[Cavernomas of the central nervous system. Historical data and changing ideas]. / Les cavernomes du système nerveux central. Historique et évolution des idées.

Since the advent of modern neuroimaging (MRI) cerebral cavernomas are usually diagnosed "in vivo". In this paper we describe the data which improved our knowledge of the disease: 1) nosologically, cerebral cavernomas belong to the group of cerebral vascular hamartomas which can be associated between themselves ("mixed" lesions); 2) hemodynamically, the annual risk of hemorrhage increases after a first bleeding and in deep located lesions (brainstem); 3) association between cavernomas and developmental venous anomalies may be observed; the later on must be left in place at operation; 4) immunocytochemical studies (PCNA) show that cavernomas should be considered more as a benign vascular tumor than as a malformation; 5) familial forms (20%) are characterized by multiple locations and "de novo" lesions; 6) better understanding of the natural history of cavernomas, which is a dynamic lesion, leads to broader surgical indications (no alternative treatment).

[The ventrolateral position]. / La position ventro-latérale.

AIM: To propose an alternative to the sitting position and the other horizontal positions while maintaining the advantages of the sitting position and assuring maximum safety for the patient particularly with respect to the risk of air embolism. POSITION: The patient is positioned as for the sitting position with the median axis of the posterior cranial fossa prolonging the spinal axis. The head is maintained by a Mayfield head holder and is inclined without force. The patient rests laterally on the apron, the thorax and the lower limbs resting on cushions. The upper limbs rest on the arm rests interdependent with the table facilitating surgical access and rolling movements. DATA: Since 1993, this position was used for 556 patients. For 81.3% of the patients lesions were located in the posterior cranial fossa and for 12.75% in the supratentorial region. Access to the cervical area was achieved for 4.7% of the patients. RESULTS: This position gave us access to the lesions without specific difficulties, irrespective of the patient's morphology. There were no air embolism events and no capnographic anomaly was reported. CONCLUSION: Since discontinuing use of the sitting position in our institution, we have found that the ventrolateral position can replace the sitting position advantageously. It allowed us to approach lesions located in a large area, from the cervical spine to the supratentorial area located behind external auditory meatus, and was compatible with anesthetic and surgical requirements.

Mutations within the MGC4607 gene cause cerebral cavernous malformations.

Cerebral cavernous malformations (CCM) are hamartomatous vascular malformations characterized by abnormally enlarged capillary cavities without intervening brain parenchyma. They cause seizures and focal neurological deficits due to cerebral hemorrhages. CCM loci have already been assigned to chromosomes 7q (CCM1), 7p (CCM2), and 3q (CCM3) and have been identified in 40%, 20%, and 40%, respectively, of families with CCM. Loss-of-function mutations have been identified in CCM1/KRIT1, the sole CCM gene identified to date. We report here the identification of MGC4607 as the CCM2 gene. We first reduced the size of the CCM2 interval from 22 cM to 7.5 cM by genetic linkage analysis. We then hypothesized that large deletions might be involved in the disorder, as already reported in other hamartomatous conditions, such as tuberous sclerosis or neurofibromatosis. We performed a high-density microsatellite genotyping of this 7.5-cM interval to search for putative null alleles in 30 unrelated families, and we identified, in 2 unrelated families, null alleles that were the result of deletions within a 350-kb interval flanked by markers D7S478 and D7S621. Additional microsatellite and single-nucleotide polymorphism genotyping showed that these two distinct deletions overlapped and that both of the two deleted the first exon of MGC4607, a known gene of unknown function. In both families, one of the two MGC4607 transcripts was not detected. We then identified eight additional point mutations within MGC4607 in eight of the remaining families. One of them led to the alteration of the initiation codon and five of them to a premature termination codon, including one nonsense, one frameshift, and three splice-site mutations. All these mutations cosegregated with the disease in the families and were not observed in 192 control chromosomes. MGC4607 is so far unrelated to any known gene family. Its implication in CCMs strongly suggests that it is a new player in vascular morphogenesis.

