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Kadir Erkmen, Svetlana Pravdenkova and Ossama Al-Mefty

Petroclival meningiomas remain one of the most challenging intracranial tumors to treat surgically. This is attributable to their location deep within the skull base and their association with multiple critical neural and vascular structures. Over the years, many skull base approaches have been described that are meant to improve resection and decrease patient morbidity. Appropriate selection of the surgical approach requires a thorough preoperative evaluation of clinical and radiological factors. In this paper the authors retrospectively reviewed 97 patients treated surgically for petroclival meningiomas by the senior author (O.A.M.) between 1995 and 2005 to assess the factors used to determine the choice of surgical approach, and to assess complication rates based on the approach selected. The skull base approaches used in these patients included the middle fossa anterior petrosal, posterior petrosal, and combined petrosal approaches, and complete petrosectomy. Factors found to be important in determining the selection of approach included the size, location, and extension of the tumor, preoperative hearing evaluation, and venous sinus anatomy.

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Svetlana Pravdenkova, Ossama Al-Mefty, Jeffrey Sawyer and Muhammad Husain

Object

The preponderance of progesterone receptors (PRs) and the scarcity of estrogen receptors (ERs) in meningiomas are well known. The expression of PRs may relate to tumor grade and recurrence. Cytogenetic abnormalities are associated with aggressive behavior, recurrence, and progression. In this study, the authors focus on the prognostic implications of hormone receptors in meningiomas to help determine the clinical and biological aggressiveness of tumors and their correlations with cytogenetic abnormalities.

Methods

Two hundred thirty-nine patients with meningiomas were separated into three groups. Group 1 (PR-positive group) comprised patients whose meningiomas displayed expression of PRs alone. Group 2 (receptor-negative group) included patients whose lesions did not have receptors for either progesterone or estrogen. Group 3 (ER-positive group) included patients whose tumors displayed expression of ERs. Clinical and histological findings, proliferative indices, tumor recurrence, and cytogenetic findings were analyzed by performing the Fisher exact test.

Compared with the receptor-negative (Group 2) and ER-positive (Group 3) groups, the PR-positive group (Group 1) had a statistically significant lower proliferative index and a smaller number of patients in whom there were aggressive histopathological findings or changes in karyotype. In Groups 1, 2, and 3, the percentages of cases with aggressive histopathological findings were 10, 31, and 33%, respectively; the percentages of cases with chromosomal abnormalities were 50, 84, and 86%, respectively; and the percentages of cases in which there initially was no residual tumor but recurrence was documented were 5, 30, and 27%, respectively. A statistically significant increase in the involvement of chromosomes 14 and 22 was identified in receptor-negative and ER-positive de novo meningiomas, when compared with the PR-positive group. Abnormalities on chromosome 19 were statistically significantly higher in receptor-negative meningiomas than in PR-positive tumors.

Conclusions

The expression of the PR alone in meningiomas signals a favorable clinical and biological outcome. A lack of receptors or the presence of ERs in meningiomas correlates with an accumulation of qualitative and quantitative karyotype abnormalities, a higher proportional involvement of chromosomes 14 and 22 in de novo tumors, and an increasing potential for aggressive clinical behavior, progression, and recurrence of these lesions. Sex hormone receptor status should routinely be studied for its prognostic value, especially in female patients, and should be taken into account in tumor grading. The initial receptor status of a tumor may change in progression or recurrence of tumor.

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Emad Aboud, Mohammad Abolfotoh, Svetlana Pravdenkova, Abdulkerim Gokoglu, Murat Gokden and Ossama Al-Mefty

OBJECT

Epidermoid tumors arise from misplaced squamous epithelium and enlarge through the accumulation of desquamated cell debris. Optimal treatment consists of total removal of the capsule; therefore, giant and multicompartmental tumors are particularly challenging. A conservative attitude in handling the tumor capsule is common given concerns about capsule adherence to neurovascular structures, and thus the possibility of recurrence is accepted with the intent of minimizing complications. This study focuses on the outcome of surgery in patients with giant epidermoid tumors for which total capsule removal was the aim.

