[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.

[Gynandroblastoma and Fragile X syndrome. Case report]. / Gynandroblastome et syndrome de l'X Fragile. À propos d'un cas.

Gynandroblastoma is a rare ovarian tumor, derived sex cord-stromal, malignant, with low scalable potential. Clinical investigations include endocrinology or gynecological troubles, or pelvic mass syndrome. After pelvic MRI of reference, optimum surgery is the treatment of gynandroblastoma. Fragile X syndrome is the most common inherited cause of mental retardation, and females are more affected. Association of both is totally new.

Wernicke encephalopathy and Creutzfeldt-Jakob disease.

We assessed the prevalence of Wernicke encephalopathy (WE) in all 657 cases suspected of Creutzfeldt-Jakob (CJD) referred from 2001 to 2006 to the French Neuropathology Network of CJD. Clinical, biological and imaging data were reviewed when the diagnosis of WE was made at autopsy. No CJD was found in five cases suspected of sporadic CJD. In these five cases, myoclonus had been observed in four, CSF 14-3-3 protein in two. In 14 other cases, WE was combined with CJD, 13 of which were sporadic. These belonged mainly to the molecular variants of sporadic CJD associated with a long duration of disease. This stresses the necessity of remaining alert to the diagnosis of WE when CJD is suspected.

Concomitant bone marrow metastasis of a glioblastoma multiforme revealed at the diagnosis.

The rare occurrence of extra-neural metastases in patients having a tumour of the central nervous system (CNS) could mean that the symptoms of a metastatic lesion are confused with a second pathology. We recently treated a patient with a glioblastoma multiforme who was developing a pancytopaenia at the initial diagnosis. The frequent red cell and platelet transfusions were transitorily active. An extensive radiological investigation and a unilateral iliac bone marrow aspirate and biopsy were performed. Cells immunoreactive to glial fibrillary acidic protein were detected in a specimen obtained from the iliac bone. Post-mortem examination confirmed metastasis to extra-cranial bone and revealed other metastases in lung, mediastinal lymph node and spleen. Therefore, in patients with malignant glioma tumours, bone marrow metastasis, though not common, should be investigated when bone pain or cytopaenia occur.

[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.

Long-term evaluation of motor function following intraneural injection of ropivacaine using walking track analysis in rats.

BACKGROUND: There is a paucity of data regarding neurologic function following nerve injury. Our objective was the long-term evaluation of motor function following intraneural injection of ropivacaine in rats using the sciatic function index (SFI), derived from walking track analysis. METHODS: Rats were randomly assigned to one of four groups of 13 animals each. A needle was inserted under magnification into the left sciatic nerve and 0.2 ml of normal saline, formalin 15%, ropivacaine 0.2 or 0.75% were injected intraneurally. The right side was sham operated. Walking track analysis was performed the day before and on days 1, 4, 7, 11, 15, 18, 21, and 67 following intraneural injection. At the end of the experiment (day 67) a semi-quantitative evaluation of neuropathologic changes was performed by three independent observers. RESULTS: Animals treated with saline and ropivacaine (0.2 and 0.75%) had no detectable impairment of motor function at any time point. In contrast, rats treated with formalin had a complete loss of motor function immediately after the intraneural injection, which persisted until day 21 and returned to normal by day 67. Important histopathologic changes (score=2) with excellent inter-observer agreement were seen only in the group treated with formalin. This applied to both axonal degeneration and Schwann cell density evaluations. CONCLUSIONS: These findings suggest that intraneural injections of ropivacaine at concentrations routinely used in clinical practice appear to have no deleterious effect on sciatic nerve motor function in this experimental rat model.

[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.

[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.

[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.

[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.

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).

The structure of the cartilaginous end-plates in elder people.

Low back pain is the leading cause of work-related disability. Degeneration of the intervertebral disc (IVD), the boundaries of which with age-related changes remain obscure, is considered to be its most important cause. The cartilaginous end-plate (CEP) is the anatomic boundary of the IVD. Since the latter is avascular in adults, the CEP is supposed to play a key role in the metabolism of the IVD. Consequently, it has been postulated that the decrease in permeability of the CEP is the main cause of degeneration of the disc. However, the permeability depends at least partially on the morphologic state of the CEP. Little is known about the age-related changes of the CEP compared to those of the IVD. The objectives of the study were to examine the CEP at different ages, to classify the age-related changes in both the CEP and IVD, and to compare them. The intervertebral discs of the five levels of ten human lumbar spines were collected from cadavers aged from 47 to 78 years, and studied macroscopically and microscopically. Morphologic features of the CEP (thickness, IVD/CEP length ratio, degree of calcification, marrow contacts, CEP-VB and CEP-IVD separations) were measured. Morphologic grades were assigned for both the CEP and the IVD. No significant differences were found with regard to these features in the different age-groups. On the other hand, no significant correlation was found between the morphologic grade of the CEP and that of the IVD, suggesting that the importance of the CEP in disc degeneration may be debatable.

Chemotherapy for unresectable and recurrent intramedullary glial tumours in children. Brain Tumours Subcommittee of the French Society of Paediatric Oncology (SFOP).

