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.

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.

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.

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.

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.

NF2 and Spinal Tumors

2006 ◽  
Vol 5 (2) ◽  
pp. 179 ◽  
Author(s):  
Dilys M. Parry
Keyword(s):  
Spinal Tumor ◽  
Spinal Tumors ◽  
Fisher Exact Test ◽  
Radiological Progression ◽  
Intramedullary Tumors ◽  
Exact Test ◽  
Extramedullary Tumor ◽  
Clinical Records ◽  
And Behavior

Object The authors conducted a study to examine the incidence, classification, and progression of spinal tumors in patients with neu-rofibromatosis 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.

Mechanisms of edema after gamma knife surgery for meningiomas

2005 ◽  
Vol 102 ◽  
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.

scholarly journals Clinical features of spinal schwannomas in 65 patients with schwannomatosis compared with 831 with solitary schwannomas and 102 with neurofibromatosis Type 2: a retrospective study at a single institution

2016 ◽  
Vol 24 (1) ◽  
pp. 145-154 ◽  
Author(s):  
Peng Li ◽  
Fu Zhao ◽  
Jing Zhang ◽  
Zhenmin Wang ◽  
Xingchao Wang ◽  
...  
Keyword(s):  
Clinical Features ◽  
Cauda Equina ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Spinal Tumors ◽  
Female Ratio ◽  
Initial Symptoms ◽  
Lumbar Area

OBJECT The aim of this study was to evaluate the clinical features of spinal schwannomas in patients with schwannomatosis and compare them with a large cohort of patients with solitary schwannomas and neurofibromatosis Type 2 (NF2). METHODS The study was a retrospective review of 831 patients with solitary schwannomas, 65 with schwannomatosis, and 102 with NF2. The clinical, radiographic, and pathological data were extracted with specific attention to the age at onset, location of tumors, initial symptoms, family history, and treatment outcome. RESULTS The male-to-female ratio of patients with schwannomatosis (72.3% vs 27.7%) was significantly higher than that of patients with solitary schwannomas (53.3% vs 46.7%) and NF2 (54.0% vs 46.0%), respectively (chi-square test, p = 0.012). The mean age at the first spinal schwannoma operation of patients with NF2 (24.7 ± 10.2 years) was significantly younger than that of patients with solitary schwannomas (44.8 ± 13.2 years) and schwannomatosis (44.4 ± 14.1 years; 1-way ANOVA, p < 0.001). The initial symptoms were similar among the 3 groups, with pain being the most common. The distribution of spinal tumors among the 3 groups was significantly different. The peak locations of spinal schwannomas in patients with solitary schwannomas were at C1–3 and T12–L3; in schwannomatosis, the peak location was at T12-L5. A preferred spinal location was not evident for intradural-extramedullary tumors in NF2. Only a slight prominence in the lumbar area could be observed. The patients in the 3 groups obtained similar benefits from the operation; the recovery rates in the patients with solitary schwannomas, NF2, and schwannomatosis were 50.1%, 38.0%, and 53.9%, respectively. The prognosis varied among spinal schwannomas in the patients with schwannomatosis. Up until the last date of follow-up, most patients with schwannomatosis (81.5%) had undergone a single spinal operation, but 12 patients (18.5%) had undergone multiple spinal operations. Patients with nonsegmental schwannomatosis or those with early onset disease seemed to have a poor prognosis; they were more likely to undergo multiple spinal operations. Small cauda equina nodules were common in patients with schwannomatosis (46.7%) and NF2 (86.9%); these small schwannomas appeared to have relatively static behavior. Two patients suspicious for schwannomatosis were diagnosed with NF2 with the detection of constitutional NF2 mutations; 1 had unilateral vestibular schwannoma, and the other had suspicious bilateral trigeminal schwannomas. CONCLUSIONS The clinical features of spinal schwannomas vary among patients with solitary schwannomas, NF2, and schwannomatosis. Spinal schwannomas of patients with NF2 appear to be more aggressive than those in patients with solitary schwannomas and schwannomatosis. Spinal schwannomas of schwannomatosis predominate in the lumbar area, and most of them can be treated successfully with surgery. The prognosis varies among spinal schwannomas of schwannomatosis; some patients may need multiple operations due to newly developed schwannomas. Sometimes, it is difficult to differentiate schwannomatosis from NF2 based on clinical manifestations. It is prudent to perform close follow-up examinations in patients with undetermined schwannomatosis and their offspring.

