Lipopolysaccharide from Escherichia coli reduces antigen-induced bronchoconstriction in actively sensitized guinea pigs.

Bronchoconstriction (BC) is the main feature of anaphylaxis in the guinea pig. Since LPS induces lung inflammation and antigen-induced BC depends on the endogenous formation of histamine and arachidonate metabolites, we studied whether LPS might modulate antigen-induced BC. Guinea pigs were sensitized subcutaneously with 10 micrograms ovalbumin (OA) on days 0 and 14. LPS (100 micrograms/kg) was injected intravenously on day 21, and daily injections of LPS were continued before the antigenic challenge on day 22, 23, 24, or 25. Intratracheal injection of 100 micrograms OA induced an abrupt and reversible BC. Single or repetitive injections of LPS reduced BC. LPS is likely to reduce the OA-induced BC by affecting the histamine-dependent component of BC, since (a) LPS induced a partial degranulation of lung mast cells; (b) BC is reduced by mepyramine, an histamine receptor antagonist; (c) LPS did not affect BC in mepyramine-treated guinea pigs; (d) LPS reduced histamine release by OA-stimulated guinea pig lungs in vitro. Moreover, the in vitro OA-induced production of arachidonate metabolites was also reduced by LPS. The decreased formation of TXB2 was not only secondary to a reduced release of histamine, since LPS inhibited TXB2 formation in the presence of mepyramine. Finally, the FMLP-induced BC and mediator release were inhibited by LPS, whereas the platelet activating factor-induced pulmonary responses were not. Thus, the protective effect of LPS is not antigen-specific and does not result from a general desensitization. These studies indicate that a single dose of LPS reduces the antigen-induced BC by reducing histamine release from lung mast cells, although a decreased formation of eicosanoids may contribute to the protective effect of LPS.

High-grade glioma in children under 5 years of age: a chemotherapy only approach with the BBSFOP protocol.

The aim of this study was to evaluate a chemotherapy strategy that avoids radiotherapy in first-line treatment of young children with high-grade glioma. A total of 21 children under 5 years of age received the BBSFOP protocol, comprising seven cycles of three drug pairs (carboplatin/procarbazine, cisplatin/etoposide and vincristine/cyclophosphamide) administered over a 16 month period. Radiotherapy was performed in case of recurrence/progression. Median age at diagnosis was 23 months. Histology was classified as World Health Organisation (WHO) grade III in 13 and grade IV in 8. Of the 13 children with a residual tumour, chemotherapy induced 2 partial responses (PR), 1 minor response (MR) and 1 stable disease (SD) with no recurrent disease. Five-year progression-free survival was 35% and 5-year overall survival was 59%, with a median follow-up of 5.2 years. At the last update, 12 children were alive (10 without radiotherapy). In conclusion, this study shows that an adjuvant chemotherapy first approach is safe and allows radiotherapy to be avoided in selected children.

Activity of fotemustine in medulloblastoma and malignant glioma xenografts in relation to O6-alkylguanine-DNA alkyltransferase and alkylpurine-DNA N-glycosylase activity.

Fotemustine is a chloroethylnitrosourea with antitumor activity in disseminated melanoma and adult primary brain tumors. Because new drugs are required for the treatment of medulloblastoma in children, we evaluated the preclinical antitumor activity of fotemustine in four s.c. medulloblastoma xenografts, in comparison with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Both drugs were administered as a single i.p. injection to nude mice bearing advanced-stage tumor. Fotemustine displayed significant antitumor activity in three of four medulloblastoma xenografts; two, IGRM34 and IGRM57, were highly sensitive, with 37 and 100% tumor-free survivors, respectively, more than 120 days after treatment at the highest nontoxic dose (50 mg/kg). Fotemustine was also highly active in a malignant glioma xenograft (IGRG88; five of six tumor-free survivors on day 177). Fotemustine proved to be significantly more active than BCNU in IGRM34 and the glioma xenograft IGRG88. The DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase) was detected in all tumor xenografts, ranging in activity from 6 to 892 fmol/mg protein. The high in vivo sensitivity to fotemustine and BCNU observed in three xenografts was clearly associated with a low ATase activity (> 20 fmol/mg), whereas the two poorly sensitive or refractory medulloblastoma xenografts showed high ATase activity (> 500 fmol/mg). Alkylpurine-DNA N-glycosylase activity was detected in all tumor xenografts but at levels ranging only from 513 to 1105 fmol/mg/h; no consistent relationship was found between alkylpurine-DNA N-glycosylase activity and the in vivo sensitivity to the two chloroethylnitrosoureas. The improved activity and tolerance of fotemustine in comparison with BCNU in pediatric medulloblastoma xenografts strongly support the clinical development of this agent in children with brain tumors, in which ATase should be examined as a potential prognostic indicator.

