[Intracranial hemorrhage in adults: place of antithrombotic treatment]. / Hémorragies intracrâniennes de l'adulte : implication de plus en plus importante des traitements antithrombotiques ?

BACKGROUND AND PURPOSE: Antithrombotic (anticoagulants and antiplatelets) are responsible for iatrogenic accidents, with a specific impact in neurosurgery. Bleeding complications are the most common and best-known. But the link to antiplatelet or to dual association of antithrombotic treatment with intracranial haemorrhage is not complete yet. We studied the proportion of patients under antithrombotic treatment, when an intracranial hemorrhage occurred, as well as the morbi-mortality of each group of patients (with or without antithrombotic treatment). Finally, we studied the proportion of off-label prescriptions. METHODS: We conducted a monocentric and comprehensive prospective study on a group of patients. All patients that had been admitted for intracranial hemorrhage to our hospital, in a 5-month period were included in the study. RESULTS: One hundred and sixty patients admitted for an intracranial hemorrhage were included during 70days of call. Seventy-four of these patients (46.25%) were under antithrombotic treatment: 40 under antiplatelet treatment (54%), 29 under anticoagulant treatment (39.2%), four under dual antithrombotic treatment (5.4%), and one under Arixtra(®). Half of the patients under antithrombotic treatment had poor prognosis as compared to 40% of patients without antithrombotic treatment. Off-label antithrombotic therapy was estimated at 27.3% of all prescriptions. CONCLUSIONS: The prevalence of antithrombotic therapy in patients is high when intracranial hemorrhage occurs. Some complications could be avoided by decreasing the number of off-label prescriptions and by better controlling their use (using standardized INR). Antiplatelet treatments and new antithrombotic therapies require better drug monitoring which could be part of the establishment of a specific register.

Current insulin therapy in patients with type 2 diabetes: results of the ADHOC survey in France.

AIM: In France, the Afssaps/HAS 2006 guidelines for insulin-treated type 2 diabetic patients recommend a target glycated haemoglobin level (HbA(1c)) of less than 7%, achieved by optimalizing the insulin dose or increasing the number of daily injections. The present study investigated to what extent these recommendations are followed in clinical practice by general practitioners (GPs) and diabetologists (DTs). METHODS: The ADHOC study (observational, transversal) was a survey of 267 GPs and 180 DTs prescribing insulin in France (participation rate: 4.45% and 11.6% of GPs and DTs, respectively). Physicians answered a questionnaire focused on aspects of insulin therapy in type 2 diabetic patients receiving oral antidiabetic drugs (OADs) and insulin for at least six months. RESULTS: A total of 1874 patients were included in the study (959 from GPs and 915 from DTs). Insulin was initiated about 10 years after the diagnosis of diabetes, when patients had high HbA(1c) levels (mean value: 9.2%). At the time of the survey, patients had been treated with insulin for 3.4 ± 3.5 years (mean ± SD), and the mean HbA(1c) was significantly reduced (P<0.05) to 7.8% and 7.9% in patients treated by GPs and DTs, respectively. However, almost 80% of patients had HbA(1c) levels greater than 7%, and 35% had levels greater than 8%. The last fasting blood glucose level was 144 ± 45 mg/dL. More than 60% of patients with HbA(1c) greater than 8% were using single daily injection therapy. On consultation day, insulin treatment (dose, number of injections and type of insulin) was not optimalized in more than 40% of the latter patients. Differences in data between patients treated by GPs and DTs were small and often not statistically significant. CONCLUSION: In this study, the main therapeutic goals of insulin therapy, as defined by the Afssaps/HAS 2006 guidelines, were only attained in around 20% of type 2 diabetic patients, irrespective of follow-up by a GP or DT. During consultation, insulin therapy was not optimalized in a large proportion of inadequately controlled patients.

[Chordoma radicular metastasis following cerebrospinal fluid dissemination]. / Métastase radiculaire d'un chordome secondaire à une dissémination dans le liquide cérébrospinal.

INTRODUCTION: Chordoma metastases are usually found at advanced stages of the disease. The metastases occur generally in lung, bones, liver and lymph nodes. We report a rare case of radicular chordoma metastasis. CLINICAL CASE: A 59-year-old man, operated for a clival chordoma six years ago, was admitted for atypical S1 radiculopathy. The MRI showed lumbar intradural tumor compressing the cauda equina. Surgery was performed. RESULTS: After opening of the dura mater, the tumor was seen tightly attached to the nerve roots and was totally removed. The histological examination confirmed a metastasis of the known chordoma without local recurrence. CONCLUSION: Chordomas are slowly growing, aggressive malignancies. Mostly complete microsurgical resection reduces local and distant recurrences. Intradural metastases are rare and follow cerebrospinal fluid dissemination from tumor cells. These metastases must be actively cured to achieve longer survival and better quality of life.

