct pattern of the TGF-beta 3 isoform that was immunolocalized to the margin of the normal patent sutures. This suggests a possible role for TGF-beta 3 in maintaining cranial suture patency. The increased immunoreactivity of both TGF-beta 2 and IGF-I in the actively fusing sutures compared with the patent control sutures indicates that these growth factors may play a role in the biology underlying premature suture closure. To our knowledge, this is the first study showing the presence of TGF-beta 1, -beta 2, and -beta 3 and IGF-I in prematurely fusing human cranial sutures. In the future, manipulating the local expression of these growth factors at the suture site may enable plastic surgeons to modulate premature suture fusion

OBJECTIVE:The optimal surgical management of arachnoid cysts remains controversial. The cerebellopontine angle (CPA) is a rare location for arachnoid cysts, and only 28 cases of arachnoid cysts occurring in the CPA have been reported in the literature. We discuss the diagnosis, radiographic imaging, and surgical management of CPA arachnoid cysts. METHODS:Five patients (three male and two female patients) with a mean age of 5.6 years have been operated on at our institution since 1980. Magnetic resonance imaging allows for the accurate diagnosis of these arachnoid cysts, which can present with only discrete symptoms, such as headache or ataxia. All five arachnoid cysts compressed the cerebellum or brain stem. One patient had associated hydrocephalus. Three patients presented with refractory headaches associated with nausea and vomiting. The remaining two patients presented with cerebellar signs. No patient had an initial cranial neuropathy. RESULTS:All patients underwent a retrosigmoid suboccipital craniotomy and microsurgical resection and fenestration of the cyst walls. One patient underwent two procedures. A cystoperitoneal shunt was inserted at the first operation. After the shunting procedure, the patient's condition deteriorated; however, after the microsurgical resection and fenestration, his symptoms improved. With a mean 5.2-year follow-up, there has been no evidence of clinical or radiographic recurrence. CONCLUSION/CONCLUSIONS:Although CPA arachnoid cysts represent a small number of total arachnoid cysts, the CPA is the second most common location for arachnoid cysts to occur. CPA cysts are congenital lesions found in children who present with subtle signs or symptoms. The definitive treatment for these arachnoid cysts is a retrosigmoid suboccipital craniotomy and microsurgical resection and fenestration of the cyst walls.

We present an unusual case of a craniopharyngioma with a visual field deficit related to optic tract compression by the anterior cerebral artery. The presentation and management of this case are described. Previous cases of visual field deficits associated with craniopharyngiomas are reviewed

Radical surgery is the most important treatment modality for ependymoma. The benefit of adjuvant radiotherapy and/or chemotherapy following a gross total resection of a low grade intracranial ependymoma is uncertain. Since 1990 we elected to defer adjuvant therapy in 7 pediatric patients with a median age of 7 years (range 3-16 years) who had a radical resection of an intracranial ependymoma and no evidence of central nervous system metastases. The primary tumor site was the cerebral hemisphere (6) and the cerebellum (1). A gross total resection was radiologically confirmed in 5 of the 7 patients. Two of the patients had a blood clot in the resection site on the postoperative magnetic resonance imaging scan. All patients are alive after a median follow-up of 44 months and the median progression-free survival is 38+ months. Five of the patients remain in continuous remission. The 2 patients with postoperative blood clots developed subclinical local recurrences, 10 and 11 months, respectively, after diagnosis. They remain in remission for 13+ and 27+ months after subsequent radical surgical procedures. Involved field radiotherapy was administered to 1 patient. After a limited period of follow-up, radical surgery alone appears to be sufficient for the majority of children with low grade ependymomas diagnosed at > 3 years of age when postoperative imaging confirms a gross total resection. This is more likely to occur in supratentorial ependymomas arising in older children

Although the incidence of elevated intracranial pressure is increased in patients with the craniosynostosis syndromes, the significance of these findings and their impact on clinical practice remain unclear. The morbidity related to elevated intracranial pressure in patients with Apert and Pfeiffer syndromes was reviewed. Sixty-seven patients with Apert syndrome and 39 patients with Pfeiffer syndrome were identified. The morbidity in 5 of the 106 patients (4.7 percent) was felt to be directly related to persistently elevated intracranial pressure. These included 2 deaths, 1 due to brainstem herniation after an elective subcranial Le Fort III advancement and 1 following removal of a lumboperitoneal shunt during the surgical release of syndactyly. The remaining 3 complications included bilateral papilledema detected 3.5 years after cranial vault remodeling in 1 patient and venous hypertension with excessive bleeding detected during elevation of the bicoronal flap in 2 patients, resulting in delay of a planned Le Fort III advancement. Patients with the syndromal craniosynostoses are at risk for complications resulting from elevated intracranial pressure from infancy through adulthood despite surgical attempts to increase cranial capacity in infancy. Clinical guidelines are proposed by which these patients should be evaluated beyond infancy in a regular fashion so as to reduce morbidity from unrecognized elevations in intracranial pressure

