Federico Di Rocco

Mortality in Children With Severe Head Trauma: Predictive Factors and Proposal for a New Predictive Scale

BACKGROUND Traumatic brain injury is a public health problem around the world, and recognition of systemic sources of secondary brain lesions is crucial to improve outcome. OBJECTIVE To identify the main predictors of mortality and to propose a grading scale to measure the risk of death. METHODS This retrospective study was based on medical records of children with severe traumatic brain injury who were hospitalized at a level I pediatric trauma center between January 2000 and December 2005. Multiple logistic regression analysis was done to identify independent factors related to mortality. A receiver-operating characteristics curve was performed to verify the accuracy of the multiple logistic regression, and associations that increased mortality were verified. RESULTS We identified 315 children with severe head injury. Median Glasgow Coma Scale score was 6, and median Pediatric Trauma Score was 4. Global mortality rate was 30%, and deaths occurred despite adequate medical management within the first 48 hours in 79% of the patients. Age<2 years (P=.02), Glasgow Coma Scale≤5 (P<10), accidental hypothermia (P=.0002), hyperglycemia (P=.0003), and coagulation disorders (P=.02) were all independent factors predicting mortality. A prognostic scale ranging from 0 to 6 that included these independent factors was then calculated for each patient and resulted in mortality rates ranging from 1% with a score of 6 to 100% with a score of 0. CONCLUSION Independent and modifiable mortality predictors could be identified and used for a new grading scale correlated with the risk of mortality in pediatric traumatic brain injury.BACKGROUND: Traumatic brain injury is a public health problem around the world, and recognition of systemic sources of secondary brain lesions is crucial to improve outcome. OBJECTIVE: To identify the main predictors of mortality and to propose a grading scale to measure the risk of death. METHODS: This retrospective study was based on medical records of children with severe traumatic brain injury who were hospitalized at a level I pediatric trauma center between January 2000 and December 2005. Multiple logistic regression analysis was done to identify independent factors related to mortality. A receiver-operating characteristics curve was performed to verify the accuracy of the multiple logistic regression, and associations that increased mortality were verified. RESULTS: We identified 315 children with severe head injury. Median Glasgow Coma Scale score was 6, and median Pediatric Trauma Score was 4. Global mortality rate was 30%, and deaths occurred despite adequate medical management within the first 48 hours in 79% of the patients. Age < 2 years (P = .02), Glasgow Coma Scale ≤ 5 (P < 10−5), accidental hypothermia (P = .0002), hyperglycemia (P = .0003), and coagulation disorders (P = .02) were all independent factors predicting mortality. A prognostic scale ranging from 0 to 6 that included these independent factors was then calculated for each patient and resulted in mortality rates ranging from 1% with a score of 6 to 100% with a score of 0. CONCLUSION: Independent and modifiable mortality predictors could be identified and used for a new grading scale correlated with the risk of mortality in pediatric traumatic brain injury.

Incomplete Penetrance of the Predisposition to Medulloblastoma Associated With Germ-Line Sufu Mutations

Methods and results Germline SUFU mutations were identified in two families with several children under 3 years of age diagnosed with medulloblastoma. All medulloblastomas in which the histology was reviewed were of the desmoplastic subtype, including three with the rare extensive nodularity subtype. In both families, the mutation detected in the SUFU gene was a frameshift mutation. Among the 25 mutation carriers identified in the two families, seven developed medulloblastomas. Conclusions This report highlights three features of SUFU related tumours. These are mainly medulloblastomas with extensive nodularity or typical desmoplastic/nodular medulloblastomas. These tumours mostly, if not exclusively, appear during the first 3 years of life. The penetrance of the mutation is incomplete.