Treatment of central nervous system B lymphoproliferative syndrome by local infusion of a B cell-specific monoclonal antibody.

A 9-month-old infant developed Epstein-Barr virus-induced lymphoproliferative syndrome with mediastinal and central nervous system localizations, associated with mediastinal tuberculosis, 5 months after heart transplantation. As a combination of anti-B cell antibodies (CD21- and CD24-specific) and recombinant interferon alpha 2b, given intravenously, was not effective on the central nervous system disease, the anti-CD21 antibody was infused intrathecally via an Ommaya reservoir. High local concentrations of monoclonal antibodies were achieved, with no adverse effects. A dramatic clinical response was obtained, with clearance of abnormal cells from the cerebrospinal fluid and a clear reduction in the abnormalities on the brain images. The patient is well 7 months later. This observation indicates that treatment of B lymphoproliferative syndrome with central nervous system localization is feasible using a nontoxic, local B cell-specific approach.

Interference of the Paf antagonist Ro 19-3704 with Paf and antigen-induced bronchoconstriction in the guinea-pig.

1. In vitro, Ro 19-3704, a structurally related antagonist of platelet-activating factor (Paf) inhibited selectively rabbit platelet aggregation. In vivo, administered intravenously, it inhibited bronchoconstriction, leukopenia, thrombocytopenia and the accompanying accumulation of platelet aggregates in guinea-pig lung microvessels induced by i.v. Paf. Administered by aerosol, Ro 19-3704 failed to inhibit bronchoconstriction, thrombocytopenia or leukopenia due to i.v. Paf. 2. Bronchoconstriction induced by Paf, in aerosol form, was blocked by Ro 19-3704 administered by the i.v. or aerosol route, which suggests that it interacts with pulmonary cells responsible for bronchoconstriction. 3. Ro 19-3704 has free radical scavenging properties, since it inhibited the production of superoxide anions by macrophages stimulated by Paf and by N-formyl-methionyl-leucyl-phenylalanine (FMLP). Ro 18-7715, another Paf antagonist and analogue of Ro 19-3704, failed to inhibit the production of superoxide anions by macrophages stimulated by FMLP at concentrations which were effective against Paf. 4. Administered intravenously, Ro 19-3704 failed to block bronchoconstriction induced by an i.v. injection of ovalbumin to guinea-pigs passively sensitized with anti-ovalbumin antiserum. Passive pulmonary anaphylaxis due to an aerosol of ovalbumin was blocked by i.v. Ro 19-3704.

Alveolar macrophages and eicosanoids but not neutrophils, mediate bronchoconstriction induced by FMLP in the guinea-pig.