[Cerebellar, pulmonary and cutaneous localizations of juvenile xanthogranuloma]. / Localisations cérébelleuse, pulmonaires et cutanées d'un xanthogranulome juvénile.

BACKGROUND: Juvenile xanthogranuloma is one of the most common non-langerhan cell histiocytoses in children. Usually cutaneous, there are disseminated forms. However, neurological localizations remain exceptional. CASE REPORT: We report the case of a cerebellar localization, associated with cutaneous and pulmonary lesions in a 13-month old child. Surgical treatment of the cerebellar lesion was associated with vinblastin chemotherapy, that led to total regression of the cutaneous and pulmonary lesions, neurological stabilization, without recurrence on the control IRM, after a period of 7 years. DISCUSSION: This is the second reported case of histologically documented cerebellar juvenile xanthogranuloma. In the event of cutaneous juvenile xanthogranuloma, the neurological examination must be attentive and supplemented, in case of any suspicion, by medical imaging. We believe that surgical treatment of neurological juvenile xanthogranuloma is necessary, in the event of symptomatic lesions and accessible to surgery. No consensus has been reached on subsequent treatments (radiotherapy, chemotherapy) and must be discussed according to the clinical profile and data in the literature.

Prospective follow-up of 33 asymptomatic patients with familial cerebral cavernous malformations.

BACKGROUND: Cerebral cavernous malformation (CCM) is one of the most common vascular malformations of the CNS. Familial CCM are increasingly diagnosed, but little is known about their natural history, especially in asymptomatic patients. OBJECTIVE: To determine the degree of spontaneous evolution of familial CCM in a population of 33 symptom-free patients. METHODS: During a previous national survey, the authors analyzed the clinical and MRI features of 173 patients from 57 unrelated French families, including 73 asymptomatic subjects. Of these 73 subjects, 33 prospectively underwent two serial clinical and MRI examinations. Cerebral MRI systematically included spin echo and gradient echo sequences. Occurrence of clinical symptoms and MRI changes of CCM, namely, hemorrhage, change in signal intensity, change in size, and appearance of new lesions, were recorded by means of comparison of the first and last MRI examinations. RESULTS: The 33 patients (234 CCM, mean 7.1 lesions/subject, range 1 to 85 lesions/subject) were followed during a mean period of 2.1 years (range 0.5 to 4.5 years). Two patients became symptomatic: One presented with brainstem hemorrhage and one with partial seizure. Comparison of the two serial MR images found changes in 15 patients (46%): 1) Bleeding occurred in three type II lesions (1.3%) in three patients (9.1%); 2) 30 new lesions appeared in 10 patients (30.3%); 3) change in signal intensity was observed in one lesion (0.4%) in one patient (3%); and 4) increase in size was observed in four lesions (1.7%) in three patients (9.1%). CONCLUSIONS: This prospective study confirms the dynamic nature of CCM. The appearance of new lesions in 30% of patients has to be retained as a hallmark of the familial condition.

Pediatric cerebral aneurysms.

OBJECT: The exceptional pediatric aneurysm can be distinguished from its adult counterpart by its location and size; however, patient outcomes remain difficult to evaluate based on the published literature. METHODS: Twenty-two children, all consecutively treated in three neurosurgery departments, were included in this study. Each patient's preoperative status was determined according to the Hunt and Hess classification. Routine computerized tomography scanning and angiography were performed in all children on the 10th postoperative day. Each patient's clinical status was evaluated 2 to 10 years postoperatively by applying the Glasgow Outcome Scale (GOS). Twenty-one children presented with a subarachnoid hemorrhage (SAH) and one child harbored an asymptomatic giant aneurysm. Thirteen patients were in good preoperative grade (Hunt and Hess Grades I to III) and eight in poor preoperative grade (Hunt and Hess Grade IV or V). The symptomatic aneurysms were located on the internal carotid artery bifurcation (36.4%); middle cerebral artery (36.4%), half of which were found on the distal portion; anterior communicating artery (18.2%); and within the vertebrobasilar system (9.1%). A giant aneurysm was observed in 14% of patients. Overall outcome was favorable (GOS Score 5) in 14 children (63.6%) and death occurred in five (22.7%). Causes of unfavorable outcome included the initial SAH in four children, a complication in procedure in three children, and edema in one child. CONCLUSIONS: Pediatric aneurysms have a specific distribution unlike that of aneurysms in the adult population. The incidence of giant aneurysms and outcomes were similar to those in the adult population. The major cause of poor outcome was the initial SAH, in particular, the high proportion of rebleeding possibly due to a delay in diagnosis.

