Biomedical subjects

C Sainte-Rose

Publications and source records attributed to C Sainte-Rose.

At least 37 records · Page 2Linked to original sources

PubMed1999

Sylvian aqueduct syndrome and global rostral midbrain dysfunction associated with shunt malfunction.

OBJECT: This study is a retrospective analysis of clinical data obtained in 28 patients affected by obstructive hydrocephalus who presented with signs of midbrain dysfunction during episodes of shunt malfunction. METHODS: All patients presented with an upward gaze palsy, sometimes associated with other signs of oculomotor dysfunction. In seven cases the ocular signs remained isolated and resolved rapidly after shunt revision. In 21 cases the ocular signs were variably associated with other clinical manifestations such as pyramidal and extrapyramidal deficits, memory disturbances, mutism, or alterations in consciousness. Resolution of these symptoms after shunt revision was usually slow. In four cases a transient paradoxical aggravation was observed at the time of shunt revision. In 11 cases ventriculocistemostomy allowed resolution of the symptoms and withdrawal of the shunt. Simultaneous supratentorial and infratentorial intracranial pressure recordings performed in seven of the patients showed a pressure gradient between the supratentorial and infratentorial compartments, with a higher supratentorial pressure before shunt revision. Inversion of this pressure gradient was observed after shunt revision and resolution of the gradient was observed in one case after third ventriculostomy. In six recent cases, a focal midbrain hyperintensity was evidenced on T2-weighted magnetic resonance imaging sequences at the time of shunt malfunction. This rapidly resolved after the patient underwent third ventriculostomy. CONCLUSIONS: It is probable that in obstructive hydrocephalus, at the time of shunt malfunction, the development of a transtentorial pressure gradient could initially induce a functional impairment of the upper midbrain, inducing upward gaze palsy. The persistence of the gradient could lead to a global dysfunction of the upper midbrain. Third ventriculostomy contributes to equalization of cerebrospinal fluid pressure across the tentorium by restoring free communication between the infratentorial and supratentorial compartments, resulting in resolution of the patient's clinical symptoms.

Adolescent↗

PubMed1999

Benign cerebellar astrocytomas in children.

OBJECT: Cerebellar astrocytomas are benign tumors of childhood known to be associated with excellent long-term survival in patients in whom complete surgical resection is possible. However, the roles of other factors--clinical, radiological, histological, and therapeutic--in the survival of the patient, tumor recurrence, and long-term patient outcome remain imprecise. The goal of this study was to examine these factors and their relationships. METHODS: To clarify these issues a retrospective review was conducted of 168 children who were surgically treated for a cerebellar astrocytoma at Hôpital Necker-Enfants Malades between 1955 and 1995. These patients' clinical files were examined, the histological characteristics of their tumors were reviewed, and their outcomes were assessed according to Bloom's scale and the Wechsler intelligence quotient test. Of the 168 patients in the study, 91 were male and 77 were female with a mean age of 6.9 years and a mean follow up lasting 7.7 years. Tumors were identified as being strictly located in the cerebellum in 76.2% of the patients and as involving the brainstem (referred to as the "transitional form") in 23.8% of the patients. Complete surgical excision was possible in 88.7% of cases. There was a total mortality rate of 4.2% and a tumor recurrence rate of 9.5%. Fifty-eight percent of the patients had no neurological sequelae at follow-up evaluation. Pejorative factors that were discovered by multivariate analysis to be important included: a long preoperative duration of symptoms and the transitional form of tumor with respect to survival; incomplete tumor excision with respect to an increased risk of recurrence; and a long preoperative duration of symptoms, an early epoch during which surgery was performed (1955-1974), severe ventricular dilation, and the transitional form of tumor with respect to a poorer long-term patient outcome. CONCLUSIONS: The presence of brainstem involvement (tumor in the transitional form) emerged as a significant negative prognostic factor and should be treated as a distinct nosological entity. The extent of surgical excision has a significant bearing on the risk of tumor recurrence.

Adolescent↗

PubMed1999

Epilepsy in children with shunted hydrocephalus.

