Spinal Hemangioblastomas Research Articles

Surgical management of isolated hemangioblastomas of the spinal cord.

Intramedullary hemangioblastomas are rare tumors, accounting for just 3% of all intraspinal neoplasms. The purpose of this study is to define the occurrence of isolated intramedullary hemangioblastomas and to analyze the role of the radiological studies and surgery for these lesions. The charts of 19 consecutive patients operated on for isolated spinal intramedullary hemangioblastoma were reviewed. Preoperatively, all patients underwent magnetic resonance imaging and nine underwent spinal angiography. For all patients, the surgical approach was via posterior laminectomy. Our study sample comprised 6 women and 13 men, with an average age of 31.5 years (range, 16-75 yr). The mean prodrome was 20.8 months. Pain was the most common complaint. In all cases, the neoplasms were associated with a syrinx or edema. Gross total resection was achieved in all patients. At last follow-up examination (mean, 50.1 mo), 13 patients (68%) had improved and 6 patients (32%) had stabilized as compared with their preoperative clinical status. Isolated intramedullary hemangioblastomas typically have an indolent clinical course. These tumors have characteristic imaging properties on magnetic resonance imaging and angiography. Surgical removal of these lesions results in excellent long-term functional outcome.

Hemangioblastomas of the central nervous system in von Hippel-Lindau syndrome and sporadic disease.

The presentation, screening, management, and clinical outcomes of patients who presented to our institution from 1973 to 1999 with central nervous system (CNS) hemangioblastomas in von Hippel-Lindau (VHL) syndrome and sporadic disease were analyzed. The surgical pathology database of our institution was searched to identify all patients with histologically verified CNS hemangioblastomas occurring from 1973 to 1999. The medical, radiological, surgical, pathological, and autopsy records from these patients were reviewed retrospectively and statistically analyzed. Forty patients (21 males and 19 females) presented with CNS hemangioblastomas. Twenty-five patients (62%) harbored sporadic hemangioblastomas. Fifteen patients (38%) had VHL syndrome. These 40 patients presented with 61 hemangioblastomas (8 patients had multiple lesions). Ten patients (25%) harbored spinal cord hemangioblastomas (5 patients had multiple lesions). Patients with VHL disease tended to present with neurological symptoms and signs at a younger age than patients with sporadic disease (P = 0.09), to present with multiple lesions (53%), and to develop new lesions (rate, 1 lesion/2.1 yr). Hemangioblastomas of the spinal cord were more prevalent in patients with VHL syndrome (P = 0.024). Neuroradiological screening of patients with VHL syndrome allowed identification of more than 75% of new lesions before they became symptomatic. Sixty-six surgical procedures were performed (12 patients required multiple operations). Six patients with VHL syndrome required surgery for new lesions. Surgical complications occurred in six patients (15%). Symptom resolution or arrest of progression at 1 year was documented in 88% of patients. Recurrence of symptoms from partially resected lesions occurred in eight patients (20%). No deaths associated with surgery occurred. One patient with sporadic disease and one patient with VHL syndrome (5%) died as a result of late medical complications from CNS hemangioblastomas. Surgical outcomes for patients with CNS hemangioblastomas are favorable. However, management of hemangioblastomas is a more difficult and prolonged endeavor for patients with VHL syndrome. In patients with VHL syndrome, neuroradiological screening allows identification of lesions before they become symptomatic. Because patients with VHL syndrome are at risk for development of new lesions, they require lifelong follow-up.