Non-invasive grading of oligodendrogliomas: correlation between in vivo metabolic pattern and histopathology.

Several studies have shown that the prognosis of oligodendrogliomas is dependent on their histological grade. In order to identify a non-invasive method for the primary diagnosis and follow-up of these tumours, we investigated the relationship between their in vivo metabolism, assessed by positron emission tomography (PET), and their histological grade assessed at the same time. Forty-seven patients with histologically confirmed oligodendrogliomas were investigated. Conventional neuroradiological assessment by computed tomography and magnetic resonance imaging (MRI) was performed in all the patients. All the histology slices were reviewed by the same pathologist after referral from various pathology laboratories. The PET investigation included a carbon-1 methionine (11C-MET) uptake study and, in the majority of cases, a fluorine-18 fluorodeoxyglucose (18F-FDG) uptake study, in order to investigate at the same time both amino acid metabolism and glycolysis. The sampled tumour region of interest (ROI) was defined from the T1-weighted 3D MR scan matched with the PET scan. Tracer concentration in each voxel of the tumour ROI was divided by the mean concentration in an ROI of the same size located in the healthy brain tissue. For each tumour and each tracer, we characterized the metabolic pattern on the basis of the mean and the maximum tumour to healthy tissue concentration ratio, and also the standard deviation and range of the ratios, which indicate the degree of metabolic heterogeneity of the tumour. The histological criteria for differentiating between high- and low-grade tumours were those of the WHO and, partially, of the Sainte-Anne-Daumas-Duport classification. Highly significant differences between high- and low-grade oligodendrogliomas (Mann-Whitney test: P<0.0001) were observed for all the assessed parameters of 11C-MET uptake. On the other hand, the pattern of 18F-FDG uptake showed only moderate differences between the two tumour groups.

The natural history of familial cerebral cavernomas: a retrospective MRI study of 40 patients.

Our objective was to determine the natural history and prognostic factors of familial forms of cerebral cavernous malformations (CCM). Cavernomas are one of the most common central nervous system vascular malformations. Familial CCM is increasingly diagnosed, but little is known about its natural history. In a national survey, we analysed clinical and MRI features of 173 patients from 57 unrelated French families. Of these 40 had undergone at least two clinical and MRI examinations. Occurrence of haemorrhage, new lesions, change in signal intensity and size of lesions have been studied by comparison between first and last MRI studies. The CCM were classified according to Zabramski et al. Mean follow-up was 3.2 years (range 0.5-6.5 years). We followed 232 cavernomas (mean 5.9 per patient, range 1-17). Serial MRI demonstrated changes in 28 patients (70%). Bleeding occurred in 21 lesions (9.1%) in 14 patients (35%). The haemorrhagic risk was 2.5% per lesion-year, higher in type I and brain-stem CCM. We saw 23 new lesions appear in 11 patients (27.5%), with an incidence of 0.2 lesions per patient year. Signal change was observed in 11 patients (27.5%), in 14 lesions (6%), while 9 lesions (3.9%) in 9 patients (22.5%) changed significantly in size.

De novo lesions in familial form of cerebral cavernous malformations: clinical and MR features in 29 non-Hispanic families.