[Functional neuronavigation. Fusion of functional MRI data in a neuronavigation system]. / Neuronavigation fonctionnelle. Fusion des données de l'IRM fonctionnelle dans un système de neuronavigation.

Neuronavigation systems integrating functional magnetic resonance imaging data have been reported recently, but generally without many details about methodology. We propose an easy method to perform functional neuronavigation by integrating functional MRI data analyzed with the Statistical Parametric Mapping 99 reference software, in the Stealth Station which is the most common neuronavigation system. Users of this new and promising technique, which requires further validation, must be aware of its limitations. Functional MRI data seem to be the major source of imprecision. As a result we do not yet recommend the use of functional neuronavigation without the control of direct cortical stimulations.

[Gross tumor volume (GTV) and clinical target volume (CTV) in radiotherapy of benign skull base tumors]. / Volume tumoral macroscopique (GTV) et volume-cible anatomoclinique (CTV) dans la radiothérapie des tumeurs bénignes de la base du crâne.

Skull base tumours represent about 35 to 40% of all intracranial tumours. There are now many reports in the literature confirming the fact that about 80 to 90% of such tumours are controlled with fractionated radiotherapy. Stereotactic and 3-dimensional treatment planning techniques increase local control and central nervous system tolerance. Definition of the gross tumor volume (GTV) is generally easy with currently available medical imaging systems and computers for 3-dimensional dosimetry. The definition of the clinical target volume (CTV) is more difficult to appreciate; it is defined from the CTV plus a margin, which depends on the histology and anterior therapeutic history of the tumour. It is important to take into account the visible tumour and its possible extension pathways (adjacent bone, holes at the base of skull) and/or an anatomic region (sella turcica + adjacent cavernous sinus). It is necessary to evaluate these volumes with CT Scan and MRI to appreciate tumor extension in a 3-dimentional approach, in order to reduce the risk of marginal recurrences. The aim of this paper is to discuss volume definition as a function of tumour site and tumour type to be irradiated.

[Fractionated radiotherapy of intracranial meningiomas: 15 years' experience at the Bordeaux University Hospital Center]. / Radiothérapie fractionnée des méningiomes intracrâniens: 15 ans d'expérience au centre hospitalier universitaire de Bordeaux.

PURPOSE: To evaluate the long-term results of external fractionated radiation therapy (RT) in the treatment of intracranial meningiomas. PATIENTS AND METHODS: From January 1981 to December 1996, 156 patients with intracranial meningiomas were treated with external fractionated RT. Median age was 57. Indications for radiation therapy were as follows: (1) completely excised histologically aggressive tumors (12 patients); (2) incomplete surgical resection (37 patients); (3) medically inoperable or basilar tumors where operation would involve considerable danger or permanent neurological damage (77 patients); and, (4) tumor recurrences (30 patients). Most patients were irradiated with 6 to 9 MV photon beams. A three to four-field technique with coned-down portals was used. Since 1993, 71 patients had a three dimensional dosimetry. Doses were calculated on the 95% or 98% isodoses, all fields were treated every day, five days a week, for a median total dose of 50 Gy (1.8 Gy/Fraction). RESULTS: Median follow-up from radiation therapy was 40 months. Acute tolerance was excellent; an early clinical improvement during radiation therapy was noted in 19 patients (17.8%). Clinical improvement or stabilization was observed in 130 patients (83.4%). Radiologically, local control was obtained in 124 cases (79.4%) and tumor recurrences occurred in 21 cases (ten progressions in the treated volume, five borderline, six new locations). Overall and cause specific-survival rates were 75% and 89% at five years, and 45 and 76% at 10 years, respectively. CONCLUSION: These results reassess the role of fractionated RT in the treatment of intracranial meningiomas. Long-term tolerance is excellent for a majority of patients. The study of recurrences confirms the importance of the definition of the target volume, and asks questions about total given doses.

[Central nervous system. Experience of the Bordeaux University Hospital Center and review of the literature]. / Les dysgerminomes du système nerveux central. Expérience du Centre Hospitalier Universitaire de Bordeaux et analyse de la littérature.

