Predictors of vestibular schwannoma growth in patients with neurofibromatosis Type 2

2002 ◽  
Vol 96 (2) ◽  
pp. 217-222 ◽  
Author(s):  
Michael E. Baser ◽  
Erini V. Makariou ◽  
Dilys M. Parry
Keyword(s):  
Disease Severity ◽  
Growth Rates ◽  
Neurofibromatosis Type ◽  
Spinal Tumors ◽  
Patient Age ◽  
Content Type ◽  
Patient Âgé ◽  
Multiple Patients ◽  
Fine Print

Object. The results of two longitudinal studies of growth rates of vestibular schwannomas (VSs) in patients with neurofibromatosis Type 2 (NF2) differ as to whether VS growth rates decrease or increase with increasing patient age. The authors undertook this study to assess the relationship between VS growth rates and patient age and type of constitutional NF2 mutation; they also examined variability in VS growth rates among multiple patients in families with NF2. Methods. Gadolinium-enhanced magnetic resonance images obtained in 18 patients with inherited NF2 from 11 unrelated families were retrospectively analyzed. The patients had been observed for a median of 4 years. Volumes of the VSs were measured using a two-component box model (intrameatal and extrameatal parts measured separately). Single-strand conformation polymorphism analysis and Southern blot analysis were used to identify constitutional NF2 mutations. Growth rates of the VSs were highly variable, but tended to decrease with increasing patient age both at onset of signs or symptoms of NF2 (r2 = 0.35, p = 0.026) and at diagnosis (r2 = 0.33, p = 0.012). The VS growth rates did not vary significantly with the type of constitutional NF2 mutation or the number of non-VS cerebral or spinal tumors. The VS growth rates were highly variable within families and did not correspond to clinical indices of NF2 disease severity, such as patient age at symptom onset and the number of non-VS cerebral and spinal tumors. Conclusions. The growth rates of VSs in patients with NF2 are highly variable, but tend to decrease with increasing patient age. Clinical treatment of multiple patients in families with NF2 cannot be based on the expectations of similar VS growth rates, even when other clinical aspects of disease severity are similar.

Vestibular schwannoma growth in patients with neurofibromatosis Type 2: a longitudinal study

2002 ◽  
Vol 96 (2) ◽  
pp. 223-228 ◽  
Author(s):  
Victor-Felix Mautner ◽  
Michael E. Baser ◽  
Sarang D. Thakkar ◽  
Urs M. Feigen ◽  
J. M. Friedman ◽  
...  
Keyword(s):  
Growth Rates ◽  
Age At Onset ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Spinal Tumors ◽  
Content Type ◽  
Gradient Gel Electrophoresis ◽  
Temperature Gradient Gel Electrophoresis ◽  
Fine Print

Object. The factors that determine the growth rates of vestibular schwannomas (VSs) in patients with neurofibromatosis Type 2 (NF2) are unknown. The authors undertook this study to determine if clinical factors or type of constitutional NF2 mutation were associated with VS growth rates in cases of NF2. Methods. The authors reviewed serial gadolinium-enhanced magnetic resonance (MR) images of the head and full spine of 37 patients with sporadic NF2 who had been observed over periods ranging from 0.2 to 8 years (median 3.9 years) at a specialized referral clinic for NF2. A box model was used to calculate VS volumes so that tumor growth rates could be estimated. Temperature-gradient gel electrophoresis was used to screen for constitutional NF2 mutations. The VS growth rates tended to decrease with increasing patient age at onset of signs or symptoms (r2 = 0.23, p = 0.003) and at the time the baseline gadolinium-enhanced MR image was obtained (r2 = 0.38, p < 0.001). The authors did not find significant associations between VS growth rates and the number of non-VS cerebral or spinal tumors or different types of constitutional NF2 mutations. Conclusions. There is considerable variability in growth rates of VSs in patients with NF2, but they tend to be higher in patients who are younger at onset of signs or symptoms.