Recurrent (Nonfamilial) Hemangioblastomas Involving Spinal Nerve Roots: Case Report

Spinal nerve root hemangioblastomas are rare and are reported mainly in patients with von Hippel-Lindau (VHL) syndrome. The pathogenesis of so-called nonfamilial lesions is virtually unknown. We discuss, mainly from a molecular perspective, a unique patient with sporadic, recurrent hemangioblastomas restricted to spinal nerve roots.A 53-year-old man who had had a surgically corrected lumbosacral meningomyelocele presented on at least three occasions during a 17-year period with multifocal capillary hemangioblastomas involving spinal nerve roots. On each occasion, tumors appeared on a different nerve root, with the majority located in the midcervical segments. The patient had no clinical features or family history of VHL syndrome.To obtain a clearer understanding of the pathogenesis of this unusual case and its relationship to VHL syndrome, molecular analysis of the VHL gene was performed by use of complete sequence analysis and loss of heterozygosity studies on deoxyribonucleic acid derived from the patient's blood leukocytes and three separately resected hemangioblastomas.Germ-line molecular analysis performed on all three exons in the VHL gene coding region did not indicate that any mutations were present. Loss of heterozygosity analysis of deoxyribonucleic acid from the three hemangioblastoma resections showed normal heterozygosity in the 3p25-26 region. Complete VHL gene sequence analysis did not demonstrate a somatic mutation in the coding region of the VHL gene in any of the three tumors, thereby supporting the loss of heterozygosity data that a molecular event directly involving the VHL gene may not be the causative factor in their tumorigenesis.

Surgical treatment of spinal hemangioblastomas.

The routine use of magnetic resonance imaging (MRI) in recent years for the diagnostic assessment of the spinal column and especially for screening patients with von Hippel-Lindau (vHL) disease has shown that spinal hemangioblastomas (sHBs) are more common than assumed so far. Since most sHBs are thus discovered while they are still asymptomatic, especially in vHL disease, the question arises whether and when these tumors should be treated. The present article reports the results of the surgical treatment of sHBs using the protocol described below and compares them to the course in a control group of patients with conservatively treated sHBs. A total of 30 sHBs were treated microsurgically in 15 patients. Hemangioblastoma-associated cysts were merely opened in 14 cases, drained with the help of Teflon cotton in 2 of these cases, and not opened in 4 instances. Laminoplasties were performed with insertion of absorbable, MRI-compatible microosteosynthesis plates. Perioperatively, all patients were administered methylprednisolone according to the NASCIS (National Acute Spinal Cord Injury Study) scheme, and sensory evoked potentials were monitored intra-operatively in all cases. Nine patients in whom the course of primarily conservative treatment of a total of 17 asymptomatic sHBs was documented served as controls. The follow-up time was 7 to 51 months (mean 20) after surgery and 10 to 51 months (mean 21) in the control group. Preoperative HB-associated pareses showed transient postoperative deterioration (n = 5). The other accompanying neurological deficits improved in 6 HBs and remained unchanged in all other HBs (n = 19), of which 16 had been asymptomatic before surgery. In the control group, 6 HBs (in 6 different patients) became permanently symptomatic despite subsequent surgical treatment according to the study protocol. With the new diagnostic tools now available, microsurgical removal of spinal hemangioblastomas has a low morbidity rate, suggesting that surgical treatment should be considered even for asymptomatic sHBs in certain circumstances.

MR imaging of spinal hemangioblastoma.

MR Imaging of Spinal HemangioblastomaKim B. Baker1 2, Christopher J. Moran1, Franz J. Wippold, II1 3, James G. Smirniotopoulos3 4, Fabio J. Rodriguez5, Steven P. Meyers6 and Todd L. Siegal7Audio Available | Share

Syringomyelia in myotonic dystrophy due to spinal hemangioblastoma

Background Syringomyelia is an uncommon, poorly understood finding in patients with myotonic dystrophy. Methods We describe a patient with myotonic dystrophy and neck pain in whom an extensive neuroradiologic diagnostic work-up was carried out. Results Magnetic resonance imaging revealed a large intramedullary cavity extending from the bulbo–medullary junction to the conus medullaris. After intravenous Gadolinium-DTPA administration, an enhanced nodule was seen at T6. Spinal arteriography showed a single hypervascular nodule and slow flow perimedullary draining veins consistent with hemangioblastoma. After removal of the nodule, a partial collapse of the intramedullary cyst was observed. Conclusions Intramedullary tumors can underlie syringomyelia in patients with myotonic dystrophy and have to be actively investigated with modern neuroradiologic investigations.