Adjuvant treatment for intramedullary tumours is based on radiotherapy. The place of chemotherapy in this setting has yet to be determined. Between May 1992 and January 1998, eight children with unresectable or recurrent intramedullary glioma were treated with the BB SFOP protocol (a 16-month chemotherapy regimen with carboplatin, procarbazine, vincristine, cyclophosphamide, etoposide and cisplatin). Six children had progressive disease following incomplete surgery and two had a post-operative relapse. Three patients had leptomeningeal dissemination at the outset of chemotherapy. Seven of the eight children responded clinically and radiologically, while one remained stable. At the end of the BB SFOP protocol four children were in radiological complete remission. After a median follow-up of 3 years from the beginning of chemotherapy, all the children but one (who died from another cause) are alive. Five patients remain progression-free, without radiotherapy, 59, 55, 40, 35 and 16 months after the beginning of chemotherapy. The efficacy of this chemotherapy in patients with intramedullary glial tumours calls for further trials in this setting, especially in young children and patients with metastases.

Gerstmann-Sträussler-Scheinker disease and the French-Alsatian A117V variant.

Gerstmann-Sträussler-Scheinker disease is a rare familial form of prion disease. This autosomal dominant disorder is constantly associated with a point mutation on the PrP gene. Eight mutations affecting respectively codons 102, 105, 117, 145, 202, 212 and 218, have been so far described. Symptoms are variable and include ataxia and dementia. They generally appear between the fourth and sixth decade. Mean duration of the disease (5 years) is on the whole longer than that of other familial forms of prion diseases. Gerstmann-Sträussler-Scheinker disease is neuropathologically characterized by the presence of numerous multicentric or unicentric PrP amyloid deposits widespread throughout the encephalon. Spongiform change is inconstant. Neurofibrillary tangles have been described in some families. Clinicopathological features show considerable variability. Pathogenesis of amyloidosis and associated lesions as well as factors underlying the phenotypic polymorphism of the disease remain only partially known.

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.

[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.

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).

Hepatitis C virus persistence in human hematopoietic cells injected into SCID mice.

The issue of infection of peripheral blood mononuclear cells (PBMC) by the hepatitis C virus (HCV) has potentially important implications, but is still debated. We have used the severe combined immunodeficiency (SCID) mouse model to test for the persistence of HCV in PBMC. Hematopoietic cells isolated from 14 subjects infected by HCV were inoculated intraperitoneally into SCID mice. Serum and blood cell samples from these mice were obtained with a mean follow-up of 8 weeks. As controls, human fibroblasts and sheep PBMC, preincubated with a human HCV-positive serum, were inoculated concomitantly into mice and analyzed. HCV-RNA positive strands were detected in 7 of 26 serum samples and 8 of 26 cell fractions from SCID mice inoculated with HCV-positive PBMC, after 8 weeks of follow-up. In contrast, no HCV RNA was detectable in the 10 control mice. HCV-RNA negative strands were detected in only 2 of 10 tested samples from 2 mice, and both positive mice had been inoculated with PBMC from HCV-positive subjects with malignant hematopoietic syndrome. Our study offers strong evidence for the persistence of HCV infection in mononuclear cells. Our results are also consistent with a low rate of HCV multiplication. This SCID mouse model might therefore be useful in analyzing the mechanisms of HCV persistence in mononuclear cells.

Cytoarchitectonic alterations in the supramarginal gyrus of late onset Alzheimer's disease.

The intellectual status of 28 women of over 75 years of age had been prospectively assessed by the Blessed test score. It ranged from nearly normal to deeply altered by dementia. After autopsy, the supramarginal gyrus was marked at the surface of the brain. Sections, 1 cm thick, were cut with a specially devised macrotome. The volume of the parietal lobe was measured by a point counting method, using Cavalieri principle. A sample from the supramarginal gyrus was taken from the previously marked area and the shrinkage due to the histological procedures was measured (it averaged 12%). More than 500 nucleolated neuronal profiles per case were mapped with a semi-automatic system. Density maps of the neuronal profiles were drawn and mean density was calculated using Dirichlet tessellation. The thickness of the cortical ribbon was standardized on the maps. The density of the neurons per unit volume was calculated, taking into account the section thickness measured for each sample with a length gauge fastened to the Z axis of the microscope. Statistical correlations were sought between the mean and laminar densities of the neurons on one hand, and Blessed test score, the densities of neurofibrillary tangles (NFT) and of senile plaques profiles, on the other hand. Finally, the total number of neurons present in the parietal lobe was estimated in each case. Neuronal loss appeared to be linked with the density of the NFT (r = -0.52; P < 0.004). The correlation was mainly due to a severe drop in neuronal number observed in the cases with more than 5 NFT/mm2. An average difference of 98 x 10(6) neurons per parietal lobe was found between the cases with less than 5 NFT/mm2 and those with more. The neuronal loss predominated in layers II and III (upper part). A multivariate analysis showed that the intellectual status was better correlated with the density of the tangles than with the neuronal loss.