BACKGROUND: To evaluate clinical and MR features of de novo lesions (DNL) in the familial form of cerebral cavernous malformation (CCM) in 40 patients belonging to 29 unrelated non-Hispanic families. METHODS: Forty patients followed up by serial cerebral MR examinations were included in this retrospective study. First and last available MR examinations were retrospectively analyzed and compared for each patient to diagnose DNL. Gradient-echo (GRE) sequences were performed in only 11 of the 40 patients and were not considered for this study. Incidence of DNL was evaluated in terms of lesions/patient-year. All DNL were characterized by their clinical and MR features (location, size, type). Type of CCM was determined according to the classification of Zabramski (1994). Patient groups with and without DNL were compared for sex, age, number of pre-existing CCMs, and follow-up. RESULTS: Twenty-three DNL were recorded in 11 patients (27.5%) and the incidence was 0.2 lesions/patient-year (mean follow-up = 3.2 years). All but one DNL were asymptomatic. Twenty DNL were supratentorial and three were infratentorial. Mean diameter was 8 mm (2-35 mm). Six DNL were classified as type 1 (subacute hemorrhage), six as type 2 (hemorrhages and thromboses of varying ages) and 11 as type 3 (chronic hemorrhage with hemosiderin staining). No statistical difference between groups was found in terms of sex, age, or number of pre-existing CCMs. On the other hand, duration of follow-up was significantly longer in the group with DNL. CONCLUSION: The occurrence of DNL seems to be a hallmark of the familial form of CCM in non-Hispanic families as well as in Hispanic families. Such DNL are usually asymptomatic and are mainly classified as type 3 (chronic hemorrhage with hemosiderin staining). Within the limits of the retrospective study design and potential selection bias introduced by the varying indications for MR scanning, it does seem that DNL may occur at any time in the lifespan of CCM patients, and occurrence does not seem to depend on age, sex, or the total number of pre-existing lesions.

Familial form of intracranial cavernous angioma: MR imaging findings in 51 families. French Society of Neurosurgery.

PURPOSE: To analyze the magnetic resonance (MR) imaging features of familial cerebral cavernous angioma in non-Hispanic families. MATERIALS AND METHODS: Between November 1996 and June 1997, 51 non-Hispanic families with familial cavernous angioma were identified. Cerebral MR images in 83 symptomatic subjects and 73 asymptomatic subjects were reviewed. Spin-echo (SE) and gradient-echo (GRE) MR imaging features of cavernous angioma were recorded and, in 91 subjects with both SE and GRE images, lesions were graded as type 1, 2, 3, or 4, according to a published classification scheme. MR imaging features were compared between symptomatic and asymptomatic subjects, and sensitivities of SE and GRE images were determined. RESULTS: Multiple lesions were more common than single lesions in both symptomatic and asymptomatic subjects, with no difference in mean number of lesions between groups. More lesions were detected on GRE images than on SE images. Type 1 and type 2 lesions were more numerous in symptomatic than in asymptomatic subjects. The numbers of types 2, 3, and 4 lesions increased with age in both groups. CONCLUSION: The familial form of cavernous angioma is characterized by multiple lesions and by a correlation between lesion number and subject age. The clinical manifestation may be more closely related to the type of lesion than to the number of lesions. GRE MR images are more sensitive than SE images for demonstration of cavernous angioma.

[Dysembryoplastic neuroepithelial tumors. Report of 8 cases including two with unusual localization]. / Tumeurs neuro-épithéliales dysembryoplasiques. A propos de 8 cas dont deux à localisation inhabituelle.

OBJECTIVES: Dysembryoplastic neuroepithelial tumors (DNTs) are usually located within the supratentorial cortex. We present a series of eight cases of DNTs including two cases with an extracortical location, one in the caudate nucleus, the other one expanded in the lateral ventricule, septum and fornix. An origin from secondary germinal layers, as previously suggested, can explain these extracortical locations. MATERIAL AND METHODS: Of the eight patients, seven had partial epileptic seizures and one intracranial hypertension. All patients underwent clinical examination, a computed tomographic (CT) scan, a magnetic resonance imaging (MRI) and a surgical removal of the lesion with histological examination. RESULTS: Clinical examination was normal except in the case with intracranial hypertension where a bilateral papillary oedema was found. In seven cases the CT scan showed a hypodense lesion of pseudocystic appearance. All lesions were hypointense on T1-weighted and hyperintense on T2-weighted MRI. Contrast enhancement was observed in two cases. The lesion was intracortical in six cases and extracortical in the remaining two: one in the head of the caudate nucleus and one in the trigonoseptal region. Histological examination identified an appearance of DNT with a specific glioneuronal element in six cases. CONCLUSION: The diagnosis of DNT can be suspected before histological examination on radiological features, chiefly because the tumor is located in the supratentorial cortex. However, extracortical locations do exist, even if unusual. As DNTs are always benign, knowledge and accurate diagnosis of these atypical cases are mandatory in order to avoid useless and even deleterious additional treatments, such as radiotherapy.

Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas.

Cavernous angiomas are vascular malformations mostly located in the central nervous system and characterized by enlarged capillary cavities without intervening brain parenchyma. Clinical symptoms include seizures, haemorrhage and focal neurological deficits. Cavernous angiomas prevalence is close to 0.5% in the general population. They may be inherited as an autosomal dominant condition in as much as 50% of cases. Cerebral cavernous malformations (CCM) loci were previously identified on 7q, 7p and 3q (refs 4,5). A strong founder effect was observed in the Hispano-American population, all families being linked to CCM1 on 7q (refs 4,7). CCM1 locus assignment was refined to a 4-cM interval bracketed by D7S2410 and D7S689 (ref. 8). Here we report a physical and transcriptional map of this interval and that CCM1, a gene whose protein product, KRIT1, interacts with RAP1A (also known as KREV1; ref. 9), a member of the RAS family of GTPases, is mutated in CCM1 families. Our data suggest the involvement of the RAP1A signal transduction pathway in vasculogenesis or angiogenesis.

[Unilateral endonasal approach to hypophyseal adenomas]. / Abord endonasal unilatéral des adénomes hypophysaires.

The endonasal approach for transsphenoidal hypophysectomy is a simple technique for exposing the floor of the sella turcica. In our institution we have operated 162 patients (64 microadenomas and 98 macroadenomas), over a ten-year period, by using that approach. The floor of the sella turcica is exposed through an incision performed posteriorly to the nostril at the junction of cartilaginous and bony septum. Postoperative rhinological complications are less frequently observed after unilateral endonasal approach than after sublabial one, and it is more comfortable for the patient. The morbidity of unilateral endonasal transsphenoidal approach is comparable to that of other series.

Brain cavernoma: a dynamic lesion.

BACKGROUND: Although the prevalence of brain cavernomas is high (0.50%), for unknown reasons, only a few of them display aggressive clinical behavior. METHODS: From a personal series of 65 operated and histopathologically verified cavernomas, we have conducted a long-term study, both retrospectively and prospectively, of the main features that cause some cavernomas to be dynamic lesions. RESULTS: Hemorrhage is the most common phenomenon. Extralesional bleeding due to the rupture of peripheral caverns is most often observed. These are never as immediately devastating as hemorrhages originating from a high-flow, high-pressure AVM. Extralesional hemorrhages tend toward spontaneous resorption, but the risk of recurrence exists and may lead to permanent disability or death (especially when the lesion is located in the brain stem). Intralesional bleeding caused by rupture of contiguous caverns is less frequently observed. This may lead to the formation of large cysts. Calcifications are mostly observed in patients presenting with chronic epilepsy. The bleeding risk of calcified cavernomas is low, but it can exist and should be taken into account in the surgical decision making. The growth of the cavernomatous matrix was obvious in three large cavernomas (two with calcification). No bleeding was found inside the lesions, suggesting a pure "intrinsic" growth. The role of pathologic angiogenic factors is highly probable in these cases. "De novo" appearing lesions were observed in five cases (four belonging to familial forms) on the magnetic resonance imaging survey of operated patients. Perilesional atrophy was observed in three cases (two operated) in patients with a long-lasting evolution. It suggests that the brain metabolism can be disturbed by slow, chronic effusion of blood around the cavernoma. CONCLUSIONS: The dynamism of cavernomas is determined by extrinsic factors, mainly hemorrhage (with its own consequences); and by intrinsic factors: the pseudotumoral growth of the cavernous matrix. Therefore, when they are symptomatic, cavernomas should be totally removed.

