Central nervous system hemangioblastomas, endolymphatic sac tumors, and von Hippel-Lindau disease.

Von Hippel-Lindau disease (VHL) is a hereditary cancer syndrome caused by germline mutations of the VHL tumor suppressor gene. Major progress has been made in the last decade in both clinical and fundamental aspects of VHL. The VHL gene product, pVHL, has major and multiple functions: pVHL regulates not only first angiogenesis but also extracellular matrix formation and the cell cycle.

Germline mutation profile of the VHL gene in von Hippel-Lindau disease and in sporadic hemangioblastoma.

von Hippel-Lindau (VHL) disease is a dominantly inherited disorder predisposing those afflicted to hemangioblastomas of the central nervous system and the retina, renal cell carcinomas, pheochromocytomas, and pancreatic tumors. The disease has been associated with mutations of the VHL gene. The screening of 92 unrelated patients with VHL disease for point mutations in this gene revealed 61 DNA variants.

Haemangioblastoma of the central nervous system in von Hippel-Lindau disease. French VHL Study Group.

Haemangioblastoma of the central nervous system (CNS) is the most characteristic lesion and the most common presenting manifestation of von Hippel-Lindau (VHL) disease and has a striking tendency to multiple occurrence. Its sites of predilection are the posterior fossa (cerebellum++), and the spinal cord. Haemangioblastoma may cause increased intracranial pressure and/or neurological deficits and remains the main cause of morbidity and mortality in VHL.

Somatic inactivation of the VHL gene in Von Hippel-Lindau disease tumors.

Von Hippel-Lindau (VHL) disease is a dominantly inherited disorder predisposing to retinal and CNS hemangioblastomas, renal cell carcinoma (RCC), pheochromocytoma, and pancreatic tumors. Interfamilial differences in predisposition to pheochromocytoma reflect allelic heterogeneity such that there is a strong association between missense mutations and risk of pheochromocytoma. We investigated the mechanism of tumorigenesis in VHL disease tumors to determine whether there were differences between tumor types or classes of germ-line mutations.

[Variety of pancreatic lesions observed in von Hippel-Lindau disease. Apropos of 8 cases].

Von Hippel-Lindau's disease is a rare genetic disease, with an autosomal dominant mode of inheritance, characterised by the development of several tumours, such as haemangioblastoma of the central nervous system and retina, renal cysts or carcinoma and pheochromocytoma. Several pancreatic lesions, mainly represented by multiple cysts, are also encountered. We report here 8 cases of pancreatic involvement in patients affected with von Hippel-Lindau's disease.

Predominant occurrence of somatic mutations of the NF2 gene in meningiomas and schwannomas.

The NF2 gene is a putative tumor-suppressor gene that, when it is altered in the germline, causes neurofibromatosis type 2, a tumor-susceptibility disease that mainly predisposes to schwannomas and meningiomas. The recent isolation of the NF2 gene on chromosome 22 allows the identification of somatic mutations in human tumors. We have searched for mutations of the NF2 gene in 331 primary human tumors using a screening method based on denaturing gradient gel electrophoresis, which allows the detection of mutations in 95% of the coding sequence.

DNA-based presymptomatic diagnosis for the von Hippel-Lindau disease by linkage analysis.

Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited condition characterized by a predisposition to the development of haemangioblastoma, renal cell carcinoma and phaeochromocytoma. The gene which, when altered, causes the disease was cloned in 1993, and maps within a series of known polymorphic loci in the 3p25-p26 region. To optimize a DNA-based presymptomatic diagnosis, we have selected six highly informative microsatellite loci, closely linked to the VHL gene.

Pheochromocytoma as the first manifestation of von Hippel-Lindau disease.

Background: von Hippel-Lindau disease is an autosomal dominant disorder characterized by the development of hemangioblastomas in the cerebellum, spinal cord, and retina, renal cell carcinoma and cysts, pancreatic cysts, and pheochromocytoma.

Methods: We have studied a series of 36 French patients affected with von Hippel-Lindau disease pheochromocytoma. Thirty (83%) of them were diagnosed as having von Hippel-Lindau disease because the disease occurred in a familial von Hippel-Lindau disease setting; six (17%) were diagnosed as having von Hippel-Lindau disease because they displayed another characteristic manifestation of that disease.

Characterization of several DNA polymorphic markers in the LIF gene region.

We describe seven restriction fragment length polymorphisms (RFLPs) in the Leukemia Inhibitory Factor (LIF) gene region. These new markers, found using a cosmid contig, have been used to map precisely the chromosome 22 long arm.

[The value of magnetic resonance imaging in the diagnosis of spinal cord hemangioblastoma. Apropos of 12 cases].

This study concerned a series of 12 patients, 4 of whom had Von Hippel-Lindau disease. Six of these patients were explored by myelography, 6 by spinal cord angiography, 8 by CT scan with contrast injection and 12 by MRI, with gadolinium injection in 8. MRI proved to be the choice examination for the diagnosis of spinal cord tumor, but gadolinium injection was necessary since it made it possible to detect the tumoral bud and its intense enhancement.