OBJECT: The incidence of epilepsy among children with hydrocephalus and its relation to shunts and their complications, raised intracranial pressure (ICP), and developmental outcome are explored in a retrospective study. METHODS: The authors studied a series of 802 children with hydrocephalus due to varying causes, who were treated by ventriculoperitoneal shunt placement between 1980 and 1990, with a mean follow-up period of 8 years. Patients who had tumoral hydrocephalus and those whose files lacked significant data were excluded. Data extracted from medical records, including history of the hydrocephalus and history of seizures, if any, were analyzed. Thirty-two percent of the children had epilepsy, the onset of which frequently occurred at approximately the same time that the diagnosis of hydrocephalus was made. The majority of the affected children had severe uncontrolled epilepsy. The incidence of epilepsy was significantly affected by the original cause of the hydrocephalus. The presence of radiological abnormalities was also found to be a significant predictor of epilepsy. Similarly, shunt complications predisposed to epilepsy. Episodes of raised ICP related to hydrocephalus or in association with shunt malfunction may also predispose to epileptic seizures. Furthermore, the presence of a shunt by itself seems able to promote an epileptogenic focus. Finally, epilepsy appears to be an important predictor of poor intellectual outcome in hydrocephalic children with shunts. CONCLUSIONS: A prospective study is needed to identify clearly and confirm avoidable factors predisposing to seizures in these children so that we can strive to reduce the incidence of these seizures and, subsequently, improve these children's quality of life.

Birth Injuries↗

PubMed1999

Failure of third ventriculostomy in the treatment of aqueductal stenosis in children.

OBJECT: The goal of this study was to analyze the types of failure and long-term efficacy of third ventriculostomy in children. METHODS: The authors retrospectively analyzed clinical data obtained in 213 children affected by obstructive triventricular hydrocephalus who were treated by third ventriculostomy between 1973 and 1997. There were 120 boys and 93 girls. The causes of the hydrocephalus included: aqueductal stenosis in 126 cases; toxoplasmosis in 23 cases, pineal, mesencephalic, or tectal tumor in 42 cases; and other causes in 22 cases. In 94 cases, the procedure was performed using ventriculographic guidance (Group I) and in 119 cases by using endoscopic guidance (Group II). In 19 cases (12 in Group I and seven in Group II) failure was related to the surgical technique. Three deaths related to the technique were observed in Group I. For the remaining patients, Kaplan-Meier survival analysis showed a functioning third ventriculostomy rate of 72% at 6 years with a mean follow-up period of 45.5 months (range 4 days-17 years). No significant differences were found during long-term follow up between the two groups. In Group I, a significantly higher failure rate was seen in children younger than 6 months of age, but this difference was not observed in Group II. Thirty-eight patients required reoperation (21 in Group I and 17 in Group II) because of persistent or recurrent intracranial hypertension. In 29 patients shunt placement was necessary. In nine patients in whom there was radiologically confirmed obstruction of the stoma, the third ventriculostomy was repeated; this was successful in seven cases. Cine phase-contrast (PC) magnetic resonance (MR) imaging studies were performed in 15 patients in Group I at least 10 years after they had undergone third ventriculostomy (range 10-17 years, median 14.3 years); this confirmed long-term patency of the stoma in all cases. CONCLUSIONS: Third ventriculostomy effectively controls obstructive triventricular hydrocephalus in more than 70% of children and should be preferred to placement of extracranial cerebrospinal shunts in this group of patients. When performed using ventriculographic guidance, the technique has a higher mortality rate and a higher failure rate in children younger than 6 months of age and is, therefore, no longer preferred. When third ventriculostomy is performed using endoscopic guidance, the same long-term results are achieved in children younger than 6 months of age as in older children and, thus, patient age should no longer be considered as a contraindication to using the technique. Delayed failures are usually secondary to obstruction of the stoma and often can be managed by repeating the procedure. Midline sagittal T2-weighted MR imaging sequences combined with cine PC MR imaging flow measurements provide a reliable tool for diagnosis of aqueductal stenosis and for ascertaining the patency of the stoma during follow-up evaluation.