Association of proliferative activity and size in acoustic neuroma: implications for timing of surgery

2003 ◽  
Vol 98 (4) ◽  
pp. 807-811 ◽  
Author(s):  
Anan Bedavanija ◽  
Jürgen Brieger ◽  
Hans-Anton Lehr ◽  
Jan Maurer ◽  
Wolf J. Mann
Keyword(s):  
Acoustic Neuroma ◽  
Growth Rates ◽  
Tumor Size ◽  
Proliferative Activity ◽  
Ki 67 ◽  
Patient Age ◽  
Duration Of Symptoms ◽  
Content Type ◽  
Patient Âgé ◽  
Fine Print

Object. Acoustic neuroma is the most frequent benign tumor of the cerebellopontine angle, and surgery is still the most common form of treatment. To gain better insight into the dysregulated mechanisms causing growth of acoustic neuroma, the authors studied the proliferative activity of 34 consecutive samples by analyzing immunohistochemical staining with Ki-67 and proliferating cell nuclear antigen (PCNA), and apoptosis based on the terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling. Data from these analyses were correlated with clinical parameters (that is, tumor size, duration of symptoms, and patient age). Methods. Apoptotic cells were found in none of the tumors. Proliferation measured on staining with Ki-67 and PCNA correlated with tumor size, but not with patient age or duration of symptoms. The authors demonstrated that tumors 18 mm or smaller in diameter have lower proliferation indices and growth rates, compared with tumors larger than 18 mm with high proliferative indices and growth rates. Additionally, they observed that these more aggressive, larger tumors occur mostly in patients younger than 50 years of age. Conclusions. Patients with tumors larger than 18 mm in diameter and who are younger than 50 years of age sustain an enhanced risk for fast-growing tumors because of these lesions' enhanced proliferative activity. For these patients the authors recommend active therapy.

Spinal tumors in neurofibromatosis Type 2. Is emerging knowledge of genotype predictive of natural history?

2005 ◽  
Vol 2 (5) ◽  
pp. 574-579 ◽  
Author(s):  
Graham Dow ◽  
Nigel Biggs ◽  
Gareth Evans ◽  
Jimmie Gillespie ◽  
Richard Ramsden ◽  
...  
Keyword(s):  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Spinal Tumors ◽  
Fisher Exact Test ◽  
Radiological Progression ◽  
Content Type ◽  
Clinical Records ◽  
Fine Print

Object. The authors conducted a study to examine the incidence, classification, and progression of spinal tumors in patients with neurofibromatosis Type 2 (NF2) treated at a single center, and to examine relationships with the known mutational subtypes of NF2. Methods. They performed a retrospective review of clinical records, neuroimaging studies, and genetic data obtained in 61 patients with NF2. Forty-one (67%) of 61 patients harbored one or more spinal tumors. Thirty-four patients had undergone serial spinal magnetic resonance imaging during a mean follow-up period of 52 months (range 10–103 months; median 53 months). In 16 patients there were multiple extramedullary tumors smaller than 5 mm, which did not progress. Fourteen patients harbored at least one extramedullary tumor that was greater than 5 mm; of these, radiological progression was demonstrated or spinal tumor excision was performed during the follow-up period in eight cases (57%). Eleven patients harbored intramedullary cord tumors in addition to small and large extramedullary tumors, three (27%) of which exhibited radiological progression. In cases in which genotypes were known, protein-truncating mutations were significantly more likely to be associated with the presence of spinal tumors than in other types (p = 0.03, Fisher exact test). No associations between clinical behavior of spinal tumors and genotype, however, could be demonstrated. Conclusions. Spinal tumors in cases involving NF2 are heterogeneous in type, distribution, and behavior but larger-size tumors are more likely to progress significantly. Intramedullary tumors usually accompany multiple extramedullary tumors. In the authors' experience subtyping of the NF2 mutation has not yet influenced management. Protein-truncating mutations are associated with an increased prevalence of spinal tumors.

Age at symptom onset and long-term survival in patients with neurofibromatosis Type 2

2003 ◽  
Vol 99 (3) ◽  
pp. 480-483 ◽  
Author(s):  
Goro Otsuka ◽  
Kiyoshi Saito ◽  
Tetsuya Nagatani ◽  
Jun Yoshida
Keyword(s):  
Symptom Onset ◽  
Survival Rates ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Content Type ◽  
Fine Print