METHODS

The authors conducted a retrospective analysis of all patients with giant epidermoid tumors treated by the senior author (O.A.), who pursued total removal of the capsule through skull base approaches. Patients were divided into 2 groups: one including patients with de novo tumors and the other consisting of patients who presented with recurrent tumors.

RESULTS

Thirty-four patients had undergone 46 operations, and the senior author performed 38 of these operations in the study period. The average tumor dimensions were 55 × 36 mm, and 25 tumors had multicompartmental extensions. Total removal of the tumor and capsule was achieved with the aid of the microscope in 73% of the 26 de novo cases but in only 17% of the 12 recurrent tumor cases. The average follow-up among all patients was 111 months (range 10–480 months), and the average postsurgical follow-up was 56.8 months (range 6–137 months). There were 4 recurrences in the de novo group, and every case had had a small piece of tumor capsule left behind. One patient died after delayed rupture of a pseudoaneurysm. In the de novo group, the average preoperative Karnofsky Performance Scale (KPS) score was 71.42%, which improved to 87.14% on long-term follow-up. In the group with recurrences, the KPS score also improved on long-term follow-up, from 64.54% to 84.54%. In the de novo group, 3 cases (11.5%) had permanent cranial nerve deficits, and 4 cases (15.4%) had a CSF leak. In the recurrence group, 3 cases (25%) had new, permanent cranial nerve deficits, and 1 (8.3%) had a CSF leak. Two patients in this group developed hydrocephalus and required a shunt.

CONCLUSIONS

Total removal of the capsule of giant epidermoid tumors was achieved in 73% of patients with de novo tumors and was associated with improved function, low morbidity and mortality, and a lower risk of recurrence. Surgery in patients with recurrent tumors was associated with higher morbidity and persistence of the disease.

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Ossama Al-Mefty, Cahide Topsakal, Svetlana Pravdenkova, Jeffrey R. Sawyer and Michael J. Harrison

Object. Radiation-induced meningiomas are known to occur after high- and low-dose cranial radiation therapy. The goal of this study was to discern the distinguishing findings and characteristics of radiation-induced meningiomas.

Methods. The records of 16 patients (seven men and nine women) who fulfilled the criteria for radiation-induced meningiomas were retrospectively reviewed. Clinical, histopathological, cytokinetic, and cytogenetic findings as well as the patients' outcome were analyzed.

The mean age of the patients was 38.8 years and the mean tumor latency was 26.5 years. Five patients had multiple meningiomas in the irradiated field. The recurrence rate was 100% after the initial resection; 62% of patients had a second recurrence and 17% had a third recurrence. Thirty-eight percent of patients had atypical or malignant histopathological findings. The presence of progesterone receptors and low proliferation indices in these patients did not correlate with benign tumor behavior. Cytogenetic analysis showed multiple clonal aberrations in all tumors studied. The most frequent aberrations were found on chromosomes 1p, 6q, and 22. Derivative, lost, or additional chromosome 1p was found in 89% of cases and loss or deletion on chromosome 6 was found in 67%.

Conclusions. The age of patients at presentation with meningioma and the latency period of radiation-induced meningiomas are dose related. These tumors are more aggressive and are certain to recur, have a higher histopathological grade, and are associated with complex cytogenetic aberrations particularly involving 1p and 6q.

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Ahmed Nageeb M. Taha, Kadir Erkmen, Ian F. Dunn, Svetlana Pravdenkova and Ossama Al-Mefty

Object

Juxtasellar meningiomas frequently extend into the optic canal. Removing these meningiomas from the optic canal is crucial for favorable visual outcome.

Methods

The authors performed a retrospective analysis of 45 patients with anterior and middle fossa meningiomas with involvement of the optic pathway in whom surgery was performed by the senior author (O.A.M.) during the period from 1993 to 2007. Extent of resection and recurrence rates were determined by pre- and postoperative MR imaging studies. Visual outcomes were evaluated with full ophthalmological examinations performed before and after surgery.