Adolescent↗

PubMed1999

Surgery of epilepsy associated with focal lesions in childhood.

OBJECT: Surgery in children with epilepsy is a new, evolving field. The important practical issues have been to define strategies for choosing the most suitable candidates and the type and optimal timing of epilepsy surgery. This study was undertaken to elucidate these points. METHODS: To identify the factors that correlated with outcome, the authors analyzed a series of 200 children (aged 1-15 years (mean 8.7 years) who underwent surgery between 1981 and 1996 at the Hôpital Necker-Enfants Malades. In 171 cases (85.5%) the epilepsy was medically refractory and was associated with focal cortical lesions. Surgery consisted of resection of the lesion without specifically attempting to identify and remove the "epileptogenic area. "In the group of children whose seizures were medically refractory, the mean follow-up period was 5.8 years. According to Engel's classification, 71.3% of these children became seizure free (Class 1a,) whereas 82% were in Class I. A multivariate statistical analysis revealed that among all the factors studied, the success of surgery in a patient in whom there was a good clinical/electroencephalogram/imaging correlation depended on the patient's having undergone a minimally traumatic operation, a complete resection of the lesion, and a short preoperative seizure duration. After the surgical control of epilepsy, behavior disorders were more improved (31% of all patients) than cognitive function (25%). The patient age at onset, duration and frequency of seizures, intractability of the disease to therapy, and seizure characteristics were correlated with cognitive, behavioral, and academic performance pre- and postoperatively. Multivariate statistical analysis revealed that cognitive dysfunction correlated highly with the duration of epilepsy prior to surgery, whereas behavioral disorders correlated more with seizure frequency. CONCLUSIONS: These data must be taken into account when selecting patients for surgical treatment and when deciding the timing of surgery. Early surgical intervention allows for optimum brain development.

Adolescent↗

PubMed1998

Late outcome of the surgical treatment of hydrocephalus.

The purpose of this report is to analyze the long-term outcome in hydrocephalic children treated by shunt placement and in particular their psycho-intellectual development. In the case of shunt placement postoperative mortality is virtually nil, and the overall mortality rate after 10 years of follow-up has been reduced to less than 5%. Morbidity, in contrast, is far from satisfactory. This study was conducted in 129 consecutive children with nontumorous hydrocephalus who underwent a first shunt insertion before the age of 2 years between 1979 and 1982 and who were followed up for at least 10 years. The final neurological examination revealed a motor deficit in 60%, visual or auditory deficits in 25%, and epilepsy in 30%. The final IQs were above 90 in 32% of the children, between 70 and 90 in 28%, between 50 and 70 in 19%, and lower than 50 in 21%. Integration into the normal school system was possible for 60% of the children, but half of them were 1-2 years behind their age group or having difficulties; 31% were attending special classes or were in institutions; and 9% were considered ineducable. The presence of behavioral disorders was a determinant factor for scholastic and social integration. Such disorders were frequent, and were characterized as severe in 30%. A relationship between final outcome and etiology, initial ventricular size, and epilepsy was observed. These results are used as the basis of a discussion on how morbidity might be improved.

Cerebrospinal Fluid Shunts↗

PubMed1998

Occipital remodeling and suboccipital decompression in severe craniosynostosis associated with tonsillar herniation.

OBJECTIVE: The goal was to describe a surgical technique allowing occipital vault remodeling and suboccipital decompression in patients affected by multiple-suture synostosis presenting severe occipital flattening and chronic tonsillar herniation (CTH). METHODS: Four patients (two with Crouzon's syndrome, one with Kleeblattschädel, and one with complex craniosynostosis) presenting multiple-suture synostosis with severe occipital flattening, posterior fingerprint impressions, and CTH were operated on in the prone position. For three patients, occipital vault remodeling and suboccipital decompression without dural opening were performed; for one patient affected by Kleeblattschädel, an upper cervical laminectomy and dural opening were performed. All patients were studied with magnetic resonance imaging pre- and postoperatively. RESULTS: No complications were observed. In all cases, postoperative magnetic resonance imaging revealed good decompression of the craniocervical junction, with resolution of brain stem displacement. In one case, CTH recurred 15 months after surgery, although in a less severe form. CONCLUSION: In selected cases of complex or syndromic craniosynostosis with predominant posterior deformity and CTH, this technique was safe and useful in the management of cranial reconstruction, allowing posterior vault remodeling and prophylactic suboccipital decompression. After validation with a larger number of patients, it could prove to be a useful option in all cases of complex craniosynostosis with CTH in which a staged repair of the craniosynostosis is to be considered.