1. N-formyl-methionyl-leucyl-phenylalanine (FMLP), when administered by aerosol to guinea-pigs, induced a dose-dependent bronchoconstriction (BC) with no overt effect on platelet and leukocyte blood counts. Repeated administration of FMLP by aerosol was followed by desensitization. 2. Electron microscopy studies showed that administration of FMLP by aerosol is accompanied by alveolar macrophage activation, accumulation and aggregation in the alveolar lumens. Non-degranulated eosinophils were observed in the lungs and a few platelet micro-aggregates in the pulmonary microvasculature. 3. No significant accumulation of 131I-labelled albumin, 111In-labelled neutrophils or 111Inlabelled platelets was detected in the lungs after the administration of FMLP by aerosol, whereas the intravenous administration was accompanied by an increase of extravascular albumin and significant neutrophil sequestration in the lungs. 4. Aspirin administered intravenously or by aerosol reduced significantly the BC induced by an aerosol of FMLP. By contrast, intravenous indomethacin reduced only BC induced by the sub-maximal dose of FMLP as an aerosol whereas, when administered by inhalation, it inhibited BC induced by FMLP administered either intravenously or by aerosol at all the concentrations tested. 5. FMLP induced a dose-dependent contraction of the guinea-pig trachea, which was not inhibited by indomethacin. 6. The dual cyclo-oxygenase/lipoxygenase inhibitor compound BW755C suppressed the BC induced by an aerosol of FMLP at all the concentrations used, whereas the histamine H1-antagonist mepyramine was inactive. 7. Leukocyte depletion with vinblastine failed to reduce BC induced by intravenous or an aerosol of FMLP. 8. Our studies indicate that: (a) FMLP administered by aerosol induces dose-dependent BC followed by desensitization, indicating that local mechanisms account for BC; (b) BC induced by i.v. FMLP, but not by its inhalation, is accompanied by albumin extravasation and neutrophil sequestration in the lungs; (c) BC by either i.v. or an aerosol of FMLP is not due to neutrophil activation; (d) inhalation of FMLP induces BC accompanied by accumulation of activated alveolar macrophages, non-degranulated eosinophils and a few platelet microaggregates in the lung; (e) both cyclo-oxygenase and lipoxygenase metabolites are involved in the BC induced by an aerosol of FMLP.

Pharmacological modulation of the effects of N-formyl-L-methionyl-L-leucyl-L-phenylalanine in guinea-pigs: involvement of the arachidonic acid cascade.

The intravenous administration of the chemotactic and secretagogue peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP; 0.3-30 micrograms kg-1) to the guinea-pig induces bronchoconstriction and dose-dependent leukopenia accompanied by mild thrombocytopenia. No electron microscopic evidence of platelet aggregation in lungs or significant accumulation of 111In-labelled platelets in the thoracic region at the height of bronchoconstriction was noted. Bronchoconstriction and leukopenia induced by FMLP were not affected by prostacyclin, by platelet depletion, by the platelet-activating factor (Paf-acether) antagonist BN 52021 or by the histamine H1-antagonist mepyramine. Bronchoconstriction, but not leukopenia, was inhibited by aspirin, whereas the peptido-leukotriene antagonist compound FPL 55712 and the cyclo-oxygenase lipoxygenase inhibitor indomethacin reduced bronchoconstriction to a limited extent only. The mixed cyclo-oxygenase/lipoxygenase inhibitor compound BW 755C was very effective in blocking bronchoconstriction by the highest dose of FMLP used, but failed to interfere with leukopenia. FMLP-induced dose-dependent contraction of parenchymal lung strips was accompanied by the formation of immuno-reactive thromboxane B2 in amounts markedly less than those formed from exogenous arachidonic acid at concentrations equieffective in inducing contractions. FMLP-induced contractions of the guinea-pig lung strip were not modified by mepyramine nor by FPL 55712. They were reduced by indomethacin and aspirin and an even greater reduction was obtained with aspirin used in combination with FPL 55712. BW 755C suppressed the effects of all the concentrations of FMLP tested, whereas tert-butyloxy-carbonyl-L-methionyl-L-leucyl-L-phenylalanine, a chemical analogue of FMLP, displaced the concentration-response curve to the right, without reducing the maximal contraction obtained. The present results indicate that: (a) bronchoconstriction by FMLP is not due to platelet activation, to cyclo-oxygenase-dependent mechanisms or to peptido-leukotriene formation. The inhibitory effect of aspirin and BW 755C involves a property other than cyclo-oxygenase inhibition, which is not shared by indomethacin. (b) The contractile effects of FMLP on parenchymal lung strips follow an interaction with specific receptor sites, as shown by the effectiveness of tert-butyloxy-carbonyl-L-methionyl-L-leucyl-L-phenylalanine, and involves the combined effects of cyclo-oxygenase and lipoxygenase metabolites.

Expression of GM-CSF receptor by Langerhans' cell histiocytosis cells.