Object. Neurofibromatosis Type 2 (NF2) is an intractable disorder predisposing to multiple, recurrent tumors of the central nervous system (CNS). To clarify the survival rate and characteristics that predict poor survival, we retrospectively reviewed clinical data in cases of NF2. Methods. From among 283 patients with neurofibromatosis who had been registered in a nationwide study in Japan between 1986 and 1987, 74 patients with bilateral vestibular schwannomas were analyzed. The mean duration of follow up after diagnosis was 121 months (range 2–287 months). Results of a Kaplan—Meier product-limit analysis indicated that overall 5-, 10-, and 20-year patient survival rates following diagnosis of NF2 were 85, 67, and 38%, respectively. Early onset of the initial symptom significantly compromised survival; 5-, 10-, and 20-year survival rates in patients with symptom onset at an age younger than 25 years were 80, 60, and 28%, respectively, whereas in patients with symptom onset at an age of 25 years or older the rates were 100, 87, and 62%, respectively. Patients with small vestibular schwannomas at diagnosis (< 2 cm in diameter) had better rates of survival. Other variables such as sex, additional tumors in the CNS, or dermal abnormalities did not significantly affect survival. Conclusions. This first report of long-term follow-up results concerning the survival of patients with NF2 indicates an adverse effect of early symptom onset.

Mechanisms of edema after gamma knife surgery for meningiomas

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 1-3 ◽  
Author(s):  
Amr El Shehaby ◽  
Jeremy C. Ganz ◽  
Wael A. Reda ◽  
Ayman Hafez
Keyword(s):  
Gamma Knife ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Gamma Knife Surgery ◽  
Skull Defect ◽  
Brain Swelling ◽  
Content Type ◽  
Multiple Tumors ◽  
Fine Print

✓ The authors describe two patients in whom tumor swelling and brain swelling (and possible tumor swelling), respectively, developed after undergoing gamma knife surgery. One had a skull defect with a palpable parasagittal tumor. One had neurofibromatosis Type 2 with multiple tumors, one of which was parasagittal.

Analysis of loss of heterozygosity for chromosome 10 in patients with malignant astrocytic tumors: correlation with patient age and survival

2001 ◽  
Vol 95 (4) ◽  
pp. 651-659 ◽  
Author(s):  
Kenji Tada ◽  
Shoji Shiraishi ◽  
Takanori Kamiryo ◽  
Hideo Nakamura ◽  
Hirofumi Hirano ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Loss Of Heterozygosity ◽  
Low Grade ◽  
Astrocytic Tumors ◽  
Chromosome 10 ◽  
Patient Age ◽  
Content Type ◽  
Unfavorable Prognostic Factor ◽  
Patient Âgé ◽  
Fine Print

Object. The most frequent genetic abnormality in human malignant gliomas is loss of heterozygosity (LOH) on chromosome 10. Candidate genes on chromosome 10 that are associated with the prognosis of patients with anaplastic astrocytoma (AA) and glioblastoma (GBM) were evaluated. Methods. The authors used 12 fluorescent microsatellite markers on both arms of chromosome 10 to study LOH in 108 primary astrocytic tumors. The LOH on chromosome 10 was observed in 11 (32%) of 34 AAs and 34 (56%) of 61 GBMs. No LOH was detected in 13 low-grade gliomas. Loss of heterozygosity was not detected in any AA in the seven patients younger than 35 years, but it was discovered in 41% of the patients older than 35 years. The prognostic significance of LOH at each locus was evaluated in 89 patients older than 15 years; 33 (37%) had supratentorial AAs and 56 (63%) had supratentorial GBMs. The Cox proportional hazards model, adjusted for patient age at surgery, the preoperative Karnofsky Performance Scale score, and the extent of surgical resection revealed that LOH on marker D10S209 near the FGFR2 and DMBT1 genes was significantly associated with shorter survival in patients with AA. The LOH on markers D10S215 and D10S541, which contain the PTEN/MMAC1 gene between them, was significantly associated with shorter survival in patients with GBM. Conclusions. In the present study it is found that LOH on chromosome 10 is an age-dependent event for patients with AAs and that LOH on marker D10S209 near the FGFR2 and DMBT1 loci is a significantly unfavorable prognostic factor. It is also reported that LOH on the PTEN/MMAC1 gene is a significantly unfavorable prognostic factor in patients with GBM.

Multiple schwannomas: schwannomatosis or neurofibromatosis type 2?