Cerebellar Diseases↗

PubMed1998

The role of endoscopic third ventriculostomy in the management of shunt malfunction.

OBJECTIVE: To evaluate the effectiveness of third ventriculostomy as an alternative to shunt revision in the management of shunt malfunction and infection in obstructive hydrocephalus. METHODS: All of the clinical notes of 30 patients treated with third ventriculostomy for malfunctioning or infected shunts between January 1, 1974, and December 31, 1996, were retrospectively reviewed. Third ventriculostomy was performed under fluoroscopic control in the first seven patients and endoscopically in the remainder. A successful outcome was achieved if further shunt revision surgery was avoided. The median follow-up duration was 8.7 years RESULTS: Twenty-three patients (76.7%) experienced successful outcomes, resulting in shunt independence. Of the seven failures, three were technical failures at the time of surgery and the remaining four were manifest within a median of 10 days, resulting in shunt revision. There have been no delayed failures. CONCLUSION: Third ventriculostomy is a valuable alternative to shunt revision in patients affected by obstructive hydrocephalus presenting with shunt malfunction or infection. It should be considered in all suitable cases as the first-line treatment for obstructive hydrocephalus of all causes. Because all failures were manifest within a short time, it is likely that these successes will be durable.

Adolescent↗

PubMed1998

Hydrocephalus and craniosynostosis.

OBJECT: A retrospective study of 1727 cases of craniosynostosis was undertaken to determine the interrelationship between abnormal cerebrospinal fluid (CSF) hydrodynamics and craniosynostosis. METHODS: The patients were divided into two groups: nonsyndromic craniosynostosis and syndromic craniosynostosis. Cases of occipital plagiocephaly without suture synostosis and cases of shunt-induced craniosynostosis were excluded from the study. The majority of patients (1297) were treated surgically for their cranial deformity; 95% of these patients had a postoperative follow-up review period lasting 5 years. Clinical and radiographic charts covering the time from presentation through the follow-up period were reviewed. CONCLUSIONS: Abnormal intracranial CSF hydrodynamics was found in 8.1% of the patients (3.4% of whom had received shunts and 4.5% of whom had not). Three types of CSF hydrodynamic disturbance were observed: progressive hydrocephalus with ventricular dilation, nonprogressive ventriculomegaly, and dilation of the subarachnoid spaces. Hydrocephalus occurred much more frequently in patients with syndromic craniosynostosis (12.1%) than in those with isolated craniosynostosis (0.3%). In fact, patients with kleeblattschädel exhibited hydrocephalus as a constant feature and patients with Crouzon's syndrome were far more likely to have hydrocephalus than those with other syndromes. In Apert's syndrome, ventricular dilation occurred very frequently, but it was almost always nonprogressive in nature. In most cases of syndromic craniosynostosis, venous sinus obstruction and/or chronic tonsillar herniation were found. Their role in the pathophysiology of hydrocephalus in craniosynostosis is discussed.

Acrocephalosyndactylia↗

PubMed1998

Papillomas and carcinomas of the choroid plexus in children.