Cervical Hemangioblastoma with a Past History of Subarachnoid Hemorrhage

Background Subarachnoid hemorrhage (SAH) with a spinal origin is a rare clinical entity. The most common source of SAH is an arteriovenous malformation. Only six cases of spinal hemangioblastomas causing SAH have been reported. Case Description This 48-year-old man had experienced severe headache 12 years earlier, which was diagnosed as SAH by computed tomography (CT) scan and lumbar puncture. However, cerebral angiography could not detect either aneurysm or arteriovenous malformation. Thereafter, he spent an uneventful life until he was incidentally diagnosed with a cervical tumor on magnetic resonance imaging (MRI) study for Meniere’s disease. The tumor was situated at the cervicomedullary junction, and fed by the left vertebral artery. Histologic findings of the tumor showed features typical of hemangioblastoma. Conclusions We describe a case of cervical spinal extramedullary hemangioblastoma with a past history of SAH. In our case, the SAH of 12 years ago perhaps occurred from the cervicomedullary junction hemangioblastoma. Since the etiology of SAH could not be detected at the first angiography, not only follow-up reangiography, but also MRI of the spinal cord and spinal angiography could have played an important role.

Mutations in the VHL tumor suppressor gene and associated lesions in families with von Hippel-Lindau disease from central Europe.

von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome predisposing to retinal, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma and pancreatic tumors. Clinically two types of the disease can be distinguished: VHL type 1 (without pheochromocytoma) and VHL type 2 (with pheochromocytoma). We report VHL germline mutations and trends in phenotypic variation in families from central Europe. We identified 28 mutations in 53/65 (81.5%) families with 18 (64%) mutations being unique to this population. Whereas types and distribution of mutations as well as a strong correlation of missense mutations with the VHL 2 phenotype were similar to those identified in other populations, these families have provided new insights into the molecular basis for variability in the VHL 2 phenotype. Seven different missense mutations in exons 1 and 3 varied in their biological consequences from a minimal VHL 2 phenotype with pheochromocytoma only to a full VHL 2 phenotype with RCC and pancreatic lesion. These findings contribute to a better understanding of the fundamental mechanisms of VHL disease and its phenotypic variability. Further, we have provided rapid VHL screening for the families in central Europe, which has resulted in improved diagnosis and clinical management.

Transthyretin (Prealbumin) Immunoreactivity in Renal Cell Carcinoma and Other Neoplasms

Transthyretin (prealbumin) previously was identified immunohistochemically in a majority of primary and metastatic renal cell carcinomas, whereas its presence was not detected in other adenocarcinomas. These findings suggested that transthyretin may be useful in differentiating renal cell carcinoma from other morphologically similar neoplasms. To further explore the use of transthyretin as immunohistochemical tumor marker, 24 primary and metastatic renal cell carcinomas of varying architectural patterns, cytoplasmic types, and nuclear grades, as well as tumors of other types that may resemble renal cell carcinoma, were examined with an antitransthyretin antibody using an avidin-biotin-peroxidase complex technique. A variety of normal tissues also was examined to define further the normal spectrum of transthyretin immunoreactivity. Transthyretin was detected in the neoplastic cells of 9 of 13 (69.2%) primary and 10 of 15 (66.7%) metastatic renal cell carcinomas. Transthyretin immunoreactivity correlated with the tumor architectural pattern but not with the type of cytoplasm or nuclear grade. In particular, tumors with an alveolar growth pattern showed consistent staining, whereas tumors with papillary or sarcomatoid growth patterns were more likely to lack transthyretin. In addition, one collecting duct carcinoma lacked prealbumin immunoreactivity. Diffuse transthyretin immunoreactivity was also detected in three of four (75%) hepatocellular carcinomas, and focal staining was present in seven of eight (87.5%) adrenocortical neoplasms, two of two spinal cord hemangioblastomas, one of two papillary carcinomas of the thyroid, one large-cell carcinoma of the lung, and one of four neuroendocrine tumors of the duodenum and pancreas. Other neoplasms studied were negative. Among normal tissues, transthyretin was found in proximal renal tubules, hepatocytes, and pancreatic islets of Langerhans but not in adrenal cortex or medulla, thyroid gland, exocrine pancreas, lung, skin, breast, duodenum, and brain. In summary, these results indicate that immunoreactive transthyretin is widely distributed in normal and neoplastic tissues. Thus, the immunohistochemical detection of transthyretin is of limited use in differentiating renal cell carcinoma from other morphologically similar neoplasms. A recent study by Jacobssen et al. (Histopathology 26:559-564, 1995) suggests that transthyretin immunoreactivity in renal cell carcinomas is due to reabsorption from serum and is not the result of synthesis by renal tubules.