Integrated imaging system for stereotactic neurosurgery.

Talairach's method remains the most universal of all stereotactic methods. It makes it possible to go back to an examination left interrupted, but above all, it provides multiple lateral and coronal approaches in matters of epilepsy, radio-isotopes or photobiology. The advances achieved in modern imaging methods, notably CT and MRI, and the performance of modern computers have enabled us to devise an integrated imaging system meant to accelerate and make feasible calculations of penetrating trajectories, according to the position of the target as previously defined by CT and MRI sections, and taking into account the position of vessels given by angiography.

Role of Gd-DOTA in the evaluation and imaging of experimental blood-brain barrier disruption in brain edemas and their improvement after anti-inflammatory drugs treatment.

This study was carried out to evaluate the effect of new anti-inflammatory drugs in the treatment of brain edema in new models. Experimental brain edema was induced in rats by stereotaxic injection of phospholipase A2 into one hemisphere. Concentrations of intravenously injected gadolinium-DOTA in the lesioned hemisphere were three times as high as in normal rat hemisphere.

[Pheochromocytoma, first manifestation of Von Hippel-Lindau disease: a possibility to be considered].

Von Hippel-Lindau (VHL) disorder is an autosomal dominant disease characterized by the almost constant development of hemangioblastomas in the central nervous system (cerebellum, spinal cord and retina). In addition, various types of tumors including renal cell carcinomas, pancreatic cysts and pheochromocytomas are frequently observed in VHL gene carriers. Linkage of the VHL locus to the RAF-1 oncogene on the short arm of chromosome 3 (3p25-26) has been recently reported.

Photodynamic treatment of normal endothelial cells or glioma cells in vitro.

Photodynamic therapy is based on the interaction of a sensitizer (hematoporphyrin derivative) selectively retained by tumor cells, which becomes toxic after light exposure. We studied the influence of exogenous prostaglandins and indomethacin on photodynamic therapy of normal human endothelial cells and glioma cells. Although differing in origin and kinetic properties, endothelial cells exhibited photodynamic therapy sensitivity quite comparable to that of C6 cells.

[Intracerebral morphine therapy in cancer patients].

An overview of recent studies concerning opioids and their pharmacokinetics is presented. In the light of these findings it is shown that intracerebral administration may be justified. The authors experience with 63 cases is detailed: all cancer patients in the final stage.

[Bone integration within calcium phosphate ceramic by creation of posterior inter-articular lumbar spine fusions in dogs].

Following earlier experiments in which several calcium phosphate ceramics were tested, the aim of this study was to evaluate bone integration within a macroporous biphasic calcium ceramic (M.B.C.

[Hemodynamic monitoring in microneurosurgical excision by sub- and retro-sinus approach in seated position in acoustic neurinoma].

Haemodynamic data (thermodilution Swan-Ganz catheter and radial artery cannula) were collected in 17 patients (52.4 +/- 8 yr) during retrosigmoid approach for removal of an acoustic tumour in the seated position. Measurements were made before stimulation of posterior fossa structures (period 1) and during tumour dissection along the brain stem (period 2).

[Vicious callus and unrecognized dislocations of the cervicothoracic junction].

Five patients were treated after a period varying between 6 weeks and 18 months following original injury. The five lesions were similar in that they could not be reduced by conventional orthopedic measures and that they were fixed during dynamic review examinations using a brilliance amplifier.

[Is osteosynthesis justified for spinal injuries in children?].

The legitimacy of osteosynthesis for the treatment of spinal injuries in children is analyzed as a function of results in 10 cases, 7 affecting the cervical, 2 the thoracic and one the lumbar region, six of the children being under 10 years of age. Five of these children had serious neurologic disorders, including 4 with high tetraplegia. Technical difficulties of osteosynthesis were not made easier by the poorly adapted nature of the material for infantile statures.

[Acute hydrocephalus in tuberculous meningitis in adults].

The authors report a case of tuberculous meningitis in a young man who developed acute hydrocephalus as soon as the fifteenth day of the course of the disease. Attention is drawn to the importance of computerized tomography in investigating sudden deterioration in patients with tuberculous meningitis. Emphasis is put on the value of a shunt procedure which, in the case reported here, led to immediate improvement before antituberculous chemotherapy could have been effective.

[Localized fast rhythms in EEG tracings following surgery for intracranial meningioma].

Forty-six patients were followed up after removal of an intracranial meningioma. Nine of the 46 patients in their 3rd month postoperative EEG had localised fast rhythms which remained stable. The fast rhythms appeared in small 20-25 Hz and 20-40 microV bursts; they were localised over the craniotomy flap as shown by the control X-ray of the sites of the electrodes; they were unaffected by eye-opening and slightly reduced by fist-clenching.