Results

Forty-five patients (31 women and 14 men) were involved in this study; their mean age was 51.6 years. Patients were followed for a mean of 29.8 months (range 6–108 months). No surgery-related death occurred. The average tumor size was 3.1 cm. Total resection of the tumor (Simpson Grade I) was achieved in 32 patients (71.1%). Gross-total resection (Simpson Grades II and III) was achieved in 13 patients (28.9%). Only 1 patient harboring a left cavernous sinus meningioma had tumor recurrence and underwent repeat resection. Meningiomas extended into 58 optic canals in these cases; 13 patients showed extension into both optic canals. Visual disturbance was the main presenting symptom in 37 patients (82.2%); 8 patients had normal vision initially. Visual improvement after surgery was seen in 21 (57%) of 37 patients and in 27 (34.6%) of 78 affected eyes. Vision remained unchanged in 48 (61.5%) of 78 eyes. Transient postoperative visual deterioration occurred in 2 eyes (2.6%), with recovery to baseline over time. Only 1 (1.3%) of 78 eyes had permanent visual deterioration after surgery. The visual outcome was affected mainly by the tumor size, the preoperative visual status, and the duration of symptoms.

Conclusions

Involvement of the optic canal in meningiomas is frequent. It occurs in a wide variety of anterior skull base meningiomas and it can be bilateral. It is a prominent factor that affects the preoperative visual status and postoperative recovery. Decompression of the optic canal and removal of the tumor inside is a crucial step in the surgical management of these tumors to optimize visual recovery and prevent tumor recurrence.

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Rami Almefty, Ian F. Dunn, Svetlana Pravdenkova, Mohammad Abolfotoh and Ossama Al-Mefty

Object

The relentless natural progression of petroclival meningiomas mandates their treatment. The management of these tumors, however, is challenging. Among the issues debated are goals of treatment, outcomes, and quality of life, appropriate extent of surgical removal, the role of skull base approaches, and the efficacy of combined decompressive surgery and radiosurgery. The authors report on the outcome in a series of patients treated with the goal of total removal.

Methods

The authors conducted a retrospective analysis of 64 cases of petroclival meningiomas operated on by the senior author (O.A.) from 1988 to 2012, strictly defined as those originating medial to the fifth cranial nerve on the upper two-thirds of the clivus. The patients' average age was 49 years; the average tumor size (maximum diameter) was 35.48 ± 10.09 mm (with 59 tumors > 20 mm), and cavernous sinus extension was present in 39 patients. The mean duration of follow-up was 71.57 months (range 4–276 months).

Results

In 42 patients, the operative reports allowed the grading of resection. Grade I resection (tumor, dura, and bone) was achieved in 17 patients (40.4%); there was no recurrence in this group (p = 0.0045). Grade II (tumor, dura) was achieved in 15 patients (36%). There was a statistically significant difference in the rate of recurrence with respect to resection grade (Grades I and II vs other grades, p = 0.0052). In all patients, tumor removal was classified based on postoperative contrast-enhanced MRI, and gross-total resection (GTR) was considered to be achieved if there was no enhancement present; on this basis, GTR was achieved in 41 (64%) of 64 patients, with a significantly lower recurrence rate in these patients than in the group with residual enhancement (p = 0.00348). One patient died from pulmonary embolism after discharge.

The mean Karnofsky Performance Status (KPS) score was 85.31 preoperatively (median 90) and improved on follow-up to 88, with 30 patients (47%) having an improved KPS score on follow-up. Three patients suffered a permanent deficit that significantly affected their KPS. Cerebrospinal fluid leak occurred in 8 patients (12.5%), with 2 of them requiring exploration. Eighty-nine percent of the patients had cranial nerve deficits on presentation; of the 54 patients with more than 2 months of follow-up, 21 (32.8%) had persisting cranial nerve deficits. The overall odds of permanent cranial nerve deficit of treated petroclival meningioma was 6.2%. There was no difference with respect to immediate postoperative cranial nerve deficit in patients who had GTR compared with those who had subtotal resection.

Conclusions

Total removal (Grade I or II resection) of petroclival meningiomas is achievable in 76.4% of cases and is facilitated by the use of skull base approaches, with good outcome and functional status. In cases in which circumstances prevent total removal, residual tumors can be followed until progression is evident, at which point further intervention can be planned.