PURPOSE: Retrospective analysis of 17 patients with intracranial germ cell tumors treated in a multidisciplinary consultation at the Bordeaux University Hospital a and literature review. MATERIALS AND METHODS: Seventeen consecutive patients were treated from 1978 to 1995 for a primary intracranial germ cell tumor. Median age was 14 (range 3-29 years). There were two malignant teratoma, six proved germinoma and nine presumed germinoma (diagnostic based on biological, radiological and treatment criteria). All received radiotherapy from 30 to 60 Gy (median 40 Gy) in different volumes. Chemotherapy was administered in 15 cases, three after surgery and 12 after radiotherapy. RESULTS: All tumours were in complete remission after initial treatment. The two malignant teratomas recurred in non-irradiated area after nine and 48 months, and the patients died. None of the germinoma recurred within a follow-up period of two to 17 years (median 65 months). Five and 10 year actuarial overall survival rates were the same: 84% for all histologies and 100% for germinomas. Only two patients developed school difficulties and six presented an hypopituitarism, of which one was consecutive to radiotherapy. Chemotherapy was well tolerated. CONCLUSION: This retrospective study and literature analysis are in favor of limited dose and volume of radiation therapy associated with chemotherapy.

[Fractionated irradiation of cerebellopontine angle neurinoma: 12 years' experience of the Bordeaux University Hospital Center]. / Irradiation fractionnée des neurinomes de l'angle pontocérébelleux: 12 ans d'expérience au centre hospitalier universitaire de Bordeaux.

PURPOSE: To evaluate retrospectively the long-term results of fractionated radiation therapy (RT) in cerebello-pontine angle neurinomas (CPA). METHODS AND MATERIAL: From January 1986 to October 1995, 29 patients with stage III and IV neurinomas were treated with external fractionated RT. One patient was irradiated on both sides and indications for RT were as follows: (1) general contraindications for surgery (16 patients); (2) hearing preservation in bilateral neurinomas after controlateral tumor exeresis (six patients); (3) partial tumor removal (five patients); and, (4) non-surgical recurrence (three patients). A three to four fields technique with coplanar static beams and conformal cerobend blocks was used; doses were calculated on a 95 to 98% isodoses and were given five days a week for a median total dose of 51 Gy (1.8 Gy/fraction). Most patients were irradiated with 6 to 10 MV photons). RESULTS: Median follow-up was 66 months (seven to 120 months). Seven patients died, two with progressive disease, five from non-tumoral causes. Tumor shrinkage was observed in 13 patients (43.3%), stable disease in 14 (46.6%), and tumor progression in three. Two patients underwent total tumor removal after RT (one stable and one growing tumor). Hearing was preserved in four out of six patients. No patient experienced facial or trigeminal neuropathy. CONCLUSION: Fractionated RT is a well tolerated and efficacious treatment of large non-surgical CPA neurinomas.

[Intramuscular myxoma. A case of myxoma of the spinal erector muscle]. / Myxome musculaire. Une observation de myxome des muscles érecteurs du rachis.

A case of intramuscular myxoma, extended in the lumbar erector spinae muscles, is reported. This soft tissue tumor is rare, about one hundred observations are indexed in the literature. The clinical findings are nonspecific, magnetic resonance imaging reveals few characteristics, and finally a histological examination is required, after surgical removal, to pinpoint the diagnosis. Recurrence is uncommon, but a systematic follow-up is necessary.

[Oculomotor paralysis and head trauma]. / Paralysies oculomotrices et traumatismes crâniens.

Few studies have dealt with post-trauma ocular motor palsy. We analyzed 31 personal cases and reviewed the literature, focusing on pathogenesis. We emphasize the importance of a complete radiological examination including magnetic resonance imaging when the CT-scan does not provide a satisfactory correlation between anatomic findings and clinical presentation. Systematic detection, early management and regular follow-up is mandatory.

Astrocytomas and choroid plexus tumors in two families with identical p53 germline mutations.

Germline p53 mutations carry an increased risk of development of breast cancer, soft tissue and osteosarcomas, brain tumors, leukemia and adrenocortical carcinomas. Cerebral neoplasms are usually of astrocytic lineage and occur in 40% of affected families. This report presents clinical, neuropathological and molecular genetic data from 2 families in France with an identical p53 germline mutation in codon 248 (CGG->TGG; Arg->Trp) and a clustering of CNS tumors. The youngest patient in each family developed a malignant choroid plexus tumor while several young adults of both kindred succumbed to low-grade astrocytoma, anaplastic astrocytoma or glioblastoma. The only non-neural neoplasm was an adrenocortical carcinoma in a boy aged 4 years who developed an anaplastic choroid plexus papilloma 2 years later. Of 2 previously reported inherited choroid plexus tumors, 1 occurred in a family which also carried a germline mutation in codon 248. It remains to be shown whether this unusual pattern of CNS tumors is due to an organ-specific effect of this particular p53 mutation or whether it reflects the genetic background of the affected families.

