[Childhood diencephalic pilocytic astrocytoma. A review of seven observations]. / Les astrocytomes pilocytiques du diencephale de l'enfant. à propos de sept observations.

BACKGROUND AND PURPOSE: Pilocytic astrocytoma (PA) is a WHO grade I tumor of the central nervous system mostly arising in children and young adults. Management of diencephalic PA is a difficult challenge. Surgical treatment has to cope with both the difficulties of deep location and eloquent area tumors. MATERIALS AND METHODS: We retrospectively reviewed seven pediatric cases (female: 4, male: 3) of diencephalic PA. Opto-chiasmatic tumors were excluded from the series. Mean age at diagnosis was 108 months (9 years) (range: 4 month-18 years), median age was 111 months. Median follow-up for the series was 125 months. Tumor locations were as followed: right thalamus: 2, both thalami: 1, hypothalamus: 3, and right basal ganglia: 1. At the onset, the first symptom was mostly raised intracranial pressure. The delay in diagnosis ranged from 48 hours up to 6 years. TREATMENT: a shunting procedure was performed in 3 patients, a direct surgical approach in 5 patients (gross total removal: 2; partial removal: 3) and one patient had only a biopsy. Three children were re-operated. Three patients were treated by radiationtherapy (RT) after surgery. Chemotherapy was delivered for 4 children. RESULTS: The overall survival rate was 71.4 months (almost 6 years) (range: 3-184 months). Median survival rate was 42 months (3.5 years). Three children died, two by tumor progression and one death related to late side-effects of RT. Four patients have a good quality of life with GOS I (n = 3) or II (n = 1). We observed tumor regression in two patients at 1 and 17 years after the beginning of treatment. Correct diagnosis was only made for two cases at the initial pathological examination. CONCLUSION: The course of diencephalic PA is still unpredictable. The tumor can be controlled by a partial surgical removal, and a residual tumor can sometimes decrease in size after surgery. Gross total removal of these tumors, although difficult, may be performed. With cranial navigation systems, the risk is low. Pathological diagnosis is sometimes difficult to assess.

[Methylation status of RARbeta gene promoter in low and high grade cerebral glioma. Comparison with normal tissue. Immuno-histochemical study of nuclear RARbeta expression in low and high grade cerebral glioma cells. Comparison with normal cells. 48 tumors]. / Statut de méthylation du promoteur du gène RARB dans les tumeurs cérébrales gliales de bas et de haut grade. Comparaison avec le tissu sain. Etude immuno-histochimique du marquage au RARbeta des noyaux des cellules tumorales dans les gliomes de bas et de haut grade. Comparaison avec les cellules saines, à propos de 48 tumeurs.

Retinoic acid receptor beta (RARbeta) is a nuclear receptor often deregulated in tumors. An immunohistochemical study was conducted to examine the level of expression of this receptor in the nucleus of glial cell tumors (low and high grade glioma) as well as a study of the methylation status of the gene promoter coding this receptor on the same tumor samples. A comparison with normal tissue was done each time. 48 tumors were eligible for the study (15 glioblastomas, 20 grade III oligodendrogliomas and 13 grade II oligodendrogliomas). A constant decrease of RARbeta expression was found by comparison with normal tissue whatever the histological grade of the tumor, suggesting a deregulation of RARbeta gene expression. Methylation of RARbeta promoter gene was a rare event (12.5% of all cases), except for grade III oligodendrogliomas (20%), and is thus not a major event of this gene deregulation. Other reasons of this deregulation of RARbeta should be studied, such as loss of 3p24 heterozygoty, mRNA studies and RARbeta interactions with other retinoid receptors.

[Breast cancer treated by antibiotherapy? Granulomatous mastitis with Corynebacterium]. / Cancer du sein traité par antibiotherapie ? Mastite granulomateuse à corynébactérie.