Hyperplasia–adenoma sequence in pituitary tumorigenesis related to aryl hydrocarbon receptor interacting protein gene mutation

Mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene are associated with pituitary adenomas that usually occur as familial isolated pituitary adenomas (FIPA). Detailed pathological and tumor genetic data on AIP mutation-related pituitary adenomas are not sufficient. Non-identical twin females presented as adolescents to the emergency department with severe progressive headache caused by large pituitary macroadenomas require emergency neurosurgery; one patient had incipient pituitary apoplexy. Post-surgically, the patients were found to have silent somatotrope adenomas on pathological examination. Furthermore, the light microscopic, immunohistochemical, and electron microscopic studies demonstrated tumors of virtually identical characteristics. The adenomas were accompanied by multiple areas of pituitary hyperplasia, which stained positively for GH, indicating somatotrope hyperplasia. Genetic analyses of the FIPA kindred revealed a novel E216X mutation of the AIP gene, which was present in both the affected patients and the unaffected father. Molecular analysis of surgical specimens revealed loss of heterozygosity (LOH) in the adenoma but showed that LOH was not present in the hyperplastic pituitary tissue from either patient. AIP immunostaining confirmed normal staining in the hyperplastic tissue and decreased staining in the adenoma in the tumors from both patients. These results demonstrate that patients with AIP germline mutation can present with silent somatotrope pituitary adenomas. The finding of somatotrope hyperplasia unaccompanied by AIP LOH suggests that LOH at the AIP locus might be a late event in a potential progression from hyperplastic to adenomatous tissue.

Lung function, diagnosis, and treatment of sleep-disordered breathing in children with achondroplasia†‡

Children with achondroplasia are at risk of sleep‐disordered breathing. The aim of the study was to evaluate lung function and sleep‐disordered breathing in children with achondroplasia. An interview, clinical examination, lung function tests with blood gases, and a polygraphic sleep study were obtained as part of routine annual evaluation in consecutive children with achondroplasia. We included 30 children (median age 3.0 years, range: 0.4–17.1) over a period of 21 months. Habitual snoring and witnessed apneas were observed in 77% and 33% of the patients, respectively. Prior to the sleep study, 10/29 (34%) patients had undergone upper airway surgery and 5/29 (17%) craniocervical decompression operation. Arterial blood gases were abnormal in two (7%) patients. Sleep findings were abnormal in 28/30 (93%) patients. Eleven (37%) patients had an apnea index ≥1 event/hr and 26 (87%) had an apnea–hypopnea index ≥5 events/hr. The ≥3% desaturation index was >5/hr in 22 (73%) patients. Sixteen (53%) patients had a minimal pulse oximetry <90% but only two (7%) patients had a maximal transcutaneous carbon dioxide pressure >50 mmHg during sleep. As a consequence, the following therapeutic interventions were performed: upper airway surgery in four patients and noninvasive positive pressure ventilation (NPPV) in five other patients, resulting in an improvement in sleep studies in all nine patients. Systematic sleep studies are recommended in children with achondroplasia because of the high prevalence of sleep‐disordered breathing. Upper airway surgery and NPPV are effective treatments of sleep‐disordered breathing.

FGFR3 mutation causes abnormal membranous ossification in achondroplasia

FGFR3 gain-of-function mutations lead to both chondrodysplasias and craniosynostoses. Achondroplasia (ACH), the most frequent dwarfism, is due to an FGFR3-activating mutation which results in impaired endochondral ossification. The effects of the mutation on membranous ossification are unknown. Fgfr3(Y367C/+) mice mimicking ACH and craniofacial analysis of patients with ACH and FGFR3-related craniosynostoses provide an opportunity to address this issue. Studying the calvaria and skull base, we observed abnormal cartilage and premature fusion of the synchondroses leading to modifications of foramen magnum shape and size in Fgfr3(Y367C/+) mice, ACH and FGFR3-related craniosynostoses patients. Partial premature fusion of the coronal sutures and non-ossified gaps in frontal bones were also present in Fgfr3(Y367C/+) mice and ACH patients. Our data provide strong support that not only endochondral ossification but also membranous ossification is severely affected in ACH. Demonstration of the impact of FGFR3 mutations on craniofacial development should initiate novel pharmacological and surgical therapeutic approaches.

Lesionectomy in the pediatric age

IntroductionDue to the development of electrophysiological recordings and the advancement in neuroimaging, which has allowed the identification of underlying focal abnormalities, in some patients with partial seizures, the surgical removal of such lesions has gained widespread recognition as a treatment modality for medically intractable epilepsy.DiscussionIn patients having a well-defined lesion, a good correlation between clinical and electrophysiological features, suggesting a zone of seizures onset around (or even in) the lesion, is the best guarantee to achieve good seizure control by “lesionectomy”. However, other factors correlate with the seizure outcome.ConclusionThe persistency of seizures was found to be significantly associated with the completeness of the resection of the lesion and the preoperative duration of epilepsy, and, in some cases, the de novo brain damage induced by the surgical procedure itself. However, given the benefits of seizure control on the developing brain and the risk of secondary epileptogenesis, early surgery is recommended in children.