1998 ◽  
Vol 89 (1) ◽  
pp. 36-41 ◽  
Author(s):  
Matti Tapio Seppälä ◽  
Markku Alarik Sainio ◽  
Matti Jouko Johannes Haltia ◽  
Jaakko Jyri Kinnunen ◽  
Kirsi Hannele Setälä ◽  
...  
Keyword(s):  
Clinical Course ◽  
Positive Family History ◽  
Neurofibromatosis Type ◽  
Magnetic Resonance Images ◽  
Neurofibromatosis Type 2 ◽  
Long Term Outcome ◽  
Content Type ◽  
Fine Print

Object. The aim of this study was to clarify the clinical outcome of schwannomatosis, a rare condition characterized by multiple nonvestibular schwannomas in the absence of meningiomas, intraspinal ependymomas, and other clinical signs of neurofibromatosis type 2 (NF2). Methods. Nine patients with schwannomatosis treated at one institution are presented and their clinical course during a median follow-up time of 9.9 years is discussed. The patients were typically middle-aged at the time of their first operation (median 43.5 years), none had a positive family history of schwannomatosis or NF2, and none showed cutaneous or ocular signs of NF2. On histopathological examination the tumors from the patients with schwannomatosis showed a lobular appearance and frequent Verocay bodies, signs indicating NF2, more often than 20 sporadic schwannomas that were investigated as controls. Two patients died of unrelated causes at 3.2 and 9.9 years, respectively, of follow up. Magnetic resonance images of the head and spine were obtained in seven patients at the end of the follow-up period. New spinal schwannomas were detected in one patient and a residual schwannoma in three. No germline mutations of the NF2 gene were found in these seven patients. Two additional patients originally included in the schwannomatosis group who were 8.6 and 11.7 years old at initial surgery had NF2. One was diagnosed at follow-up review and the other developed a fulminant disease that led to death in 4 years. Conclusions. The clinical course, long-term outcome, and genetic mechanism of schwannomatosis differ from that of NF2.

Sizes of ruptured and unruptured aneurysms in relation to their sites and the ages of patients

2002 ◽  
Vol 96 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Bryce Weir ◽  
Lew Disney ◽  
Theodore Karrison
Keyword(s):  
Cerebral Artery ◽  
Patient Age ◽  
Content Type ◽  
Unruptured Aneurysms ◽  
Ruptured Aneurysms ◽  
Patient Âgé ◽  
Risk Of Rupture ◽  
Mean Size ◽  
The Mean ◽  
Fine Print

Object. The authors explore the risk of rupture in aneurysms categorized by size. Methods. A computerized database of 945 patients with aneurysms treated between 1967 and 1987 was retrospectively established. All available clinical and radiological studies were abstracted. Because of the recent interest in the size of intracranial aneurysms in relation to their likelihood of rupture, the database was searched with respect to this parameter. In 390 patients representing 41% of all cases, aneurysms were measured by neuroradiologists at the time of diagnosis. In 78% of the 945 patients there was only one aneurysm, and of the 507 aneurysms that were measured, 60% were solitary. Of all patients, 86% had ruptured aneurysms. The average age of all patients was 47 years, and for those with ruptured aneurysms it was 46 years. Of the ruptured aneurysms, 77% were 10 mm or smaller, compared with 85% of the unruptured aneurysms. It was found that 40.3% of the ruptured aneurysms were on the anterior cerebral artery or anterior communicating artery, compared with 13% of the unruptured aneurysms. None of the cavernous internal carotid artery (ICA) aneurysms were ruptured and 65% of the ophthalmic artery (OphA) aneurysms were. Of the unruptured aneurysms, 15% were located in the cavernous ICA or the OphA. Of the ruptured aneurysms, 29% were on the middle cerebral artery, compared with 36% of the unruptured aneurysms. The mean size of ruptured and unruptured aneurysms showed no statistically significant increase with patient age, although the difference in size between the ruptured and unruptured aneurysms decreased with increasing age. The mean size of all ruptured aneurysms (10.8 mm) was significantly larger than the mean size of all unruptured aneurysms (7.8 mm, p < 0.001); the median sizes were 10 mm and 5 mm, respectively. The size of ruptured aneurysms in patients who died in the hospital was significantly larger than those in the patients who survived (12 mm compared with 9.9 mm, p = 0.004). Symptomatic unruptured aneurysms were significantly larger than incidental unruptured aneurysms (14.6 mm compared with 6.9 mm, p = 0.032), which were, in turn, larger than aneurysms that were unruptured and part of a multiple aneurysm constellation. Both ruptured and unruptured aneurysms were larger in male than in female patients, but not significantly. Conclusions. Site and patient age, as well as lesion size, may affect the chance of rupture.

