Francesco Velardi

A survey of the first complication of newly implanted CSF shunt devices for the treatment of nontumoral hydrocephalus

The results of an international multicenter study concerning the first complication of newly implanted cerebrospinal fluid shunts in nontumoral hydrocephalus are the subject of the present report. The authors have collected information on 773 cases from four continents. In particular, the following data were evaluated in relation to the general incidence of complications recorded in the first follow-up year: the patients age at the operation, the etiology of hydrocephalus, the type of CSF shunt device used, and the modality of the surgical procedures. The overall complication rate in the series was 29%. Age and etiology of hydrocephalus appear to play a major role in influencing the complication rate; on the other hand, the choice of a specific CSF shunt device seems to be less important in this respect.

Decreased Proliferation and Altered Differentiation in Osteoblasts from Genetically and Clinically Distinct Craniosynostotic Disorders

Craniosynostoses are a heterogeneous group of disorders characterized by premature fusion of cranial sutures. Mutations in fibroblast growth factor receptors (FGFRs) have been associated with a number of such conditions. Nevertheless, the cellular mechanism(s) involved remain unknown. We analyzed cell proliferation and differentiation in osteoblasts obtained from patients with three genetically and clinically distinct craniosynostoses: Pfeiffer syndrome carrying the FGFR2 C342R substitution, Apert syndrome with FGFR2 P253R change, and a nonsyndromic craniosynostosis without FGFR canonic mutations, as compared with control osteoblasts. Osteoblasts from craniosynostotic patients exhibited a lower proliferation rate than control osteoblasts. P253R and nonsyndromic craniosynostosis osteoblasts showed a marked differentiated phenotype, characterized by high alkaline phosphatase activity, increased mineralization and expression of noncollagenous matrix proteins, associated with high expression and activation of protein kinase Calpha and protein kinase Cepsilon isoenzymes. By contrast, the low proliferation rate of C342R osteoblasts was not associated with a differentiated phenotype. Although they showed higher alkaline phosphatase activity than control, C342R osteoblasts failed to mineralize and expressed low levels of osteopontin and osteonectin and high protein kinase Czeta levels. Stimulation of proliferation and inhibition of differentiation were observed in all cultures on FGF2 treatment. Our results suggest that an anticipated proliferative/differentiative switch, associated with alterations of the FGFR transduction pathways, could be the causative common feature in craniosynostosis and that mutations in distinct FGFR2 domains are associated with an in vitro heterogeneous differentiative phenotype.

Communicating hydrocephalus induced by mechanically increased amplitude of the intraventricular cerebrospinal fluid pressure: Experimental studies

Abstract Acute and chronic hydrocephalus was induced in lambs by mechanically increasing the amplitude of the cerebrospinal fluid (CSF) intraventricular pulse pressure without modifying the mean CSF pressure and without interfering with CSF circulation or absorption. The characteristics of the hydrocephalus so obtained, namely, the asymmetry of ventricular dilation, the dilation of the distal portions of the ventricular system, and the absence of obstructions in CSF pathways, indicated a direct role of high-amplitude intraventricular CSF pulsations in the genesis of ventricular enlargement. As no impairment in CSF circulation or absorption was induced nor variations in CSF mean pressure, this experimental model is proposed as a model for communicating hydrocephalus.

Acquired Chiari type I malformation managed by supratentorial cranial enlargement

IntroductionAcquired Chiari type-I malformation in hydrocephalic patients who have undergone surgical treatment was initially thought to depend on a craniocephalic disproportion induced by the cerebrospinal (CSF) shunt. However, most of the reports in the literature deal with children with lumbo-peritoneal shunts and emphasize the pathogenic role of the cranio–spinal pressure differential across the foramen magnum brought about by this type of shunt.MethodIn the present report, the authors describe two further cases of symptomatic acquired Chiari type-I malformation observed in two adolescents operated on for correction of pseudotumor cerebri in one (lumbo-peritoneal shunt) and of a suprasellar arachnoid cyst (cysto-ventriculo-peritoneal shunt) in the other.ResultsIn both subjects, both the clinical manifestations and the cerebellar tonsillar herniation regressed after supratentorial cranial expansion, without the need for any manipulation of the shunt devices implanted earlier.DiscussionThese results, together with the observation of the concomitant upward and downward herniation of the cerebellum in both patients, indicate that secondary craniocephalic disproportion plays a relevant role in the genesis of acquired Chiari type-I malformation in children bearing extrathecal CSF shunts.

'No allogeneic blood transfusion' protocol for the surgical correction of craniosynostoses. II. Clinical application

Abstract The authors describe the results obtained in 13 consecutive cases of craniosynostosis operated on according to a protocol devised at avoiding allogeneic blood transfusion. The protocol is based on pre- and postoperative treatment with erythropoietin, preoperative autologous blood donation, preoperative normovolemic hemodilution and intraoperative blood salvage. Nine subjects were affected by simple forms of craniosynostosis, whereas the remaining 4 presented with oxycephaly or craniofacial syndromes. Five of the 13 children were under 7 months and a further 3, under 10 months of age at the time of the surgical operation. Seven children weighed less than 10 kg. Allogeneic blood transfusion was avoided in 11 of the 13 children considered. Two failures – defined as the necessity to reinfuse the patient with an allogeneic blood transfusion – were recorded, 1 of them resulting from an unexpected hemorrhage during surgery. The results obtained indicate that this protocol designed to avoid allogeneic blood transfusion can be safely applied in the great majority of children with craniosynostosis, even when the surgical correction is carried out early in life.