Cranial aneurysmal bone cysts presenting with raised intracranial pressure: report of two cases.

Aneurysmal bone cysts in the skull vault are reported in two patients 7 and 9 years old, who presented with vomiting and headaches caused by raised intracranial pressure. CT showed the cystic lesion in the diploë, with predominantly inward expansion. Fluid-fluid levels were seen on both CT and MRI; the latter also showed bleeding within the cyst. MR angiography showed compression of the superior sagittal sinus in the second case.

[Clinical case: apropos of a case of unilateral bifocal, temporal and occipital cholesteatoma]. / Cas clinique: a propos d'un cas de cholestéatome unilatéral bifocal, temporal, occipital.

A 23 year-old woman presented a double located cholesteatomas in the temporal and occipital bones. The two locations were anatomically well separated. No other case was found in the literature. This was a fortuitous association of an acquired temporal cholesteatomas and a congenital occipital one. A single surgical treatment with only one surgical access.

Psammomatous melanotic schwannoma of a spinal nerve root. Relationship with the Carney complex.

A 36-year-old man had an oval, black, extradural tumor partly removed from the left C4 spinal root, with total removal 4 months later. In both specimens, most tumor cells were spindle-shaped. A few cells were large, epithelioid-like, with a prominent nucleolus. Mitoses were rarely seen. Many tumor cells contained coarse or fine granules of a brown pigment. Such cells were immunopositive for S-100 protein and HMB-45. Additionally, psammoma bodies were numerous in certain areas, indicating a diagnosis of psammomatous melanotic schwannoma (PMS). Periumbilical spotty pigmentation was found in the patient and in six of his siblings and their mother. The search for cardiac myxoma and endocrine overactivity was negative in the patient. Features of Carney's complex must be sought in a patient with PMS and in their primary relatives. So far, more than 150 patients and seven families with Carney's complex have been reported.

Use of a biodegradable elastin-fibrin material, Neuroplast, as a dural substitute.

Since the new Neuroplast biomaterial is now commonly used in several domains of restorative and curative surgery, its preliminary evaluation as a dura mater substitute in the rabbit was performed and is described herein. Whereas the importance of prosthesis thickness was implicated and solved (0.2 rather than 1.0 mm), both macroscopic examination and histological studies revealed for the neotissue an effective patency, a good continuity and especially no or almost no adherence at all. As Neuroplast is now available for use everywhere in humans, this material is being developed in several fields of neurosurgery.

[Clinical presentation and prognosis of brain tumors]. / Présentation clinique et pronostic des tumeurs cérébrales.

The diagnosis of a cerebral tumor is received as dramatic by the patient or his family on account of the fonctional and symbolic idea of the brain and the perspectives of neurosurgical and psychological disabilities. Nowadays it is simplified because actual techniques of imagery are atraumatic and reliable. So the first signs are not to be undervaluated. Prognostic depends of identifiable factors. They lead the choice of therapy and help the medical doctor for the treatment follow-up and for answering to the patient's life questions.

Fractionated radiation therapy in the treatment of intracranial meningiomas: local control, functional efficacy, and tolerance in 91 patients.

PURPOSE: To evaluate efficacy and tolerance of external fractionated radiation therapy (RT) in the treatment of intracranial meningiomas. METHODS AND MATERIALS: From January 1981 to September 1993, 91 patients with intracranial meningiomas were treated with fractionated RT. Indications were as follows: (a) incomplete surgical resection, 29 patients; (b) tumor recurrences without considering the amount of the second resection, if performed, 14 patients; (c) completely excised angioblastic, aggressive benign, and anaplastic tumors, 8 patients; (d) medically inoperable and basilar tumors where operation would involve considerable danger or permanent neurological damage, 44 patients. Most patients were irradiated with 6 to 9 MV photon beams. A three- to four-field technique with coned-down portals was used. Doses were calculated on the 95% isodose and were given 5 days a week for a median total dose of 52 Gy (1.80 Gy/fraction). RESULTS: Median follow-up from radiation therapy was 40 months. Acute tolerance was excellent, but there were six late delayed injuries. Tumor recurrences occurred in six cases. Six patients died from their tumor or RT complications, 19 from nontumoral reasons. Three, 5- and 10-year survival rates were 82, 71, and 40%, respectively. The most significant prognostic factor was age: 5-year survival rate was 86% for patients less than 65 years and 37% for patients more than 65. However, there were no differences in recurrence-free survival rates between patients younger than 65 and the oldest ones. Of 60 symptomatic patients with neurological deficits, 43 had neurological improvement (72%), beginning in some cases within 15 to 20 days after starting RT. CONCLUSION: These results reassess the role of fractionated RT in the treatment of meningiomas, and stress on its efficacy, especially on cranial nerves palsies, without severe toxicity in most cases.