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Ossama Al-Mefty, Paulo A. S. Kadri, David M. Hasan, Gustavo Rassier Isolan and Svetlana Pravdenkova

Object

Midline clival lesions, whether involving the clivus or simply situated anterior to the brainstem, present a technical challenge for adequate exposure and safe resection. The authors describe, as a minimally invasive technique, an anterior clivectomy performed via an expanded transsphenoidal approach coupled with the use of a neuronavigation on mobile head and endoscopic-assisted technique. Wide and direct exposure, with the ability to resect extra- and intradural tumors, was achieved without mortality and with a low rate of complications.

Methods

Cadaveric dissections were performed to outline the landmarks and measure the window that is created by resecting the clivus anteriorly. The technique was used in 43 patients to resect tumors located at or invading the clivus. The initial exposure of the clivus was obtained via the sublabial transsphenoidal approach. The wall of the anterior maxilla, often on 1 side, was removed to allow a wide side-to-side opening of the nasal speculum. Using neuronavigation, the authors made clivectomy windows by drilling the clivus between anatomical landmarks. Bilateral intraoperative neurophysiological monitoring was used (somatosensory evoked potentials, brainstem auditory evoked responses, and cranial nerves VI–XII).

Results

Of the 43 patients, 26 were female and 17 were male, and they ranged in age from 3.5 to 76 years (mean 41.5 years). Thirty-eight patients harbored a chordoma and 5 a giant invasive pituitary adenoma.

Gross-total resection of the tumor was achieved in 34 cases (79%). Nine patients (21%) had residual tumor unreachable through the anterior clivectomy, and this required a second-stage resection. Four patients developed new transient extraocular movement deficits. One patient developed a permanent cranial nerve VI palsy. Twenty-seven patients with chordoma underwent postoperative proton-beam radiotherapy. Tumor recurred in 19% of these cases. In 3 patients a cerebrospinal fluid leak developed during hospitalization and was treated successfully. Two other patients presented with a delayed cerebrospinal fluid leak after radiotherapy. Only 1 patient, who had previously undergone Gamma Knife surgery, experienced postoperative hemiparesis.

Conclusions

A complete anterior clivectomy via a simple extension of the transsphenoidal approach allows the surgeon access to different lesions involving the clivus or situated anterior to the brainstem. The exposure is similar to that provided by more extensive transfacial approaches. Instrument manipulation is easy. Neuronavigation, endoscopy, and intraoperative monitoring are easily incorporated and enhance the capability and safety of this approach.

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Kaith K. Almefty, Svetlana Pravdenkova, Jeffrey R. Sawyer and Ossama Al-Mefty

Object

Cytogenetic studies of chordomas are scarce and show multiple changes involving different chromosomes. These abnormalities are implicated in the pathogenesis of chordoma, but the clinical significance of these changes is yet to be determined. In this study, the authors discuss the cytogenetic changes in a large series of skull base chordomas with long-term follow-up and focus on the impact of these changes on the prognosis, progression, and management of the disease.

Methods

The karyotypes of chordomas in 64 patients (36 men and 28 women) were studied in relation to survival and recurrence or progression over a mean follow-up period of 48 ± 37.5 months. The standard G-banding technique was used for karyotype analysis. Statistical analysis was performed with the Fisher exact test and ORs, and Kaplan-Meier curves were generated for survival and recurrence/progression of disease.

Results

Seventy-four percent of de novo chordomas had normal karyotypes and a 3% recurrence rate; there was a 45% recurrence rate in de novo tumors with abnormal karyotypes (p < 0.01). Recurrent tumors were associated with a high incidence of abnormal karyotype (75%). The OR for recurrence in lesions with an abnormal versus a normal karyotype was 12. Aberrations in chromosomes 3, 4, 12, 13, and 14 were associated with frequent recurrence and decreased survival time. Ninety-five percent of cases with progression involved chromosome 3 and/or 13. The median survival time was 4 months when both of these chromosomes had aberrations (p = 0.02).

Conclusions

Chordomas with normal karyotypes were associated with a low rate of recurrence and a long patient survival, and recurrent chordomas were associated with an abnormal karyotype, disease progression, and poor survival. De novo chordomas with normal karyotypes may be amenable to radical resection and adjunctive proton beam therapy. Recurrent and de novo chordomas with abnormal karyotypes were associated with complex cytogenetic abnormalities and a poor prognosis, particularly in the presence of aberrations underlying tumor progression in chromosomes 3, 4, 12, 13, and 14.