OBJECT: Choroid plexus tumors are rare intraventricular tumors (1% of all intracranial tumors) that occur mainly in children. The pathophysiological characteristics of associated hydrocephalus, surgical management, and oncological issues related to these tumors remain a matter of debate. To understand more about these tumors, the authors have reviewed their experience with the management of 38 children with choroid plexus tumors. METHODS: There were 25 cases of papilloma and 13 of carcinoma. The mean age of the patients at presentation was 22.5 months, and one-half of the patients were younger than 2 years of age. Hydrocephalus was present in 33 patients and poorly correlated with the size, site, and pathological characteristics of the tumor. In nine children, a ventriculoperitoneal shunt was required after tumor excision, calling into question the notion that cerebrospinal fluid oversecretion is the only cause of hydrocephalus. Complete excision was achieved in 96% of the cases of papilloma and 61.5% of the cases of carcinoma. These surgical procedures were complicated by the risks of intraoperative hemorrhage, which proved to be fatal in two cases, and postoperative brain collapse, which led to subdural fluid collections requiring subdural shunt placement in six patients. Preoperative embolization was partially successful in four cases and significantly assisted surgery. Preoperative controlled drainage of excessively dilated ventricles and intraoperative gluing of the cortical incision have been used to address the problem of postoperative brain collapse. Patients with carcinomas were treated postoperatively by chemotherapy alone (seven cases), radiotherapy (one case), or chemotherapy plus radiotherapy (one case). The overall 5-year survival rate was 100% for patients with papillomas and 40% for those with carcinomas. CONCLUSIONS: Total surgical excision is curative in cases of papillomas. For carcinomas, the most effective treatment remains total surgical excision; however, adjuvant treatment in the form of chemotherapy in patients younger than age 3 years, supplemented by radiation therapy in older children, can moderately reduce the risk of recurrence.

Adolescent↗

PubMed1998

Mechanical dysfunction of ventriculoperitoneal shunts caused by calcification of the silicone rubber catheter.

OBJECT: The authors studied new and calcified shunt catheters to identify the prevalence of failures caused by aging materials in the shunt. Complications associated with these devices have various origins. Among late complications, fracture or migration of the system is related to the subcutaneous adhesion of the distal tubing in a growing child. A review of a cohort of 64 children who underwent shunt placement in 1980 with barium-impregnated distal catheters showed that 10 of these patients underwent reoperation for complications related to aging of the shunt material. This group represents 15% of the whole series and 30% of those children who were followed for more than 3 years. The true impact of aging of materials on shunt function is probably underestimated. METHODS: The authors performed physical, chemical, and mechanical analyses of the retrieved aged catheters and also of new catheters, resulting in the following findings: 1) calcifications were observed only on the external surface of the catheter, predominantly in its subcutaneous segment at the level of the neck and anterior chest wall; 2) calcifications contained particles of free silicon and barium sulfate, signifying fragmentation of the polymer; 3) the microstructure of the silicone polymer was modified: microfractures and alteration of the polymeric network were observed; 4) silanol groups were observed on the external surface of the catheter; and 5) the mechanical properties of the silicone rubber were degraded, and the aged catheters were more brittle than the new ones, with ruptures at elongations and fracture energy much lower than that seen in new catheters. Furthermore, in vitro testing with a metastable solution of simulated body fluid demonstrated the critical impact of pH variations in liquid media and surface degradation of the catheters on the precipitation of hydroxylapatite crystals. CONCLUSIONS: Although most shunt complications can be addressed by better patient management and surgical technique, late complications appear to be partly related to aging of the material. Distal tubing calcifications have been observed in barium-impregnated catheters. The industry recently responded to these observations by introducing plain silicone-coated shunt tubing; further evaluation will show what improvement can be expected.

Adolescent↗

PubMed1997

Potent therapeutic activity of irinotecan (CPT-11) and its schedule dependency in medulloblastoma xenografts in nude mice.