Expression of the von Hippel-Lindau disease tumour suppressor gene during human embryogenesis.

The von Hippel-Lindau (VHL) disease product is thought to down-regulate transcription by antagonizing elongin-enhanced transcriptional elongation. Germline VHL gene mutations predispose to the development of retinal, cerebellar and spinal haemangioblastomas, renal cell carcinoma and phaeochromocytoma. In addition, somatic Inactivation of the VHL gene is frequent in sporadic renal cell carcinoma and haemangioblastoma. Regulation of transcript elongation is an important control mechanism for gene expression and the VHL gene might modify the expression of proto-oncogenes and growth suppressor genes during embryogenesis. We therefore investigated the expression of VHL mRNA during human embryogenesis by in situ hybridization studies at 4, 6 and 10 weeks post conception. Although VHL mRNA was expressed in all three germ layers, strong expression was noted in the central nervous system, kidneys, testis and lung. Within the kidney, VHL mRNA was differentially expressed within renal tubules suggesting that the VHL gene product may have a specific role in kidney development. Two alternatively spliced VHL mRNAs characterized by inclusion (isoform I) or exclusion (isoform II) of exon 2 are transcribed in adult tissues. To investigate if the two isoforms are differentially expressed during embryogenesis, VHL mRNA was reverse transcribed from 13 fetal tissues (8-10 weeks gestation). The quantitative distribution of VHL mRNA within fetal tissues reflected that seen by in situ hybridization and the ratio of the two VHL isoforms was similar between tissues. Although the genes regulated by the VHL gene product have not yet been identified, our findings are compatible with the hypothesis that VHL-mediated control of transcriptional elongation may have a role in normal human development.

A genetic register for von Hippel-Lindau disease.

A genetic register for von Hippel-Lindau disease was set up in the north west of England in 1990. Population statistics, clinical features, age at onset, and survival of 83 people affected with von Hippel-Lindau (VHL) disease were studied. In addition, the effectiveness of the screening programme used and the occurrence of central nervous system haemangioblastomas in the general population were examined. The diagnostic point prevalence of heterozygotes in the North Western Region was 1 center dot 18/100 000 (1/85 000) people, with an estimated birth incidence of 2 center dot 20/100 000 (1/45 500) live births. The mutation rate was estimated directly to be 1 center dot 4 x 10(-6)/gene/generation (1/714 200). The mean age at onset of first symptoms was 26 center dot 25 years, with cerebellar haemangioblastoma being the most common presenting manifestation (34 center dot 9% of cases). The mean age at diagnosis of VHL disease was 30 center dot 87 years. Overall, 50 patients (60 center dot 2%) developed a cerebellar haemangioblastoma, 34 (41 center dot 0%) a retinal angioma, 21 (25 center dot 3%) a renal cell carcinoma, 12 (14 center dot 5%) a spinal haemangioblastoma, and 12 (14 center dot 5%) a phaeochromocytoma. Mean age at diagnosis of renal cell carcinoma (38 center dot 9 years) was significantly higher than that for cerebellar haemangioblastoma (30 center dot 0 years) and retinal angioma (21.1 years). Mean age at death was 40 center dot 9 years with cerebellar haemangioblastoma being the most common cause (47 center dot 7% of deaths). A total of 65 VHL manifestations were diagnosed asymptomatically following appropriate clinical and radiological screening tests, and failure to detect manifestations of VHL disease in spite of appropriate screening occurred on only two occasions. The use of DNA linkage analysis and direct mutation testing reduced the personal risk of carrying the VHL gene to below 1% in 14 people. In addition to the 83 clinically affected subjects, three obligate carriers who were considered to be lesion free in spite of extensive screening tests were identified. Fourteen percent of all CNS haemangioblastomas on the regionally based Cancer Registry were found to occur as part of VHL disease, but investigations for VHL in apparently sporadic disease appeared to be limited.