The influence of hemocoagulative disorders on the outcome of children with head injury.

Background: Although disseminated intravascular coagulation (DIC) and other hemocoagulative abnormalities are severe complications of head injury, their effect on clinical outcome remains unclear, particularly among children. Objectives: To evaluate the frequency of hemocoagulative abnormalities and their influence on outcome among children with head injury. Study Design: We conducted a prospective observational study among 60 children with head injury, immediately evaluating severity of head injury (Glasgow Coma Scale, GCS); cerebral axial tomography; prothrombin time; activated partial thromboplastin time (aPTT); fibrinogen level; concentration of fibrin-fibrinogen degradation products (FDP), and platelet count. Two months after injury, we applied the Glasgow Outcome Score (GOS). Associations with GOS were evaluated using univariate and multivariate logistic models. Results: Among children with severe head injury, 22.2% (6/27) developed DIC, all of whom died and had shown severe brain edema. Among those with severe head injury yet without DIC, the mortality was only 14.2%. A low GOS was significantly and independently associated with a low GCS, multiple trauma, delayed aPTT, low fibrinogen level, elevated FDP and low platelet count. Brain edema was also associated with a low GOS, though not significantly. Conclusions: In addition to GCS, type of trauma, type of brain lesion and certain coagulation abnormalities are predictors of GOS.

'No allogeneic blood transfusion' protocol for the surgical correction of craniosynostoses. I. Rationale

Abstract Improved anesthesiological and surgical care has resulted in a progressively declining need for allogeneic blood transfusion. In infants with craniosynostosis, however, allogeneic blood transfusion is still performed as a routine procedure. In the present paper, the authors describe a protocol they have devised with the aim of limiting or even avoiding allogeneic blood transfusion even in very young patients, consequently avoiding the risks of infective or immunologic reactions associated with the procedure. The protocol is based on stimulation of the hematopoietic system with erythropoietin, selection of an appropriate age for operation when a favorable balance between fetal and adult-type hemoglobin is established (that is after 4–6 months), preoperative preparation of the autologous blood supply, and intraoperative blood salvage.

Communicating hydrocephalus induced by mechanically increased amplitude of the intraventricular cerebrospinal fluid pulse pressure: Rationale and method

Abstract The effect of increasing the amplitude of the intraventricular cerebrospinal fluid (CSF) pulse pressure in lambs was studied in acute experiments. The intraventricular CSF pulse pressure was mechanically increased by a device which rhythmically inflated and deflated an intraventricular balloon synchronously with the cardiac rate. No variation in mean intraventricular CSF pressure was recorded following the increase in CSF pulse pressure. The neuropathological findings indicated a direct pathogenic effect on periventricular structures exerted by the intraventricular CSF pulsations, which were increased to three to six times the normal values.

Safety and Efficacy of Remifentanil in Craniosynostosis Repair in Children Less than 1 Year Old

Few studies on analgesia with remifentanil (Rf) in children are available, and there are no data on the use of this drug in pediatric neurosurgery. Rf is a new μ-receptor opioid agonist, acting through the activation of pain inhibitory mechanisms. We conducted a prospective trial on the analgesic effects of Rf in 20 children less than 1 year of age undergoing a neurosurgical procedure for craniosynostosis repair. Rf was administered at doses of 0.25 μg/kg/min, by continuous infusion, 1 h after admission to the pediatric intensive care unit (PICU). The treatment was prolonged for 12 h after the operation. The postoperative pain was evaluated in our PICU, comparing the changing of behavioral (AFS and CHEOPS score) and hemodynamic (heart rate, respiratory rate, systolic and diastolic blood pressure, oxygen saturation, O2 and CO2 partial pressure) parameters, before and after treatment with Rf. This drug showed a satisfactory pain control in all the children treated. No significant side effects were noticed, except for one episode of urinary retention. In conclusion, Rf appears to be safe and effective for the treatment of acute pain in the very young child submitted to craniosynostosis repair.

Metopic synostosis: in favour of a "simplified" surgical treatment

Metopic synostosis is a relatively simple form of craniosynostosis, resulting from premature fusion of the metopic suture. In this pathology different degrees of dysmorphia of the anterior cranial fossa and the presence of associated anomalies of the skull might enable specific subgroups to be identified. Since most functional and cosmetic anomalies benefit from early surgical treatment, over the last few years neurosurgeons have been forced to elaborate less drastic, but nonetheless effective, surgical techniques. In the present report we analyze the surgical results obtained in a series of 62 infants with trigonocephaly operated on within their 1st year of life. Patients were subdivided into two groups (group I: 8 patients; group II: 54 patients) according to the specific dysmorphic characteristics of the frontal bone and anterior cranial fossa, and the presence of compensatory deformities affecting the anterior cranial base and temporo-parietal region. All the patients were treated using one of two relatively simple surgical techniques (procedure A: inversion of two hemifrontal bone flaps-48 cases; procedure B: the “shell” operation-14 cases). Both surgical procedures appeared to be effective, allowing adequate functional and cosmetic correction of the cranial deformity. In patients operated on following procedure B surgical time and and blood loss were dramatically reduced. Long-term outcomes were satisfactory in all cases, irrespective of the surgical technique used. In the group II patients, however, progressive normalization of the interorbital distance was constantly observed, suggesting a different degree of stenotic involvement at the level of the anterior cranial base in these patients.