Molecular alterations in the neurofibromatosis Type 2 gene and its protein rarely occurring in meningothelial meningiomas

2001 ◽  
Vol 94 (1) ◽  
pp. 111-117 ◽  
Author(s):  
James J. Evans ◽  
Sin-Soo Jeun ◽  
Joung H. Lee ◽  
Jyoti A. Harwalkar ◽  
Yigal Shoshan ◽  
...  
Keyword(s):  
Protein Expression ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Content Type ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Single Stranded Conformational Polymorphism ◽  
Fisher’S Exact Test ◽  
Fine Print

Object. The neurofibromatosis Type 2 (NF2) gene is the only tumor suppressor gene that has been clearly implicated in the development of benign meningiomas. Interestingly, previous data obtained by the authors indicate that reduced NF2 protein expression seldom occurs in meningothelial meningiomas, the most common histological type of meningioma. The goal of the current study was to explore further the hypothesis of NF2 gene-independent tumorigenesis of meningothelial meningiomas. Methods. The authors performed a mutational analysis of all 17 exons of the NF2 gene by using single-stranded conformational polymorphism (SSCP). In addition, expression levels of the NF2 protein and (µ-calpain, a protease suggested to inactivate the NF2 protein, were determined by immunoblotting analysis of 27 meningiomas (20 meningothelial and seven nonmeningothelial). Mutations of the NF2 gene were found in only one (5%) of 20 meningothelial meningiomas and three (43%) of seven nonmeningothelial tumors (Fisher's exact test, p = 0.042). The levels of NF2 protein were severely reduced in six (28.5%) of 21 meningothelial meningiomas, in contrast to six (86%) of seven nonmeningothelial meningiomas (Fisher's exact test, p = 0.023). Activation of (µ-calpain did not correlate with the status of NF2 protein expression in the meningiomas analyzed, demonstrating that (µ-calpain activation does not account for the loss of NF2 protein in meningiomas with apparently normal NF2 genes. Conclusions. These results clearly demonstrate that NF2 gene mutations and decreased NF2 protein expression rarely occur in meningothelial meningiomas compared with other histological types of meningiomas. The clinical behavior of meningothelial meningiomas, however, is similar to that of other benign meningiomas. It is likely, therefore, that the tumorigenesis of meningothelial meningiomas is the result of deleterious alterations of genes that have final phenotypical effects similar to inactivation of the NF2 gene.

Surgical management of brain-stem tumors in children: results and statistical analysis of 75 cases

1993 ◽  
Vol 79 (6) ◽  
pp. 845-852 ◽  
Author(s):  
Alain Pierre-Kahn ◽  
Jean-François Hirsch ◽  
Mathieu Vinchon ◽  
Christine Payan ◽  
Christian Sainte-Rose ◽  
...  
Keyword(s):  
Brain Stem ◽  
Malignant Tumors ◽  
Benign Tumors ◽  
Patient Age ◽  
Content Type ◽  
Patient Âgé ◽  
Significant Difference ◽  
Brain Stem Tumors ◽  
Subtotal Removal ◽  
Fine Print

A study was made of 75 children treated between 1970 and 1990, with partial, subtotal, or total removal of three intrinsic and 72 exophytic or surface brain-stem tumors. In all cases, the goal of surgery was to remove as much tumor as possible. Extent of removal was defined according to data obtained from postoperative computerized tomography or magnetic resonance imaging, and was considered partial when only a small amount of tumor was removed, subtotal when a few cubic millimeters of tumor was left, and total when no residual tumor was seen on postoperative radiological investigations. An ultrasonic aspirator was used for the 43 most recent operations. Among tumor removals without the aspirator, 24 (75%) were partial, eight (25%) subtotal, and none total; with the use of the aspirator, the number of partial removals decreased to 44.5% while that of subtotal and total removals increased to 32% and 23.5%, respectively. There were 69 gliomas (92%) and 47 benign tumors (62.6%). Forty-nine patients were irradiated postoperatively, and 14 of the 23 patients whose benign tumors were removed totally or subtotally did not undergo irradiation. This study showed that: 1) the overall prognosis of patients with malignant tumors was poor and was not improved by surgery; 2) the survival rate of those with benign tumors was significantly (p < 0.01) lower after partial removal than after total or subtotal removal (52% and 94%, respectively, at 5 years); 3) comparison of means and proportions (Student's and chi-squared tests) between benign and malignant tumors showed a significant difference relating to patient age (p < 0.03), peritumoral hypodensity (p < 0.001), and preoperative duration of symptoms (p < 0.001); 4) stepwise logistic regression analysis confirmed that two of these three variables were related to malignancy: namely, patient age at surgery (p < 0.03) and presence of peritumoral hypodensity (p < 0.001); and 5) routine postoperative irradiation was contraindicated after total or subtotal removal of benign tumors.

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