Granulomatous mastitis is a rare disease, often associated with Corynebacterium infection. It raises the problem of diagnosis of breast tumor with a fast evolution and inflammatory character. We report two cases of granulomatous mastitis with Corynebacterium. It concerns the clinical and radiological description, followed by the therapeutic alternatives and future of the patients. The clinical presentation is variable. The treatment consists in a surgical procedure of resection. The medical treatment based of corticosteroids also proves efficient. The association between Corynebacterium presence and this pathology seems frequent and needs a specific bacteriological search.

Modeling the relation between neurofibrillary tangles and intellectual status.

The relationship between the neurofibrillary tangles and the intellectual deficit observed in senile dementia of the Alzheimer type was studied in 27 patients over the age of 75. The presence and density of tau positive tangles were assessed in six areas including limbic, paralimbic, and isocortical cortices. In the isocortical areas, the presence [1] or absence [0] of neurofibrillary tangles was better correlated with the Blessed test score than the density of the neurofibrillary tangles profiles. Multivariate analysis showed that the number of areas containing at least one neurofibrillary tangle was the best explanatory variable of the intellectual status. The cortical areas were ranked according to the prevalence of their involvement. The presence of tangles in an area of a given rank took place only if the areas of lower ranks were also involved. It is proposed that the presence of tangles in a given area is a more significant information than the value of their density. These data may lead to new diagnostic procedures.

The progression of the lesions in Alzheimer disease: insights from a prospective clinicopathological study.

Senile plaques and neurofibrillary tangles are the markers of Alzheimer's disease. They are also found in old patients who have been considered to be intellectually normal throughout their life, a situation referred to as "physiological aging". The neurofibrillary tangles are made of abnormally phosphorylated tau. The anti-tau antibody labels not only the neurofibrillary tangles, but also the crown of the senile plaques and the neuropil threads interspersed between the cell bodies and the plaques. The senile plaque comprises a core made of A beta peptide surrounded by a neuritic crown. The anti-A beta antibody also labels "diffuse deposits", i.e. ill limited areas of immunoreactivity which lacks the characteristics of the amyloid substance. The intellectual deficit appears to be statistically linked with the density of the tau-positive alterations-tangles, threads and plaque crowns--which usually appear simultaneously in a given cortical area. In the entorhinal area, their density increases proportionally to the intellectual deficit without threshold, suggesting that ageing and disease are a continuum. In the isocortex, the progression of the tau positive alterations is, on the contrary, stepwise--in a "all or none" fashion--from the hippocampus to the primary cortices, through the associative multimodal areas. The tau positive lesions probably progress through connections: they indeed disappear from areas, that have been disconnected by additional lesions (such as infarcts).

Necrotizing encephalopathy and macrocephaly with mitochondrial complex I deficiency.

A neonate presented in the first weeks after birth with vomiting. He was unresponsive, with hypotonia, macrocephaly, and lactic acidosis. The cranial computed tomographic scan revealed a hypodense brain, with increased brain volume and extensive cerebral edema. He died at 6 weeks of age; postmortem examination revealed necrotizing encephalopathy with marked brain edema, spongiosis, thalamic necrosis, and basal ganglia calcifications. Enzyme studies of the mitochondrial respiratory chain revealed complex I deficiency in both muscle and liver.

In vitro and in vivo studies on chelation of manganese.

This work deals with new chelating agents of manganese (Mn). Out of 24 compounds chosen for their chemical structure supposed to be favorable for Mn complexation, six polyaminopolycarboxylic acids proved to be efficient for displacing Mn bound to serum bovine proteins in vitro: TTHA, DTPA, DPTA, DPTA-OH, HBED, EDTA (mobilization > or =50%). The first five compounds were then tested in vivo on rats pretreated with MnCl2. They exhibited only slight to moderate efficacy to diminish Mn in tissues and were ineffective on increased Mn concentration in whole blood; in addition, they had different and specific mobilizing effects on other essential elements (Fe, Zn, Cu). Their limited efficacy in vivo could be due to the formation of very stable complexes between Mn2+ and different molecules such as hemoglobin and certain cytochromes, instead of Fe2+. This could disturb the functioning of the cellular respiratory chain, leading to an incomplete reduction of O2 with formation of free oxygenated radicals, reduction in the energy supply, and disturbance of the cytochromes renewal mechanism. All of these phenomena could accelerate cellular aging and explain the lack of efficacy of the chelating agents towards Mn neurotoxicity (Parkinson's syndrome).