Endoscopic Third Ventriculostomy and Posterior Fossa Tumors

BACKGROUND The management of hydrocephalus associated with a posterior fossa tumor is debated. Some authors emphasize the advantages of an immediate tumor removal that may normalize the cerebrospinal fluid (CSF) dynamics. However, in clinical practice, the mere excision of the lesion has been demonstrated to be accompanied by a persisting hydrocephalus in about one third of the cases. Preoperative endoscopic third ventriculostomy (ETV) offers several advantages. It may control the intracranial pressure (ICP), avoid the necessity of an emergency procedure, allow appropriate scheduling of the operation for tumor removal, and eliminate the risks related to the presence of an external drainage. The procedure also reduces the incidence of postoperative hydrocephalus. A final advantage, more difficult to weight, but obvious to the neurosurgeon, is the possibility to remove the lesion with a relaxed brain and normal ICP. In the postoperative phase, ETV can be used in case of persisting hydrocephalus, both in patients who underwent only the excision of the tumor and in those whose preoperative ETV failed as a consequence of intraventricular bleeding with secondary closure of the stoma (redoETV). The main advantage of postoperative ETV is that the procedure is carried out only in case of persisting hydrocephalus; its use is consequently more selective than preoperative ETV. The disadvantage consists in the common use of an external CSF drainage in the first few postoperative days, which is necessary to control the pressure and for ruling out those cases that reach a spontaneous cure of the hydrocephalus. METHODS The authors review the criteria for patient selection and the results of ETV performed in case of hydrocephalus secondary to a posterior fossa tumor. RESULTS AND CONCLUSIONS Preoperative ETV constitutes an effective procedure for controlling the hydrocephalus associated with posterior fossa tumors. It might lower the rate of persistent postoperative hydrocephalus and result in a short hospital stay. Low rates of patients requiring an extrathecal-CSF shunt device are also reported by authors who utilize ETV postoperatively. As, however, the assessment of the persistent hydrocephalus in these children is based on prolonged ICP monitoring through an external CSF drainage, their results are weighted by a major risk of infective complications and longer hospital stay.

Epilepsy associated with shaken baby syndrome

ObjectThe shaken baby syndrome (SBS) is an important cause of developmental delay in infants. Epileptic seizures are a common feature of this syndrome. The aim if this study is to analyse the impact of the early and late seizures disorder.Materials and methodsWe have retrospectively reviewed the clinical and electrophysiological findings in a series of 404 children hospitalised with SBS.ResultsIn the acute phase, clinical epileptic seizures of various semiologies were found in 73% of the infants. Only 11% of the children had a normal EEG on admission. A poor outcome was found in 88% of the children in case of persisting EEG anomalies despite anti-epileptic treatment with 48% mortality in these patients. The development of refractory epilepsy was also associated with a poor outcome in this series. In fact 96% of the children with seizure recurrence had behavioural problems.ConclusionsThe early recognition and subsequent management of these seizures is vital to prevent further neurological injury. Delayed or recurrent epileptic seizures may occur with a different semiology to the seizures in the acute phase and are also associated with a poor prognosis.

Removal of a chopstick out of the cavernous sinus, pons, and cerebellar vermis through the superior orbital fissure.

Penetrating non-missile orbito cranial injuries are rare in a civilian pediatric setting. We describe a case of a trans-orbital penetration by a wooden chopstick deep down into the cerebellar vermis detected at neuroradiological examination in a child presenting for head injury. The foreign body was successfully pulled out in one piece surgically.

Anterior fronto-orbital remodeling for trigonocephay

IntroductionTrigonocephaly secondary to the premature fusion of the metopic synostosis is associated to a risk of cerebral compression and several craniofacial morphological alterations. Numerous surgical techniques have been proposed. They all carry a risk of secondary temporal hollowingPurpose The aim of this paper is to describe the surgical technique used for trigonocephaly at the craniofacial unit of Hopital Necker Enfants Malades (French National Referral Center for Faciocraniosynostosis) focusing on its advantages and limitations. Resorbable osteosynthesis should be part of the current techniques.