Familial cavernous malformations in a large French kindred: mapping of the gene to the CCM1 locus on chromosome 7q.

OBJECTIVES: To characterise clinically a large French family affected with cerebral cavernomas and to check for linkage of this condition to chromosome 7. METHODS: A family, originating from Normandy and in which five members had undergone surgery for cavernomas, was extended. All members older than 18 were studied clinically and by neuroimaging. Genetic linkage analysis was conducted using 11 polymorphic microsatellite markers located between D7S502 and D7S479. RESULTS: The family included three generations. Among the 25 members investigated, 11 had an abnormal cerebral MRI, eight of them being symptomatic, and 12 were asymptomatic with a normal MRI. The status of the two remaining members could not be established on the basis of clinical and MRI data. The family reported shares some striking features with other previously linked families--namely, a high clinical penetrance and the presence of multiple lesions within most of the affected members. A lod score of 4.04 was obtained with marker D7S657 with no recombinant. Significant lod scores were also obtained with D7S524 (Zmax=3.32 at 0=0.00) and D7S630 (Zmax=3.44 at 0=0.00). These results establish linkage of the condition found in this family to chromosome 7. Haplotype analysis strongly suggests that the gene is telomeric to D7S802 and centromeric to D7S479. CONCLUSIONS: These data confirm linkage of cerebral cavernous malformations to chromosome 7 in a non-Hispanic family.

Proliferating cell nuclear antigen (PCNA) in cerebral cavernomas: an immunocytochemical study of 42 cases.

BACKGROUND: The natural history and growth mechanisms of cerebral cavernous angiomas are unclear, which makes them difficult to manage. We attempted to evaluate the evolutive potential of cavernomas by studying the proliferative capacity of cells. METHODS: We studied 42 histologically verified cavernomas with monoclonal antibody to proliferating cell nuclear antigen (PCNA), an accessory protein of the cell cycle, the rate of which is increased in proliferative cells. The PCNA Labeling Index (PCNA LI) was calculated in each case, and the results were compared with histologic findings (lacy areas, thick walls, thrombi, hemosiderin) and clinical features (epilepsy, hematomas, pseudotumorous signs). RESULTS: Thirty-six of 42 cases (85.7%) revealed stained cells. PCNA LI ranged from 1 to 48% (mean: 23.39%). Statistical analyses showed a positive correlation between PCNA LI and the extent of lacy areas (p < 0.05). On the contrary, collagenous-walled and thrombotic areas rarely showed positively stained cells. We found no relationship between PCNA LI and clinical features. CONCLUSIONS: A proliferative capacity of endothelial cells does exist in some areas of cavernomas and may explain, besides thromboses and hemhorrages, the growth and even de novo appearance of these lesions. Occurrence of fragile blood cavities, thickening of others, and changes in blood flow may influence the evolution of lesions. Our results suggest that in cavernomas, some areas may undergo specific changes, which makes them more dynamic lesions than previously thought.

The in vivo metabolic pattern of low-grade brain gliomas: a positron emission tomographic study using 18F-fluorodeoxyglucose and 11C-L-methylmethionine.

OBJECTIVE: The object of the present study was to identify metabolic differences between low-grade astrocytomas and oligodendrogliomas and to improve their diagnosis and noninvasive assessment, because both types of tumors look very similar from the point of view of clinical and radiological data (as assessed by computed tomography and magnetic resonance imaging). METHODS: Before any aggressive treatment, 22 patients with primary low-grade gliomas (astrocytomas in 12 patients and oligodendrogliomas in 10) were investigated with positron emission tomography for both glucose metabolism (18F-fluorodeoxyglucose) and amino acid uptake (11C-L-methylmethionine). An original software that allows a full metabolic analysis of the tumor region of interest (defined from the T1-weighted magnetic resonance image) and compares tumor tissue uptake tracer concentrations with average healthy tissue values has been implemented for data processing. Heterogeneity of each individual tumor has been taken into account and was expressed in histograms, which provided data about the mean and also extreme and intermediate values of tracer concentrations and the way these values are distributed among the full tumor mass. RESULTS: It has been shown that both tumor types exhibit a glucose hypometabolism (slightly more pronounced with astrocytomas), whereas they strongly differ in methionine uptake, which is high in all oligodendrogliomas and either decreased, normal, or moderately increased in astrocytomas. This latter metabolic difference between both tumor populations may be partially explained by their different cell densities. CONCLUSION: This study suggests that despite similar radiological and clinical presentations, these two kinds of low-grade gliomas are metabolically different and could therefore have specific responses to different therapies. Moreover, their in vivo metabolic follow-up with positron emission tomography should rely on different parameters, depending on their histological type; methionine uptake may be more relevant than glucose metabolism in the follow-up of oligodendrogliomas.