Benign spinal nerve sheath tumors: their occurrence sporadically and in neurofibromatosis types 1 and 2

1991 ◽  
Vol 74 (2) ◽  
pp. 248-253 ◽  
Author(s):  
Andrea L. Halliday ◽  
Raymond A. Sobel ◽  
Robert L. Martuza
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Spinal Nerve ◽  
Neurofibromatosis Type 2 ◽  
Content Type ◽  
Nerve Sheath Tumors ◽  
Nerve Sheath ◽  
Fine Print

✓ Benign spinal nerve sheath tumors (neurofibromas and schwannomas) often occur on dorsal nerve roots sporadically or in neurofibromatosis types 1 and 2. These are histologically benign tumors, and distinction between them is frequently not made by clinicians. To determine if there is a correlation between the histological pattern of benign spinal nerve sheath tumors and the type of neurofibromatosis, the clinical and pathological features of these tumors (86 surgical specimens and five autopsies) in 68 patients were reviewed. The patients were classified into one of four categories: neurofibromatosis type 1, neurofibromatosis type 2, uncertain, or sporadic. The diagnostic criteria used for neurofibromatosis types 1 and 2 were established by the National Institutes of Health. Patients who did not fulfill criteria for either neurofibromatosis type 1 or 2 but who had multiple nervous system tumors or other stigmata of neurofibromatosis were designated “uncertain.” Spinal nerve sheath tumors were considered sporadic in 42 cases (40 schwannomas and two neurofibromas). In the 14 patients with neurofibromatosis type 1, all spinal nerve sheath tumors were neurofibromas. In six of the seven patients with neurofibromatosis type 2, all spinal nerve sheath tumors were schwannomas. One patient with neurofibromatosis type 2 had a spinal nerve sheath schwannoma and a tumor with features of both tumor types. The authors conclude that spinal nerve sheath tumors in patients with neurofibromatosis type 1 are neurofibromas. In contrast, spinal nerve sheath tumors occurring in neurofibromatosis type 2 or sporadically are most frequently schwannomas. The distinct histological features of these tumors may reflect different pathogenetic mechanisms even though they arise at identical sites in neurofibromatosis types 1 and 2.

Stereotactic radiosurgery in the management of acoustic neuromas associated with neurofibromatosis Type 2

1999 ◽  
Vol 90 (5) ◽  
pp. 815-822 ◽  
Author(s):  
Brian R. Subach ◽  
Douglas Kondziolka ◽  
L. Dade Lunsford ◽  
David J. Bissonette ◽  
John C. Flickinger ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Neurofibromatosis Type ◽  
Tumor Control ◽  
Nerve Function ◽  
Content Type ◽  
Acoustic Neuromas ◽  
The Mean ◽  
Fine Print

Object. Stereotactically guided radiosurgery is one of the primary treatment modalities for patients with acoustic neuromas (vestibular schwannomas). The goal of radiosurgery is to arrest tumor growth while preserving neurological function. Patients with acoustic neuromas associated with neurofibromatosis Type 2 (NF2) represent a special challenge because of the risk of complete deafness. To define better the tumor control rate and long-term functional outcome, the authors reviewed their 10-year experience in treating these lesions.Methods. Forty patients underwent stereotactic radiosurgery at the University of Pittsburgh, 35 of them for solitary tumors. The other five underwent staged procedures for bilateral lesions (10 tumors, 45 total). Thirteen patients (with 29% of tumors) had undergone a median of two prior resections. The mean tumor volume at radiosurgery was 4.8 ml, and the mean tumor margin dose was 15 Gy (range 12–20 Gy).The overall tumor control rate was 98%. During the median follow-up period of 36 months, 16 tumors (36%) regressed, 28 (62%) remained unchanged, and one (2%) grew. In the 10 patients for whom more than 5 years of clinical and neuroimaging follow-up results were available (median 92 months), five tumors were smaller and five remained unchanged. Surgical resection was performed in three patients (7%) after radiosurgery; only one showed radiographic evidence of progression. Useful hearing (Gardner—Robertson Class I or II) was preserved in six (43%) of 14 patients, and this rate improved to 67% after modifications made in 1992. Normal facial nerve function (House—Brackmann Grade 1) was preserved in 25 (81%) of 31 patients. Normal trigeminal nerve function was preserved in 34 (94%) of 36 patients.Conclusions. Stereotactically guided radiosurgery is a safe and effective treatment for patients with acoustic tumors in the setting of NF2. The rate of hearing preservation may be better with radiosurgery than with other available techniques.

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