Compensatory renal growth post fetal nephrectomy in the rabbit.

Compensatory renal growth post-nephrectomy is well documented both clinically and experimentally. However, little is known about the capacity for compensatory growth in utero. We performed unilateral nephrectomy in fetal rabbits and studied the growth of the contralateral kidney. Thirty fetal rabbits underwent in utero uninephrectomies at day 25 of gestation. On gestational day 28, all the fetuses were delivered by cesarean section and the ratios kidney weight/body weight of the operated fetuses were compared to those of control littermates. The kidneys were then analysed by histology. A significant increase in renal weight was observed. The histological study of the remaining kidneys indicated a statistically significant increase of the glomerular area which confirmed the renal hypertrophy. This experiment demonstrates the capacity for the rabbit to develop in utero compensatory renal growth.

[Nervous system borreliosis with pseudo-lymphoma cells in cerebrospinal fluid]. / Neuroborréliose avec cellules pseudolymphomateuses dans le liquide céphalorachidien.

We report the case of a 44-year-old woman, who experienced acute back pains, leg paraesthesia, and diplopia. Analysis of the cerebrospinal fluid revealed, in addition to increased protein and decreased glucose levels, an elevated number of large atypical cells, resembling lymphoma cells. Magnetic resonance imaging of the brain and spine was normal. High levels of antibodies against Borrelia burgdorferi were found in both serum and cerebrospinal fluid. The patient completely recovered with ceftriaxone therapy.

[MNGIE syndrome in 2 siblings]. / Le MNGIE syndrome: deux cas dans une même fratrie.

Two siblings (one man, one woman), presenting with diarrhea, severe weight loss peripheral neuropathy, ophthalmoparesis, asymptomatic leukoencephalopathy were diagnosed as a new cases of Mitochondrial Neuro Gastro Intestinal Encephalomyopathy syndrome (MNGIE). Hirano (1994) defined four criteria for the diagnostic: peripheral neuropathy, ophthalmoparesis, gastro intestinal dysmotility, muscle biopsy with histologic features of mitochondrial myopathy (ragged-red fibers, muscle fibers with increased succinate deshydrogenase stain or ultra structurally abnormal mitochondria). In a review of the literature, we found 31 cases with MNGIE. With our two cases, we study this group of 33 patients. First symptoms begin about 13.5 years with a median of 10 years and extremes for 1 to 32 years. The first signs are gastro intestinal symptoms (recurrent nausea, vomiting or diarrhea with intestinal dysmotility) in 22 cases, an ophthalmoparesia in 4 cases, intestinal and ocular signs in 1 case, gait ataxia or peripheral neuropathy in 3 cases, hearing loss in 1 case, gait ataxia or peripheral neuropathy in 3 cases, hearing loss in 1 case. During the evolution, besides the cardinal signs, the following features have been observed with a variable frequency: hearing loss, short stature, facial palsy, dysphonia, dysarthria, sweating, orthostatic hypotension, bladder dysfunction, hepatomegalia, The laboratory features are: abnormal Nerve Condition Studies/EMG compatible with a sensory motor neuropathy, lactic acidosis, mitochondrial respiratory chain defect (essentially complex IV deficiency, complex I deficiency or multiple complex defect), MRI leukodystrophy, elevated CSF protein, heart block, ragged-red fibers or increased SDH stain. The prognosis is poor, due to a severe weight loss bordering on cachexia 13 patients died with a mean age of 28.5 years (median 24 years, extreme 3 years to 51 years). The prognosis seems to be worsened by a young age of onset. The 33 patients belong to 19 families with 7 cases of consanguinity. 25 patients had a brother, a sister or a cousin affected. The study of these families is compatible with an autosomic recessive transmission, suggesting a pathology of the nuclear genomi, probably impliying the control of the mitochondrial DNA replication. In fact, in 13 cases, a study of the mt DNA was realized: multiple deletions were founded in 6 cases, multiples mutations in one case, unique mutation in 1 case. In 5 cases ther was no evidence of abnormality. These precise etiology and pathophysiologic significance of the mt DNA deletions, and the heterogeneity of the modifications of the mt DNA remain unknown. However, the possibility of various phenotypes for a same genotype or inversely is known in mitochondriopathies.