Langerhans' cell histiocytosis (LCH) is characterized by the proliferation of large mononucleated cells containing Birbeck granules and expressing CD1a. Recent studies have demonstrated that LCH is a clonal proliferation; however, its aetiology is still unknown. Growth and differentiation of bone-marrow-derived cells are controlled by cytokines. The proliferation, differentiation and activation of normal Langerhans cells are controlled by granulocyte/macrophage colony-stimulating factor (GM-CSF) in vitro. Therefore, GM-CSF could be implicated in the pathogenesis of LCH. Indeed, LCH cells contain GM-CSF, and children with disseminated LCH have an elevated GM-CSF serum level. As a cytokine only acts on cells expressing a specific receptor, we investigated the presence of GM-CSF receptor on LCH cells. Fourteen frozen tissue samples from children with LCH were studied by in situ immunohistochemistry with two mouse monoclonal antibodies specific for the alpha chain of the GM-CSF receptor (CDw116). LCH cells of all the samples were positively stained with both antibodies. This study suggests that GM-CSF may be a growth factor for LCH cells.

Experimental infection of gnotobiotic mice with Campylobacter jejuni: colonisation of intestine and spread to lymphoid and reticulo-endothelial organs.

Axenic and monoxenic C3H mice were used to develop an animal model for enteroinvasiveness and translocation of Campylobacter jejuni. After oral administration of 10(7)-10(8) viable cells of C. jejuni on day 0 (D0), bacterial colonisation was followed quantitatively during 23 days by counting free luminal bacteria and tissue-associated bacteria in the duodenum, ileum and colon. The kinetics of bacterial colonisation were the same in axenic and monoxenic mice; bacteria were more numerous in distal than in proximal intestinal segments. Electronmicroscope studies of axenic infected mice showed C. jejuni free in the intestinal lumen on D2 and D7, and adhering to microvilli or included in enterocyte vacuoles in the colon on D2 without inflammatory reaction; C. jejuni was isolated from mesenteric lymph nodes until D23, but from blood, spleen, liver and bile until D1 only. In monoxenic infected mice, C. jejuni was found from D1 to D4 in mesenteric lymph nodes and Peyer's patches, whereas the associated bacterium (Clostridium perenne) was never cultured from any organs. On the basis of our observations in this gnotobiotic model, C. jejuni appears to be an enteroinvasive bacterium with a particular affinity for lymphoid organs.

Pertussis toxin induces bronchopulmonary hyperresponsiveness in guinea-pigs while antagonizing the effects of formyl-L-methionyl-L-leucyl-L-phenylalanine.

Pertussis toxin injected i.v. at 0.8-20 micrograms/kg markedly enhanced bronchoconstriction induced by the i.v. administration of histamine or serotonin (5-HT) (0.5-16 micrograms/kg) to propranolol-treated guinea-pigs, under conditions where propranolol or pertussis toxin alone were poorly effective. In contrast, bronchoconstriction and the accompanying leukopenia induced by the i.v. administration of the secretagogue formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) were suppressed by pertussis toxin. Bronchoconstriction induced by histamine or 5-HT was not enhanced when perfused lungs from pertussis toxin-treated guinea-pigs were studied in vitro, under conditions where bronchoconstriction and thromboxane A2 release evoked by fMLP were suppressed. Pertussis toxin negatively modifies signal transduction in cells involved in the lung responses to fMLP both in vivo and in vitro, but positively and only in vivo it modifies signal transduction in cells involved in the lung responses to the direct constricting agents histamine and 5-HT. As hyperresponsiveness to histamine and 5-HT were exclusively found in vivo, the target for pertussis toxin is probably not the adrenergic nor the cholinergic systems, since neither hexamethonium, isoprenaline, atropine nor vagotomy were effective. In addition, since dexamethasone and nedocromil sodium were inactive and enrichment of bronchoalveolar lavage with inflammatory cells was not noted, despite lung invasion by neutrophils and lymphocytes, acute inflammation does not account for pertussis toxin-induced hyperresponsiveness.

Reactivation of herpes virus after surgery for epilepsy in a pediatric patient with mesial temporal sclerosis: case report.