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Marcio S. Rassi, Sashank Prasad, Anil Can, Svetlana Pravdenkova, Rami Almefty and Ossama Al-Mefty

OBJECTIVE

Although meningiomas frequently involve the optic nerve, primary optic nerve sheath meningiomas (ONSMs) are rare, accounting for only 1% of all meningiomas. Given the high risk of vision loss with these tumors, surgical intervention is seldom considered, and radiation or observation is commonly applied. Here, the authors describe the visual outcomes for a series of patients who were treated with surgery aiming at maximal tumor resection and highlight their prognostic factors.

METHODS

The authors retrospectively analyzed the data for 8 patients with intracanalicular ONSMs who had been surgically treated by the senior author (O.A.) between 1998 and 2016. Meningiomas extending into the optic canal from the intracranial cavity (i.e., clinoid, sphenoid wing, tuberculum sellae, diaphragma sellae) were excluded. Diagnosis was based on ophthalmological, radiological, and intraoperative findings, which were confirmed by the typical histological findings. Preoperative, postoperative, and follow-up visual assessments were performed by neuro-ophthalmologists in all cases.

RESULTS

The patients included 7 females and 1 male. The mean age at diagnosis was 45.1 years (range 25.0–70.0 years). Mean duration of follow-up was 38.9 months (range 3.0–88.0 months). All patients reported visual complaints, and all had objective evidence of optic nerve dysfunction. Their evaluation included visual field, visual acuity, funduscopy, and retinal fiber thickness. Total resection was obtained in 4 cases. Comparing preoperative and postoperative visual function revealed that 4 patients had improvement at the last follow-up, 1 patient had stable vision, and 3 patients had decreased function but none had total vision loss. All patients with good preoperative visual acuity maintained this status following surgical treatment. There was no surgical mortality or infection. Operative complications included binocular diplopia in 4 patients, which remitted spontaneously.

CONCLUSIONS

Surgery can play a beneficial role in the primary treatment of ONSM, especially lesions located in the posterior third of the nerve. Total removal can be achieved with vision preservation or improvement, without major surgical complications, especially at early stages of the disease. Patients with good preoperative vision and CSF flow in the optic sheath have better chances of a favorable outcome than those with poor vision.

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Ossama Al-Mefty, Paulo A. S. Kadri, Svetlana Pravdenkova, Jeffrey R. Sawyer, Colin Stangeby and Muhammad Husain

Object. The malignant progression of benign tumors is well documented in gliomas and other systemic lesions. It is also well known that some meningiomas become progressively aggressive despite their original benign status. The theory of clonal evolution is widely believed to explain malignant progression in meningioma; however, the data used to explain stepwise progression have typically been derived from the cytogenetic analysis of different types of tumors of different grades and in different patients. In this study, the authors examined the data obtained in a group of patients with meningiomas that showed clear histopathological progression toward a higher grade of malignancy and then analyzed the underlying cytogenetic findings.

Methods. Among 175 patients with recurrent meningiomas, 11 tumors showed a histopathological progression toward a higher grade that was associated with an aggressive clinical course. Six tumors progressed to malignancy and five to the atypical category over a period averaging 112 months. Tests for MIB-1 and p53 and cytogenetic studies with the fluorescence in situ hybridization (FISH) method were performed in successive specimens obtained in four patients.

The MIB-1 value increased in subsequent samples of tumors. Cytogenetic analysis with FISH showed deletions of 22, 1p, and 14q. In all but one case, these aberrations were also present in the previous specimen despite its lower hispathological grade.

Conclusions. The authors documented the progression of meningiomas from benign to a higher histological grade. These tumors were associated with a complex karyotype that was present ab initio in a histologically lower-grade tumor, contradicting the stepwise clonal evolution model. Although it was limited to the tested probes, the FISH method appears to be more accurate than the standard cytogenetic one in detecting these alterations. Tumors that present with complex genetic alterations, even those with a benign histological grade, are potentially aggressive and require closer follow up.