[Multifocal progressive leukoencephalitis in a patient given fludarabine for chronic lymphoid leukemia]. / Leucoencéphalopathie multifocale progressive après traitement par fludarabine dans une leucémie lymphoïde chronique.

A 74-year- man was hospitalized for subacute aphasia and right hemiparesis. He had had chronic lymphoid leukemia for 11 years and had been treated 5 months earlier with 3 courses of fludarabine. Magnetic resonance imaging showed lesions of the temporo-occipital white matter compatible with progressive multifocal leukoencephalitis (PML). The presence of JC virus was demonstrated first by in situ hybridation after a brain biopsy and second with polymerase chain reaction on CSF. The diagnosis of PML was confirmed. The causality of fludarabine treatment is discussed.

[Mesangial IgA deposits nephropathy]. / La néphropathie à dépôts mésangiaux d'IgA.

Idiopathic IgA nephropathy of Berger's disease is characterized by prominent and diffuse IgA deposits in the mesangium. In many countries, it is the most common type of primary chronic glomerulonephritis. Typically, it is revealed by recurrent episodes of gross hematuria in association with ENT infection, but it can progress insidiously with microscopic hematuria and proteinuria. Serum IgA levels are increased in about 50% of cases. IgA nephropathy is not a minor condition: 20% of patients develop end-stage chronic renal failure 10 years after diagnosis and 50% after 20 years. IgA nephropathy can recur in a transplanted kidney suggesting that this disease is a systemic disorder although it has a remarkable tropism for the kidney. Even though many points remain to be elucidated, its pathogenesis appears to be linked to a genetic factor responsible for a lymphocyte dysfunction and an acquired environmental factor such as penetration of an antigen via the mucosa which may give rise to an excessive and inappropriate IgA immune response with the deposition of IgA in the mesangium and the development of progressive renal alterations. No treatment has been shown to be effective but tonsillectomy advised in case of a recurrent tonsillar focal infection is most often accompanied by a decrease in the incidence of gross hematuria. Corticosteroid therapy can be of benefit in cases involving a nephrotic syndrome associated with minimal glomerular lesions. In all cases, control of possible hypertension is of value in slowing the progression of this disease.

[Extra-cardiac rhabdomyoma of the fetal type]. / Rhabdomyome extra-cardiaque de type foetal.

Rhabdomyomas are benign tumors of striated muscle. They are distinguished by topographic data: cardiac or genital and by histological criteria: foetal or adult type. The foetal type is the most heterogeneous, with either a majority of immature cells or a mixture of maturing elements. This diversity has led to distinguish immature (or standard) foetal Rhabdomyomas from intermediate foetal Rhabdomyomas. One observation of this last type is reported. The authors highlight the essential characteristics of foetal Rhabdomyomas, however the exact meaning remains unclear: an anomaly in the differentiation of the striated muscle? or a true tumoral process through genetic anomaly?

[Pleomorphic xanthoastrocytoma. A review of five observations]. / Le xanthoastrocytome pléomorphe. A propos de cinq observations.