The anti-tumor activity of irinotecan (CPT-11), a DNA-topoisomerase 1 inhibitor, was evaluated in 5 advanced stage subcutaneous medulloblastoma xenografts in nude mice, using different schedules of administration. With a 5-day schedule, the highest i.v. dose tested (40 mg kg-1 day-1) induced complete regressions in all xenografts but 1, and delays in tumor growth always exceeded 30 days. Two xenografts, IGRM11 and IGRM33, were highly sensitive, and animals survived tumor-free beyond 120 days after treatment. CPT-11 clearly retained its anti-tumor activity at a lower dosage (27 mg kg-1 day-1). CPT-11 was significantly more active than cyclophosphamide, thiotepa and etoposide against the 3 xenografts evaluated. To study the schedule dependency of its anti-tumor activity, CPT-11 was given i.v. at the same total doses over the same period (33 days) using either a protracted or a sequential schedule in IGRM34-bearing mice. With a dose of 10 mg kg-1 day-1 given on days 0-4, days 7-11, days 21-25 and days 28-32 (total dose, 200 mg kg-1), 3 of 6 animals were tumor free on day 378. The same total dose given with a sequential schedule, i.e., 20 mg kg-1 day-1 on days 0-4 and days 28-32, failed to induce complete regression. The plasma pharmacokinetics of CPT-11 and SN-38 were studied in IGRM34-bearing animals after a single i.v. dose of 10 and 40 mg kg-1. The plasma clearance rate of CPT-11 was dose dependent. The ratio between the SN-38 and CPT-11 area under the curve in plasma was 0.4-0.65, i.e., significantly higher than that observed in humans at the maximum tolerated dose (0.01-0.05). Conversely, this ratio was 10-fold lower in tumor than in plasma. Clinical development of irinotecan is warranted in pediatric malignancies.

Animals↗

PubMed1997

Congenital lumbosacral lipomas.

Congenital lumbosacral lipomas can be responsible for progressive defects. The general feeling is that tethering of roots, filum, or cord probably explains this evolution, and that untethering of these structures could prevent late deterioration. Like the vast majority of neurosurgeons, we too have routinely and systematically operated on lumbosacral lipomas, even in the absence of neurological deficits. This policy stemmed from our belief that spontaneous neurological deterioration was frequent, recovery from preoperative deficits rare, and surgery both efficient and benign in nature. After 22 years of experience, we felt that it was necessary to review our series of 291 lipomas (38 lipomas of the filum and 253 of the conus) operated on from 1972 to 1994. To reassess the value of prophylactic surgery, we attempted an accurate evaluation of (1) the risk of pathology, (2) the risks involved in surgery, (3) the postoperative outcome with respect to preoperative deficits, and (4) the postoperative outcome in asymptomatic patients at 1 year and at maximum follow-up. Special attention was paid to 93 patients whose postoperative follow-up was more than 5 years (average 8.7, median 8, range 5-23 years). Of these 93 patients, 39 were asymptomatic preoperatively (7 with lipoma of the filum and 32 with lipoma of the conus). Lipomas of the filum and of the conus are entirely different lesions and were studied separately. In 6 cases prenatal diagnosis had been possible. The mean age at surgery was 6.4 years. Low back skin stigmata were present in 89.4% of cases. Preoperative neurological deficits existed in 57% of the patients and were congenital in 22%. Clinical signs and symptoms recorded were pain in 13.3% of the patients and/or neurological deficits affecting sphincter (52%), motor (27.6%) and sensory (22.4%) functions. Deficits were progressive in 22.4% of cases, slowly progressive in 58.8% of these and rapidly progressive in the remaining 41.2%. In 36 patients (13.2%) the lipomas were seen to grow either subcutaneously or intraspinally. Among these patients, 21 were infants, 2 were obese adolescents, and 10 were pregnant women. The metabolism of the fat within the lipomas was studied in 11 patients and found to be similar to that at other sites. Lipomas were associated with various other malformations, either intra- or extraspinal. These associated anomalies were rare in the case of lipomatous filum (5.2%) but frequent with lipomas of the conus, except for intracranial malformations (3.6%). Therapeutic objectives were spinal cord untethering and decompression, sparing of functional neural tissue and prevention of retethering. Procedures used to achieve these goals were subtotal removal of the lipoma, intraoperative monitoring, duroplasty, and sometimes closure of the placode. Histologically, lipomas consisted of normal mature fat. However, 77% of them also included a wide variety of other tissues, originating from ectoderm, mesoderm, or entoderm. This indicates that lipomas are either simple or complex teratomas. The results of the study are as follows. (1) Surgery was easy and safe when performed for treatment of lipomas of the filum (no complications), but difficult and hazardous in the case of lipomas of the conus (20% local, 3.9% neurological complications). (2) All types of deficit could be improved by surgery, which was beneficial in all cases of lipoma of the filum and 50% of cases of lipoma of the conus. (3) In asymptomatic patients long-term surgical results depended on the anatomical type of the lipoma. They were excellent in lipomas of the filum. In lipomas of the conus they were good in the short term but eroded with time. At more than 5 years of follow-up only 53.1% of the patients were still free of symptoms. (4) Reoperations were performed in 16 patients (5.5%), 5 (31.2%) of whom improved postoperatively, while in 7 (43.7%) progression stopped, in 3 (18.7%) deterioration continued and in 1 (6.2%) the condition was wor