Hemangioblastomas of the spinal cord and the brainstem: diagnostic and therapeutic features.

Hemangioblastomas of the spinal cord and the brainstem make up 4% of all spinal tumors and are less common than cerebellar hemangioblastomas. CT and MRI are essential for preoperative diagnosis. Nevertheless, cerebral and spinal angiography are also mandatory, since they allow a detailed study of the vascular situation, which is decisive for exact planning of a surgical strategy. The purpose of this study was to evaluate the diagnostic and therapeutic factors which influence surgical morbidity and postoperative outcome. Twelve patients harbouring spinal(8 cases) or medullary (4 cases) hemangioblastomas, all symptomatic with sensorimotor deficits corresponding to the level of the lesion were evaluated. All patients were treated in our department between December 1989 and September 1994. Complete resection of the lesion was achieved in each case. Postoperatively, none of the patients showed deterioration. Nine patients had immediate postoperative improvement of neurological signs and symptoms; in three patients the initial neurological deficits remained unchanged during the in-patient period. Late postoperative outcome demonstrated a clear improvement; in only one patient was there no change of the clinical signs, while in the other 11 patients a significant improvement of pre-existing neurological deficits was experienced. We conclude that microsurgical resection of spinal and medullary hemangioblastomas with low morbidity is feasible.

Neurofibromatosis type 2 and von Hippel-Lindau disease: from gene cloning to function.

Most of the genes for hereditary tumor syndromes cloned thus far have subsequently been shown to be mutated not only in the germlines and tumors from patients with the relatively rare inherited disease, but also in the much more common sporadic tumor counterparts in the general population. Thus, the isolation and functional characterization of genes associated with hereditary tumor syndromes have emerged as a major strategy to gain insights into some of the most fundamental mechanisms of tumorigenesis. The search for the genes causing two hereditary tumor syndromes of the nervous system, neurofibromatosis type 2 (NF2) and von Hippel-Lindau disease (VHL), has recently culminated in the cloning of both disease genes. This represents another successful application of the so-called positional cloning approach, i.e., the isolation of a hereditary disease gene with unknown function, based on the determination of its chromosomal location in the human genome. The gene for NF2, a syndrome typically associated with vestibular schwannomas and meningiomas, is homologous with a family of genes whose members appear to play an important role in bridging the cell membrane with the intracellular cytoskeleton, including moesin, ezrin, radixin, and protein 4.1. Recent mutation analyses have revealed that the NF2 tumor suppressor gene is frequently mutated not only in vestibular schwannomas and meningiomas from NF2 patients, but also in their sporadic counterparts, which represent approximately one-third of all human brain tumors. Furthermore, malignant human tumors seemingly unrelated to the NF2 syndrome, such as neural crest-derived malignant melanomas, as well as malignant mesotheliomas (a pleural mesoderm-derived tumor), have also been found to be frequently mutated or deleted in the NF2 locus, suggesting a broader role for the NF2 gene in the initiation and progression of human neoplasms. VHL is a rare tumor syndrome characterized by certain types of nervous system tumors (cerebellar and spinal hemangioblastomas as well as retinal angiomas), in conjunction with bilateral renal cell carcinomas and pheochromocytomas. Similar to NF2, recent genetic mutation studies have revealed that the VHL tumor suppressor gene is not only mutated in the hereditary tumors from VHL patients, but also in their sporadic counterparts. Importantly, the VHL gene represents the most frequently mutated cancer-related gene thus far identified in sporadic renal cell carcinoma. In contrast to most other hereditary cancer syndromes, however, VHL mutations are surprisingly specific for tumors typically associated with the VHL syndrome, and have not been detected in any other tumor type unrelated to VHL. The cloning and initial genetic characterization of the NF2 and VHL genes have now provided a rational basis for subsequent functional studies on the elucidation of the normal and tumor-associated cellular signaling pathways of these tumor suppressor genes.