OBJECTIVE: This case report is presented to raise the awareness of the potential risk of reactivation of herpes simplex virus (HSV) encephalitis after intracranial surgery. CLINICAL PRESENTATION: The case of an 8-year-old male patient who suffered a reactivation of HSV encephalitis after undergoing amygdalohippocampectomy for complex partial seizures is reported. This patient had previously contracted HSV 1 meningoencephalitis at the age of 16 months. Six years later, a left amygdalohippocampectomy was proposed after the development of intractable partial epilepsy associated with left mesial temporal lesions. During the postoperative period, the patient suffered severe clinical deterioration with partial status epilepticus, aphasia, and hyperthermia, which resolved after intensive antiepileptic treatment supported by acyclovir. CONCLUSION: We advise prophylactic pre-, peri-, and postoperative treatment with acyclovir for patients with known histories of HSV encephalitis who undergo intracranial procedures.

Choroid plexus carcinomas in childhood: clinical features and prognostic factors.

OBJECTIVE: Choroid plexus carcinomas are rare tumors with dismal prognosis. The role of surgery has been well established, but the benefit of either chemotherapy or radiotherapy remains controversial. To determine prognostic factors and effects of different therapeutic modalities on the outcome, we have reviewed the French experience of choroid plexus carcinoma. METHODS: Twenty-two children were registered in the Société Française d'Oncologie Pédiatrique between 1984 and 1995. All these children underwent surgical resection of the primary tumor. The intent of postoperative treatment was to delay or to avoid radiation therapy. Nineteen children received postoperative treatment, with chemotherapy in 17 and radiation therapy in 2. Two responding patients underwent high-dose chemotherapy with stem cell rescue. RESULTS: The 5-year survival rate was 26%. The sole relevant prognostic factor was the extent of surgery. Patients with total or gross total resection had a 86% survival rate. Survival did not correlate with age, sex, delay between first appearance of symptoms and diagnosis, location of the primary tumor, tumor volume, or response to postoperative treatment. All but one patient with incomplete surgery had tumor recurrence within 2 to 23 months. CONCLUSION: Choroid plexus carcinoma has a very poor prognosis when surgery is incomplete. Aggressive surgical resection of the tumor is necessary for survival. Although chemotherapy gives promising responses, local control remains the main challenge, and "second look" surgery has to be considered for patients with incomplete resection.

Hydrocephalus associated with intramedullary low-grade glioma. Illustrative cases and review of the literature.

Over the past 15 years, eight children affected by intramedullary low-grade gliomas associated with hydrocephalus were treated at l'Hôpital des Enfants Malades. In all cases the diagnosis of hydrocephalus was made prior to that of the spinal tumor. Neuroradiological examination of all patients revealed contrast enhancement of the intracranial subarachnoid spaces. In six cases this was progressive, suggesting subarachnoid spread of the tumor, which was confirmed in two cases by histological examination. The authors analyzed 38 cases of intramedullary low-grade glioma associated with hydrocephalus that were reported in the literature. Fifteen of the cases had intracranial leptomeningeal seeding. Several hypotheses have been proposed to explain this unusual association, such as 1) increase in cerebrospinal fluid (CSF) viscosity because of elevated fluid protein content; 2) obliteration of the cisterna magna due to a rostral extension of the tumor; and 3) blockage of the spinal subarachnoid pathways of CSF resorption. Two other theories seem of particular interest. Bamford and Labadie suggested that the abnormal presence of fibrinogen in the CSF and its transformation into fibrin at the level of the basal cisterns and Pacchioni's granulation may alter CSF hydrodynamics. This mechanism alone is sufficient to induce hydrocephalus of the communicating type. In addition, as suggested by Maurice-Williams and Lucey, the resulting leptomeningeal fibrosis might predispose secondary implantation of neoplastic elements in the subarachnoid spaces of the intracranial compartment.

Subdural sarcoma associated with chronic subdural hematoma. Report of two cases and review of the literature.

The authors report the cases of two children who presented in the first months of life with progressive macrocrania related to chronic pericerebral fluid collection. This condition resolved spontaneously without treatment after a few months in the first case, whereas it required several aspirations of blood-stained fluid via the fontanel in the second case. Both patients developed normally without evidence of disease in the earliest years of life and presented at the ages of 3 1/2 and 4 1/2 years, respectively, with symptoms and signs of rapidly progressing intracranial hypertension. In both cases contrast-enhanced computerized tomography and magnetic resonance imaging revealed masses in the subdural space of the skull base and the cranial vault associated with significant subdural fluid collections. In the first case the lesion was misdiagnosed in the initial phase and treated, by means of multiple craniotomies, as an organized subdural hematoma. After a diagnosis of liposarcoma had been made, the patient was treated with chemotherapy, which resulted in a good resolution of the lesions at 3-month follow-up review. In the second case a biopsy allowed the diagnosis of fibrohistiocytic sarcoma and the patient was treated with chemotherapy. The authors review the literature of the few reported cases and discuss the possible pathophysiological association between pericerebral fluid collection and the subsequent development of a subdural sarcoma.