[Does hemangioblastoma exist outside von Hippel-Lindau disease?]. / L'hémangioblastome existe-t-il en dehors de la maladie de von Hippel-Lindau?

Hemangioblastoma may arise in isolation ("sporadic" cases) or as a major manifestation of von Hippel-Lindau (VHL) disease, an autosomal dominant disorder with a prevalence of at least 1/36,000. In addition of central nervous system hemangioblastomas (cerebellum, spinal cord and retina), affected patients may develop renal cysts or carcinomas, pheochromocytomas and pancreatic cysts. A multidisciplinary group including neurosurgeons, geneticists, pathologists and clinicians from all involved specialities has been organized to develop a national registration of all hemangioblastoma and VHL patients. The findings of a preliminary 10-year study (1983-1993) conducted in France are presented. Two hundred thirteen cases of hemangioblastoma were reviewed for their location and genetic features. The majority (77%) of the tumors were located in the cerebellum whereas 23% were located inside the spinal canal. By thorough clinical examination of the patients and systematic genetic inquiry of their family background, it was found that 34.3% of the total (58.7% before age 30) were afflicted with VHL disease. Spinal hemangioblastomas were more often related to VHL disease than infra-tentorial locations (50% versus 36.6%). In addition, mean age at diagnosis in VHL disease was significantly younger than in sporadic cases (33.5 +/- 10 versus 43.6 +/- 15 years). Recent progress in VHL molecular genetics led to the identification of the mutated gene to the distal part of the short arm of chromosome 3 (3p25-3p26), paving the way to presymptomatic diagnosis and, hopefully, to elucidation of pathogenesis, which may offer a further glimpse into tumorigenesis in general. Because of the usually early adulthood onset, accurate presymptomatic diagnosis of affected members would be of great benefit to VHL families. However, the fact that very few mutations in the VHL gene are identified precludes molecular diagnosis of "sporadic" hemangioblastomas. In summary, this study reveals that VHL-related hemangioblastoma is a more common clinical problem that it was previously reported. Thus, all patients with an apparently isolated central nervous system hemangioblastoma should be investigated for evidence of VHL disease.

[Extramedullary hematopoiesis of thoracic and vertebral intraductal localization. Apropos of a case. Review of the literature]. / Hématopoïèse extra-médullaire de localisation thoracique et intra-canalaire vertébrale. A propos d'un cas. Revue de la littérature.

The authors report a case of extramedullary haematopoiesis, presenting in the form of several tumor masses in the posterior mediastinum and in the vertebral canal. The patient presented with oedema in his lower limbs due to compression of the inferior vena cava by the mediastinal masses. The asymptomatic mass in the vertebral canal was detected by magnetic resonance imaging. The patient was first operated on to avoid spinal cord compression by the tumor and subsequently to relieve compression of the inferior vena cava. The masses removed from the vertebral canal and the mediastinum were found on histologic examination to be extramedullary haematopoiesis. The cause of the disease was unknown in this case. Such disease is often disclosed in the course of hemolytic anaemias or other medullar deficiency diseases as a compensatory phenomenon when the bone marrow fails. An other explanation is that it is a manifestation of a myeloproliferative disorder in which heterotopic pluripotential cells are transformed into haematopoietic cells. The authors review 88 cases reported in the world literature.