Pregnancy complicated by von Hippel-Lindau disease

Von Hippel-Lindau disease is an autosomal-dominant genetic disorder with variable penetrance characterized by multiorgan hemangioblastomas and a predisposition to carcinoma. A 23-year-old pregnant woman at 35 weeks' gestation, with a family history of von Hippel-Lindau disease, presented with paraplegia caused by an acute intramedullary hemorrhage from a spinal hemangioma at the thoracic (T) 4-5 level. An unruptured hemangioblastoma was noted at the T7-8 level. A T3-6 laminectomy resulted in the improvement of symptoms. The postoperative period was complicated by autonomic dysreflexia and preterm labor. The woman was delivered by cesarean under epidural anesthesia. Pregnant patients with von Hippel-Lindau disease present problems related to hemangioblastomas of the central nervous system. Imaging studies of the central nervous system are mandatory for prompt recognition and treatment of complications related to intramedullary hemorrhage. If spinal hemangioblastomas are identified, cesarean delivery may be the most sensible choice.

Intramedullary hemorrhage in spinal cord hemangioblastoma

The authors describe two cases of intramedullary hemorrhage caused by thoracic hemangioblastoma. Both patients presented with acute paraplegia. The lesion in the first case was diagnosed by myelography and in the second by magnetic resonance imaging. Emergency surgical evacuation of the intramedullary hematoma and tumor was performed in these patients. Hemangioblastoma was confirmed by histopathological examination in both cases. Both patients remain paraplegic after 7 and 1 years, respectively. Intramedullary hemorrhage is a rare and devastating effect of spinal hemangioblastoma.

Identification of intragenic mutations in the von Hippel-Lindau disease tumour suppressor gene and correlation with disease phenotype.

Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign neoplasms, most frequently retinal, cerebellar and spinal haemangioblastoma, renal cell carcinoma, phaeochromocytoma and pancreatic tumours. We have previously detected large germline deletions by Southern analysis and pulsed field gel electrophoresis in 19% and 3% of VHL patients respectively. We have now investigated 94 VHL patients without large deletions for intragenic mutations using single strand conformation polymorphism and heteroduplex analysis. Forty different mutations were identified in 55 unrelated kindreds. A wide variety of mutations were detected including missense (n = 19), nonsense (n = 6), frameshift deletions or insertions (n = 12), in frame deletions (n = 2) and a splice donor site mutation (n = 1). The two most frequent mutations, were missense mutations at codon 238 (Arg-->Gln and Arg-->Trp) and were detected in five and four unrelated kindreds, respectively. VHL disease shows marked phenotypic variability and although phaeochromocytoma occurs in only about 7% of patients, marked interfamilial differences are observed. We examined the relationship between VHL gene mutations and phenotype in 65 kindreds. Large deletions or intragenic mutations predicted to cause a truncated protein were found in 36 of 53 families without phaeochromocytoma but only two of 12 families with phaeochromocytoma (chi 2 = 8.58; P < 0.01). Of 12 families with phaeochromocytoma 10 had missense mutations compared with 13 of 53 kindreds without phaeochromocytoma (chi 2 = 12.33; P < 0.001). In particular, substitution of an arginine at codon 238 (Arg-->Trp or Arg-->Gln) was associated with a high risk (62%) of phaeochromocytoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Preoperative Embolization of Brain and Spinal Hemangioblastomas