BACKGROUND AND PURPOSE: We present a review of five patients who developed pleomorphic xanthoastrocytomas, presenting the clinical features, pathology findings and therapeutic approach of these rare tumours which almost always occur in children and young adults. METHODS: This paper is a retrospective study of five patients (three males and two females), treated from 1985 to 1996. RESULTS: Seizure was the most frequent symptom. The tumor was located in the temporal or temporo-parietal lobe in two patients, in the parietal lobe in one, the frontal in one and in hypothalamus and third ventricle in the final patient. To our knowledge, no case of pleomorphic xanthoastrocytoma located in the area of hypothalamus/third ventricle has been reported in the literature. All patients underwent surgery which was complete for two patients, subtotal for two others and partial for one. Four were given post-operative cerebral radiation therapy (two recurrences and malignant transformation and two erroneous diagnoses) (mean dose: 44.75 Gy), for two patients surgery was followed by chemotherapy. One patient was lost for follow-up. Two patients presented at least one tumor recurrence. Two died from malignant transformation. Two patients are alive without recurrence at 12 and 16 years from diagnosis with excellent quality-of-life (Glasgow Outcome Scale=I). CONCLUSION: Surgery is the gold standard treatment. Prognosis is very good (except for malignant transformation), so that a close long-term clinical and radiological follow-up is mandatory.

[Adult medulloblastoma. Review of 22 patients]. / Médulloblastome de l'adulte. A propos de 22 cas, revue de la littérature et perspectives thérapeutiques.

BACKGROUND AND PURPOSE: Medulloblastoma is a malignant neuro-ectodermal tumor classically considered as a pediatric tumor. Adult medulloblastoma is rare. This low incidence results in a lack of data concerning the management of treatment. We report our experience and propose a review of the literature to clarify the main therapeutic options that are nowadays suggested. METHODS: We reviewed 22 adult patients treated for cerebellar medulloblastoma between 1979 and 1999. Actuarial relapse-free and overall survival were determined by the Kaplan-Meier method. Prognosis factors were studied by Log- Rank test. RESULTS: The five years relapse free and overall survival rates were respectively 63.1% and 81.3%. These rates are superior to those reported in the literature. None of the studied factors (age, gender, histological subtype, total or partial surgery, presence of a CSF derivation device, radiotherapy, chemotherapy) were significantly associated to remission or survival. However our statistical results should be interpreted with caution in this small population. CONCLUSION: Adult medulloblastoma prognosis seems to improve since chemotherapy has been introduced in the therapeutic protocols. Prospective and multicentric studies should determine the exact pattern of treatment.

[Is the topography of Alzheimer's disease lesions a clue to their pathogenesis?]. / La topographie des lésions de la maladie d'Alzheimer permet-elle de soupçonner leur mécanisme?

Neurofibrillary changes, labelled by antitau antibodies and deposits, labelled by anti-A beta antibodies, were counted in 6 cortical areas in 29 prospectively studied cases (Charles Foix Longitudinal Study). The intellectual status had been assessed by the Blessed test score; 10% of the cases were found to be normal (score > 27), 10 other percents were deeply demented (score < 2) and the other cases were regularly distributed over the intermediate values. Tau positive neurofibrillary changes were present in the hippocampus and in the parahippocampal gyrus even in intellectually normal cases. They were found in a primary sensory cortex (the visual cortex) only in the most severely affected cases. Associative cortices were spared in the normal cases and in the least demented patients. They were involved only at a critical value of the Blessed Test Score. A beta deposits involved more areas than the neurofibrillary pathology and their distribution was less systematically organized. Their density was poorly correlated with the intellectual status. Neuritic plaques, made of an amyloid core and of a crown of tau positive neurites, were present only in those areas that also contained neurofibrillary tangles. Our findings support the contention that neurofibrillary pathology, involving a set of short range, "feed-backward", cortico-cortical connections, is a close correlate of dementia. The role of A beta deposits remains unclear. Although poorly connected with dementia, they could be the remote initiator of the pathological cascade that leads to the neurofibrillary pathology, immediate cause of the cortical dysfunction.