Gonadotropin-releasing hormone induced Ca2+ influx in nonsecreting pituitary adenoma cells: role of voltage-dependent Ca2+ channels and protein kinase C.

The action mechanism of gonadotropin-releasing hormone (GnRH) on the cytosolic free calcium concentration ([Ca2+]i) and high-threshold voltage-dependent Ca2+ channel activity was studied in human nonsecreting (NS) pituitary adenoma cells. [Ca2+]i was monitored in individual cells by dual emission microspectrofluorimetry using indo 1 as intracellular fluorescent Ca2+ probe. The whole-cell recording patch-clamp technique was used to study Ca2+ channels. A short application of GnRH (1 to 100 nM) induced an increase in [Ca2+]i due to Ca2+ entry through plasma membrane voltage-sensitive L-type Ca2+ channels. Protein kinase C (PKC) depletion induced by a pretreatment with 1 microM PMA for 24 h abolished spontaneous Ca2+ transients and the action of GnRH on [Ca2+]i and Ca2+ channels. Phloretin (250 microM) and staurosporine (20 nM), two protein kinase C inhibitors, inhibited Ca2+ channel activity, thereby suppressing the effect of GnRH. On the other hand, activation of PKC by a short application of phorbol myristate acetate (10 nM) stimulated Ca2+ influx through Ca2+ channels. These findings demonstrate that, in human NS adenoma cells, GnRH (1 to 100 nM) induces an increase in [Ca2+]i, principally due to Ca2+ entry through L-type voltage-activated Ca2+ channels. PKC regulates this mechanism as well as basal ion channel activity, thus exerting both positive and negative control of [Ca2+]i in stimulated and unstimulated NS adenoma cells.

Thyrotropin-releasing hormone and gonadotropin-releasing hormone-associated peptide modulation of [Ca2+]i in human lactotrophs.

The effect of thyrotropin-releasing hormone (TRH) and gonadotropin-releasing hormone-associated peptide (GAP) was studied on both secretion and intracellular free Ca2+ concentrations ([Ca2+]i) in human pituitary cells cultured from prolactin (PRL)-secreting tumors. Secretion was measured during a 30-min incubation period and we used a microspectrofluorimetric method in individual cells and indo-1 as the fluorescent probe. TRH (10(-8) M) significantly increased PRL release in five out of the six cell populations. In these five cases, more than 68% of individual cells responded to TRH by an increase in [Ca2+]i. No significant increase in PRL secretion was found in another culture in which TRH increased [Ca2+]i in only 37% of the cells. The effect of GAP (10(-7) M) was studied in five cell populations. In three of them, a decrease of 20% to 51% of the PRL basal secretory rate was observed under GAP. GAP inhibited [Ca2+]i in respectively 59%, 46% and 94% of the cells from these cultures. The inhibitory effect of GAP was blocked by a pertussis toxin (PT) pretreatment which demonstrates the involvement of a PT-sensitive G-protein in GAP action. In two other cultures, GAP did not significantly alter PRL secretion or individual cell [Ca2+]i. These observations suggest that GAP might play a role in the control of PRL secretion in the human.

[Transfrontonasal approach: development of a mixed approach to ethmoid tumors. Experience of 12 cases]. / La voie trans-fronto-nasale: évolution de la chirurgie par voie mixte des tumeurs ethmoïdales. Expérience de 12 cas.

Our experience in approaching ethmoid tumors through a combined pathway is currently based on 81 patients. 69 of them were malignant tumors treated by the neurosurgical subfrontal and paralateronasal transfacial rhinological approach. For the past two years, we have adopted the technical modification described in Bordeaux by Pinsolle and San-Galli enabling the approach of the ethmoid bone by means of a unique (Unterberger's scalp) incision and a unical frontonasal flap. 12 patients benefitted from this transfrontofacial access. The advantages and disadvantages of the technique are discussed.