Adolescent↗

PubMed1996

Tumorigenicity of cerebellar primitive neuro-ectodermal tumors in athymic mice correlates with poor prognosis in children.

The histogenesis of medulloblastoma, also described as a cerebellar primitive neuro-ectodermal tumor (PNET), remains controversial and unresolved. In addition, genetic markers which characterize cerebellar PNETs with poor prognosis in children have not been identified. Since xenografts can be valuable tools for better understanding the genetic events involved in cerebellar PNETs, small fragments of tumor samples from 17 children with newly diagnosed cerebellar PNETs were transplanted s.c. into female athymic Swiss mice. Eleven were non-metastatic and 6 were metastatic PNETs. Eight tumors (47%) were tumorigenic. Histological analysis showed 6 typical medulloblastomas, 1 PNET with melanin pigment and 1 PNET with a rhabdoid phenotype. Wide heterogeneity was observed in tumor growth, with a doubling time ranging from 8 to 81 days after the first passage. Tumorigenicity was correlated with the metastatic phenotype of the tumor (p < 0.001). All the patients but one with a tumorigenic tumor relapsed and died. The survival of patients with a non-tumorigenic PNET (67%) was significantly higher than that of patients with a tumorigenic PNET (13%) (p < 0.02). None of the xenografts or tumors from patients exhibited N-myc-gene alteration. Only one xenograft showed c-myc amplification, with an abnormal 15-kilobase fragment. None of the 17 tumors from patients showed amplification or c-myc-gene rearrangement. In conclusion, tumorigenicity of cerebellar PNETs strongly correlates both with the metastatic phenotype of the tumors and with the disease-free survival of the patients. In addition, genetic events other than c-myc-gene amplification might be involved in cerebellar PNETs with poor prognosis.

Animals↗

PubMed1996

[Mental prognosis of Apert syndrome].

BACKGROUND: Mental retardation, considered as common in Apert syndrome could be in part due to associated brain abnormalities. POPULATION AND METHODS: Sixty patients (32 males, 28 females) were included in the study. Patient age at the last examination was over 3 years (mean 10 years, range 3-28 years) in 38 patients. IQ was assessed from psychometric tests adapted for age. Brain anatomy was studied by MRI. Age at operation and quality of familial environment were also evaluated. RESULTS: The IQ was over 70 in 12 patients (32%), over 90 in five (13%) and the mean IQ was 62 (10-114). Thirty percent of patients had abnormalities of the corpus callosum, 43% of the cerebral ventricles and 55% of the septum pellucidum. There was no anomaly in 28% of the patients. One or more operations were performed in 53 patients, before one year of age in 37. Ten children were institutionalized or in deleterious family situation. The main factor influencing the mental prognosis was the age at operation: the final IQ was over 70 in 50% of the children operated on before one year of age versus 8% in those operated on later (P = 0.01). Only the anomalies of the septum pellucidum seemed to play a role: 50% of the patients with normal septum had an IQ > 70 compared to 18% in those with septum anomalies (P < 0.04). The quality of the familial environment also influenced the mental development: 12.5% of the patients who were institutionalized or in difficult familial situation had an IQ > 70 compared to 39% of those who live in a normal family. CONCLUSIONS: Careful investigation including MRI is necessary for detecting associated brain abnormalities. The patients must be operated on early, if possible before the age of nine months. Attention has also to be paid to quality of the sociofamilial environment.

Acrocephalosyndactylia↗

PubMed1996

[Chiari "malformation" in Crouzon syndrome].