[Contribution of bronchoalveolar lavage and transbronchial biopsy to diagnosis and prognosis of drug-induced pneumopathies]. / Contribution du lavage broncho-alvéolaire et de la biopsie transbronchique au diagnostic et au pronostic des pneumopathies médicamenteuses.

This survey reports on 10 case-studies of drug-induced pneumonitis. The drugs under consideration are amiodarone, methotrexate, chlorambucil, sulindac, nilutamide-leuproreline, cyclothiazide, with the possible addition of bleomycin. In each case, one or more bronchoalveolar lavage were carried out and in most cases it was also possible to perform a transbronchoscopic lung biopsy. The results of these tests are analysed in order to ascertain their contribution to diagnosis and prognosis. Regarding diagnosis, bronchoalveolar lavage does not evidence a typical cellular configuration characterizing drug-induced alveolitis. Moreover, transbronchoscopic lung biopsy plays no part in diagnosing this pathology. Both these tests, however, help to eliminate other hypotheses. Regarding prognosis, transbronchoscopic lung biopsy provides no information, unlike bronchoalveolar lavage in which a high rate of neutrophils in the lavage fluid is sometimes associated with the development of pulmonary fibrosis.

[Spontaneously involuting metastatic seminoma of the testis ("burned-out seminoma"). Report of a case presenting with supraclavicular adenopathy]. / Séminome testiculaire métastatique spontanément involué ("Burned-out seminoma"). A propos d'un cas révélé par une adénopathie sus-claviculaire.

Metastatic testicular germ cell tumours with complete involution of the primary site, or "burned-out tumour", constitute a classical but rare entity, whether the initial cell type is seminomatous or non-seminomatous. The authors report one case of this type of tumour. The diagnosis is primarily based on ultrasonography, indicating the need for orchidectomy in the presence of an anomaly, followed by histology, revealing a fibrous scar with no tumour cells. Aetiopathogenic hypotheses are divided between ischaemic and immunological theories. Scrotal ultrasonography and tumour marker assays should be performed systematically in the presence of retroperitoneal adenopathy with normal testicular clinical examination.

[Nephronogenic nephroma: a benign kidney tumor in adults. Two case reports]. / Le néphrome néphronogène: tumeur bénigne du rein de l'adulte. A propos de 2 cas.

The authors report 2 cases of a benign and uncommon type of renal tumour in adult, the nephronogenic nephroma. The pathology is discussed and compared to other groups of solid renal tumour. The confusion with malign tumour is usual. According to radiological investigations and pathological analysis, aspects of surgical treatment are presented and discussed.

[Tubulo-papillary tumors of the kidney. Clinical, histologic and cytogenetic aspects. 15 new cases]. / Les tumeurs tubulo-papillaires du rein. Particularités cliniques, histologiques et cytogénétiques. A propos de 15 nouvelles observations.

Between 1987 and 1992, we operated on 15 patients with tubulopapillary tumours (TPT) of the kidney, corresponding to 10% of all renal cancers operated during this 5-year period, which brings the total number of published cases to 418. TPT differ from non-tubulopapillary tumours in several ways. The medical imaging findings may differ when the tumour is not necrotic (20 to 30% of cases). The histology differs not only in terms of the tumour architecture, but also by the frequent association (9/15 cases) with other ipsilateral or contralateral renal anomalies: 2 bilateral tumours, 3 tumours associated with multiple cysts and 4 multifocal tumours. These characteristics, combined with the finding of 12 familial cases suggest a genetic origin for TPT, especially as the genetic abnormalities detected (tri-or tetrasomy 17) differ from the anomalies usually detected in non-tubulopapillary tumours (anomalies of 3p and 5q). This study is the first to report familial cases of TPT. The prognosis of these tumours, generally better than that of non-tubulopapillary tumours, suggests the possibility of conservative surgery when the diagnosis can be established preoperative or at operation.