We reviewed the data of children with high-stage primitive neuroectodermal tumors (medulloblastomas) who were treated on Children's Cancer Group-921 protocol to evaluate the correlation between tumor resection and prognosis. Patients enrolled in the study had either tumors that were operatively categorized to be Chang tumor stage 3b or 4, postoperative residual tumors > 1.5 cm2, or evidence of tumor dissemination (Chang metastasis Stages [M Stages] 1-4) at diagnosis. Resections were analyzed in two ways, as follows: 1) by the extent of resection (percent of the tumor that was removed), as estimated by the treating neurosurgeon; and 2) by the extent of residual tumor (how much of the tumor was left), as estimated from postoperative scans. Two hundred and three children were enrolled in the study with institutional diagnoses of primitive neuroectodermal tumors-medulloblastomas; diagnoses were confirmed by central neuropathological review in 188 patients. Progression-free survival (PFS) at 5 years was 54% (standard error, 5%). As in previous Children's Cancer Group studies, age and M stage correlated with survival; PFS was significantly lower in children 1.5 to 3.0 years old at diagnosis and in those with any evidence of tumor dissemination (M Stage 1-4). On univariate analysis, neither extent of resection nor extent of residual tumor correlated with PFS. However, adjusting for other factors, extent of residual tumor was important; PFS was 20% (standard error, 14%) better at 5 years in children with no dissemination (M Stage 0) who had < 1.5 cm2 of residual tumor (P = 0.065) and was 24% (standard error, 14%) better at 5 years in children > 3 years old with no tumor dissemination (M Stage 0) and with < 1.5 cm2 residual tumor (P = 0.033). On the basis of our observations, we conclude that extent of tumor resection, as estimated by the neurosurgeon, does not correlate with outcome but that extent of residual tumor does correlate with prognosis in certain children (those who are > 3 years old, with no tumor dissemination). In contrast to age and M stage, the major factors associated with outcome, residual tumor is an important variable in outcome, one that neurosurgeons can control

In April 1992, the American Academy of Pediatrics recommended back or side sleeping for healthy newborns to reduce the risk of sudden infant death syndrome. Subsequently, the US Public Health Service organized a health care coalition to promote a 'Back to Sleep Campaign' to advocate back or side sleeping for infants. Since 1992, our craniofacial anomalies center has witnessed a marked increase in the incidence of infants with defomational changes of the cranium and face. The purpose of this project was to study the etiologies of deformational plagiocephaly and possible correlation with infant head position. We reviewed 52 consecutive patients presenting with deformational plagiocephaly from January 1992 to December 1994. A diagnosis of deformational plagiocephaly was determined by (1) history (date when head shape change was first noted), (2) clinical examination (occipital flattening, contralateral forehead flattening, lowering of the eyebrow, and ear shearing), and (3) skull radiographs (patent cranial sutures). All infants had medical photography to document baseline craniofacial morphology and any follow-up changes after nonsurgical therapy. Cranial asymmetry was first noted after birth at a mean time of 3.6 months. All infants were initially positioned on their back/side. In 52 patients, 61% had right-sided flattening of the occiput (vs 39% left-sided). All infants had flattening of the occiput, contralateral brow lowering or inferior displacement of the brow, contralateral forehead flattening, and posterioinferior displacement of the ear. All skull radiographs demonstrated patent sutures. Follow-up of patients ranged from 3 to 22 months with a mean of 10.5 months. Follow-up clinical examination and photography demonstrated significant improvement of cranial form in all patients with recommended frequent head turning (73%), helmet molding (23%), and surgery (4%). Our unit has seen an increase in the number of infants with deformational plagiocephaly over the last three years. All of the affected infants in this study had been managed according to the officially recommended protocol of back/side positioning. These findings suggest a possible relationship between this type of infant positioning and the development of a deformational plagiocephaly. However, cranial asymmetry in this group of patients decreased significantly with nonsurgical therapy. We have not recommended cranial vault remodeling surgery for the mild and moderate types of this deformity. However, if there is evidence of increasing asymmetry of deformational plagiocephalic infants during follow-up and evidence of severe variants of these deformities, surgical correction of the cranial vault is recommended