BACKGROUND: Use of MRI makes the association Chiari malformation-cranio-facial synostosis more frequent than expected. The aim of this work was to ascertain the true incidence of Chiari malformation and to understand the reasons of the association between a bone pathology and a CNS malformation. PATIENTS AND METHODS: The anatomy of the posterior cranial fossa in Crouzon syndrome was retrospectively studied on MRI scan in 49 patients. RESULTS: A chronic tonsillar herniation, similar to a Chiari malformation, was observed in 71.4% of the cases. All the patients with Crouzon syndrome and progressive hydrocephalus had a Chiari malformation, but only 19 out of the 33 patients without associated hydrocephalus had a Chiari malformation (57.6%). Significant differences between the pattern of lambdoid suture closure were founded between both groups, with and without Chiari malformation, the lambdoid closure appearing earlier in patients with Chiari malformation. CONCLUSION: The high incidence of chronic tonsillar herniation in Crouzon syndrome seems related to the premature synostosis of the lambdoid suture.

Actuarial Analysis↗

PubMed1996

A high-dose busulfan-thiotepa combination followed by autologous bone marrow transplantation in childhood recurrent ependymoma. A phase-II study.

Sixteen children with refractory or relapsed ependymoma were entered in a phase-II study of high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT). The conditioning regimen consisted of busulfan 150 mg/m2/day for 4 days and thiotepa 300 mg/m2/day for the 3 following days. All patients had previously been treated by surgery and conventional chemotherapy. Eight of them had also received irradiation at doses ranging from 45 to 55 Gy at the tumor site. At the time of transplantation, 9 patients were in first relapse, 5 in second relapse and 2 in third relapse or more; all had measurable disease; 15 patients were evaluable for response. No radiologic response > 50% was observed. Stable disease and progressive disease were documented in 10 and 5 cases, respectively. The duration of response to this treatment, which lasted for a median time of 7 months (range: 5-8 months), was only evaluable in 5 patients who did not receive further treatment after ABMT. To date, there are 3 disease-free survivors at 15, 25 and 27 months all of whom were treated with second complete surgical resection and local radiotherapy (55 Gy). Toxicity was severe, mainly digestive and cutaneous, and 1 toxicity-related death occurred. Unlike medulloblastomas, ependymomas do not appear to be sensitive to this combination therapy. New therapeutic approaches are warranted.

Adolescent↗

PubMed1995

Intellectual outcome in children with malignant tumors of the posterior fossa: influence of the field of irradiation and quality of surgery.

The purpose of this study was to determine the respective parts played by cerebral hemisphere irradiation, posterior fossa irradiation, and surgery in the poor late functional results often observed in children treated for medulloblastoma. To do this we compared the intellectual outcome in a series of 59 children operated on for medulloblastoma, who had received whole-brain irradiation, to that observed in a series of 37 children operated on for ependymoma of the posterior fossa, who had received radiotherapy only on the posterior fossa. Only patients who had survived for more than 2 years without recurrence were included. At the assessment 1 year after treatment, intellectual outcome was somewhat better in the ependymoma group, but the difference was not statistically significant. At the long-term follow-ups at 5 and 10 years the results remained stable in the children treated for ependymoma, around 60% having an IQ above 90, whereas the intellectual level of the children treated for medulloblastoma was seen to have deteriorated progressively: 20% had an IQ above 90 5 years after treatment and only 10% at the 10-year follow-up. This progressive degradation is most likely due to the irradiation of the cerebral hemispheres, as this prophylactic irradiation constituted the only difference between the two groups. Moreover, irradiation to the posterior fossa did not seem to affect intellectual functions, since in the group of children with ependymomas the proportion of IQs above 90 was high and remained stable over the years. Surgery was certainly responsible for some poor results. The percentage of IQs above 90 observed 1-2 years after treatment was between 70 and 80 when no postoperative complications occurred, and only between 20-40% in the presence of postoperative complications. Postoperative aggravation was in most cases related to a brain-stem lesion. These results encourage the reduction, when possible, of irradiation to the cerebral hemispheres and underline the importance of the quality of surgery.

Achievement↗