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.

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.

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.

Cardiac rhabdomyoma and tuberous sclerosis in three fetuses: a neuropathological study.

In spite of the development of modern imaging, most lesions of tuberous sclerosis (TS) remain difficult to detect before birth. Particularly, brain involvement at a fetal stage of development is poorly documented. We report three cases of fetuses examined after pregnancy was interrupted because of the detection of cardiac rhabdomyoma. In two of the three cases there were brain lesions suggestive of TS, including cortical tubers, subependymal nodules and scattered bizarre giant cells in the white matter. These observations confirm that brain lesions of TS can be present before birth; they can show, at an early period of development, an aspect quite similar to lesions described at an adult stage. The most characteristic cell abnormality is the so-called balloon cell. The majority of these cells exhibit a strong immunoreactivity with glial antibodies (GFAP, vimentin, S100). Immunoreactivity with neuronal markers (synaptophysin) is present in a small percentage of balloon cells.

Nasal eosinophilia in children: its use in the nasal allergen provocation test.

This pediatric cytological and clinical study aimed at assessing the value of nasal eosinophilia during nasal provocation tests for identifying an offending allergen. The population studied comprised 50 children aged from 4 to 18 yr; 39 of these had well-characterized allergic rhinitis, which in 21 cases was combined with asthma, and the remaining 11 had nonatopic chronic rhinitis. Nasal secretions, collected by nose blowing, were stained with May-Grünwald-Giemsa or Wright stain. The percentage of nasal eosinophils was obtained by examining the cells in the whole slides. Counts were carried out on secretions collected before challenge, after insufflation of saline solution (for verification), and 40 min after insufflation into each nostril of an allergen (housedust mite extract). The nasal provocation test was considered positive when insufflation of the allergen increased nasal eosinophilia by more than 10%, provided that the prechallenge proportion of eosinophils was less than 50%. No increase in specific bronchial resistance was noted. These results indicate that nasal provocation tests are safe, even in asthmatic children.

[Histologic classification and prevalence of tumors of the central nervous system in infants. Study of 100 excision samples]. / Classification histologique et prévalence des tumeurs du système nerveux central chez le nourrisson. Etude de cent pièces d'exérèse.

In order to assess the epidemiological and histological distributions of brain tumors in infants under 2 years of age, 100 cases collected in the Neurosurgery Department of Hôpital Necker-Enfants Malades in Paris during an 11 year period, were reviewed. Histopathological diagnoses were analyzed with special reference to age at the time of diagnosis, sex, topography and grading. Brain tumors were classified into 2 groups: under one year of age, and between 1 and 2 years of age. Certain neoplasms were reclassified after review of the slides. The male-to-female ratio was 1.09:1 for the first group, and 1.25:1 for the second one. In the group of tumors diagnosed under 1 year of age, 60% were supratentorial, and 40% were infratentorial. The percentages reversed after 1 year of age in favor of those of the posterior fossa. The histopathological distribution of these tumors was assessed in the two groups according to Rorke's classification. The three most common histological types were astrocytoma (27% under 1 year versus 36% after 1 year), ependymoma (25% versus 16%) and medulloblastoma (14% in each group). There was a significantly higher prevalence of some types of tumors in the first year of life as compared with those diagnosed after one year.: ependymomas (25% versus 16%), primitive neuroectodermal tumors (PNET) other than medulloblastomas (9% versus 3.5%), choroid plexus tumors (9% versus 17%), and teratomas (5% versus 1.7%). Craniopharyngiomas (2%) and non-tumoral lesions (vascular malformations) (7%) had similar distributions in both groups. There was a preponderance of malignant tumors in the first year of life. Our study demonstrates that brain tumors diagnosed during the first year of life have characteristic and specific features in terms of topography, histopathological distribution and grading.