Preoperative Embolization of Brain and Spinal Hemangioblastomas

Preoperative Embolization of Brain and Spinal Hemangioblastomas

Large hemangioblastomas can be difficult to resect because of excessive bleeding. We report our experience with two patients whose large hemangioblastomas were embolized preoperatively and were totally resected with minimal blood loss and satisfactory postoperative outcome. Embolizations were carried out within 3 days of surgery, with the patient under general anesthesia, with 150- to 250-microns Contour emboli. A 65-year-old woman with progressive, severe myelopathy from a 4.5 x 2.1 x 1.4 cm intramedullary hemangioblastoma at T4 underwent embolization of the left T2 and T3 intercostal arteries; a 29-year-old man with Lindau's syndrome and posterior fossa hemorrhage from a 3.8 x 1.8 x 1.8 cm right cerebellar hemangioblastoma underwent embolization of the right posterior inferior cerebellar artery, two right anterior inferior cerebellar arteries, and a dural branch of the right vertebral artery. Embolization led to the complete obliteration of the tumoral blush without neurological sequelae. Both lesions were completely resected with a blood loss of 50 to 100 ml, with bleeding occurring mainly from the pseudocapsule of the lesion. Preoperative embolization of hemangioblastomas is a useful and relatively safe procedure that reduces blood loss at the time of surgery and allows complete resection.

Caesarean section and phaeochromocytoma resection in a patient with Von Hippel Lindau disease

This report describes the anaesthetic management of a women with a term gestation, Von Hippel Lindau disease (VHLD), and a phaeochromocytoma, scheduled for a combined phaeochromocytoma resection and Caesarean section. Von Hippel Lindau disease is characterized by diffuse haemangioblastomas of the central nervous system (CNS) and viscera. It is also associated with phaeochromocytomas and renal cell carcinomas. Patients frequently have asymptomatic spinal cord and intracranial pathology. The patient and her fetus presented a challenge because of the anaesthetic restrictions imposed by VHLD, and her pregnancy. She was also at risk of developing malignant hypertension from the phaeochromocytoma. The patient was not a candidate for regional anaesthesia because of the possibility of spinal cord haemangioblastomas. She had received adrenergic blockade with phentolamine (total 30 mg a day) and propranolol (total 40 mg a day) since the 27th wk of gestation in order to control hypertension secondary to the phaeochromocytoma. General anaesthesia was administered with aggressive management of hypertension with adrenergic blockers (labetalol 1.0 mg.kg-1 and esmolol 0.75 mg.kg-1) and sodium nitroprusside 1.5 micrograms.kg-1 (total). Before delivery of the baby, opioids, which could have resulted in a fetus with CNS depression, were avoided. After delivery, opioids (sufentanil 0.4 microgram.kg-1 x hr-1) were used to limit the use of inhalational anaesthesia which may contribute to uterine atony. Postoperative pain was managed with an intravenous narcotic infusion. Both patients had uneventful postoperative courses.

Isolated haemangioblastoma of spinal cord: report of 18 cases and a review of the literature.

Eighteen cases of isolated spinal haemangioblastoma are presented. 13 patients were male and 5 female; average age was 34 years. The site of the tumour was bulbo-cervical in 1 case, cervical in 6, cervico-thoracic in 2, thoracic in 7, thoraco-lumbar in 2. Surgical excision of the tumor was total in all cases and peri-operative mortality was 5%. At average follow-up of 11 years, 8 patients had died (4 from neurological causes and 4 from non-neurological disease), and 9 survived; symptoms and signs improved in 11 cases, and were not improved in 6. The biological and pathological characteristics of this tumour are reported in the light of the present 18 cases and those reported in the literature.